nursing considerations in advanced midgut net · abdominal imaging (ct or mri) biochemical...
TRANSCRIPT
1
The case study presented in this brochure is based on a fictional patient Individual results may vary
Indication for Sandostatinreg LARreg Sandostatinreg LARreg (octreotide) is indicated for the treatment of patients with symptoms associated with functional gastro-entero-pancreatic endocrine tumors (eg carcinoid tumors with features of the carcinoid syndrome) and for the treatment of patients with advanced neuroendocrine tumors of the midgut or of unknown primary origin where non-midgut sites of origin have been excluded
Please see Important Safety Information on pages 8-13
NURSING CONSIDERATIONS IN ADVANCED MIDGUT NET
UNDERSTANDING THE APPROPRIATE
PATIENT FOR SANDOSTATINreg L ARreg
(OCTREOTIDE)
Not an actual patient or healthcare provider Copyright Rocketclips IncShutterstockcom
2
Consider the following patient
MEET WILLIAM55-YEAR-OLD MAN LIVING WITH CARCINOID SYNDROME
Diagnosis
Functional advanced midgut NET of the jejunum with hepatic metastases
Surgical History1-3
William has undergone 2 surgical procedures
1 ndash Resection of his midgut NET 2 ndash Hepatic arterial embolization
Ongoing Monitoring145dagger
Abdominal imaging (CT or MRI) Biochemical monitoring of CgA and 5-HIAA Echocardiogram as clinically indicated
Current Symptoms45
Flushing (~3x daily) and diarrhea (~10x daily)
Physician Recommendation6Dagger
Initiation of Sandostatinreg LARreg 20 mg every 4 weeks
Important NotesOften William is not able to leave the house due to the frequency of his symptoms
He hopes to get his symptoms under control and spend more time with his grandchildren
5-HIAA 5-hydroxyindoleacetic acid CgA chromogranin A CT computed tomography MRI magnetic resonance imaging NET neuroendocrine tumor
EVEN AFTER SURGERY SOME PATIENTS WILL STILL EXPERIENCE
SYMPTOMS PARTICULARLY IN THE PRESENCE OF HEPATIC METASTASES 23
MEDICAL THERAPY FOLLOWING SURGERYSandostatinreg LARreg is often prescribed for patients to help control symptoms associated with carcinoid syndrome and for patients with advanced midgut NET to help inhibit tumor growth6
Please see Important Safety Information on pages 8-13
The information on this page is a representative patient snapshot not a complete patient profile
dagger Please see recommended monitoring during Sandostatinreg LARreg treatment on page 5
DaggerPlease see important dosing information on page 5
Not an actual patient Copyright LeventeGyoriShutterstockcom
3
TALKING TO THE PATIENTIt is important to help William understand that it is normal to still have symptoms following surgery23 Medical therapy and lifestyle decisions can help William see improvements in his episodes of flushing and diarrhea6
Educate William on the goals of Sandostatinreg LARreg which include6
Inhibiting tumor growth
Alleviating symptoms associated with carcinoid syndrome (flushing and diarrhea)
In addition to discussing Williamrsquos medical therapy you can also help him identify lifestyle variables that can help with symptom control
CARCINOID SYNDROME AND THE 5 ldquoErsquosrdquoThere are 5 important variables that can cause or exacerbate symptoms of carcinoid syndrome
Eat78
Avoid caffeine dairy spicy and high-fat foods Consume smaller meals Keep a food diary to track symptom occurrence and
identify potential triggers
Exercise9
Talk to the physician prior to starting a new exercise routine Start slow Vigorous exercise can increase the risk of flushing episodes Stop exercise and notify the doctor if shortness of breath or chest
paindiscomfort is experienced
Emotions9 Keep stress levels low as it can trigger symptoms Identify stress-relief techniques (ie walking reading a book
meditation)
Epinephrine10
Avoid medicines containing epinephrinemdashit is one of the worst symptom triggers
- Commonly found in over-the-counter cold and allergy medications and Novocain
Ethanol7 Limit or avoid alcohol
The 5 Ersquos Advice for Patients
Please see Important Safety Information on pages 8-13
4
TREATMENT WITH SANDOSTATINreg LARreg
HOW IT WORKSSandostatinreg LARreg is a somatostatin analogue Somatostatin is the hormone in the brain that inhibits secretion of peptides and serotonin produced within the gastroenteropancreatic endocrine system Somatostatin also inhibits increased secretion of growth hormone6
Administration of Sandostatinreg LARreg in patients with carcinoid syndrome may result in improvement of symptoms particularly of flushing and diarrhea In many cases this is accompanied by a fall in plasma serotonin and reduced urinary excretion of 5-HIAA Administration of Sandostatinreg LARreg also works at the tumor site to inhibit growth in advanced NET of midgut or unknown primary tumor location6
Not an actual patient or healthcare provider Copyright PumtekShutterstockcom
A Phase III randomized double-blind placebo-controlled study11
IN THE PROMID TRIAL SANDOSTATINreg L ARreg MORE
THAN DOUBLED THE MEDIAN TIME TO PROGRESSION
VERSUS PL ACEBO REDUCING THE RELATIVE RISK OF
DISEASE PROGRESSION BY 6611
Please see Important Safety Information on pages 8-13
5
TREATMENT WITH SANDOSTATINreg LARreg
(cont)
IMPORTANT DOSING INFORMATIONIt is recommended to start treatment with the administration of 20-mg Sandostatinreg LARreg at 4-week intervals Patients on treatment with subcutaneous Sandostatinreg (octreotide acetate) should continue at the previously effective dosage for 2 weeks after the first injection of Sandostatinreg LARreg6
For patients in whom symptoms and biological markers are well controlled after 3 months of treatment the dose may be reduced to 10-mg Sandostatinreg LARreg every 4 weeks6
For patients in whom symptoms are only partially controlled after 3 months of treatment the dose may be increased to 30-mg Sandostatinreg LARreg every 4 weeks6
The recommended dose of Sandostatinreg LARreg for patients with advanced NET of the midgut or unknown primary tumor location is 30-mg every 4 weeks Treatment with Sandostatinreg LARreg for tumor control should be continued in the absence of tumor progression6
RECOMMENDED MONITORING DURING SANDOSTATIN reg LAR reg THERAPYThyroid function hepatic function glucose tolerance and antidiabetic treatment should be monitored during treatment with Sandostatinreg LARreg6
Ultrasonic examination of the gallbladder should occur prior to therapy initiation and at 6-month intervals to check for gallstones6
Patients with a history of vitamin B12 deprivation should have B12 levels monitored during therapy6
COMMON SIDE EFFECTS OF SANDOSTATIN reg LAR reg6
Diarrhea
Abdominal pain
Nausea
Flatulence
Headache
Gallstones
Hyperglycemia
Constipation
LEARN MORE ABOUT SANDOSTATINreg LARreg AT WWWSANDOSTATINCOM
Please see Important Safety Information on pages 8-13
6
NURSING CONSIDERATIONSThe following information should be reviewed with patients during their Sandostatinreg LARreg initiation visit
Goals of treatment6
Treatment schedule6 - Sandostatinreg LARreg injections by a healthcare
professional every 4 weeks
Current symptoms - Frequency and severity
The 5 Ersquos of carcinoid syndrome
Current medication list
Diarrhea and flushing episodes can put patients at risk for other problems Assess for
Risks associated with chronic diarrhea812-14
- Electrolyte imbalances
- Altered nutritional status
- Dehydration
- Impaired skin integrity
Respiratory and cardiac dysfunction related to flushing episodes9
- Wheezing
- Shortness of breath
- Tachycardia andor palpitations
Please see Important Safety Information on pages 8-13
7
PATIENT SUPPORT GROUPS Encourage your patients to find a support group with other patients with NET either online or in their area if they havenrsquot done so already A support group is a place where they can share their feelings and concerns hear othersrsquo stories and even help those who are just beginning their own journey
It may be harder for patients to find live support groups specific to NET Support groups dedicated to cancer in general should also be considered for the patient and their loved ones
Not an actual patient or healthcare provider Copyright RawpixelcomShutterstockcom
Please see Important Safety Information on pages 8-13
8
SANDOSTATINreg LARreg IMPORTANT SAFETY INFORMATION
Contraindications
Known hypersensitivity to octreotide or to any of the excipients (see list of excipients)
Special warnings and precautions for use
General
As GH-secreting pituitary tumors may sometimes expand causing serious complications (eg visual field defects) it is essential that all patients be carefully monitored If evidence of tumor expansion appears alternative procedures may be advisable
Thyroid function should be monitored in patients receiving prolonged treatment with octreotide
Hepatic function should be monitored during octreotide therapy
Cardiovascular related events
Common cases of bradycardia have been reported Dose adjustment of medicinal products such as beta blockers calcium channel blockers or agents to control fluid and electrolyte balance may be necessary (see section Interaction with other medicinal products and other forms of interaction)
Gallbladder and related events
Octreotide inhibits secretion of cholecystokinin resulting in reduced contractility of the gallbladder and an increased risk of sludge and stone formation Development of gallstones has been reported in 15 to 30 of long-term recipients of sc Sandostatinreg The prevalence in the general population (aged 40 to 60 years) is about 5 to 20 Long-term exposure to Sandostatinreg LARreg of patients with acromegaly or gastro-entero-pancreatic tumors suggests that treatment with Sandostatinreg LARreg does not increase the incidence of gallstone formation compared with sc treatment Ultrasonic examination of the gallbladder before and at about 6-monthly intervals during Sandostatinreg LARreg therapy is however recommended If gallstones do occur they are usually asymptomatic symptomatic stones should be treated either by dissolution therapy with bile acids or by surgery
Glucose metabolism
Because of its inhibitory action on growth hormone glucagon and insulin release Sandostatinreg LARreg may affect glucose regulation Post-prandial glucose tolerance may be impaired As reported for patients treated with sc Sandostatinreg in some instances the state of persistent hyperglycemia may be induced as a result of chronic administration Hypoglycemia has also been reported
In patients with concomitant Type I diabetes mellitus Sandostatinreg LARreg is likely to affect glucose regulation and insulin requirements may be reduced In non-diabetics and type II diabetics with partially intact insulin reserves Sandostatinreg sc administration may result in increases in post-prandial glycaemia It is therefore recommended to monitor glucose tolerance and antidiabetic treatment
In patients with insulinomas octreotide because of its greater relative potency in inhibiting the secretion of GH and glucagon than that of insulin and because of the shorter duration of its inhibitory action on insulin may increase the depth and prolong the duration of hypoglycemia These patients should be closely monitored
Please see Important Safety Information on pages 8-13
9
Nutrition
Octreotide may alter absorption of dietary fats in some patients
Depressed vitamin B12 levels and abnormal Schillingrsquos tests have been observed in some patients receiving octreotide therapy Monitoring of vitamin B12 levels is recommended during therapy with Sandostatinreg LARreg in patients who have a history of vitamin B12 deprivation
Sodium content
Sandostatinreg LARreg contains less than 1 mmol (23 mg) sodium per dose ie is essentially ldquosodium-freerdquo
Interaction with other medicinal products and other forms of interactionDose adjustment of medicinal products such as beta blockers calcium channel blockers or agents to control fluid and electrolyte balance may be necessary when Sandostatinreg LARreg is administered concomitantly (see Special warnings and precautions for use)
Dose adjustments of insulin and antidiabetic medicinal products may be required when Sandostatinreg LARreg is administered concomitantly (see Special warnings and precautions for use)
Octreotide has been found to reduce the intestinal absorption of ciclosporin and to delay that of cimetidine
Concomitant administration of octreotide and bromocriptine increases the bioavailability of bromocriptine
Limited published data indicate that somatostatin analogs might decrease the metabolic clearance of compounds known to be metabolized by cytochrome P450 enzymes which may be due to the suppression of growth hormone Since it cannot be excluded that octreotide may have this effect other drugs mainly metabolized by CYP3A4 and which have a low therapeutic index (eg quinidine terfenadine) should therefore be used with caution
Pregnancy breastfeeding and fertilityPregnancy
There is a limited amount of data (less than 300 pregnancy outcomes) from the use of octreotide in pregnant women and in approximately one third of the cases the pregnancy outcomes are unknown The majority of reports were received after postmarketing use of octreotide and more than 50 of exposed pregnancies were reported in patients with acromegaly Most women were exposed to octreotide during the first trimester of pregnancy at doses ranging from 100-1200 microgramsday of Sandostatinreg sc or 10-40 mgmonth of Sandostatinreg LARreg Congenital anomalies were reported in about 4 of pregnancy cases for which the outcome is known No causal relationship to octreotide is suspected for these cases
Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see Preclinical safety data)
As a precautionary measure it is preferable to avoid the use of Sandostatinreg LARreg during pregnancy (see Special warnings and precautions for use)
SANDOSTATINreg LARreg IMPORTANT SAFETY INFORMATION (cont)
Please see Important Safety Information on pages 8-13
10
Breastfeeding
It is unknown whether octreotide is excreted in human breast milk Animal studies have shown excretion of octreotide in breast milk Patients should not breastfeed during Sandostatinreg LARreg treatment
Fertility
It is not known whether octreotide has an effect on human fertility Late descent of the testes was found for male offsprings of dams treated during pregnancy and lactation Octreotide however did not impair fertility in male and female rats at doses of up to 1 mgkg body weight per day (see Preclinical safety data)
Effects on ability to drive and use machinesSandostatinreg LARreg has no or negligible influence on the ability to drive and use machines Patients should be advised to be cautious when driving or using machines if they experience dizziness astheniafatigue or headache during treatment with Sandostatinreg LARreg
Undesirable effects and adverse drug reactionsSummary of the safety profile
The most frequent adverse reactions reported during octreotide therapy include gastrointestinal disorders nervous system disorders hepatobiliary disorders and metabolism and nutritional disorders
The most commonly reported adverse reactions in clinical trials with octreotide administration were diarrhea abdominal pain nausea flatulence headache cholelithiasis hyperglycemia and constipation Other commonly reported adverse reactions were dizziness localized pain biliary sludge thyroid dysfunction (eg decreased thyroid stimulating hormone [TSH] decreased total T4 and decreased free T4) loose stools impaired glucose tolerance vomiting asthenia and hypoglycemia
Tabulated list of adverse reactions
The following adverse drug reactions listed in Table 1 have been accumulated from clinical studies with octreotide
Adverse drug reactions (Table 1) are ranked under heading of frequency the most frequent first using the following convention very common (ge110) common (ge1100 lt110) uncommon (ge11000 lt1100) rare (ge110000 lt11000) very rare (lt110000) including isolated reports Within each frequency grouping adverse reactions are ranked in order of decreasing seriousness
SANDOSTATINreg LARreg IMPORTANT SAFETY INFORMATION (cont)
Please see Important Safety Information on pages 8-13
11
Table 1 Adverse drug reactions reported in clinical studies
Gastrointestinal disorders
Very common Diarrhea abdominal pain nausea constipation flatulence
Common Dyspepsia vomiting abdominal bloating steatorrhea loose stools discoloration of feces
Nervous system disorders
Very common Headache
Common Dizziness
Endocrine disorders
Common Hypothyroidism thyroid dysfunction (eg decreased TSH decreased total T4 and decreased free T4)
Hepatobiliary disorders
Very common Cholelithiasis
Common Cholecystitis biliary sludge hyperbilirubinemia
Metabolism and nutrition disorders
Very common Hyperglycemia
Common Hypoglycemia impaired glucose tolerance anorexia
Uncommon Dehydration
General disorders and administration site conditions
Very common Injection site reactions
Common Asthenia
Investigations
Common Elevated transaminase levels
Skin and subcutaneous tissue disorders
Common Pruritus rash alopecia
Respiratory disorders
Common Dyspnea
Cardiac disorders
Common Bradycardia
Uncommon Tachycardia
SANDOSTATINreg LARreg IMPORTANT SAFETY INFORMATION (cont)
Please see Important Safety Information on pages 8-13
12
Table 2 Adverse drug reactions derived from spontaneous reports
Post-marketing
Spontaneously reported adverse reactions presented in Table 2 are reported voluntarily and it is not always possible to reliably establish frequency or a causal relationship to drug exposure
Description of selected adverse reactionsGastrointestinal disorders
In rare instances gastrointestinal side effects may resemble acute intestinal obstruction with progressive abdominal distension severe epigastric pain abdominal tenderness and guarding
The frequency of gastrointestinal adverse events is known to decrease over time with continued treatment
Injection site reactions
Injection site related reactions including pain burning redness hematoma hemorrhage pruritus or swelling were commonly reported in patients receiving Sandostatinreg LARreg however these events did not require any clinical intervention in the majority of the cases
Metabolism and nutrition disorders
Although measured fecal fat excretion may increase there is no evidence to date that long-term treatment with octreotide has led to nutritional deficiency due to malabsorption
Pancreatic enzymes
In very rare instances acute pancreatitis has been reported within the first hours or days of Sandostatinreg sc treatment and resolved on withdrawal of the drug In addition cholelithiasis induced pancreatitis has been reported for patients on long term Sandostatinreg sc treatment
Immune system disorders Anaphylaxis allergyhypersensitivity reactions
Skin and subcutaneous tissue disorders
Urticaria
Hepatobiliary disorders Acute pancreatitis acute hepatitis without cholestasis cholestatic hepatitis cholestasis jaundice cholestatic jaundice
Cardiac disorders Arrhythmias
Investigations Increased alkaline phosphatase levels increased gamma glutamyl transferase levels
SANDOSTATINreg LARreg IMPORTANT SAFETY INFORMATION (cont)
Please see Important Safety Information on pages 8-13
13
Cardiac disorders
In both acromegalic and carcinoid syndrome patients ECG changes were observed such as QT prolongation axis shifts early repolarization low voltage RS transition early R wave progression and nonspecific ST-T wave changes The relationship of these events to octreotide acetate is not established because many of these patients have underlying cardiac diseases (see Special warnings and precautions)
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorization of the medicinal product is important It allows continued monitoring of the benefitrisk balance of the medicinal product Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system
Overdose
A limited number of accidental overdoses of Sandostatinreg LARreg have been reported The doses ranged from 100 mg to 163 mgmonth of Sandostatinreg LARreg The only adverse event reported was hot flushes
Cancer patients receiving doses of Sandostatinreg LARreg up to 60 mgmonth and up to 90 mg2 weeks have been reported These doses were in general well tolerated however the following adverse events have been reported frequent urination fatigue depression anxiety and lack of concentration
The management of overdosage is symptomatic
List of excipients
Vial
Poly (DL-lactide-co-glycolide) 7835 of nominal1048790ll weight sterile mannitol 170 of nominal fill weight
Prefilled syringe
Kit without vial adaptersafety needle
One prefilled syringe (solvent for parenteral use) containing sodium carboxymethylcellulose 125 mg mannitol 15 mg water for injection qs ad 25 mL
Kit with vial adaptersafety needle
One prefilled syringe (solvent for parenteral use) containing sodium carboxymethylcellulose (14 mg) mannitol (12 mg) poloxamer 188 (4 mg) water for injection qs ad 2 mL
Pharmaceutical formulations may vary between countries
Please see the Summary of Product Characteristics
SANDOSTATINreg LARreg IMPORTANT SAFETY INFORMATION (cont)
Please see Important Safety Information on pages 8-13
14G-SAS-1157173317copy Novartis 2017
Novartis Pharma AG CH-4002 Basel Switzerland
References 1 Kunz PL Reidy-Lagunes D Anthony LB et al Consensus guidelines for the management and treatment of neuroendocrine tumors Pancreas 201342(4)557-577 2 Veenendaal LM Rinkes IHMB Lips CJM Hillegersberg RV Liver metastases of neuroendocrine tumours early reduction of tumour load to improve life expectancy World J Surg Oncol 2006435 3 Lee E Pachter HL Sarpel U Hepatic arterial embolization for the treatment of metastatic neuroendocrine tumors Int J Hepatol 20122012471203 4 Vinik AI Woltering EA OrsquoDorisio TM Go VLW Mamikunian G Diagnosing and treating gastroenteropancreatic tumors including ICD-9 codes In Neuroendocrine Tumors A Comprehensive Guide to Diagnosis and Management 5th ed Inglewood CA Inter Science Institute 20121-56 5 Grozinsky-Glasberg S Grossman AB Gross DJ Carcinoid heart disease from pathophysiology to treatmentndashlsquoSomething in the way it movesrsquo Neuroendocrinology 2015101(4)263- 273 6 Sandostatin LAR [Summary of Product Characteristics] Novartis 2016 7 Warner ME The Carcinoid Cancer Foundation Nutritional concerns for the carcinoid patient developing nutritional guidelines for persons with carcinoid disease httpwwwcarcinoidorgfor-patientsgeneral -informationnutritionnutritional-concerns-for-the-carcinoid-patient-developing-nutrition-guidelines -for-persons-with-carcinoid-disease Accessed January 30 2017 8 Cancer Research UK Tips on coping with diarrhea httpwwwcancerresearchukorgabout-cancercoping-with-cancercoping -physicallyboweltypesdiarrhoeamanagingtips-on-how-to-cope-with-diarrhoea Accessed January 30 2017 9 CancerNet Carcinoid tumor symptoms and signs httpwwwcancernetcancertypes carcinoidtumorsymptomsandsigns Accessed February 1 2017 10 Powell B Mukhtar AA Mills GH Carcinoid the disease and its implications for anaesthesia Continuing Education in Anaesthesia Critical Care amp Pain 201111(1)9-13 11 Rinke A Muumlller HH Schade-Brittinger C et al Placebo-controlled double-blind prospective randomized study on the effect of octreotide LAR in the control of tumor growth in patients with metastatic neuroendocrine midgut tumors a report from the PROMID study group J Clin Oncol 200927(28)4656-4663 12 Greenberger NJ Merck Manual Diarrhea httpwww merckmanualscomprofessionalgastrointestinal-disorderssymptoms-of-gi-disordersdiarrhea Accessed January 30 2017 13 Anthony L Freda PU From somatostatin to octreotide LAR evolution of a somatostatin analogue Curr Med Res Opin 200925(12)2989-2999 14 Litchford MD Dorner B Posthauer ME Malnutrition as a precursor of pressure ulcers Adv Wound Care 20143(1)54-63
Please see Important Safety Information on pages 8-13
2
Consider the following patient
MEET WILLIAM55-YEAR-OLD MAN LIVING WITH CARCINOID SYNDROME
Diagnosis
Functional advanced midgut NET of the jejunum with hepatic metastases
Surgical History1-3
William has undergone 2 surgical procedures
1 ndash Resection of his midgut NET 2 ndash Hepatic arterial embolization
Ongoing Monitoring145dagger
Abdominal imaging (CT or MRI) Biochemical monitoring of CgA and 5-HIAA Echocardiogram as clinically indicated
Current Symptoms45
Flushing (~3x daily) and diarrhea (~10x daily)
Physician Recommendation6Dagger
Initiation of Sandostatinreg LARreg 20 mg every 4 weeks
Important NotesOften William is not able to leave the house due to the frequency of his symptoms
He hopes to get his symptoms under control and spend more time with his grandchildren
5-HIAA 5-hydroxyindoleacetic acid CgA chromogranin A CT computed tomography MRI magnetic resonance imaging NET neuroendocrine tumor
EVEN AFTER SURGERY SOME PATIENTS WILL STILL EXPERIENCE
SYMPTOMS PARTICULARLY IN THE PRESENCE OF HEPATIC METASTASES 23
MEDICAL THERAPY FOLLOWING SURGERYSandostatinreg LARreg is often prescribed for patients to help control symptoms associated with carcinoid syndrome and for patients with advanced midgut NET to help inhibit tumor growth6
Please see Important Safety Information on pages 8-13
The information on this page is a representative patient snapshot not a complete patient profile
dagger Please see recommended monitoring during Sandostatinreg LARreg treatment on page 5
DaggerPlease see important dosing information on page 5
Not an actual patient Copyright LeventeGyoriShutterstockcom
3
TALKING TO THE PATIENTIt is important to help William understand that it is normal to still have symptoms following surgery23 Medical therapy and lifestyle decisions can help William see improvements in his episodes of flushing and diarrhea6
Educate William on the goals of Sandostatinreg LARreg which include6
Inhibiting tumor growth
Alleviating symptoms associated with carcinoid syndrome (flushing and diarrhea)
In addition to discussing Williamrsquos medical therapy you can also help him identify lifestyle variables that can help with symptom control
CARCINOID SYNDROME AND THE 5 ldquoErsquosrdquoThere are 5 important variables that can cause or exacerbate symptoms of carcinoid syndrome
Eat78
Avoid caffeine dairy spicy and high-fat foods Consume smaller meals Keep a food diary to track symptom occurrence and
identify potential triggers
Exercise9
Talk to the physician prior to starting a new exercise routine Start slow Vigorous exercise can increase the risk of flushing episodes Stop exercise and notify the doctor if shortness of breath or chest
paindiscomfort is experienced
Emotions9 Keep stress levels low as it can trigger symptoms Identify stress-relief techniques (ie walking reading a book
meditation)
Epinephrine10
Avoid medicines containing epinephrinemdashit is one of the worst symptom triggers
- Commonly found in over-the-counter cold and allergy medications and Novocain
Ethanol7 Limit or avoid alcohol
The 5 Ersquos Advice for Patients
Please see Important Safety Information on pages 8-13
4
TREATMENT WITH SANDOSTATINreg LARreg
HOW IT WORKSSandostatinreg LARreg is a somatostatin analogue Somatostatin is the hormone in the brain that inhibits secretion of peptides and serotonin produced within the gastroenteropancreatic endocrine system Somatostatin also inhibits increased secretion of growth hormone6
Administration of Sandostatinreg LARreg in patients with carcinoid syndrome may result in improvement of symptoms particularly of flushing and diarrhea In many cases this is accompanied by a fall in plasma serotonin and reduced urinary excretion of 5-HIAA Administration of Sandostatinreg LARreg also works at the tumor site to inhibit growth in advanced NET of midgut or unknown primary tumor location6
Not an actual patient or healthcare provider Copyright PumtekShutterstockcom
A Phase III randomized double-blind placebo-controlled study11
IN THE PROMID TRIAL SANDOSTATINreg L ARreg MORE
THAN DOUBLED THE MEDIAN TIME TO PROGRESSION
VERSUS PL ACEBO REDUCING THE RELATIVE RISK OF
DISEASE PROGRESSION BY 6611
Please see Important Safety Information on pages 8-13
5
TREATMENT WITH SANDOSTATINreg LARreg
(cont)
IMPORTANT DOSING INFORMATIONIt is recommended to start treatment with the administration of 20-mg Sandostatinreg LARreg at 4-week intervals Patients on treatment with subcutaneous Sandostatinreg (octreotide acetate) should continue at the previously effective dosage for 2 weeks after the first injection of Sandostatinreg LARreg6
For patients in whom symptoms and biological markers are well controlled after 3 months of treatment the dose may be reduced to 10-mg Sandostatinreg LARreg every 4 weeks6
For patients in whom symptoms are only partially controlled after 3 months of treatment the dose may be increased to 30-mg Sandostatinreg LARreg every 4 weeks6
The recommended dose of Sandostatinreg LARreg for patients with advanced NET of the midgut or unknown primary tumor location is 30-mg every 4 weeks Treatment with Sandostatinreg LARreg for tumor control should be continued in the absence of tumor progression6
RECOMMENDED MONITORING DURING SANDOSTATIN reg LAR reg THERAPYThyroid function hepatic function glucose tolerance and antidiabetic treatment should be monitored during treatment with Sandostatinreg LARreg6
Ultrasonic examination of the gallbladder should occur prior to therapy initiation and at 6-month intervals to check for gallstones6
Patients with a history of vitamin B12 deprivation should have B12 levels monitored during therapy6
COMMON SIDE EFFECTS OF SANDOSTATIN reg LAR reg6
Diarrhea
Abdominal pain
Nausea
Flatulence
Headache
Gallstones
Hyperglycemia
Constipation
LEARN MORE ABOUT SANDOSTATINreg LARreg AT WWWSANDOSTATINCOM
Please see Important Safety Information on pages 8-13
6
NURSING CONSIDERATIONSThe following information should be reviewed with patients during their Sandostatinreg LARreg initiation visit
Goals of treatment6
Treatment schedule6 - Sandostatinreg LARreg injections by a healthcare
professional every 4 weeks
Current symptoms - Frequency and severity
The 5 Ersquos of carcinoid syndrome
Current medication list
Diarrhea and flushing episodes can put patients at risk for other problems Assess for
Risks associated with chronic diarrhea812-14
- Electrolyte imbalances
- Altered nutritional status
- Dehydration
- Impaired skin integrity
Respiratory and cardiac dysfunction related to flushing episodes9
- Wheezing
- Shortness of breath
- Tachycardia andor palpitations
Please see Important Safety Information on pages 8-13
7
PATIENT SUPPORT GROUPS Encourage your patients to find a support group with other patients with NET either online or in their area if they havenrsquot done so already A support group is a place where they can share their feelings and concerns hear othersrsquo stories and even help those who are just beginning their own journey
It may be harder for patients to find live support groups specific to NET Support groups dedicated to cancer in general should also be considered for the patient and their loved ones
Not an actual patient or healthcare provider Copyright RawpixelcomShutterstockcom
Please see Important Safety Information on pages 8-13
8
SANDOSTATINreg LARreg IMPORTANT SAFETY INFORMATION
Contraindications
Known hypersensitivity to octreotide or to any of the excipients (see list of excipients)
Special warnings and precautions for use
General
As GH-secreting pituitary tumors may sometimes expand causing serious complications (eg visual field defects) it is essential that all patients be carefully monitored If evidence of tumor expansion appears alternative procedures may be advisable
Thyroid function should be monitored in patients receiving prolonged treatment with octreotide
Hepatic function should be monitored during octreotide therapy
Cardiovascular related events
Common cases of bradycardia have been reported Dose adjustment of medicinal products such as beta blockers calcium channel blockers or agents to control fluid and electrolyte balance may be necessary (see section Interaction with other medicinal products and other forms of interaction)
Gallbladder and related events
Octreotide inhibits secretion of cholecystokinin resulting in reduced contractility of the gallbladder and an increased risk of sludge and stone formation Development of gallstones has been reported in 15 to 30 of long-term recipients of sc Sandostatinreg The prevalence in the general population (aged 40 to 60 years) is about 5 to 20 Long-term exposure to Sandostatinreg LARreg of patients with acromegaly or gastro-entero-pancreatic tumors suggests that treatment with Sandostatinreg LARreg does not increase the incidence of gallstone formation compared with sc treatment Ultrasonic examination of the gallbladder before and at about 6-monthly intervals during Sandostatinreg LARreg therapy is however recommended If gallstones do occur they are usually asymptomatic symptomatic stones should be treated either by dissolution therapy with bile acids or by surgery
Glucose metabolism
Because of its inhibitory action on growth hormone glucagon and insulin release Sandostatinreg LARreg may affect glucose regulation Post-prandial glucose tolerance may be impaired As reported for patients treated with sc Sandostatinreg in some instances the state of persistent hyperglycemia may be induced as a result of chronic administration Hypoglycemia has also been reported
In patients with concomitant Type I diabetes mellitus Sandostatinreg LARreg is likely to affect glucose regulation and insulin requirements may be reduced In non-diabetics and type II diabetics with partially intact insulin reserves Sandostatinreg sc administration may result in increases in post-prandial glycaemia It is therefore recommended to monitor glucose tolerance and antidiabetic treatment
In patients with insulinomas octreotide because of its greater relative potency in inhibiting the secretion of GH and glucagon than that of insulin and because of the shorter duration of its inhibitory action on insulin may increase the depth and prolong the duration of hypoglycemia These patients should be closely monitored
Please see Important Safety Information on pages 8-13
9
Nutrition
Octreotide may alter absorption of dietary fats in some patients
Depressed vitamin B12 levels and abnormal Schillingrsquos tests have been observed in some patients receiving octreotide therapy Monitoring of vitamin B12 levels is recommended during therapy with Sandostatinreg LARreg in patients who have a history of vitamin B12 deprivation
Sodium content
Sandostatinreg LARreg contains less than 1 mmol (23 mg) sodium per dose ie is essentially ldquosodium-freerdquo
Interaction with other medicinal products and other forms of interactionDose adjustment of medicinal products such as beta blockers calcium channel blockers or agents to control fluid and electrolyte balance may be necessary when Sandostatinreg LARreg is administered concomitantly (see Special warnings and precautions for use)
Dose adjustments of insulin and antidiabetic medicinal products may be required when Sandostatinreg LARreg is administered concomitantly (see Special warnings and precautions for use)
Octreotide has been found to reduce the intestinal absorption of ciclosporin and to delay that of cimetidine
Concomitant administration of octreotide and bromocriptine increases the bioavailability of bromocriptine
Limited published data indicate that somatostatin analogs might decrease the metabolic clearance of compounds known to be metabolized by cytochrome P450 enzymes which may be due to the suppression of growth hormone Since it cannot be excluded that octreotide may have this effect other drugs mainly metabolized by CYP3A4 and which have a low therapeutic index (eg quinidine terfenadine) should therefore be used with caution
Pregnancy breastfeeding and fertilityPregnancy
There is a limited amount of data (less than 300 pregnancy outcomes) from the use of octreotide in pregnant women and in approximately one third of the cases the pregnancy outcomes are unknown The majority of reports were received after postmarketing use of octreotide and more than 50 of exposed pregnancies were reported in patients with acromegaly Most women were exposed to octreotide during the first trimester of pregnancy at doses ranging from 100-1200 microgramsday of Sandostatinreg sc or 10-40 mgmonth of Sandostatinreg LARreg Congenital anomalies were reported in about 4 of pregnancy cases for which the outcome is known No causal relationship to octreotide is suspected for these cases
Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see Preclinical safety data)
As a precautionary measure it is preferable to avoid the use of Sandostatinreg LARreg during pregnancy (see Special warnings and precautions for use)
SANDOSTATINreg LARreg IMPORTANT SAFETY INFORMATION (cont)
Please see Important Safety Information on pages 8-13
10
Breastfeeding
It is unknown whether octreotide is excreted in human breast milk Animal studies have shown excretion of octreotide in breast milk Patients should not breastfeed during Sandostatinreg LARreg treatment
Fertility
It is not known whether octreotide has an effect on human fertility Late descent of the testes was found for male offsprings of dams treated during pregnancy and lactation Octreotide however did not impair fertility in male and female rats at doses of up to 1 mgkg body weight per day (see Preclinical safety data)
Effects on ability to drive and use machinesSandostatinreg LARreg has no or negligible influence on the ability to drive and use machines Patients should be advised to be cautious when driving or using machines if they experience dizziness astheniafatigue or headache during treatment with Sandostatinreg LARreg
Undesirable effects and adverse drug reactionsSummary of the safety profile
The most frequent adverse reactions reported during octreotide therapy include gastrointestinal disorders nervous system disorders hepatobiliary disorders and metabolism and nutritional disorders
The most commonly reported adverse reactions in clinical trials with octreotide administration were diarrhea abdominal pain nausea flatulence headache cholelithiasis hyperglycemia and constipation Other commonly reported adverse reactions were dizziness localized pain biliary sludge thyroid dysfunction (eg decreased thyroid stimulating hormone [TSH] decreased total T4 and decreased free T4) loose stools impaired glucose tolerance vomiting asthenia and hypoglycemia
Tabulated list of adverse reactions
The following adverse drug reactions listed in Table 1 have been accumulated from clinical studies with octreotide
Adverse drug reactions (Table 1) are ranked under heading of frequency the most frequent first using the following convention very common (ge110) common (ge1100 lt110) uncommon (ge11000 lt1100) rare (ge110000 lt11000) very rare (lt110000) including isolated reports Within each frequency grouping adverse reactions are ranked in order of decreasing seriousness
SANDOSTATINreg LARreg IMPORTANT SAFETY INFORMATION (cont)
Please see Important Safety Information on pages 8-13
11
Table 1 Adverse drug reactions reported in clinical studies
Gastrointestinal disorders
Very common Diarrhea abdominal pain nausea constipation flatulence
Common Dyspepsia vomiting abdominal bloating steatorrhea loose stools discoloration of feces
Nervous system disorders
Very common Headache
Common Dizziness
Endocrine disorders
Common Hypothyroidism thyroid dysfunction (eg decreased TSH decreased total T4 and decreased free T4)
Hepatobiliary disorders
Very common Cholelithiasis
Common Cholecystitis biliary sludge hyperbilirubinemia
Metabolism and nutrition disorders
Very common Hyperglycemia
Common Hypoglycemia impaired glucose tolerance anorexia
Uncommon Dehydration
General disorders and administration site conditions
Very common Injection site reactions
Common Asthenia
Investigations
Common Elevated transaminase levels
Skin and subcutaneous tissue disorders
Common Pruritus rash alopecia
Respiratory disorders
Common Dyspnea
Cardiac disorders
Common Bradycardia
Uncommon Tachycardia
SANDOSTATINreg LARreg IMPORTANT SAFETY INFORMATION (cont)
Please see Important Safety Information on pages 8-13
12
Table 2 Adverse drug reactions derived from spontaneous reports
Post-marketing
Spontaneously reported adverse reactions presented in Table 2 are reported voluntarily and it is not always possible to reliably establish frequency or a causal relationship to drug exposure
Description of selected adverse reactionsGastrointestinal disorders
In rare instances gastrointestinal side effects may resemble acute intestinal obstruction with progressive abdominal distension severe epigastric pain abdominal tenderness and guarding
The frequency of gastrointestinal adverse events is known to decrease over time with continued treatment
Injection site reactions
Injection site related reactions including pain burning redness hematoma hemorrhage pruritus or swelling were commonly reported in patients receiving Sandostatinreg LARreg however these events did not require any clinical intervention in the majority of the cases
Metabolism and nutrition disorders
Although measured fecal fat excretion may increase there is no evidence to date that long-term treatment with octreotide has led to nutritional deficiency due to malabsorption
Pancreatic enzymes
In very rare instances acute pancreatitis has been reported within the first hours or days of Sandostatinreg sc treatment and resolved on withdrawal of the drug In addition cholelithiasis induced pancreatitis has been reported for patients on long term Sandostatinreg sc treatment
Immune system disorders Anaphylaxis allergyhypersensitivity reactions
Skin and subcutaneous tissue disorders
Urticaria
Hepatobiliary disorders Acute pancreatitis acute hepatitis without cholestasis cholestatic hepatitis cholestasis jaundice cholestatic jaundice
Cardiac disorders Arrhythmias
Investigations Increased alkaline phosphatase levels increased gamma glutamyl transferase levels
SANDOSTATINreg LARreg IMPORTANT SAFETY INFORMATION (cont)
Please see Important Safety Information on pages 8-13
13
Cardiac disorders
In both acromegalic and carcinoid syndrome patients ECG changes were observed such as QT prolongation axis shifts early repolarization low voltage RS transition early R wave progression and nonspecific ST-T wave changes The relationship of these events to octreotide acetate is not established because many of these patients have underlying cardiac diseases (see Special warnings and precautions)
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorization of the medicinal product is important It allows continued monitoring of the benefitrisk balance of the medicinal product Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system
Overdose
A limited number of accidental overdoses of Sandostatinreg LARreg have been reported The doses ranged from 100 mg to 163 mgmonth of Sandostatinreg LARreg The only adverse event reported was hot flushes
Cancer patients receiving doses of Sandostatinreg LARreg up to 60 mgmonth and up to 90 mg2 weeks have been reported These doses were in general well tolerated however the following adverse events have been reported frequent urination fatigue depression anxiety and lack of concentration
The management of overdosage is symptomatic
List of excipients
Vial
Poly (DL-lactide-co-glycolide) 7835 of nominal1048790ll weight sterile mannitol 170 of nominal fill weight
Prefilled syringe
Kit without vial adaptersafety needle
One prefilled syringe (solvent for parenteral use) containing sodium carboxymethylcellulose 125 mg mannitol 15 mg water for injection qs ad 25 mL
Kit with vial adaptersafety needle
One prefilled syringe (solvent for parenteral use) containing sodium carboxymethylcellulose (14 mg) mannitol (12 mg) poloxamer 188 (4 mg) water for injection qs ad 2 mL
Pharmaceutical formulations may vary between countries
Please see the Summary of Product Characteristics
SANDOSTATINreg LARreg IMPORTANT SAFETY INFORMATION (cont)
Please see Important Safety Information on pages 8-13
14G-SAS-1157173317copy Novartis 2017
Novartis Pharma AG CH-4002 Basel Switzerland
References 1 Kunz PL Reidy-Lagunes D Anthony LB et al Consensus guidelines for the management and treatment of neuroendocrine tumors Pancreas 201342(4)557-577 2 Veenendaal LM Rinkes IHMB Lips CJM Hillegersberg RV Liver metastases of neuroendocrine tumours early reduction of tumour load to improve life expectancy World J Surg Oncol 2006435 3 Lee E Pachter HL Sarpel U Hepatic arterial embolization for the treatment of metastatic neuroendocrine tumors Int J Hepatol 20122012471203 4 Vinik AI Woltering EA OrsquoDorisio TM Go VLW Mamikunian G Diagnosing and treating gastroenteropancreatic tumors including ICD-9 codes In Neuroendocrine Tumors A Comprehensive Guide to Diagnosis and Management 5th ed Inglewood CA Inter Science Institute 20121-56 5 Grozinsky-Glasberg S Grossman AB Gross DJ Carcinoid heart disease from pathophysiology to treatmentndashlsquoSomething in the way it movesrsquo Neuroendocrinology 2015101(4)263- 273 6 Sandostatin LAR [Summary of Product Characteristics] Novartis 2016 7 Warner ME The Carcinoid Cancer Foundation Nutritional concerns for the carcinoid patient developing nutritional guidelines for persons with carcinoid disease httpwwwcarcinoidorgfor-patientsgeneral -informationnutritionnutritional-concerns-for-the-carcinoid-patient-developing-nutrition-guidelines -for-persons-with-carcinoid-disease Accessed January 30 2017 8 Cancer Research UK Tips on coping with diarrhea httpwwwcancerresearchukorgabout-cancercoping-with-cancercoping -physicallyboweltypesdiarrhoeamanagingtips-on-how-to-cope-with-diarrhoea Accessed January 30 2017 9 CancerNet Carcinoid tumor symptoms and signs httpwwwcancernetcancertypes carcinoidtumorsymptomsandsigns Accessed February 1 2017 10 Powell B Mukhtar AA Mills GH Carcinoid the disease and its implications for anaesthesia Continuing Education in Anaesthesia Critical Care amp Pain 201111(1)9-13 11 Rinke A Muumlller HH Schade-Brittinger C et al Placebo-controlled double-blind prospective randomized study on the effect of octreotide LAR in the control of tumor growth in patients with metastatic neuroendocrine midgut tumors a report from the PROMID study group J Clin Oncol 200927(28)4656-4663 12 Greenberger NJ Merck Manual Diarrhea httpwww merckmanualscomprofessionalgastrointestinal-disorderssymptoms-of-gi-disordersdiarrhea Accessed January 30 2017 13 Anthony L Freda PU From somatostatin to octreotide LAR evolution of a somatostatin analogue Curr Med Res Opin 200925(12)2989-2999 14 Litchford MD Dorner B Posthauer ME Malnutrition as a precursor of pressure ulcers Adv Wound Care 20143(1)54-63
Please see Important Safety Information on pages 8-13
3
TALKING TO THE PATIENTIt is important to help William understand that it is normal to still have symptoms following surgery23 Medical therapy and lifestyle decisions can help William see improvements in his episodes of flushing and diarrhea6
Educate William on the goals of Sandostatinreg LARreg which include6
Inhibiting tumor growth
Alleviating symptoms associated with carcinoid syndrome (flushing and diarrhea)
In addition to discussing Williamrsquos medical therapy you can also help him identify lifestyle variables that can help with symptom control
CARCINOID SYNDROME AND THE 5 ldquoErsquosrdquoThere are 5 important variables that can cause or exacerbate symptoms of carcinoid syndrome
Eat78
Avoid caffeine dairy spicy and high-fat foods Consume smaller meals Keep a food diary to track symptom occurrence and
identify potential triggers
Exercise9
Talk to the physician prior to starting a new exercise routine Start slow Vigorous exercise can increase the risk of flushing episodes Stop exercise and notify the doctor if shortness of breath or chest
paindiscomfort is experienced
Emotions9 Keep stress levels low as it can trigger symptoms Identify stress-relief techniques (ie walking reading a book
meditation)
Epinephrine10
Avoid medicines containing epinephrinemdashit is one of the worst symptom triggers
- Commonly found in over-the-counter cold and allergy medications and Novocain
Ethanol7 Limit or avoid alcohol
The 5 Ersquos Advice for Patients
Please see Important Safety Information on pages 8-13
4
TREATMENT WITH SANDOSTATINreg LARreg
HOW IT WORKSSandostatinreg LARreg is a somatostatin analogue Somatostatin is the hormone in the brain that inhibits secretion of peptides and serotonin produced within the gastroenteropancreatic endocrine system Somatostatin also inhibits increased secretion of growth hormone6
Administration of Sandostatinreg LARreg in patients with carcinoid syndrome may result in improvement of symptoms particularly of flushing and diarrhea In many cases this is accompanied by a fall in plasma serotonin and reduced urinary excretion of 5-HIAA Administration of Sandostatinreg LARreg also works at the tumor site to inhibit growth in advanced NET of midgut or unknown primary tumor location6
Not an actual patient or healthcare provider Copyright PumtekShutterstockcom
A Phase III randomized double-blind placebo-controlled study11
IN THE PROMID TRIAL SANDOSTATINreg L ARreg MORE
THAN DOUBLED THE MEDIAN TIME TO PROGRESSION
VERSUS PL ACEBO REDUCING THE RELATIVE RISK OF
DISEASE PROGRESSION BY 6611
Please see Important Safety Information on pages 8-13
5
TREATMENT WITH SANDOSTATINreg LARreg
(cont)
IMPORTANT DOSING INFORMATIONIt is recommended to start treatment with the administration of 20-mg Sandostatinreg LARreg at 4-week intervals Patients on treatment with subcutaneous Sandostatinreg (octreotide acetate) should continue at the previously effective dosage for 2 weeks after the first injection of Sandostatinreg LARreg6
For patients in whom symptoms and biological markers are well controlled after 3 months of treatment the dose may be reduced to 10-mg Sandostatinreg LARreg every 4 weeks6
For patients in whom symptoms are only partially controlled after 3 months of treatment the dose may be increased to 30-mg Sandostatinreg LARreg every 4 weeks6
The recommended dose of Sandostatinreg LARreg for patients with advanced NET of the midgut or unknown primary tumor location is 30-mg every 4 weeks Treatment with Sandostatinreg LARreg for tumor control should be continued in the absence of tumor progression6
RECOMMENDED MONITORING DURING SANDOSTATIN reg LAR reg THERAPYThyroid function hepatic function glucose tolerance and antidiabetic treatment should be monitored during treatment with Sandostatinreg LARreg6
Ultrasonic examination of the gallbladder should occur prior to therapy initiation and at 6-month intervals to check for gallstones6
Patients with a history of vitamin B12 deprivation should have B12 levels monitored during therapy6
COMMON SIDE EFFECTS OF SANDOSTATIN reg LAR reg6
Diarrhea
Abdominal pain
Nausea
Flatulence
Headache
Gallstones
Hyperglycemia
Constipation
LEARN MORE ABOUT SANDOSTATINreg LARreg AT WWWSANDOSTATINCOM
Please see Important Safety Information on pages 8-13
6
NURSING CONSIDERATIONSThe following information should be reviewed with patients during their Sandostatinreg LARreg initiation visit
Goals of treatment6
Treatment schedule6 - Sandostatinreg LARreg injections by a healthcare
professional every 4 weeks
Current symptoms - Frequency and severity
The 5 Ersquos of carcinoid syndrome
Current medication list
Diarrhea and flushing episodes can put patients at risk for other problems Assess for
Risks associated with chronic diarrhea812-14
- Electrolyte imbalances
- Altered nutritional status
- Dehydration
- Impaired skin integrity
Respiratory and cardiac dysfunction related to flushing episodes9
- Wheezing
- Shortness of breath
- Tachycardia andor palpitations
Please see Important Safety Information on pages 8-13
7
PATIENT SUPPORT GROUPS Encourage your patients to find a support group with other patients with NET either online or in their area if they havenrsquot done so already A support group is a place where they can share their feelings and concerns hear othersrsquo stories and even help those who are just beginning their own journey
It may be harder for patients to find live support groups specific to NET Support groups dedicated to cancer in general should also be considered for the patient and their loved ones
Not an actual patient or healthcare provider Copyright RawpixelcomShutterstockcom
Please see Important Safety Information on pages 8-13
8
SANDOSTATINreg LARreg IMPORTANT SAFETY INFORMATION
Contraindications
Known hypersensitivity to octreotide or to any of the excipients (see list of excipients)
Special warnings and precautions for use
General
As GH-secreting pituitary tumors may sometimes expand causing serious complications (eg visual field defects) it is essential that all patients be carefully monitored If evidence of tumor expansion appears alternative procedures may be advisable
Thyroid function should be monitored in patients receiving prolonged treatment with octreotide
Hepatic function should be monitored during octreotide therapy
Cardiovascular related events
Common cases of bradycardia have been reported Dose adjustment of medicinal products such as beta blockers calcium channel blockers or agents to control fluid and electrolyte balance may be necessary (see section Interaction with other medicinal products and other forms of interaction)
Gallbladder and related events
Octreotide inhibits secretion of cholecystokinin resulting in reduced contractility of the gallbladder and an increased risk of sludge and stone formation Development of gallstones has been reported in 15 to 30 of long-term recipients of sc Sandostatinreg The prevalence in the general population (aged 40 to 60 years) is about 5 to 20 Long-term exposure to Sandostatinreg LARreg of patients with acromegaly or gastro-entero-pancreatic tumors suggests that treatment with Sandostatinreg LARreg does not increase the incidence of gallstone formation compared with sc treatment Ultrasonic examination of the gallbladder before and at about 6-monthly intervals during Sandostatinreg LARreg therapy is however recommended If gallstones do occur they are usually asymptomatic symptomatic stones should be treated either by dissolution therapy with bile acids or by surgery
Glucose metabolism
Because of its inhibitory action on growth hormone glucagon and insulin release Sandostatinreg LARreg may affect glucose regulation Post-prandial glucose tolerance may be impaired As reported for patients treated with sc Sandostatinreg in some instances the state of persistent hyperglycemia may be induced as a result of chronic administration Hypoglycemia has also been reported
In patients with concomitant Type I diabetes mellitus Sandostatinreg LARreg is likely to affect glucose regulation and insulin requirements may be reduced In non-diabetics and type II diabetics with partially intact insulin reserves Sandostatinreg sc administration may result in increases in post-prandial glycaemia It is therefore recommended to monitor glucose tolerance and antidiabetic treatment
In patients with insulinomas octreotide because of its greater relative potency in inhibiting the secretion of GH and glucagon than that of insulin and because of the shorter duration of its inhibitory action on insulin may increase the depth and prolong the duration of hypoglycemia These patients should be closely monitored
Please see Important Safety Information on pages 8-13
9
Nutrition
Octreotide may alter absorption of dietary fats in some patients
Depressed vitamin B12 levels and abnormal Schillingrsquos tests have been observed in some patients receiving octreotide therapy Monitoring of vitamin B12 levels is recommended during therapy with Sandostatinreg LARreg in patients who have a history of vitamin B12 deprivation
Sodium content
Sandostatinreg LARreg contains less than 1 mmol (23 mg) sodium per dose ie is essentially ldquosodium-freerdquo
Interaction with other medicinal products and other forms of interactionDose adjustment of medicinal products such as beta blockers calcium channel blockers or agents to control fluid and electrolyte balance may be necessary when Sandostatinreg LARreg is administered concomitantly (see Special warnings and precautions for use)
Dose adjustments of insulin and antidiabetic medicinal products may be required when Sandostatinreg LARreg is administered concomitantly (see Special warnings and precautions for use)
Octreotide has been found to reduce the intestinal absorption of ciclosporin and to delay that of cimetidine
Concomitant administration of octreotide and bromocriptine increases the bioavailability of bromocriptine
Limited published data indicate that somatostatin analogs might decrease the metabolic clearance of compounds known to be metabolized by cytochrome P450 enzymes which may be due to the suppression of growth hormone Since it cannot be excluded that octreotide may have this effect other drugs mainly metabolized by CYP3A4 and which have a low therapeutic index (eg quinidine terfenadine) should therefore be used with caution
Pregnancy breastfeeding and fertilityPregnancy
There is a limited amount of data (less than 300 pregnancy outcomes) from the use of octreotide in pregnant women and in approximately one third of the cases the pregnancy outcomes are unknown The majority of reports were received after postmarketing use of octreotide and more than 50 of exposed pregnancies were reported in patients with acromegaly Most women were exposed to octreotide during the first trimester of pregnancy at doses ranging from 100-1200 microgramsday of Sandostatinreg sc or 10-40 mgmonth of Sandostatinreg LARreg Congenital anomalies were reported in about 4 of pregnancy cases for which the outcome is known No causal relationship to octreotide is suspected for these cases
Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see Preclinical safety data)
As a precautionary measure it is preferable to avoid the use of Sandostatinreg LARreg during pregnancy (see Special warnings and precautions for use)
SANDOSTATINreg LARreg IMPORTANT SAFETY INFORMATION (cont)
Please see Important Safety Information on pages 8-13
10
Breastfeeding
It is unknown whether octreotide is excreted in human breast milk Animal studies have shown excretion of octreotide in breast milk Patients should not breastfeed during Sandostatinreg LARreg treatment
Fertility
It is not known whether octreotide has an effect on human fertility Late descent of the testes was found for male offsprings of dams treated during pregnancy and lactation Octreotide however did not impair fertility in male and female rats at doses of up to 1 mgkg body weight per day (see Preclinical safety data)
Effects on ability to drive and use machinesSandostatinreg LARreg has no or negligible influence on the ability to drive and use machines Patients should be advised to be cautious when driving or using machines if they experience dizziness astheniafatigue or headache during treatment with Sandostatinreg LARreg
Undesirable effects and adverse drug reactionsSummary of the safety profile
The most frequent adverse reactions reported during octreotide therapy include gastrointestinal disorders nervous system disorders hepatobiliary disorders and metabolism and nutritional disorders
The most commonly reported adverse reactions in clinical trials with octreotide administration were diarrhea abdominal pain nausea flatulence headache cholelithiasis hyperglycemia and constipation Other commonly reported adverse reactions were dizziness localized pain biliary sludge thyroid dysfunction (eg decreased thyroid stimulating hormone [TSH] decreased total T4 and decreased free T4) loose stools impaired glucose tolerance vomiting asthenia and hypoglycemia
Tabulated list of adverse reactions
The following adverse drug reactions listed in Table 1 have been accumulated from clinical studies with octreotide
Adverse drug reactions (Table 1) are ranked under heading of frequency the most frequent first using the following convention very common (ge110) common (ge1100 lt110) uncommon (ge11000 lt1100) rare (ge110000 lt11000) very rare (lt110000) including isolated reports Within each frequency grouping adverse reactions are ranked in order of decreasing seriousness
SANDOSTATINreg LARreg IMPORTANT SAFETY INFORMATION (cont)
Please see Important Safety Information on pages 8-13
11
Table 1 Adverse drug reactions reported in clinical studies
Gastrointestinal disorders
Very common Diarrhea abdominal pain nausea constipation flatulence
Common Dyspepsia vomiting abdominal bloating steatorrhea loose stools discoloration of feces
Nervous system disorders
Very common Headache
Common Dizziness
Endocrine disorders
Common Hypothyroidism thyroid dysfunction (eg decreased TSH decreased total T4 and decreased free T4)
Hepatobiliary disorders
Very common Cholelithiasis
Common Cholecystitis biliary sludge hyperbilirubinemia
Metabolism and nutrition disorders
Very common Hyperglycemia
Common Hypoglycemia impaired glucose tolerance anorexia
Uncommon Dehydration
General disorders and administration site conditions
Very common Injection site reactions
Common Asthenia
Investigations
Common Elevated transaminase levels
Skin and subcutaneous tissue disorders
Common Pruritus rash alopecia
Respiratory disorders
Common Dyspnea
Cardiac disorders
Common Bradycardia
Uncommon Tachycardia
SANDOSTATINreg LARreg IMPORTANT SAFETY INFORMATION (cont)
Please see Important Safety Information on pages 8-13
12
Table 2 Adverse drug reactions derived from spontaneous reports
Post-marketing
Spontaneously reported adverse reactions presented in Table 2 are reported voluntarily and it is not always possible to reliably establish frequency or a causal relationship to drug exposure
Description of selected adverse reactionsGastrointestinal disorders
In rare instances gastrointestinal side effects may resemble acute intestinal obstruction with progressive abdominal distension severe epigastric pain abdominal tenderness and guarding
The frequency of gastrointestinal adverse events is known to decrease over time with continued treatment
Injection site reactions
Injection site related reactions including pain burning redness hematoma hemorrhage pruritus or swelling were commonly reported in patients receiving Sandostatinreg LARreg however these events did not require any clinical intervention in the majority of the cases
Metabolism and nutrition disorders
Although measured fecal fat excretion may increase there is no evidence to date that long-term treatment with octreotide has led to nutritional deficiency due to malabsorption
Pancreatic enzymes
In very rare instances acute pancreatitis has been reported within the first hours or days of Sandostatinreg sc treatment and resolved on withdrawal of the drug In addition cholelithiasis induced pancreatitis has been reported for patients on long term Sandostatinreg sc treatment
Immune system disorders Anaphylaxis allergyhypersensitivity reactions
Skin and subcutaneous tissue disorders
Urticaria
Hepatobiliary disorders Acute pancreatitis acute hepatitis without cholestasis cholestatic hepatitis cholestasis jaundice cholestatic jaundice
Cardiac disorders Arrhythmias
Investigations Increased alkaline phosphatase levels increased gamma glutamyl transferase levels
SANDOSTATINreg LARreg IMPORTANT SAFETY INFORMATION (cont)
Please see Important Safety Information on pages 8-13
13
Cardiac disorders
In both acromegalic and carcinoid syndrome patients ECG changes were observed such as QT prolongation axis shifts early repolarization low voltage RS transition early R wave progression and nonspecific ST-T wave changes The relationship of these events to octreotide acetate is not established because many of these patients have underlying cardiac diseases (see Special warnings and precautions)
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorization of the medicinal product is important It allows continued monitoring of the benefitrisk balance of the medicinal product Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system
Overdose
A limited number of accidental overdoses of Sandostatinreg LARreg have been reported The doses ranged from 100 mg to 163 mgmonth of Sandostatinreg LARreg The only adverse event reported was hot flushes
Cancer patients receiving doses of Sandostatinreg LARreg up to 60 mgmonth and up to 90 mg2 weeks have been reported These doses were in general well tolerated however the following adverse events have been reported frequent urination fatigue depression anxiety and lack of concentration
The management of overdosage is symptomatic
List of excipients
Vial
Poly (DL-lactide-co-glycolide) 7835 of nominal1048790ll weight sterile mannitol 170 of nominal fill weight
Prefilled syringe
Kit without vial adaptersafety needle
One prefilled syringe (solvent for parenteral use) containing sodium carboxymethylcellulose 125 mg mannitol 15 mg water for injection qs ad 25 mL
Kit with vial adaptersafety needle
One prefilled syringe (solvent for parenteral use) containing sodium carboxymethylcellulose (14 mg) mannitol (12 mg) poloxamer 188 (4 mg) water for injection qs ad 2 mL
Pharmaceutical formulations may vary between countries
Please see the Summary of Product Characteristics
SANDOSTATINreg LARreg IMPORTANT SAFETY INFORMATION (cont)
Please see Important Safety Information on pages 8-13
14G-SAS-1157173317copy Novartis 2017
Novartis Pharma AG CH-4002 Basel Switzerland
References 1 Kunz PL Reidy-Lagunes D Anthony LB et al Consensus guidelines for the management and treatment of neuroendocrine tumors Pancreas 201342(4)557-577 2 Veenendaal LM Rinkes IHMB Lips CJM Hillegersberg RV Liver metastases of neuroendocrine tumours early reduction of tumour load to improve life expectancy World J Surg Oncol 2006435 3 Lee E Pachter HL Sarpel U Hepatic arterial embolization for the treatment of metastatic neuroendocrine tumors Int J Hepatol 20122012471203 4 Vinik AI Woltering EA OrsquoDorisio TM Go VLW Mamikunian G Diagnosing and treating gastroenteropancreatic tumors including ICD-9 codes In Neuroendocrine Tumors A Comprehensive Guide to Diagnosis and Management 5th ed Inglewood CA Inter Science Institute 20121-56 5 Grozinsky-Glasberg S Grossman AB Gross DJ Carcinoid heart disease from pathophysiology to treatmentndashlsquoSomething in the way it movesrsquo Neuroendocrinology 2015101(4)263- 273 6 Sandostatin LAR [Summary of Product Characteristics] Novartis 2016 7 Warner ME The Carcinoid Cancer Foundation Nutritional concerns for the carcinoid patient developing nutritional guidelines for persons with carcinoid disease httpwwwcarcinoidorgfor-patientsgeneral -informationnutritionnutritional-concerns-for-the-carcinoid-patient-developing-nutrition-guidelines -for-persons-with-carcinoid-disease Accessed January 30 2017 8 Cancer Research UK Tips on coping with diarrhea httpwwwcancerresearchukorgabout-cancercoping-with-cancercoping -physicallyboweltypesdiarrhoeamanagingtips-on-how-to-cope-with-diarrhoea Accessed January 30 2017 9 CancerNet Carcinoid tumor symptoms and signs httpwwwcancernetcancertypes carcinoidtumorsymptomsandsigns Accessed February 1 2017 10 Powell B Mukhtar AA Mills GH Carcinoid the disease and its implications for anaesthesia Continuing Education in Anaesthesia Critical Care amp Pain 201111(1)9-13 11 Rinke A Muumlller HH Schade-Brittinger C et al Placebo-controlled double-blind prospective randomized study on the effect of octreotide LAR in the control of tumor growth in patients with metastatic neuroendocrine midgut tumors a report from the PROMID study group J Clin Oncol 200927(28)4656-4663 12 Greenberger NJ Merck Manual Diarrhea httpwww merckmanualscomprofessionalgastrointestinal-disorderssymptoms-of-gi-disordersdiarrhea Accessed January 30 2017 13 Anthony L Freda PU From somatostatin to octreotide LAR evolution of a somatostatin analogue Curr Med Res Opin 200925(12)2989-2999 14 Litchford MD Dorner B Posthauer ME Malnutrition as a precursor of pressure ulcers Adv Wound Care 20143(1)54-63
Please see Important Safety Information on pages 8-13
4
TREATMENT WITH SANDOSTATINreg LARreg
HOW IT WORKSSandostatinreg LARreg is a somatostatin analogue Somatostatin is the hormone in the brain that inhibits secretion of peptides and serotonin produced within the gastroenteropancreatic endocrine system Somatostatin also inhibits increased secretion of growth hormone6
Administration of Sandostatinreg LARreg in patients with carcinoid syndrome may result in improvement of symptoms particularly of flushing and diarrhea In many cases this is accompanied by a fall in plasma serotonin and reduced urinary excretion of 5-HIAA Administration of Sandostatinreg LARreg also works at the tumor site to inhibit growth in advanced NET of midgut or unknown primary tumor location6
Not an actual patient or healthcare provider Copyright PumtekShutterstockcom
A Phase III randomized double-blind placebo-controlled study11
IN THE PROMID TRIAL SANDOSTATINreg L ARreg MORE
THAN DOUBLED THE MEDIAN TIME TO PROGRESSION
VERSUS PL ACEBO REDUCING THE RELATIVE RISK OF
DISEASE PROGRESSION BY 6611
Please see Important Safety Information on pages 8-13
5
TREATMENT WITH SANDOSTATINreg LARreg
(cont)
IMPORTANT DOSING INFORMATIONIt is recommended to start treatment with the administration of 20-mg Sandostatinreg LARreg at 4-week intervals Patients on treatment with subcutaneous Sandostatinreg (octreotide acetate) should continue at the previously effective dosage for 2 weeks after the first injection of Sandostatinreg LARreg6
For patients in whom symptoms and biological markers are well controlled after 3 months of treatment the dose may be reduced to 10-mg Sandostatinreg LARreg every 4 weeks6
For patients in whom symptoms are only partially controlled after 3 months of treatment the dose may be increased to 30-mg Sandostatinreg LARreg every 4 weeks6
The recommended dose of Sandostatinreg LARreg for patients with advanced NET of the midgut or unknown primary tumor location is 30-mg every 4 weeks Treatment with Sandostatinreg LARreg for tumor control should be continued in the absence of tumor progression6
RECOMMENDED MONITORING DURING SANDOSTATIN reg LAR reg THERAPYThyroid function hepatic function glucose tolerance and antidiabetic treatment should be monitored during treatment with Sandostatinreg LARreg6
Ultrasonic examination of the gallbladder should occur prior to therapy initiation and at 6-month intervals to check for gallstones6
Patients with a history of vitamin B12 deprivation should have B12 levels monitored during therapy6
COMMON SIDE EFFECTS OF SANDOSTATIN reg LAR reg6
Diarrhea
Abdominal pain
Nausea
Flatulence
Headache
Gallstones
Hyperglycemia
Constipation
LEARN MORE ABOUT SANDOSTATINreg LARreg AT WWWSANDOSTATINCOM
Please see Important Safety Information on pages 8-13
6
NURSING CONSIDERATIONSThe following information should be reviewed with patients during their Sandostatinreg LARreg initiation visit
Goals of treatment6
Treatment schedule6 - Sandostatinreg LARreg injections by a healthcare
professional every 4 weeks
Current symptoms - Frequency and severity
The 5 Ersquos of carcinoid syndrome
Current medication list
Diarrhea and flushing episodes can put patients at risk for other problems Assess for
Risks associated with chronic diarrhea812-14
- Electrolyte imbalances
- Altered nutritional status
- Dehydration
- Impaired skin integrity
Respiratory and cardiac dysfunction related to flushing episodes9
- Wheezing
- Shortness of breath
- Tachycardia andor palpitations
Please see Important Safety Information on pages 8-13
7
PATIENT SUPPORT GROUPS Encourage your patients to find a support group with other patients with NET either online or in their area if they havenrsquot done so already A support group is a place where they can share their feelings and concerns hear othersrsquo stories and even help those who are just beginning their own journey
It may be harder for patients to find live support groups specific to NET Support groups dedicated to cancer in general should also be considered for the patient and their loved ones
Not an actual patient or healthcare provider Copyright RawpixelcomShutterstockcom
Please see Important Safety Information on pages 8-13
8
SANDOSTATINreg LARreg IMPORTANT SAFETY INFORMATION
Contraindications
Known hypersensitivity to octreotide or to any of the excipients (see list of excipients)
Special warnings and precautions for use
General
As GH-secreting pituitary tumors may sometimes expand causing serious complications (eg visual field defects) it is essential that all patients be carefully monitored If evidence of tumor expansion appears alternative procedures may be advisable
Thyroid function should be monitored in patients receiving prolonged treatment with octreotide
Hepatic function should be monitored during octreotide therapy
Cardiovascular related events
Common cases of bradycardia have been reported Dose adjustment of medicinal products such as beta blockers calcium channel blockers or agents to control fluid and electrolyte balance may be necessary (see section Interaction with other medicinal products and other forms of interaction)
Gallbladder and related events
Octreotide inhibits secretion of cholecystokinin resulting in reduced contractility of the gallbladder and an increased risk of sludge and stone formation Development of gallstones has been reported in 15 to 30 of long-term recipients of sc Sandostatinreg The prevalence in the general population (aged 40 to 60 years) is about 5 to 20 Long-term exposure to Sandostatinreg LARreg of patients with acromegaly or gastro-entero-pancreatic tumors suggests that treatment with Sandostatinreg LARreg does not increase the incidence of gallstone formation compared with sc treatment Ultrasonic examination of the gallbladder before and at about 6-monthly intervals during Sandostatinreg LARreg therapy is however recommended If gallstones do occur they are usually asymptomatic symptomatic stones should be treated either by dissolution therapy with bile acids or by surgery
Glucose metabolism
Because of its inhibitory action on growth hormone glucagon and insulin release Sandostatinreg LARreg may affect glucose regulation Post-prandial glucose tolerance may be impaired As reported for patients treated with sc Sandostatinreg in some instances the state of persistent hyperglycemia may be induced as a result of chronic administration Hypoglycemia has also been reported
In patients with concomitant Type I diabetes mellitus Sandostatinreg LARreg is likely to affect glucose regulation and insulin requirements may be reduced In non-diabetics and type II diabetics with partially intact insulin reserves Sandostatinreg sc administration may result in increases in post-prandial glycaemia It is therefore recommended to monitor glucose tolerance and antidiabetic treatment
In patients with insulinomas octreotide because of its greater relative potency in inhibiting the secretion of GH and glucagon than that of insulin and because of the shorter duration of its inhibitory action on insulin may increase the depth and prolong the duration of hypoglycemia These patients should be closely monitored
Please see Important Safety Information on pages 8-13
9
Nutrition
Octreotide may alter absorption of dietary fats in some patients
Depressed vitamin B12 levels and abnormal Schillingrsquos tests have been observed in some patients receiving octreotide therapy Monitoring of vitamin B12 levels is recommended during therapy with Sandostatinreg LARreg in patients who have a history of vitamin B12 deprivation
Sodium content
Sandostatinreg LARreg contains less than 1 mmol (23 mg) sodium per dose ie is essentially ldquosodium-freerdquo
Interaction with other medicinal products and other forms of interactionDose adjustment of medicinal products such as beta blockers calcium channel blockers or agents to control fluid and electrolyte balance may be necessary when Sandostatinreg LARreg is administered concomitantly (see Special warnings and precautions for use)
Dose adjustments of insulin and antidiabetic medicinal products may be required when Sandostatinreg LARreg is administered concomitantly (see Special warnings and precautions for use)
Octreotide has been found to reduce the intestinal absorption of ciclosporin and to delay that of cimetidine
Concomitant administration of octreotide and bromocriptine increases the bioavailability of bromocriptine
Limited published data indicate that somatostatin analogs might decrease the metabolic clearance of compounds known to be metabolized by cytochrome P450 enzymes which may be due to the suppression of growth hormone Since it cannot be excluded that octreotide may have this effect other drugs mainly metabolized by CYP3A4 and which have a low therapeutic index (eg quinidine terfenadine) should therefore be used with caution
Pregnancy breastfeeding and fertilityPregnancy
There is a limited amount of data (less than 300 pregnancy outcomes) from the use of octreotide in pregnant women and in approximately one third of the cases the pregnancy outcomes are unknown The majority of reports were received after postmarketing use of octreotide and more than 50 of exposed pregnancies were reported in patients with acromegaly Most women were exposed to octreotide during the first trimester of pregnancy at doses ranging from 100-1200 microgramsday of Sandostatinreg sc or 10-40 mgmonth of Sandostatinreg LARreg Congenital anomalies were reported in about 4 of pregnancy cases for which the outcome is known No causal relationship to octreotide is suspected for these cases
Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see Preclinical safety data)
As a precautionary measure it is preferable to avoid the use of Sandostatinreg LARreg during pregnancy (see Special warnings and precautions for use)
SANDOSTATINreg LARreg IMPORTANT SAFETY INFORMATION (cont)
Please see Important Safety Information on pages 8-13
10
Breastfeeding
It is unknown whether octreotide is excreted in human breast milk Animal studies have shown excretion of octreotide in breast milk Patients should not breastfeed during Sandostatinreg LARreg treatment
Fertility
It is not known whether octreotide has an effect on human fertility Late descent of the testes was found for male offsprings of dams treated during pregnancy and lactation Octreotide however did not impair fertility in male and female rats at doses of up to 1 mgkg body weight per day (see Preclinical safety data)
Effects on ability to drive and use machinesSandostatinreg LARreg has no or negligible influence on the ability to drive and use machines Patients should be advised to be cautious when driving or using machines if they experience dizziness astheniafatigue or headache during treatment with Sandostatinreg LARreg
Undesirable effects and adverse drug reactionsSummary of the safety profile
The most frequent adverse reactions reported during octreotide therapy include gastrointestinal disorders nervous system disorders hepatobiliary disorders and metabolism and nutritional disorders
The most commonly reported adverse reactions in clinical trials with octreotide administration were diarrhea abdominal pain nausea flatulence headache cholelithiasis hyperglycemia and constipation Other commonly reported adverse reactions were dizziness localized pain biliary sludge thyroid dysfunction (eg decreased thyroid stimulating hormone [TSH] decreased total T4 and decreased free T4) loose stools impaired glucose tolerance vomiting asthenia and hypoglycemia
Tabulated list of adverse reactions
The following adverse drug reactions listed in Table 1 have been accumulated from clinical studies with octreotide
Adverse drug reactions (Table 1) are ranked under heading of frequency the most frequent first using the following convention very common (ge110) common (ge1100 lt110) uncommon (ge11000 lt1100) rare (ge110000 lt11000) very rare (lt110000) including isolated reports Within each frequency grouping adverse reactions are ranked in order of decreasing seriousness
SANDOSTATINreg LARreg IMPORTANT SAFETY INFORMATION (cont)
Please see Important Safety Information on pages 8-13
11
Table 1 Adverse drug reactions reported in clinical studies
Gastrointestinal disorders
Very common Diarrhea abdominal pain nausea constipation flatulence
Common Dyspepsia vomiting abdominal bloating steatorrhea loose stools discoloration of feces
Nervous system disorders
Very common Headache
Common Dizziness
Endocrine disorders
Common Hypothyroidism thyroid dysfunction (eg decreased TSH decreased total T4 and decreased free T4)
Hepatobiliary disorders
Very common Cholelithiasis
Common Cholecystitis biliary sludge hyperbilirubinemia
Metabolism and nutrition disorders
Very common Hyperglycemia
Common Hypoglycemia impaired glucose tolerance anorexia
Uncommon Dehydration
General disorders and administration site conditions
Very common Injection site reactions
Common Asthenia
Investigations
Common Elevated transaminase levels
Skin and subcutaneous tissue disorders
Common Pruritus rash alopecia
Respiratory disorders
Common Dyspnea
Cardiac disorders
Common Bradycardia
Uncommon Tachycardia
SANDOSTATINreg LARreg IMPORTANT SAFETY INFORMATION (cont)
Please see Important Safety Information on pages 8-13
12
Table 2 Adverse drug reactions derived from spontaneous reports
Post-marketing
Spontaneously reported adverse reactions presented in Table 2 are reported voluntarily and it is not always possible to reliably establish frequency or a causal relationship to drug exposure
Description of selected adverse reactionsGastrointestinal disorders
In rare instances gastrointestinal side effects may resemble acute intestinal obstruction with progressive abdominal distension severe epigastric pain abdominal tenderness and guarding
The frequency of gastrointestinal adverse events is known to decrease over time with continued treatment
Injection site reactions
Injection site related reactions including pain burning redness hematoma hemorrhage pruritus or swelling were commonly reported in patients receiving Sandostatinreg LARreg however these events did not require any clinical intervention in the majority of the cases
Metabolism and nutrition disorders
Although measured fecal fat excretion may increase there is no evidence to date that long-term treatment with octreotide has led to nutritional deficiency due to malabsorption
Pancreatic enzymes
In very rare instances acute pancreatitis has been reported within the first hours or days of Sandostatinreg sc treatment and resolved on withdrawal of the drug In addition cholelithiasis induced pancreatitis has been reported for patients on long term Sandostatinreg sc treatment
Immune system disorders Anaphylaxis allergyhypersensitivity reactions
Skin and subcutaneous tissue disorders
Urticaria
Hepatobiliary disorders Acute pancreatitis acute hepatitis without cholestasis cholestatic hepatitis cholestasis jaundice cholestatic jaundice
Cardiac disorders Arrhythmias
Investigations Increased alkaline phosphatase levels increased gamma glutamyl transferase levels
SANDOSTATINreg LARreg IMPORTANT SAFETY INFORMATION (cont)
Please see Important Safety Information on pages 8-13
13
Cardiac disorders
In both acromegalic and carcinoid syndrome patients ECG changes were observed such as QT prolongation axis shifts early repolarization low voltage RS transition early R wave progression and nonspecific ST-T wave changes The relationship of these events to octreotide acetate is not established because many of these patients have underlying cardiac diseases (see Special warnings and precautions)
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorization of the medicinal product is important It allows continued monitoring of the benefitrisk balance of the medicinal product Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system
Overdose
A limited number of accidental overdoses of Sandostatinreg LARreg have been reported The doses ranged from 100 mg to 163 mgmonth of Sandostatinreg LARreg The only adverse event reported was hot flushes
Cancer patients receiving doses of Sandostatinreg LARreg up to 60 mgmonth and up to 90 mg2 weeks have been reported These doses were in general well tolerated however the following adverse events have been reported frequent urination fatigue depression anxiety and lack of concentration
The management of overdosage is symptomatic
List of excipients
Vial
Poly (DL-lactide-co-glycolide) 7835 of nominal1048790ll weight sterile mannitol 170 of nominal fill weight
Prefilled syringe
Kit without vial adaptersafety needle
One prefilled syringe (solvent for parenteral use) containing sodium carboxymethylcellulose 125 mg mannitol 15 mg water for injection qs ad 25 mL
Kit with vial adaptersafety needle
One prefilled syringe (solvent for parenteral use) containing sodium carboxymethylcellulose (14 mg) mannitol (12 mg) poloxamer 188 (4 mg) water for injection qs ad 2 mL
Pharmaceutical formulations may vary between countries
Please see the Summary of Product Characteristics
SANDOSTATINreg LARreg IMPORTANT SAFETY INFORMATION (cont)
Please see Important Safety Information on pages 8-13
14G-SAS-1157173317copy Novartis 2017
Novartis Pharma AG CH-4002 Basel Switzerland
References 1 Kunz PL Reidy-Lagunes D Anthony LB et al Consensus guidelines for the management and treatment of neuroendocrine tumors Pancreas 201342(4)557-577 2 Veenendaal LM Rinkes IHMB Lips CJM Hillegersberg RV Liver metastases of neuroendocrine tumours early reduction of tumour load to improve life expectancy World J Surg Oncol 2006435 3 Lee E Pachter HL Sarpel U Hepatic arterial embolization for the treatment of metastatic neuroendocrine tumors Int J Hepatol 20122012471203 4 Vinik AI Woltering EA OrsquoDorisio TM Go VLW Mamikunian G Diagnosing and treating gastroenteropancreatic tumors including ICD-9 codes In Neuroendocrine Tumors A Comprehensive Guide to Diagnosis and Management 5th ed Inglewood CA Inter Science Institute 20121-56 5 Grozinsky-Glasberg S Grossman AB Gross DJ Carcinoid heart disease from pathophysiology to treatmentndashlsquoSomething in the way it movesrsquo Neuroendocrinology 2015101(4)263- 273 6 Sandostatin LAR [Summary of Product Characteristics] Novartis 2016 7 Warner ME The Carcinoid Cancer Foundation Nutritional concerns for the carcinoid patient developing nutritional guidelines for persons with carcinoid disease httpwwwcarcinoidorgfor-patientsgeneral -informationnutritionnutritional-concerns-for-the-carcinoid-patient-developing-nutrition-guidelines -for-persons-with-carcinoid-disease Accessed January 30 2017 8 Cancer Research UK Tips on coping with diarrhea httpwwwcancerresearchukorgabout-cancercoping-with-cancercoping -physicallyboweltypesdiarrhoeamanagingtips-on-how-to-cope-with-diarrhoea Accessed January 30 2017 9 CancerNet Carcinoid tumor symptoms and signs httpwwwcancernetcancertypes carcinoidtumorsymptomsandsigns Accessed February 1 2017 10 Powell B Mukhtar AA Mills GH Carcinoid the disease and its implications for anaesthesia Continuing Education in Anaesthesia Critical Care amp Pain 201111(1)9-13 11 Rinke A Muumlller HH Schade-Brittinger C et al Placebo-controlled double-blind prospective randomized study on the effect of octreotide LAR in the control of tumor growth in patients with metastatic neuroendocrine midgut tumors a report from the PROMID study group J Clin Oncol 200927(28)4656-4663 12 Greenberger NJ Merck Manual Diarrhea httpwww merckmanualscomprofessionalgastrointestinal-disorderssymptoms-of-gi-disordersdiarrhea Accessed January 30 2017 13 Anthony L Freda PU From somatostatin to octreotide LAR evolution of a somatostatin analogue Curr Med Res Opin 200925(12)2989-2999 14 Litchford MD Dorner B Posthauer ME Malnutrition as a precursor of pressure ulcers Adv Wound Care 20143(1)54-63
Please see Important Safety Information on pages 8-13
5
TREATMENT WITH SANDOSTATINreg LARreg
(cont)
IMPORTANT DOSING INFORMATIONIt is recommended to start treatment with the administration of 20-mg Sandostatinreg LARreg at 4-week intervals Patients on treatment with subcutaneous Sandostatinreg (octreotide acetate) should continue at the previously effective dosage for 2 weeks after the first injection of Sandostatinreg LARreg6
For patients in whom symptoms and biological markers are well controlled after 3 months of treatment the dose may be reduced to 10-mg Sandostatinreg LARreg every 4 weeks6
For patients in whom symptoms are only partially controlled after 3 months of treatment the dose may be increased to 30-mg Sandostatinreg LARreg every 4 weeks6
The recommended dose of Sandostatinreg LARreg for patients with advanced NET of the midgut or unknown primary tumor location is 30-mg every 4 weeks Treatment with Sandostatinreg LARreg for tumor control should be continued in the absence of tumor progression6
RECOMMENDED MONITORING DURING SANDOSTATIN reg LAR reg THERAPYThyroid function hepatic function glucose tolerance and antidiabetic treatment should be monitored during treatment with Sandostatinreg LARreg6
Ultrasonic examination of the gallbladder should occur prior to therapy initiation and at 6-month intervals to check for gallstones6
Patients with a history of vitamin B12 deprivation should have B12 levels monitored during therapy6
COMMON SIDE EFFECTS OF SANDOSTATIN reg LAR reg6
Diarrhea
Abdominal pain
Nausea
Flatulence
Headache
Gallstones
Hyperglycemia
Constipation
LEARN MORE ABOUT SANDOSTATINreg LARreg AT WWWSANDOSTATINCOM
Please see Important Safety Information on pages 8-13
6
NURSING CONSIDERATIONSThe following information should be reviewed with patients during their Sandostatinreg LARreg initiation visit
Goals of treatment6
Treatment schedule6 - Sandostatinreg LARreg injections by a healthcare
professional every 4 weeks
Current symptoms - Frequency and severity
The 5 Ersquos of carcinoid syndrome
Current medication list
Diarrhea and flushing episodes can put patients at risk for other problems Assess for
Risks associated with chronic diarrhea812-14
- Electrolyte imbalances
- Altered nutritional status
- Dehydration
- Impaired skin integrity
Respiratory and cardiac dysfunction related to flushing episodes9
- Wheezing
- Shortness of breath
- Tachycardia andor palpitations
Please see Important Safety Information on pages 8-13
7
PATIENT SUPPORT GROUPS Encourage your patients to find a support group with other patients with NET either online or in their area if they havenrsquot done so already A support group is a place where they can share their feelings and concerns hear othersrsquo stories and even help those who are just beginning their own journey
It may be harder for patients to find live support groups specific to NET Support groups dedicated to cancer in general should also be considered for the patient and their loved ones
Not an actual patient or healthcare provider Copyright RawpixelcomShutterstockcom
Please see Important Safety Information on pages 8-13
8
SANDOSTATINreg LARreg IMPORTANT SAFETY INFORMATION
Contraindications
Known hypersensitivity to octreotide or to any of the excipients (see list of excipients)
Special warnings and precautions for use
General
As GH-secreting pituitary tumors may sometimes expand causing serious complications (eg visual field defects) it is essential that all patients be carefully monitored If evidence of tumor expansion appears alternative procedures may be advisable
Thyroid function should be monitored in patients receiving prolonged treatment with octreotide
Hepatic function should be monitored during octreotide therapy
Cardiovascular related events
Common cases of bradycardia have been reported Dose adjustment of medicinal products such as beta blockers calcium channel blockers or agents to control fluid and electrolyte balance may be necessary (see section Interaction with other medicinal products and other forms of interaction)
Gallbladder and related events
Octreotide inhibits secretion of cholecystokinin resulting in reduced contractility of the gallbladder and an increased risk of sludge and stone formation Development of gallstones has been reported in 15 to 30 of long-term recipients of sc Sandostatinreg The prevalence in the general population (aged 40 to 60 years) is about 5 to 20 Long-term exposure to Sandostatinreg LARreg of patients with acromegaly or gastro-entero-pancreatic tumors suggests that treatment with Sandostatinreg LARreg does not increase the incidence of gallstone formation compared with sc treatment Ultrasonic examination of the gallbladder before and at about 6-monthly intervals during Sandostatinreg LARreg therapy is however recommended If gallstones do occur they are usually asymptomatic symptomatic stones should be treated either by dissolution therapy with bile acids or by surgery
Glucose metabolism
Because of its inhibitory action on growth hormone glucagon and insulin release Sandostatinreg LARreg may affect glucose regulation Post-prandial glucose tolerance may be impaired As reported for patients treated with sc Sandostatinreg in some instances the state of persistent hyperglycemia may be induced as a result of chronic administration Hypoglycemia has also been reported
In patients with concomitant Type I diabetes mellitus Sandostatinreg LARreg is likely to affect glucose regulation and insulin requirements may be reduced In non-diabetics and type II diabetics with partially intact insulin reserves Sandostatinreg sc administration may result in increases in post-prandial glycaemia It is therefore recommended to monitor glucose tolerance and antidiabetic treatment
In patients with insulinomas octreotide because of its greater relative potency in inhibiting the secretion of GH and glucagon than that of insulin and because of the shorter duration of its inhibitory action on insulin may increase the depth and prolong the duration of hypoglycemia These patients should be closely monitored
Please see Important Safety Information on pages 8-13
9
Nutrition
Octreotide may alter absorption of dietary fats in some patients
Depressed vitamin B12 levels and abnormal Schillingrsquos tests have been observed in some patients receiving octreotide therapy Monitoring of vitamin B12 levels is recommended during therapy with Sandostatinreg LARreg in patients who have a history of vitamin B12 deprivation
Sodium content
Sandostatinreg LARreg contains less than 1 mmol (23 mg) sodium per dose ie is essentially ldquosodium-freerdquo
Interaction with other medicinal products and other forms of interactionDose adjustment of medicinal products such as beta blockers calcium channel blockers or agents to control fluid and electrolyte balance may be necessary when Sandostatinreg LARreg is administered concomitantly (see Special warnings and precautions for use)
Dose adjustments of insulin and antidiabetic medicinal products may be required when Sandostatinreg LARreg is administered concomitantly (see Special warnings and precautions for use)
Octreotide has been found to reduce the intestinal absorption of ciclosporin and to delay that of cimetidine
Concomitant administration of octreotide and bromocriptine increases the bioavailability of bromocriptine
Limited published data indicate that somatostatin analogs might decrease the metabolic clearance of compounds known to be metabolized by cytochrome P450 enzymes which may be due to the suppression of growth hormone Since it cannot be excluded that octreotide may have this effect other drugs mainly metabolized by CYP3A4 and which have a low therapeutic index (eg quinidine terfenadine) should therefore be used with caution
Pregnancy breastfeeding and fertilityPregnancy
There is a limited amount of data (less than 300 pregnancy outcomes) from the use of octreotide in pregnant women and in approximately one third of the cases the pregnancy outcomes are unknown The majority of reports were received after postmarketing use of octreotide and more than 50 of exposed pregnancies were reported in patients with acromegaly Most women were exposed to octreotide during the first trimester of pregnancy at doses ranging from 100-1200 microgramsday of Sandostatinreg sc or 10-40 mgmonth of Sandostatinreg LARreg Congenital anomalies were reported in about 4 of pregnancy cases for which the outcome is known No causal relationship to octreotide is suspected for these cases
Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see Preclinical safety data)
As a precautionary measure it is preferable to avoid the use of Sandostatinreg LARreg during pregnancy (see Special warnings and precautions for use)
SANDOSTATINreg LARreg IMPORTANT SAFETY INFORMATION (cont)
Please see Important Safety Information on pages 8-13
10
Breastfeeding
It is unknown whether octreotide is excreted in human breast milk Animal studies have shown excretion of octreotide in breast milk Patients should not breastfeed during Sandostatinreg LARreg treatment
Fertility
It is not known whether octreotide has an effect on human fertility Late descent of the testes was found for male offsprings of dams treated during pregnancy and lactation Octreotide however did not impair fertility in male and female rats at doses of up to 1 mgkg body weight per day (see Preclinical safety data)
Effects on ability to drive and use machinesSandostatinreg LARreg has no or negligible influence on the ability to drive and use machines Patients should be advised to be cautious when driving or using machines if they experience dizziness astheniafatigue or headache during treatment with Sandostatinreg LARreg
Undesirable effects and adverse drug reactionsSummary of the safety profile
The most frequent adverse reactions reported during octreotide therapy include gastrointestinal disorders nervous system disorders hepatobiliary disorders and metabolism and nutritional disorders
The most commonly reported adverse reactions in clinical trials with octreotide administration were diarrhea abdominal pain nausea flatulence headache cholelithiasis hyperglycemia and constipation Other commonly reported adverse reactions were dizziness localized pain biliary sludge thyroid dysfunction (eg decreased thyroid stimulating hormone [TSH] decreased total T4 and decreased free T4) loose stools impaired glucose tolerance vomiting asthenia and hypoglycemia
Tabulated list of adverse reactions
The following adverse drug reactions listed in Table 1 have been accumulated from clinical studies with octreotide
Adverse drug reactions (Table 1) are ranked under heading of frequency the most frequent first using the following convention very common (ge110) common (ge1100 lt110) uncommon (ge11000 lt1100) rare (ge110000 lt11000) very rare (lt110000) including isolated reports Within each frequency grouping adverse reactions are ranked in order of decreasing seriousness
SANDOSTATINreg LARreg IMPORTANT SAFETY INFORMATION (cont)
Please see Important Safety Information on pages 8-13
11
Table 1 Adverse drug reactions reported in clinical studies
Gastrointestinal disorders
Very common Diarrhea abdominal pain nausea constipation flatulence
Common Dyspepsia vomiting abdominal bloating steatorrhea loose stools discoloration of feces
Nervous system disorders
Very common Headache
Common Dizziness
Endocrine disorders
Common Hypothyroidism thyroid dysfunction (eg decreased TSH decreased total T4 and decreased free T4)
Hepatobiliary disorders
Very common Cholelithiasis
Common Cholecystitis biliary sludge hyperbilirubinemia
Metabolism and nutrition disorders
Very common Hyperglycemia
Common Hypoglycemia impaired glucose tolerance anorexia
Uncommon Dehydration
General disorders and administration site conditions
Very common Injection site reactions
Common Asthenia
Investigations
Common Elevated transaminase levels
Skin and subcutaneous tissue disorders
Common Pruritus rash alopecia
Respiratory disorders
Common Dyspnea
Cardiac disorders
Common Bradycardia
Uncommon Tachycardia
SANDOSTATINreg LARreg IMPORTANT SAFETY INFORMATION (cont)
Please see Important Safety Information on pages 8-13
12
Table 2 Adverse drug reactions derived from spontaneous reports
Post-marketing
Spontaneously reported adverse reactions presented in Table 2 are reported voluntarily and it is not always possible to reliably establish frequency or a causal relationship to drug exposure
Description of selected adverse reactionsGastrointestinal disorders
In rare instances gastrointestinal side effects may resemble acute intestinal obstruction with progressive abdominal distension severe epigastric pain abdominal tenderness and guarding
The frequency of gastrointestinal adverse events is known to decrease over time with continued treatment
Injection site reactions
Injection site related reactions including pain burning redness hematoma hemorrhage pruritus or swelling were commonly reported in patients receiving Sandostatinreg LARreg however these events did not require any clinical intervention in the majority of the cases
Metabolism and nutrition disorders
Although measured fecal fat excretion may increase there is no evidence to date that long-term treatment with octreotide has led to nutritional deficiency due to malabsorption
Pancreatic enzymes
In very rare instances acute pancreatitis has been reported within the first hours or days of Sandostatinreg sc treatment and resolved on withdrawal of the drug In addition cholelithiasis induced pancreatitis has been reported for patients on long term Sandostatinreg sc treatment
Immune system disorders Anaphylaxis allergyhypersensitivity reactions
Skin and subcutaneous tissue disorders
Urticaria
Hepatobiliary disorders Acute pancreatitis acute hepatitis without cholestasis cholestatic hepatitis cholestasis jaundice cholestatic jaundice
Cardiac disorders Arrhythmias
Investigations Increased alkaline phosphatase levels increased gamma glutamyl transferase levels
SANDOSTATINreg LARreg IMPORTANT SAFETY INFORMATION (cont)
Please see Important Safety Information on pages 8-13
13
Cardiac disorders
In both acromegalic and carcinoid syndrome patients ECG changes were observed such as QT prolongation axis shifts early repolarization low voltage RS transition early R wave progression and nonspecific ST-T wave changes The relationship of these events to octreotide acetate is not established because many of these patients have underlying cardiac diseases (see Special warnings and precautions)
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorization of the medicinal product is important It allows continued monitoring of the benefitrisk balance of the medicinal product Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system
Overdose
A limited number of accidental overdoses of Sandostatinreg LARreg have been reported The doses ranged from 100 mg to 163 mgmonth of Sandostatinreg LARreg The only adverse event reported was hot flushes
Cancer patients receiving doses of Sandostatinreg LARreg up to 60 mgmonth and up to 90 mg2 weeks have been reported These doses were in general well tolerated however the following adverse events have been reported frequent urination fatigue depression anxiety and lack of concentration
The management of overdosage is symptomatic
List of excipients
Vial
Poly (DL-lactide-co-glycolide) 7835 of nominal1048790ll weight sterile mannitol 170 of nominal fill weight
Prefilled syringe
Kit without vial adaptersafety needle
One prefilled syringe (solvent for parenteral use) containing sodium carboxymethylcellulose 125 mg mannitol 15 mg water for injection qs ad 25 mL
Kit with vial adaptersafety needle
One prefilled syringe (solvent for parenteral use) containing sodium carboxymethylcellulose (14 mg) mannitol (12 mg) poloxamer 188 (4 mg) water for injection qs ad 2 mL
Pharmaceutical formulations may vary between countries
Please see the Summary of Product Characteristics
SANDOSTATINreg LARreg IMPORTANT SAFETY INFORMATION (cont)
Please see Important Safety Information on pages 8-13
14G-SAS-1157173317copy Novartis 2017
Novartis Pharma AG CH-4002 Basel Switzerland
References 1 Kunz PL Reidy-Lagunes D Anthony LB et al Consensus guidelines for the management and treatment of neuroendocrine tumors Pancreas 201342(4)557-577 2 Veenendaal LM Rinkes IHMB Lips CJM Hillegersberg RV Liver metastases of neuroendocrine tumours early reduction of tumour load to improve life expectancy World J Surg Oncol 2006435 3 Lee E Pachter HL Sarpel U Hepatic arterial embolization for the treatment of metastatic neuroendocrine tumors Int J Hepatol 20122012471203 4 Vinik AI Woltering EA OrsquoDorisio TM Go VLW Mamikunian G Diagnosing and treating gastroenteropancreatic tumors including ICD-9 codes In Neuroendocrine Tumors A Comprehensive Guide to Diagnosis and Management 5th ed Inglewood CA Inter Science Institute 20121-56 5 Grozinsky-Glasberg S Grossman AB Gross DJ Carcinoid heart disease from pathophysiology to treatmentndashlsquoSomething in the way it movesrsquo Neuroendocrinology 2015101(4)263- 273 6 Sandostatin LAR [Summary of Product Characteristics] Novartis 2016 7 Warner ME The Carcinoid Cancer Foundation Nutritional concerns for the carcinoid patient developing nutritional guidelines for persons with carcinoid disease httpwwwcarcinoidorgfor-patientsgeneral -informationnutritionnutritional-concerns-for-the-carcinoid-patient-developing-nutrition-guidelines -for-persons-with-carcinoid-disease Accessed January 30 2017 8 Cancer Research UK Tips on coping with diarrhea httpwwwcancerresearchukorgabout-cancercoping-with-cancercoping -physicallyboweltypesdiarrhoeamanagingtips-on-how-to-cope-with-diarrhoea Accessed January 30 2017 9 CancerNet Carcinoid tumor symptoms and signs httpwwwcancernetcancertypes carcinoidtumorsymptomsandsigns Accessed February 1 2017 10 Powell B Mukhtar AA Mills GH Carcinoid the disease and its implications for anaesthesia Continuing Education in Anaesthesia Critical Care amp Pain 201111(1)9-13 11 Rinke A Muumlller HH Schade-Brittinger C et al Placebo-controlled double-blind prospective randomized study on the effect of octreotide LAR in the control of tumor growth in patients with metastatic neuroendocrine midgut tumors a report from the PROMID study group J Clin Oncol 200927(28)4656-4663 12 Greenberger NJ Merck Manual Diarrhea httpwww merckmanualscomprofessionalgastrointestinal-disorderssymptoms-of-gi-disordersdiarrhea Accessed January 30 2017 13 Anthony L Freda PU From somatostatin to octreotide LAR evolution of a somatostatin analogue Curr Med Res Opin 200925(12)2989-2999 14 Litchford MD Dorner B Posthauer ME Malnutrition as a precursor of pressure ulcers Adv Wound Care 20143(1)54-63
Please see Important Safety Information on pages 8-13
6
NURSING CONSIDERATIONSThe following information should be reviewed with patients during their Sandostatinreg LARreg initiation visit
Goals of treatment6
Treatment schedule6 - Sandostatinreg LARreg injections by a healthcare
professional every 4 weeks
Current symptoms - Frequency and severity
The 5 Ersquos of carcinoid syndrome
Current medication list
Diarrhea and flushing episodes can put patients at risk for other problems Assess for
Risks associated with chronic diarrhea812-14
- Electrolyte imbalances
- Altered nutritional status
- Dehydration
- Impaired skin integrity
Respiratory and cardiac dysfunction related to flushing episodes9
- Wheezing
- Shortness of breath
- Tachycardia andor palpitations
Please see Important Safety Information on pages 8-13
7
PATIENT SUPPORT GROUPS Encourage your patients to find a support group with other patients with NET either online or in their area if they havenrsquot done so already A support group is a place where they can share their feelings and concerns hear othersrsquo stories and even help those who are just beginning their own journey
It may be harder for patients to find live support groups specific to NET Support groups dedicated to cancer in general should also be considered for the patient and their loved ones
Not an actual patient or healthcare provider Copyright RawpixelcomShutterstockcom
Please see Important Safety Information on pages 8-13
8
SANDOSTATINreg LARreg IMPORTANT SAFETY INFORMATION
Contraindications
Known hypersensitivity to octreotide or to any of the excipients (see list of excipients)
Special warnings and precautions for use
General
As GH-secreting pituitary tumors may sometimes expand causing serious complications (eg visual field defects) it is essential that all patients be carefully monitored If evidence of tumor expansion appears alternative procedures may be advisable
Thyroid function should be monitored in patients receiving prolonged treatment with octreotide
Hepatic function should be monitored during octreotide therapy
Cardiovascular related events
Common cases of bradycardia have been reported Dose adjustment of medicinal products such as beta blockers calcium channel blockers or agents to control fluid and electrolyte balance may be necessary (see section Interaction with other medicinal products and other forms of interaction)
Gallbladder and related events
Octreotide inhibits secretion of cholecystokinin resulting in reduced contractility of the gallbladder and an increased risk of sludge and stone formation Development of gallstones has been reported in 15 to 30 of long-term recipients of sc Sandostatinreg The prevalence in the general population (aged 40 to 60 years) is about 5 to 20 Long-term exposure to Sandostatinreg LARreg of patients with acromegaly or gastro-entero-pancreatic tumors suggests that treatment with Sandostatinreg LARreg does not increase the incidence of gallstone formation compared with sc treatment Ultrasonic examination of the gallbladder before and at about 6-monthly intervals during Sandostatinreg LARreg therapy is however recommended If gallstones do occur they are usually asymptomatic symptomatic stones should be treated either by dissolution therapy with bile acids or by surgery
Glucose metabolism
Because of its inhibitory action on growth hormone glucagon and insulin release Sandostatinreg LARreg may affect glucose regulation Post-prandial glucose tolerance may be impaired As reported for patients treated with sc Sandostatinreg in some instances the state of persistent hyperglycemia may be induced as a result of chronic administration Hypoglycemia has also been reported
In patients with concomitant Type I diabetes mellitus Sandostatinreg LARreg is likely to affect glucose regulation and insulin requirements may be reduced In non-diabetics and type II diabetics with partially intact insulin reserves Sandostatinreg sc administration may result in increases in post-prandial glycaemia It is therefore recommended to monitor glucose tolerance and antidiabetic treatment
In patients with insulinomas octreotide because of its greater relative potency in inhibiting the secretion of GH and glucagon than that of insulin and because of the shorter duration of its inhibitory action on insulin may increase the depth and prolong the duration of hypoglycemia These patients should be closely monitored
Please see Important Safety Information on pages 8-13
9
Nutrition
Octreotide may alter absorption of dietary fats in some patients
Depressed vitamin B12 levels and abnormal Schillingrsquos tests have been observed in some patients receiving octreotide therapy Monitoring of vitamin B12 levels is recommended during therapy with Sandostatinreg LARreg in patients who have a history of vitamin B12 deprivation
Sodium content
Sandostatinreg LARreg contains less than 1 mmol (23 mg) sodium per dose ie is essentially ldquosodium-freerdquo
Interaction with other medicinal products and other forms of interactionDose adjustment of medicinal products such as beta blockers calcium channel blockers or agents to control fluid and electrolyte balance may be necessary when Sandostatinreg LARreg is administered concomitantly (see Special warnings and precautions for use)
Dose adjustments of insulin and antidiabetic medicinal products may be required when Sandostatinreg LARreg is administered concomitantly (see Special warnings and precautions for use)
Octreotide has been found to reduce the intestinal absorption of ciclosporin and to delay that of cimetidine
Concomitant administration of octreotide and bromocriptine increases the bioavailability of bromocriptine
Limited published data indicate that somatostatin analogs might decrease the metabolic clearance of compounds known to be metabolized by cytochrome P450 enzymes which may be due to the suppression of growth hormone Since it cannot be excluded that octreotide may have this effect other drugs mainly metabolized by CYP3A4 and which have a low therapeutic index (eg quinidine terfenadine) should therefore be used with caution
Pregnancy breastfeeding and fertilityPregnancy
There is a limited amount of data (less than 300 pregnancy outcomes) from the use of octreotide in pregnant women and in approximately one third of the cases the pregnancy outcomes are unknown The majority of reports were received after postmarketing use of octreotide and more than 50 of exposed pregnancies were reported in patients with acromegaly Most women were exposed to octreotide during the first trimester of pregnancy at doses ranging from 100-1200 microgramsday of Sandostatinreg sc or 10-40 mgmonth of Sandostatinreg LARreg Congenital anomalies were reported in about 4 of pregnancy cases for which the outcome is known No causal relationship to octreotide is suspected for these cases
Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see Preclinical safety data)
As a precautionary measure it is preferable to avoid the use of Sandostatinreg LARreg during pregnancy (see Special warnings and precautions for use)
SANDOSTATINreg LARreg IMPORTANT SAFETY INFORMATION (cont)
Please see Important Safety Information on pages 8-13
10
Breastfeeding
It is unknown whether octreotide is excreted in human breast milk Animal studies have shown excretion of octreotide in breast milk Patients should not breastfeed during Sandostatinreg LARreg treatment
Fertility
It is not known whether octreotide has an effect on human fertility Late descent of the testes was found for male offsprings of dams treated during pregnancy and lactation Octreotide however did not impair fertility in male and female rats at doses of up to 1 mgkg body weight per day (see Preclinical safety data)
Effects on ability to drive and use machinesSandostatinreg LARreg has no or negligible influence on the ability to drive and use machines Patients should be advised to be cautious when driving or using machines if they experience dizziness astheniafatigue or headache during treatment with Sandostatinreg LARreg
Undesirable effects and adverse drug reactionsSummary of the safety profile
The most frequent adverse reactions reported during octreotide therapy include gastrointestinal disorders nervous system disorders hepatobiliary disorders and metabolism and nutritional disorders
The most commonly reported adverse reactions in clinical trials with octreotide administration were diarrhea abdominal pain nausea flatulence headache cholelithiasis hyperglycemia and constipation Other commonly reported adverse reactions were dizziness localized pain biliary sludge thyroid dysfunction (eg decreased thyroid stimulating hormone [TSH] decreased total T4 and decreased free T4) loose stools impaired glucose tolerance vomiting asthenia and hypoglycemia
Tabulated list of adverse reactions
The following adverse drug reactions listed in Table 1 have been accumulated from clinical studies with octreotide
Adverse drug reactions (Table 1) are ranked under heading of frequency the most frequent first using the following convention very common (ge110) common (ge1100 lt110) uncommon (ge11000 lt1100) rare (ge110000 lt11000) very rare (lt110000) including isolated reports Within each frequency grouping adverse reactions are ranked in order of decreasing seriousness
SANDOSTATINreg LARreg IMPORTANT SAFETY INFORMATION (cont)
Please see Important Safety Information on pages 8-13
11
Table 1 Adverse drug reactions reported in clinical studies
Gastrointestinal disorders
Very common Diarrhea abdominal pain nausea constipation flatulence
Common Dyspepsia vomiting abdominal bloating steatorrhea loose stools discoloration of feces
Nervous system disorders
Very common Headache
Common Dizziness
Endocrine disorders
Common Hypothyroidism thyroid dysfunction (eg decreased TSH decreased total T4 and decreased free T4)
Hepatobiliary disorders
Very common Cholelithiasis
Common Cholecystitis biliary sludge hyperbilirubinemia
Metabolism and nutrition disorders
Very common Hyperglycemia
Common Hypoglycemia impaired glucose tolerance anorexia
Uncommon Dehydration
General disorders and administration site conditions
Very common Injection site reactions
Common Asthenia
Investigations
Common Elevated transaminase levels
Skin and subcutaneous tissue disorders
Common Pruritus rash alopecia
Respiratory disorders
Common Dyspnea
Cardiac disorders
Common Bradycardia
Uncommon Tachycardia
SANDOSTATINreg LARreg IMPORTANT SAFETY INFORMATION (cont)
Please see Important Safety Information on pages 8-13
12
Table 2 Adverse drug reactions derived from spontaneous reports
Post-marketing
Spontaneously reported adverse reactions presented in Table 2 are reported voluntarily and it is not always possible to reliably establish frequency or a causal relationship to drug exposure
Description of selected adverse reactionsGastrointestinal disorders
In rare instances gastrointestinal side effects may resemble acute intestinal obstruction with progressive abdominal distension severe epigastric pain abdominal tenderness and guarding
The frequency of gastrointestinal adverse events is known to decrease over time with continued treatment
Injection site reactions
Injection site related reactions including pain burning redness hematoma hemorrhage pruritus or swelling were commonly reported in patients receiving Sandostatinreg LARreg however these events did not require any clinical intervention in the majority of the cases
Metabolism and nutrition disorders
Although measured fecal fat excretion may increase there is no evidence to date that long-term treatment with octreotide has led to nutritional deficiency due to malabsorption
Pancreatic enzymes
In very rare instances acute pancreatitis has been reported within the first hours or days of Sandostatinreg sc treatment and resolved on withdrawal of the drug In addition cholelithiasis induced pancreatitis has been reported for patients on long term Sandostatinreg sc treatment
Immune system disorders Anaphylaxis allergyhypersensitivity reactions
Skin and subcutaneous tissue disorders
Urticaria
Hepatobiliary disorders Acute pancreatitis acute hepatitis without cholestasis cholestatic hepatitis cholestasis jaundice cholestatic jaundice
Cardiac disorders Arrhythmias
Investigations Increased alkaline phosphatase levels increased gamma glutamyl transferase levels
SANDOSTATINreg LARreg IMPORTANT SAFETY INFORMATION (cont)
Please see Important Safety Information on pages 8-13
13
Cardiac disorders
In both acromegalic and carcinoid syndrome patients ECG changes were observed such as QT prolongation axis shifts early repolarization low voltage RS transition early R wave progression and nonspecific ST-T wave changes The relationship of these events to octreotide acetate is not established because many of these patients have underlying cardiac diseases (see Special warnings and precautions)
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorization of the medicinal product is important It allows continued monitoring of the benefitrisk balance of the medicinal product Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system
Overdose
A limited number of accidental overdoses of Sandostatinreg LARreg have been reported The doses ranged from 100 mg to 163 mgmonth of Sandostatinreg LARreg The only adverse event reported was hot flushes
Cancer patients receiving doses of Sandostatinreg LARreg up to 60 mgmonth and up to 90 mg2 weeks have been reported These doses were in general well tolerated however the following adverse events have been reported frequent urination fatigue depression anxiety and lack of concentration
The management of overdosage is symptomatic
List of excipients
Vial
Poly (DL-lactide-co-glycolide) 7835 of nominal1048790ll weight sterile mannitol 170 of nominal fill weight
Prefilled syringe
Kit without vial adaptersafety needle
One prefilled syringe (solvent for parenteral use) containing sodium carboxymethylcellulose 125 mg mannitol 15 mg water for injection qs ad 25 mL
Kit with vial adaptersafety needle
One prefilled syringe (solvent for parenteral use) containing sodium carboxymethylcellulose (14 mg) mannitol (12 mg) poloxamer 188 (4 mg) water for injection qs ad 2 mL
Pharmaceutical formulations may vary between countries
Please see the Summary of Product Characteristics
SANDOSTATINreg LARreg IMPORTANT SAFETY INFORMATION (cont)
Please see Important Safety Information on pages 8-13
14G-SAS-1157173317copy Novartis 2017
Novartis Pharma AG CH-4002 Basel Switzerland
References 1 Kunz PL Reidy-Lagunes D Anthony LB et al Consensus guidelines for the management and treatment of neuroendocrine tumors Pancreas 201342(4)557-577 2 Veenendaal LM Rinkes IHMB Lips CJM Hillegersberg RV Liver metastases of neuroendocrine tumours early reduction of tumour load to improve life expectancy World J Surg Oncol 2006435 3 Lee E Pachter HL Sarpel U Hepatic arterial embolization for the treatment of metastatic neuroendocrine tumors Int J Hepatol 20122012471203 4 Vinik AI Woltering EA OrsquoDorisio TM Go VLW Mamikunian G Diagnosing and treating gastroenteropancreatic tumors including ICD-9 codes In Neuroendocrine Tumors A Comprehensive Guide to Diagnosis and Management 5th ed Inglewood CA Inter Science Institute 20121-56 5 Grozinsky-Glasberg S Grossman AB Gross DJ Carcinoid heart disease from pathophysiology to treatmentndashlsquoSomething in the way it movesrsquo Neuroendocrinology 2015101(4)263- 273 6 Sandostatin LAR [Summary of Product Characteristics] Novartis 2016 7 Warner ME The Carcinoid Cancer Foundation Nutritional concerns for the carcinoid patient developing nutritional guidelines for persons with carcinoid disease httpwwwcarcinoidorgfor-patientsgeneral -informationnutritionnutritional-concerns-for-the-carcinoid-patient-developing-nutrition-guidelines -for-persons-with-carcinoid-disease Accessed January 30 2017 8 Cancer Research UK Tips on coping with diarrhea httpwwwcancerresearchukorgabout-cancercoping-with-cancercoping -physicallyboweltypesdiarrhoeamanagingtips-on-how-to-cope-with-diarrhoea Accessed January 30 2017 9 CancerNet Carcinoid tumor symptoms and signs httpwwwcancernetcancertypes carcinoidtumorsymptomsandsigns Accessed February 1 2017 10 Powell B Mukhtar AA Mills GH Carcinoid the disease and its implications for anaesthesia Continuing Education in Anaesthesia Critical Care amp Pain 201111(1)9-13 11 Rinke A Muumlller HH Schade-Brittinger C et al Placebo-controlled double-blind prospective randomized study on the effect of octreotide LAR in the control of tumor growth in patients with metastatic neuroendocrine midgut tumors a report from the PROMID study group J Clin Oncol 200927(28)4656-4663 12 Greenberger NJ Merck Manual Diarrhea httpwww merckmanualscomprofessionalgastrointestinal-disorderssymptoms-of-gi-disordersdiarrhea Accessed January 30 2017 13 Anthony L Freda PU From somatostatin to octreotide LAR evolution of a somatostatin analogue Curr Med Res Opin 200925(12)2989-2999 14 Litchford MD Dorner B Posthauer ME Malnutrition as a precursor of pressure ulcers Adv Wound Care 20143(1)54-63
Please see Important Safety Information on pages 8-13
7
PATIENT SUPPORT GROUPS Encourage your patients to find a support group with other patients with NET either online or in their area if they havenrsquot done so already A support group is a place where they can share their feelings and concerns hear othersrsquo stories and even help those who are just beginning their own journey
It may be harder for patients to find live support groups specific to NET Support groups dedicated to cancer in general should also be considered for the patient and their loved ones
Not an actual patient or healthcare provider Copyright RawpixelcomShutterstockcom
Please see Important Safety Information on pages 8-13
8
SANDOSTATINreg LARreg IMPORTANT SAFETY INFORMATION
Contraindications
Known hypersensitivity to octreotide or to any of the excipients (see list of excipients)
Special warnings and precautions for use
General
As GH-secreting pituitary tumors may sometimes expand causing serious complications (eg visual field defects) it is essential that all patients be carefully monitored If evidence of tumor expansion appears alternative procedures may be advisable
Thyroid function should be monitored in patients receiving prolonged treatment with octreotide
Hepatic function should be monitored during octreotide therapy
Cardiovascular related events
Common cases of bradycardia have been reported Dose adjustment of medicinal products such as beta blockers calcium channel blockers or agents to control fluid and electrolyte balance may be necessary (see section Interaction with other medicinal products and other forms of interaction)
Gallbladder and related events
Octreotide inhibits secretion of cholecystokinin resulting in reduced contractility of the gallbladder and an increased risk of sludge and stone formation Development of gallstones has been reported in 15 to 30 of long-term recipients of sc Sandostatinreg The prevalence in the general population (aged 40 to 60 years) is about 5 to 20 Long-term exposure to Sandostatinreg LARreg of patients with acromegaly or gastro-entero-pancreatic tumors suggests that treatment with Sandostatinreg LARreg does not increase the incidence of gallstone formation compared with sc treatment Ultrasonic examination of the gallbladder before and at about 6-monthly intervals during Sandostatinreg LARreg therapy is however recommended If gallstones do occur they are usually asymptomatic symptomatic stones should be treated either by dissolution therapy with bile acids or by surgery
Glucose metabolism
Because of its inhibitory action on growth hormone glucagon and insulin release Sandostatinreg LARreg may affect glucose regulation Post-prandial glucose tolerance may be impaired As reported for patients treated with sc Sandostatinreg in some instances the state of persistent hyperglycemia may be induced as a result of chronic administration Hypoglycemia has also been reported
In patients with concomitant Type I diabetes mellitus Sandostatinreg LARreg is likely to affect glucose regulation and insulin requirements may be reduced In non-diabetics and type II diabetics with partially intact insulin reserves Sandostatinreg sc administration may result in increases in post-prandial glycaemia It is therefore recommended to monitor glucose tolerance and antidiabetic treatment
In patients with insulinomas octreotide because of its greater relative potency in inhibiting the secretion of GH and glucagon than that of insulin and because of the shorter duration of its inhibitory action on insulin may increase the depth and prolong the duration of hypoglycemia These patients should be closely monitored
Please see Important Safety Information on pages 8-13
9
Nutrition
Octreotide may alter absorption of dietary fats in some patients
Depressed vitamin B12 levels and abnormal Schillingrsquos tests have been observed in some patients receiving octreotide therapy Monitoring of vitamin B12 levels is recommended during therapy with Sandostatinreg LARreg in patients who have a history of vitamin B12 deprivation
Sodium content
Sandostatinreg LARreg contains less than 1 mmol (23 mg) sodium per dose ie is essentially ldquosodium-freerdquo
Interaction with other medicinal products and other forms of interactionDose adjustment of medicinal products such as beta blockers calcium channel blockers or agents to control fluid and electrolyte balance may be necessary when Sandostatinreg LARreg is administered concomitantly (see Special warnings and precautions for use)
Dose adjustments of insulin and antidiabetic medicinal products may be required when Sandostatinreg LARreg is administered concomitantly (see Special warnings and precautions for use)
Octreotide has been found to reduce the intestinal absorption of ciclosporin and to delay that of cimetidine
Concomitant administration of octreotide and bromocriptine increases the bioavailability of bromocriptine
Limited published data indicate that somatostatin analogs might decrease the metabolic clearance of compounds known to be metabolized by cytochrome P450 enzymes which may be due to the suppression of growth hormone Since it cannot be excluded that octreotide may have this effect other drugs mainly metabolized by CYP3A4 and which have a low therapeutic index (eg quinidine terfenadine) should therefore be used with caution
Pregnancy breastfeeding and fertilityPregnancy
There is a limited amount of data (less than 300 pregnancy outcomes) from the use of octreotide in pregnant women and in approximately one third of the cases the pregnancy outcomes are unknown The majority of reports were received after postmarketing use of octreotide and more than 50 of exposed pregnancies were reported in patients with acromegaly Most women were exposed to octreotide during the first trimester of pregnancy at doses ranging from 100-1200 microgramsday of Sandostatinreg sc or 10-40 mgmonth of Sandostatinreg LARreg Congenital anomalies were reported in about 4 of pregnancy cases for which the outcome is known No causal relationship to octreotide is suspected for these cases
Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see Preclinical safety data)
As a precautionary measure it is preferable to avoid the use of Sandostatinreg LARreg during pregnancy (see Special warnings and precautions for use)
SANDOSTATINreg LARreg IMPORTANT SAFETY INFORMATION (cont)
Please see Important Safety Information on pages 8-13
10
Breastfeeding
It is unknown whether octreotide is excreted in human breast milk Animal studies have shown excretion of octreotide in breast milk Patients should not breastfeed during Sandostatinreg LARreg treatment
Fertility
It is not known whether octreotide has an effect on human fertility Late descent of the testes was found for male offsprings of dams treated during pregnancy and lactation Octreotide however did not impair fertility in male and female rats at doses of up to 1 mgkg body weight per day (see Preclinical safety data)
Effects on ability to drive and use machinesSandostatinreg LARreg has no or negligible influence on the ability to drive and use machines Patients should be advised to be cautious when driving or using machines if they experience dizziness astheniafatigue or headache during treatment with Sandostatinreg LARreg
Undesirable effects and adverse drug reactionsSummary of the safety profile
The most frequent adverse reactions reported during octreotide therapy include gastrointestinal disorders nervous system disorders hepatobiliary disorders and metabolism and nutritional disorders
The most commonly reported adverse reactions in clinical trials with octreotide administration were diarrhea abdominal pain nausea flatulence headache cholelithiasis hyperglycemia and constipation Other commonly reported adverse reactions were dizziness localized pain biliary sludge thyroid dysfunction (eg decreased thyroid stimulating hormone [TSH] decreased total T4 and decreased free T4) loose stools impaired glucose tolerance vomiting asthenia and hypoglycemia
Tabulated list of adverse reactions
The following adverse drug reactions listed in Table 1 have been accumulated from clinical studies with octreotide
Adverse drug reactions (Table 1) are ranked under heading of frequency the most frequent first using the following convention very common (ge110) common (ge1100 lt110) uncommon (ge11000 lt1100) rare (ge110000 lt11000) very rare (lt110000) including isolated reports Within each frequency grouping adverse reactions are ranked in order of decreasing seriousness
SANDOSTATINreg LARreg IMPORTANT SAFETY INFORMATION (cont)
Please see Important Safety Information on pages 8-13
11
Table 1 Adverse drug reactions reported in clinical studies
Gastrointestinal disorders
Very common Diarrhea abdominal pain nausea constipation flatulence
Common Dyspepsia vomiting abdominal bloating steatorrhea loose stools discoloration of feces
Nervous system disorders
Very common Headache
Common Dizziness
Endocrine disorders
Common Hypothyroidism thyroid dysfunction (eg decreased TSH decreased total T4 and decreased free T4)
Hepatobiliary disorders
Very common Cholelithiasis
Common Cholecystitis biliary sludge hyperbilirubinemia
Metabolism and nutrition disorders
Very common Hyperglycemia
Common Hypoglycemia impaired glucose tolerance anorexia
Uncommon Dehydration
General disorders and administration site conditions
Very common Injection site reactions
Common Asthenia
Investigations
Common Elevated transaminase levels
Skin and subcutaneous tissue disorders
Common Pruritus rash alopecia
Respiratory disorders
Common Dyspnea
Cardiac disorders
Common Bradycardia
Uncommon Tachycardia
SANDOSTATINreg LARreg IMPORTANT SAFETY INFORMATION (cont)
Please see Important Safety Information on pages 8-13
12
Table 2 Adverse drug reactions derived from spontaneous reports
Post-marketing
Spontaneously reported adverse reactions presented in Table 2 are reported voluntarily and it is not always possible to reliably establish frequency or a causal relationship to drug exposure
Description of selected adverse reactionsGastrointestinal disorders
In rare instances gastrointestinal side effects may resemble acute intestinal obstruction with progressive abdominal distension severe epigastric pain abdominal tenderness and guarding
The frequency of gastrointestinal adverse events is known to decrease over time with continued treatment
Injection site reactions
Injection site related reactions including pain burning redness hematoma hemorrhage pruritus or swelling were commonly reported in patients receiving Sandostatinreg LARreg however these events did not require any clinical intervention in the majority of the cases
Metabolism and nutrition disorders
Although measured fecal fat excretion may increase there is no evidence to date that long-term treatment with octreotide has led to nutritional deficiency due to malabsorption
Pancreatic enzymes
In very rare instances acute pancreatitis has been reported within the first hours or days of Sandostatinreg sc treatment and resolved on withdrawal of the drug In addition cholelithiasis induced pancreatitis has been reported for patients on long term Sandostatinreg sc treatment
Immune system disorders Anaphylaxis allergyhypersensitivity reactions
Skin and subcutaneous tissue disorders
Urticaria
Hepatobiliary disorders Acute pancreatitis acute hepatitis without cholestasis cholestatic hepatitis cholestasis jaundice cholestatic jaundice
Cardiac disorders Arrhythmias
Investigations Increased alkaline phosphatase levels increased gamma glutamyl transferase levels
SANDOSTATINreg LARreg IMPORTANT SAFETY INFORMATION (cont)
Please see Important Safety Information on pages 8-13
13
Cardiac disorders
In both acromegalic and carcinoid syndrome patients ECG changes were observed such as QT prolongation axis shifts early repolarization low voltage RS transition early R wave progression and nonspecific ST-T wave changes The relationship of these events to octreotide acetate is not established because many of these patients have underlying cardiac diseases (see Special warnings and precautions)
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorization of the medicinal product is important It allows continued monitoring of the benefitrisk balance of the medicinal product Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system
Overdose
A limited number of accidental overdoses of Sandostatinreg LARreg have been reported The doses ranged from 100 mg to 163 mgmonth of Sandostatinreg LARreg The only adverse event reported was hot flushes
Cancer patients receiving doses of Sandostatinreg LARreg up to 60 mgmonth and up to 90 mg2 weeks have been reported These doses were in general well tolerated however the following adverse events have been reported frequent urination fatigue depression anxiety and lack of concentration
The management of overdosage is symptomatic
List of excipients
Vial
Poly (DL-lactide-co-glycolide) 7835 of nominal1048790ll weight sterile mannitol 170 of nominal fill weight
Prefilled syringe
Kit without vial adaptersafety needle
One prefilled syringe (solvent for parenteral use) containing sodium carboxymethylcellulose 125 mg mannitol 15 mg water for injection qs ad 25 mL
Kit with vial adaptersafety needle
One prefilled syringe (solvent for parenteral use) containing sodium carboxymethylcellulose (14 mg) mannitol (12 mg) poloxamer 188 (4 mg) water for injection qs ad 2 mL
Pharmaceutical formulations may vary between countries
Please see the Summary of Product Characteristics
SANDOSTATINreg LARreg IMPORTANT SAFETY INFORMATION (cont)
Please see Important Safety Information on pages 8-13
14G-SAS-1157173317copy Novartis 2017
Novartis Pharma AG CH-4002 Basel Switzerland
References 1 Kunz PL Reidy-Lagunes D Anthony LB et al Consensus guidelines for the management and treatment of neuroendocrine tumors Pancreas 201342(4)557-577 2 Veenendaal LM Rinkes IHMB Lips CJM Hillegersberg RV Liver metastases of neuroendocrine tumours early reduction of tumour load to improve life expectancy World J Surg Oncol 2006435 3 Lee E Pachter HL Sarpel U Hepatic arterial embolization for the treatment of metastatic neuroendocrine tumors Int J Hepatol 20122012471203 4 Vinik AI Woltering EA OrsquoDorisio TM Go VLW Mamikunian G Diagnosing and treating gastroenteropancreatic tumors including ICD-9 codes In Neuroendocrine Tumors A Comprehensive Guide to Diagnosis and Management 5th ed Inglewood CA Inter Science Institute 20121-56 5 Grozinsky-Glasberg S Grossman AB Gross DJ Carcinoid heart disease from pathophysiology to treatmentndashlsquoSomething in the way it movesrsquo Neuroendocrinology 2015101(4)263- 273 6 Sandostatin LAR [Summary of Product Characteristics] Novartis 2016 7 Warner ME The Carcinoid Cancer Foundation Nutritional concerns for the carcinoid patient developing nutritional guidelines for persons with carcinoid disease httpwwwcarcinoidorgfor-patientsgeneral -informationnutritionnutritional-concerns-for-the-carcinoid-patient-developing-nutrition-guidelines -for-persons-with-carcinoid-disease Accessed January 30 2017 8 Cancer Research UK Tips on coping with diarrhea httpwwwcancerresearchukorgabout-cancercoping-with-cancercoping -physicallyboweltypesdiarrhoeamanagingtips-on-how-to-cope-with-diarrhoea Accessed January 30 2017 9 CancerNet Carcinoid tumor symptoms and signs httpwwwcancernetcancertypes carcinoidtumorsymptomsandsigns Accessed February 1 2017 10 Powell B Mukhtar AA Mills GH Carcinoid the disease and its implications for anaesthesia Continuing Education in Anaesthesia Critical Care amp Pain 201111(1)9-13 11 Rinke A Muumlller HH Schade-Brittinger C et al Placebo-controlled double-blind prospective randomized study on the effect of octreotide LAR in the control of tumor growth in patients with metastatic neuroendocrine midgut tumors a report from the PROMID study group J Clin Oncol 200927(28)4656-4663 12 Greenberger NJ Merck Manual Diarrhea httpwww merckmanualscomprofessionalgastrointestinal-disorderssymptoms-of-gi-disordersdiarrhea Accessed January 30 2017 13 Anthony L Freda PU From somatostatin to octreotide LAR evolution of a somatostatin analogue Curr Med Res Opin 200925(12)2989-2999 14 Litchford MD Dorner B Posthauer ME Malnutrition as a precursor of pressure ulcers Adv Wound Care 20143(1)54-63
Please see Important Safety Information on pages 8-13
8
SANDOSTATINreg LARreg IMPORTANT SAFETY INFORMATION
Contraindications
Known hypersensitivity to octreotide or to any of the excipients (see list of excipients)
Special warnings and precautions for use
General
As GH-secreting pituitary tumors may sometimes expand causing serious complications (eg visual field defects) it is essential that all patients be carefully monitored If evidence of tumor expansion appears alternative procedures may be advisable
Thyroid function should be monitored in patients receiving prolonged treatment with octreotide
Hepatic function should be monitored during octreotide therapy
Cardiovascular related events
Common cases of bradycardia have been reported Dose adjustment of medicinal products such as beta blockers calcium channel blockers or agents to control fluid and electrolyte balance may be necessary (see section Interaction with other medicinal products and other forms of interaction)
Gallbladder and related events
Octreotide inhibits secretion of cholecystokinin resulting in reduced contractility of the gallbladder and an increased risk of sludge and stone formation Development of gallstones has been reported in 15 to 30 of long-term recipients of sc Sandostatinreg The prevalence in the general population (aged 40 to 60 years) is about 5 to 20 Long-term exposure to Sandostatinreg LARreg of patients with acromegaly or gastro-entero-pancreatic tumors suggests that treatment with Sandostatinreg LARreg does not increase the incidence of gallstone formation compared with sc treatment Ultrasonic examination of the gallbladder before and at about 6-monthly intervals during Sandostatinreg LARreg therapy is however recommended If gallstones do occur they are usually asymptomatic symptomatic stones should be treated either by dissolution therapy with bile acids or by surgery
Glucose metabolism
Because of its inhibitory action on growth hormone glucagon and insulin release Sandostatinreg LARreg may affect glucose regulation Post-prandial glucose tolerance may be impaired As reported for patients treated with sc Sandostatinreg in some instances the state of persistent hyperglycemia may be induced as a result of chronic administration Hypoglycemia has also been reported
In patients with concomitant Type I diabetes mellitus Sandostatinreg LARreg is likely to affect glucose regulation and insulin requirements may be reduced In non-diabetics and type II diabetics with partially intact insulin reserves Sandostatinreg sc administration may result in increases in post-prandial glycaemia It is therefore recommended to monitor glucose tolerance and antidiabetic treatment
In patients with insulinomas octreotide because of its greater relative potency in inhibiting the secretion of GH and glucagon than that of insulin and because of the shorter duration of its inhibitory action on insulin may increase the depth and prolong the duration of hypoglycemia These patients should be closely monitored
Please see Important Safety Information on pages 8-13
9
Nutrition
Octreotide may alter absorption of dietary fats in some patients
Depressed vitamin B12 levels and abnormal Schillingrsquos tests have been observed in some patients receiving octreotide therapy Monitoring of vitamin B12 levels is recommended during therapy with Sandostatinreg LARreg in patients who have a history of vitamin B12 deprivation
Sodium content
Sandostatinreg LARreg contains less than 1 mmol (23 mg) sodium per dose ie is essentially ldquosodium-freerdquo
Interaction with other medicinal products and other forms of interactionDose adjustment of medicinal products such as beta blockers calcium channel blockers or agents to control fluid and electrolyte balance may be necessary when Sandostatinreg LARreg is administered concomitantly (see Special warnings and precautions for use)
Dose adjustments of insulin and antidiabetic medicinal products may be required when Sandostatinreg LARreg is administered concomitantly (see Special warnings and precautions for use)
Octreotide has been found to reduce the intestinal absorption of ciclosporin and to delay that of cimetidine
Concomitant administration of octreotide and bromocriptine increases the bioavailability of bromocriptine
Limited published data indicate that somatostatin analogs might decrease the metabolic clearance of compounds known to be metabolized by cytochrome P450 enzymes which may be due to the suppression of growth hormone Since it cannot be excluded that octreotide may have this effect other drugs mainly metabolized by CYP3A4 and which have a low therapeutic index (eg quinidine terfenadine) should therefore be used with caution
Pregnancy breastfeeding and fertilityPregnancy
There is a limited amount of data (less than 300 pregnancy outcomes) from the use of octreotide in pregnant women and in approximately one third of the cases the pregnancy outcomes are unknown The majority of reports were received after postmarketing use of octreotide and more than 50 of exposed pregnancies were reported in patients with acromegaly Most women were exposed to octreotide during the first trimester of pregnancy at doses ranging from 100-1200 microgramsday of Sandostatinreg sc or 10-40 mgmonth of Sandostatinreg LARreg Congenital anomalies were reported in about 4 of pregnancy cases for which the outcome is known No causal relationship to octreotide is suspected for these cases
Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see Preclinical safety data)
As a precautionary measure it is preferable to avoid the use of Sandostatinreg LARreg during pregnancy (see Special warnings and precautions for use)
SANDOSTATINreg LARreg IMPORTANT SAFETY INFORMATION (cont)
Please see Important Safety Information on pages 8-13
10
Breastfeeding
It is unknown whether octreotide is excreted in human breast milk Animal studies have shown excretion of octreotide in breast milk Patients should not breastfeed during Sandostatinreg LARreg treatment
Fertility
It is not known whether octreotide has an effect on human fertility Late descent of the testes was found for male offsprings of dams treated during pregnancy and lactation Octreotide however did not impair fertility in male and female rats at doses of up to 1 mgkg body weight per day (see Preclinical safety data)
Effects on ability to drive and use machinesSandostatinreg LARreg has no or negligible influence on the ability to drive and use machines Patients should be advised to be cautious when driving or using machines if they experience dizziness astheniafatigue or headache during treatment with Sandostatinreg LARreg
Undesirable effects and adverse drug reactionsSummary of the safety profile
The most frequent adverse reactions reported during octreotide therapy include gastrointestinal disorders nervous system disorders hepatobiliary disorders and metabolism and nutritional disorders
The most commonly reported adverse reactions in clinical trials with octreotide administration were diarrhea abdominal pain nausea flatulence headache cholelithiasis hyperglycemia and constipation Other commonly reported adverse reactions were dizziness localized pain biliary sludge thyroid dysfunction (eg decreased thyroid stimulating hormone [TSH] decreased total T4 and decreased free T4) loose stools impaired glucose tolerance vomiting asthenia and hypoglycemia
Tabulated list of adverse reactions
The following adverse drug reactions listed in Table 1 have been accumulated from clinical studies with octreotide
Adverse drug reactions (Table 1) are ranked under heading of frequency the most frequent first using the following convention very common (ge110) common (ge1100 lt110) uncommon (ge11000 lt1100) rare (ge110000 lt11000) very rare (lt110000) including isolated reports Within each frequency grouping adverse reactions are ranked in order of decreasing seriousness
SANDOSTATINreg LARreg IMPORTANT SAFETY INFORMATION (cont)
Please see Important Safety Information on pages 8-13
11
Table 1 Adverse drug reactions reported in clinical studies
Gastrointestinal disorders
Very common Diarrhea abdominal pain nausea constipation flatulence
Common Dyspepsia vomiting abdominal bloating steatorrhea loose stools discoloration of feces
Nervous system disorders
Very common Headache
Common Dizziness
Endocrine disorders
Common Hypothyroidism thyroid dysfunction (eg decreased TSH decreased total T4 and decreased free T4)
Hepatobiliary disorders
Very common Cholelithiasis
Common Cholecystitis biliary sludge hyperbilirubinemia
Metabolism and nutrition disorders
Very common Hyperglycemia
Common Hypoglycemia impaired glucose tolerance anorexia
Uncommon Dehydration
General disorders and administration site conditions
Very common Injection site reactions
Common Asthenia
Investigations
Common Elevated transaminase levels
Skin and subcutaneous tissue disorders
Common Pruritus rash alopecia
Respiratory disorders
Common Dyspnea
Cardiac disorders
Common Bradycardia
Uncommon Tachycardia
SANDOSTATINreg LARreg IMPORTANT SAFETY INFORMATION (cont)
Please see Important Safety Information on pages 8-13
12
Table 2 Adverse drug reactions derived from spontaneous reports
Post-marketing
Spontaneously reported adverse reactions presented in Table 2 are reported voluntarily and it is not always possible to reliably establish frequency or a causal relationship to drug exposure
Description of selected adverse reactionsGastrointestinal disorders
In rare instances gastrointestinal side effects may resemble acute intestinal obstruction with progressive abdominal distension severe epigastric pain abdominal tenderness and guarding
The frequency of gastrointestinal adverse events is known to decrease over time with continued treatment
Injection site reactions
Injection site related reactions including pain burning redness hematoma hemorrhage pruritus or swelling were commonly reported in patients receiving Sandostatinreg LARreg however these events did not require any clinical intervention in the majority of the cases
Metabolism and nutrition disorders
Although measured fecal fat excretion may increase there is no evidence to date that long-term treatment with octreotide has led to nutritional deficiency due to malabsorption
Pancreatic enzymes
In very rare instances acute pancreatitis has been reported within the first hours or days of Sandostatinreg sc treatment and resolved on withdrawal of the drug In addition cholelithiasis induced pancreatitis has been reported for patients on long term Sandostatinreg sc treatment
Immune system disorders Anaphylaxis allergyhypersensitivity reactions
Skin and subcutaneous tissue disorders
Urticaria
Hepatobiliary disorders Acute pancreatitis acute hepatitis without cholestasis cholestatic hepatitis cholestasis jaundice cholestatic jaundice
Cardiac disorders Arrhythmias
Investigations Increased alkaline phosphatase levels increased gamma glutamyl transferase levels
SANDOSTATINreg LARreg IMPORTANT SAFETY INFORMATION (cont)
Please see Important Safety Information on pages 8-13
13
Cardiac disorders
In both acromegalic and carcinoid syndrome patients ECG changes were observed such as QT prolongation axis shifts early repolarization low voltage RS transition early R wave progression and nonspecific ST-T wave changes The relationship of these events to octreotide acetate is not established because many of these patients have underlying cardiac diseases (see Special warnings and precautions)
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorization of the medicinal product is important It allows continued monitoring of the benefitrisk balance of the medicinal product Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system
Overdose
A limited number of accidental overdoses of Sandostatinreg LARreg have been reported The doses ranged from 100 mg to 163 mgmonth of Sandostatinreg LARreg The only adverse event reported was hot flushes
Cancer patients receiving doses of Sandostatinreg LARreg up to 60 mgmonth and up to 90 mg2 weeks have been reported These doses were in general well tolerated however the following adverse events have been reported frequent urination fatigue depression anxiety and lack of concentration
The management of overdosage is symptomatic
List of excipients
Vial
Poly (DL-lactide-co-glycolide) 7835 of nominal1048790ll weight sterile mannitol 170 of nominal fill weight
Prefilled syringe
Kit without vial adaptersafety needle
One prefilled syringe (solvent for parenteral use) containing sodium carboxymethylcellulose 125 mg mannitol 15 mg water for injection qs ad 25 mL
Kit with vial adaptersafety needle
One prefilled syringe (solvent for parenteral use) containing sodium carboxymethylcellulose (14 mg) mannitol (12 mg) poloxamer 188 (4 mg) water for injection qs ad 2 mL
Pharmaceutical formulations may vary between countries
Please see the Summary of Product Characteristics
SANDOSTATINreg LARreg IMPORTANT SAFETY INFORMATION (cont)
Please see Important Safety Information on pages 8-13
14G-SAS-1157173317copy Novartis 2017
Novartis Pharma AG CH-4002 Basel Switzerland
References 1 Kunz PL Reidy-Lagunes D Anthony LB et al Consensus guidelines for the management and treatment of neuroendocrine tumors Pancreas 201342(4)557-577 2 Veenendaal LM Rinkes IHMB Lips CJM Hillegersberg RV Liver metastases of neuroendocrine tumours early reduction of tumour load to improve life expectancy World J Surg Oncol 2006435 3 Lee E Pachter HL Sarpel U Hepatic arterial embolization for the treatment of metastatic neuroendocrine tumors Int J Hepatol 20122012471203 4 Vinik AI Woltering EA OrsquoDorisio TM Go VLW Mamikunian G Diagnosing and treating gastroenteropancreatic tumors including ICD-9 codes In Neuroendocrine Tumors A Comprehensive Guide to Diagnosis and Management 5th ed Inglewood CA Inter Science Institute 20121-56 5 Grozinsky-Glasberg S Grossman AB Gross DJ Carcinoid heart disease from pathophysiology to treatmentndashlsquoSomething in the way it movesrsquo Neuroendocrinology 2015101(4)263- 273 6 Sandostatin LAR [Summary of Product Characteristics] Novartis 2016 7 Warner ME The Carcinoid Cancer Foundation Nutritional concerns for the carcinoid patient developing nutritional guidelines for persons with carcinoid disease httpwwwcarcinoidorgfor-patientsgeneral -informationnutritionnutritional-concerns-for-the-carcinoid-patient-developing-nutrition-guidelines -for-persons-with-carcinoid-disease Accessed January 30 2017 8 Cancer Research UK Tips on coping with diarrhea httpwwwcancerresearchukorgabout-cancercoping-with-cancercoping -physicallyboweltypesdiarrhoeamanagingtips-on-how-to-cope-with-diarrhoea Accessed January 30 2017 9 CancerNet Carcinoid tumor symptoms and signs httpwwwcancernetcancertypes carcinoidtumorsymptomsandsigns Accessed February 1 2017 10 Powell B Mukhtar AA Mills GH Carcinoid the disease and its implications for anaesthesia Continuing Education in Anaesthesia Critical Care amp Pain 201111(1)9-13 11 Rinke A Muumlller HH Schade-Brittinger C et al Placebo-controlled double-blind prospective randomized study on the effect of octreotide LAR in the control of tumor growth in patients with metastatic neuroendocrine midgut tumors a report from the PROMID study group J Clin Oncol 200927(28)4656-4663 12 Greenberger NJ Merck Manual Diarrhea httpwww merckmanualscomprofessionalgastrointestinal-disorderssymptoms-of-gi-disordersdiarrhea Accessed January 30 2017 13 Anthony L Freda PU From somatostatin to octreotide LAR evolution of a somatostatin analogue Curr Med Res Opin 200925(12)2989-2999 14 Litchford MD Dorner B Posthauer ME Malnutrition as a precursor of pressure ulcers Adv Wound Care 20143(1)54-63
Please see Important Safety Information on pages 8-13
9
Nutrition
Octreotide may alter absorption of dietary fats in some patients
Depressed vitamin B12 levels and abnormal Schillingrsquos tests have been observed in some patients receiving octreotide therapy Monitoring of vitamin B12 levels is recommended during therapy with Sandostatinreg LARreg in patients who have a history of vitamin B12 deprivation
Sodium content
Sandostatinreg LARreg contains less than 1 mmol (23 mg) sodium per dose ie is essentially ldquosodium-freerdquo
Interaction with other medicinal products and other forms of interactionDose adjustment of medicinal products such as beta blockers calcium channel blockers or agents to control fluid and electrolyte balance may be necessary when Sandostatinreg LARreg is administered concomitantly (see Special warnings and precautions for use)
Dose adjustments of insulin and antidiabetic medicinal products may be required when Sandostatinreg LARreg is administered concomitantly (see Special warnings and precautions for use)
Octreotide has been found to reduce the intestinal absorption of ciclosporin and to delay that of cimetidine
Concomitant administration of octreotide and bromocriptine increases the bioavailability of bromocriptine
Limited published data indicate that somatostatin analogs might decrease the metabolic clearance of compounds known to be metabolized by cytochrome P450 enzymes which may be due to the suppression of growth hormone Since it cannot be excluded that octreotide may have this effect other drugs mainly metabolized by CYP3A4 and which have a low therapeutic index (eg quinidine terfenadine) should therefore be used with caution
Pregnancy breastfeeding and fertilityPregnancy
There is a limited amount of data (less than 300 pregnancy outcomes) from the use of octreotide in pregnant women and in approximately one third of the cases the pregnancy outcomes are unknown The majority of reports were received after postmarketing use of octreotide and more than 50 of exposed pregnancies were reported in patients with acromegaly Most women were exposed to octreotide during the first trimester of pregnancy at doses ranging from 100-1200 microgramsday of Sandostatinreg sc or 10-40 mgmonth of Sandostatinreg LARreg Congenital anomalies were reported in about 4 of pregnancy cases for which the outcome is known No causal relationship to octreotide is suspected for these cases
Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see Preclinical safety data)
As a precautionary measure it is preferable to avoid the use of Sandostatinreg LARreg during pregnancy (see Special warnings and precautions for use)
SANDOSTATINreg LARreg IMPORTANT SAFETY INFORMATION (cont)
Please see Important Safety Information on pages 8-13
10
Breastfeeding
It is unknown whether octreotide is excreted in human breast milk Animal studies have shown excretion of octreotide in breast milk Patients should not breastfeed during Sandostatinreg LARreg treatment
Fertility
It is not known whether octreotide has an effect on human fertility Late descent of the testes was found for male offsprings of dams treated during pregnancy and lactation Octreotide however did not impair fertility in male and female rats at doses of up to 1 mgkg body weight per day (see Preclinical safety data)
Effects on ability to drive and use machinesSandostatinreg LARreg has no or negligible influence on the ability to drive and use machines Patients should be advised to be cautious when driving or using machines if they experience dizziness astheniafatigue or headache during treatment with Sandostatinreg LARreg
Undesirable effects and adverse drug reactionsSummary of the safety profile
The most frequent adverse reactions reported during octreotide therapy include gastrointestinal disorders nervous system disorders hepatobiliary disorders and metabolism and nutritional disorders
The most commonly reported adverse reactions in clinical trials with octreotide administration were diarrhea abdominal pain nausea flatulence headache cholelithiasis hyperglycemia and constipation Other commonly reported adverse reactions were dizziness localized pain biliary sludge thyroid dysfunction (eg decreased thyroid stimulating hormone [TSH] decreased total T4 and decreased free T4) loose stools impaired glucose tolerance vomiting asthenia and hypoglycemia
Tabulated list of adverse reactions
The following adverse drug reactions listed in Table 1 have been accumulated from clinical studies with octreotide
Adverse drug reactions (Table 1) are ranked under heading of frequency the most frequent first using the following convention very common (ge110) common (ge1100 lt110) uncommon (ge11000 lt1100) rare (ge110000 lt11000) very rare (lt110000) including isolated reports Within each frequency grouping adverse reactions are ranked in order of decreasing seriousness
SANDOSTATINreg LARreg IMPORTANT SAFETY INFORMATION (cont)
Please see Important Safety Information on pages 8-13
11
Table 1 Adverse drug reactions reported in clinical studies
Gastrointestinal disorders
Very common Diarrhea abdominal pain nausea constipation flatulence
Common Dyspepsia vomiting abdominal bloating steatorrhea loose stools discoloration of feces
Nervous system disorders
Very common Headache
Common Dizziness
Endocrine disorders
Common Hypothyroidism thyroid dysfunction (eg decreased TSH decreased total T4 and decreased free T4)
Hepatobiliary disorders
Very common Cholelithiasis
Common Cholecystitis biliary sludge hyperbilirubinemia
Metabolism and nutrition disorders
Very common Hyperglycemia
Common Hypoglycemia impaired glucose tolerance anorexia
Uncommon Dehydration
General disorders and administration site conditions
Very common Injection site reactions
Common Asthenia
Investigations
Common Elevated transaminase levels
Skin and subcutaneous tissue disorders
Common Pruritus rash alopecia
Respiratory disorders
Common Dyspnea
Cardiac disorders
Common Bradycardia
Uncommon Tachycardia
SANDOSTATINreg LARreg IMPORTANT SAFETY INFORMATION (cont)
Please see Important Safety Information on pages 8-13
12
Table 2 Adverse drug reactions derived from spontaneous reports
Post-marketing
Spontaneously reported adverse reactions presented in Table 2 are reported voluntarily and it is not always possible to reliably establish frequency or a causal relationship to drug exposure
Description of selected adverse reactionsGastrointestinal disorders
In rare instances gastrointestinal side effects may resemble acute intestinal obstruction with progressive abdominal distension severe epigastric pain abdominal tenderness and guarding
The frequency of gastrointestinal adverse events is known to decrease over time with continued treatment
Injection site reactions
Injection site related reactions including pain burning redness hematoma hemorrhage pruritus or swelling were commonly reported in patients receiving Sandostatinreg LARreg however these events did not require any clinical intervention in the majority of the cases
Metabolism and nutrition disorders
Although measured fecal fat excretion may increase there is no evidence to date that long-term treatment with octreotide has led to nutritional deficiency due to malabsorption
Pancreatic enzymes
In very rare instances acute pancreatitis has been reported within the first hours or days of Sandostatinreg sc treatment and resolved on withdrawal of the drug In addition cholelithiasis induced pancreatitis has been reported for patients on long term Sandostatinreg sc treatment
Immune system disorders Anaphylaxis allergyhypersensitivity reactions
Skin and subcutaneous tissue disorders
Urticaria
Hepatobiliary disorders Acute pancreatitis acute hepatitis without cholestasis cholestatic hepatitis cholestasis jaundice cholestatic jaundice
Cardiac disorders Arrhythmias
Investigations Increased alkaline phosphatase levels increased gamma glutamyl transferase levels
SANDOSTATINreg LARreg IMPORTANT SAFETY INFORMATION (cont)
Please see Important Safety Information on pages 8-13
13
Cardiac disorders
In both acromegalic and carcinoid syndrome patients ECG changes were observed such as QT prolongation axis shifts early repolarization low voltage RS transition early R wave progression and nonspecific ST-T wave changes The relationship of these events to octreotide acetate is not established because many of these patients have underlying cardiac diseases (see Special warnings and precautions)
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorization of the medicinal product is important It allows continued monitoring of the benefitrisk balance of the medicinal product Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system
Overdose
A limited number of accidental overdoses of Sandostatinreg LARreg have been reported The doses ranged from 100 mg to 163 mgmonth of Sandostatinreg LARreg The only adverse event reported was hot flushes
Cancer patients receiving doses of Sandostatinreg LARreg up to 60 mgmonth and up to 90 mg2 weeks have been reported These doses were in general well tolerated however the following adverse events have been reported frequent urination fatigue depression anxiety and lack of concentration
The management of overdosage is symptomatic
List of excipients
Vial
Poly (DL-lactide-co-glycolide) 7835 of nominal1048790ll weight sterile mannitol 170 of nominal fill weight
Prefilled syringe
Kit without vial adaptersafety needle
One prefilled syringe (solvent for parenteral use) containing sodium carboxymethylcellulose 125 mg mannitol 15 mg water for injection qs ad 25 mL
Kit with vial adaptersafety needle
One prefilled syringe (solvent for parenteral use) containing sodium carboxymethylcellulose (14 mg) mannitol (12 mg) poloxamer 188 (4 mg) water for injection qs ad 2 mL
Pharmaceutical formulations may vary between countries
Please see the Summary of Product Characteristics
SANDOSTATINreg LARreg IMPORTANT SAFETY INFORMATION (cont)
Please see Important Safety Information on pages 8-13
14G-SAS-1157173317copy Novartis 2017
Novartis Pharma AG CH-4002 Basel Switzerland
References 1 Kunz PL Reidy-Lagunes D Anthony LB et al Consensus guidelines for the management and treatment of neuroendocrine tumors Pancreas 201342(4)557-577 2 Veenendaal LM Rinkes IHMB Lips CJM Hillegersberg RV Liver metastases of neuroendocrine tumours early reduction of tumour load to improve life expectancy World J Surg Oncol 2006435 3 Lee E Pachter HL Sarpel U Hepatic arterial embolization for the treatment of metastatic neuroendocrine tumors Int J Hepatol 20122012471203 4 Vinik AI Woltering EA OrsquoDorisio TM Go VLW Mamikunian G Diagnosing and treating gastroenteropancreatic tumors including ICD-9 codes In Neuroendocrine Tumors A Comprehensive Guide to Diagnosis and Management 5th ed Inglewood CA Inter Science Institute 20121-56 5 Grozinsky-Glasberg S Grossman AB Gross DJ Carcinoid heart disease from pathophysiology to treatmentndashlsquoSomething in the way it movesrsquo Neuroendocrinology 2015101(4)263- 273 6 Sandostatin LAR [Summary of Product Characteristics] Novartis 2016 7 Warner ME The Carcinoid Cancer Foundation Nutritional concerns for the carcinoid patient developing nutritional guidelines for persons with carcinoid disease httpwwwcarcinoidorgfor-patientsgeneral -informationnutritionnutritional-concerns-for-the-carcinoid-patient-developing-nutrition-guidelines -for-persons-with-carcinoid-disease Accessed January 30 2017 8 Cancer Research UK Tips on coping with diarrhea httpwwwcancerresearchukorgabout-cancercoping-with-cancercoping -physicallyboweltypesdiarrhoeamanagingtips-on-how-to-cope-with-diarrhoea Accessed January 30 2017 9 CancerNet Carcinoid tumor symptoms and signs httpwwwcancernetcancertypes carcinoidtumorsymptomsandsigns Accessed February 1 2017 10 Powell B Mukhtar AA Mills GH Carcinoid the disease and its implications for anaesthesia Continuing Education in Anaesthesia Critical Care amp Pain 201111(1)9-13 11 Rinke A Muumlller HH Schade-Brittinger C et al Placebo-controlled double-blind prospective randomized study on the effect of octreotide LAR in the control of tumor growth in patients with metastatic neuroendocrine midgut tumors a report from the PROMID study group J Clin Oncol 200927(28)4656-4663 12 Greenberger NJ Merck Manual Diarrhea httpwww merckmanualscomprofessionalgastrointestinal-disorderssymptoms-of-gi-disordersdiarrhea Accessed January 30 2017 13 Anthony L Freda PU From somatostatin to octreotide LAR evolution of a somatostatin analogue Curr Med Res Opin 200925(12)2989-2999 14 Litchford MD Dorner B Posthauer ME Malnutrition as a precursor of pressure ulcers Adv Wound Care 20143(1)54-63
Please see Important Safety Information on pages 8-13
10
Breastfeeding
It is unknown whether octreotide is excreted in human breast milk Animal studies have shown excretion of octreotide in breast milk Patients should not breastfeed during Sandostatinreg LARreg treatment
Fertility
It is not known whether octreotide has an effect on human fertility Late descent of the testes was found for male offsprings of dams treated during pregnancy and lactation Octreotide however did not impair fertility in male and female rats at doses of up to 1 mgkg body weight per day (see Preclinical safety data)
Effects on ability to drive and use machinesSandostatinreg LARreg has no or negligible influence on the ability to drive and use machines Patients should be advised to be cautious when driving or using machines if they experience dizziness astheniafatigue or headache during treatment with Sandostatinreg LARreg
Undesirable effects and adverse drug reactionsSummary of the safety profile
The most frequent adverse reactions reported during octreotide therapy include gastrointestinal disorders nervous system disorders hepatobiliary disorders and metabolism and nutritional disorders
The most commonly reported adverse reactions in clinical trials with octreotide administration were diarrhea abdominal pain nausea flatulence headache cholelithiasis hyperglycemia and constipation Other commonly reported adverse reactions were dizziness localized pain biliary sludge thyroid dysfunction (eg decreased thyroid stimulating hormone [TSH] decreased total T4 and decreased free T4) loose stools impaired glucose tolerance vomiting asthenia and hypoglycemia
Tabulated list of adverse reactions
The following adverse drug reactions listed in Table 1 have been accumulated from clinical studies with octreotide
Adverse drug reactions (Table 1) are ranked under heading of frequency the most frequent first using the following convention very common (ge110) common (ge1100 lt110) uncommon (ge11000 lt1100) rare (ge110000 lt11000) very rare (lt110000) including isolated reports Within each frequency grouping adverse reactions are ranked in order of decreasing seriousness
SANDOSTATINreg LARreg IMPORTANT SAFETY INFORMATION (cont)
Please see Important Safety Information on pages 8-13
11
Table 1 Adverse drug reactions reported in clinical studies
Gastrointestinal disorders
Very common Diarrhea abdominal pain nausea constipation flatulence
Common Dyspepsia vomiting abdominal bloating steatorrhea loose stools discoloration of feces
Nervous system disorders
Very common Headache
Common Dizziness
Endocrine disorders
Common Hypothyroidism thyroid dysfunction (eg decreased TSH decreased total T4 and decreased free T4)
Hepatobiliary disorders
Very common Cholelithiasis
Common Cholecystitis biliary sludge hyperbilirubinemia
Metabolism and nutrition disorders
Very common Hyperglycemia
Common Hypoglycemia impaired glucose tolerance anorexia
Uncommon Dehydration
General disorders and administration site conditions
Very common Injection site reactions
Common Asthenia
Investigations
Common Elevated transaminase levels
Skin and subcutaneous tissue disorders
Common Pruritus rash alopecia
Respiratory disorders
Common Dyspnea
Cardiac disorders
Common Bradycardia
Uncommon Tachycardia
SANDOSTATINreg LARreg IMPORTANT SAFETY INFORMATION (cont)
Please see Important Safety Information on pages 8-13
12
Table 2 Adverse drug reactions derived from spontaneous reports
Post-marketing
Spontaneously reported adverse reactions presented in Table 2 are reported voluntarily and it is not always possible to reliably establish frequency or a causal relationship to drug exposure
Description of selected adverse reactionsGastrointestinal disorders
In rare instances gastrointestinal side effects may resemble acute intestinal obstruction with progressive abdominal distension severe epigastric pain abdominal tenderness and guarding
The frequency of gastrointestinal adverse events is known to decrease over time with continued treatment
Injection site reactions
Injection site related reactions including pain burning redness hematoma hemorrhage pruritus or swelling were commonly reported in patients receiving Sandostatinreg LARreg however these events did not require any clinical intervention in the majority of the cases
Metabolism and nutrition disorders
Although measured fecal fat excretion may increase there is no evidence to date that long-term treatment with octreotide has led to nutritional deficiency due to malabsorption
Pancreatic enzymes
In very rare instances acute pancreatitis has been reported within the first hours or days of Sandostatinreg sc treatment and resolved on withdrawal of the drug In addition cholelithiasis induced pancreatitis has been reported for patients on long term Sandostatinreg sc treatment
Immune system disorders Anaphylaxis allergyhypersensitivity reactions
Skin and subcutaneous tissue disorders
Urticaria
Hepatobiliary disorders Acute pancreatitis acute hepatitis without cholestasis cholestatic hepatitis cholestasis jaundice cholestatic jaundice
Cardiac disorders Arrhythmias
Investigations Increased alkaline phosphatase levels increased gamma glutamyl transferase levels
SANDOSTATINreg LARreg IMPORTANT SAFETY INFORMATION (cont)
Please see Important Safety Information on pages 8-13
13
Cardiac disorders
In both acromegalic and carcinoid syndrome patients ECG changes were observed such as QT prolongation axis shifts early repolarization low voltage RS transition early R wave progression and nonspecific ST-T wave changes The relationship of these events to octreotide acetate is not established because many of these patients have underlying cardiac diseases (see Special warnings and precautions)
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorization of the medicinal product is important It allows continued monitoring of the benefitrisk balance of the medicinal product Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system
Overdose
A limited number of accidental overdoses of Sandostatinreg LARreg have been reported The doses ranged from 100 mg to 163 mgmonth of Sandostatinreg LARreg The only adverse event reported was hot flushes
Cancer patients receiving doses of Sandostatinreg LARreg up to 60 mgmonth and up to 90 mg2 weeks have been reported These doses were in general well tolerated however the following adverse events have been reported frequent urination fatigue depression anxiety and lack of concentration
The management of overdosage is symptomatic
List of excipients
Vial
Poly (DL-lactide-co-glycolide) 7835 of nominal1048790ll weight sterile mannitol 170 of nominal fill weight
Prefilled syringe
Kit without vial adaptersafety needle
One prefilled syringe (solvent for parenteral use) containing sodium carboxymethylcellulose 125 mg mannitol 15 mg water for injection qs ad 25 mL
Kit with vial adaptersafety needle
One prefilled syringe (solvent for parenteral use) containing sodium carboxymethylcellulose (14 mg) mannitol (12 mg) poloxamer 188 (4 mg) water for injection qs ad 2 mL
Pharmaceutical formulations may vary between countries
Please see the Summary of Product Characteristics
SANDOSTATINreg LARreg IMPORTANT SAFETY INFORMATION (cont)
Please see Important Safety Information on pages 8-13
14G-SAS-1157173317copy Novartis 2017
Novartis Pharma AG CH-4002 Basel Switzerland
References 1 Kunz PL Reidy-Lagunes D Anthony LB et al Consensus guidelines for the management and treatment of neuroendocrine tumors Pancreas 201342(4)557-577 2 Veenendaal LM Rinkes IHMB Lips CJM Hillegersberg RV Liver metastases of neuroendocrine tumours early reduction of tumour load to improve life expectancy World J Surg Oncol 2006435 3 Lee E Pachter HL Sarpel U Hepatic arterial embolization for the treatment of metastatic neuroendocrine tumors Int J Hepatol 20122012471203 4 Vinik AI Woltering EA OrsquoDorisio TM Go VLW Mamikunian G Diagnosing and treating gastroenteropancreatic tumors including ICD-9 codes In Neuroendocrine Tumors A Comprehensive Guide to Diagnosis and Management 5th ed Inglewood CA Inter Science Institute 20121-56 5 Grozinsky-Glasberg S Grossman AB Gross DJ Carcinoid heart disease from pathophysiology to treatmentndashlsquoSomething in the way it movesrsquo Neuroendocrinology 2015101(4)263- 273 6 Sandostatin LAR [Summary of Product Characteristics] Novartis 2016 7 Warner ME The Carcinoid Cancer Foundation Nutritional concerns for the carcinoid patient developing nutritional guidelines for persons with carcinoid disease httpwwwcarcinoidorgfor-patientsgeneral -informationnutritionnutritional-concerns-for-the-carcinoid-patient-developing-nutrition-guidelines -for-persons-with-carcinoid-disease Accessed January 30 2017 8 Cancer Research UK Tips on coping with diarrhea httpwwwcancerresearchukorgabout-cancercoping-with-cancercoping -physicallyboweltypesdiarrhoeamanagingtips-on-how-to-cope-with-diarrhoea Accessed January 30 2017 9 CancerNet Carcinoid tumor symptoms and signs httpwwwcancernetcancertypes carcinoidtumorsymptomsandsigns Accessed February 1 2017 10 Powell B Mukhtar AA Mills GH Carcinoid the disease and its implications for anaesthesia Continuing Education in Anaesthesia Critical Care amp Pain 201111(1)9-13 11 Rinke A Muumlller HH Schade-Brittinger C et al Placebo-controlled double-blind prospective randomized study on the effect of octreotide LAR in the control of tumor growth in patients with metastatic neuroendocrine midgut tumors a report from the PROMID study group J Clin Oncol 200927(28)4656-4663 12 Greenberger NJ Merck Manual Diarrhea httpwww merckmanualscomprofessionalgastrointestinal-disorderssymptoms-of-gi-disordersdiarrhea Accessed January 30 2017 13 Anthony L Freda PU From somatostatin to octreotide LAR evolution of a somatostatin analogue Curr Med Res Opin 200925(12)2989-2999 14 Litchford MD Dorner B Posthauer ME Malnutrition as a precursor of pressure ulcers Adv Wound Care 20143(1)54-63
Please see Important Safety Information on pages 8-13
11
Table 1 Adverse drug reactions reported in clinical studies
Gastrointestinal disorders
Very common Diarrhea abdominal pain nausea constipation flatulence
Common Dyspepsia vomiting abdominal bloating steatorrhea loose stools discoloration of feces
Nervous system disorders
Very common Headache
Common Dizziness
Endocrine disorders
Common Hypothyroidism thyroid dysfunction (eg decreased TSH decreased total T4 and decreased free T4)
Hepatobiliary disorders
Very common Cholelithiasis
Common Cholecystitis biliary sludge hyperbilirubinemia
Metabolism and nutrition disorders
Very common Hyperglycemia
Common Hypoglycemia impaired glucose tolerance anorexia
Uncommon Dehydration
General disorders and administration site conditions
Very common Injection site reactions
Common Asthenia
Investigations
Common Elevated transaminase levels
Skin and subcutaneous tissue disorders
Common Pruritus rash alopecia
Respiratory disorders
Common Dyspnea
Cardiac disorders
Common Bradycardia
Uncommon Tachycardia
SANDOSTATINreg LARreg IMPORTANT SAFETY INFORMATION (cont)
Please see Important Safety Information on pages 8-13
12
Table 2 Adverse drug reactions derived from spontaneous reports
Post-marketing
Spontaneously reported adverse reactions presented in Table 2 are reported voluntarily and it is not always possible to reliably establish frequency or a causal relationship to drug exposure
Description of selected adverse reactionsGastrointestinal disorders
In rare instances gastrointestinal side effects may resemble acute intestinal obstruction with progressive abdominal distension severe epigastric pain abdominal tenderness and guarding
The frequency of gastrointestinal adverse events is known to decrease over time with continued treatment
Injection site reactions
Injection site related reactions including pain burning redness hematoma hemorrhage pruritus or swelling were commonly reported in patients receiving Sandostatinreg LARreg however these events did not require any clinical intervention in the majority of the cases
Metabolism and nutrition disorders
Although measured fecal fat excretion may increase there is no evidence to date that long-term treatment with octreotide has led to nutritional deficiency due to malabsorption
Pancreatic enzymes
In very rare instances acute pancreatitis has been reported within the first hours or days of Sandostatinreg sc treatment and resolved on withdrawal of the drug In addition cholelithiasis induced pancreatitis has been reported for patients on long term Sandostatinreg sc treatment
Immune system disorders Anaphylaxis allergyhypersensitivity reactions
Skin and subcutaneous tissue disorders
Urticaria
Hepatobiliary disorders Acute pancreatitis acute hepatitis without cholestasis cholestatic hepatitis cholestasis jaundice cholestatic jaundice
Cardiac disorders Arrhythmias
Investigations Increased alkaline phosphatase levels increased gamma glutamyl transferase levels
SANDOSTATINreg LARreg IMPORTANT SAFETY INFORMATION (cont)
Please see Important Safety Information on pages 8-13
13
Cardiac disorders
In both acromegalic and carcinoid syndrome patients ECG changes were observed such as QT prolongation axis shifts early repolarization low voltage RS transition early R wave progression and nonspecific ST-T wave changes The relationship of these events to octreotide acetate is not established because many of these patients have underlying cardiac diseases (see Special warnings and precautions)
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorization of the medicinal product is important It allows continued monitoring of the benefitrisk balance of the medicinal product Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system
Overdose
A limited number of accidental overdoses of Sandostatinreg LARreg have been reported The doses ranged from 100 mg to 163 mgmonth of Sandostatinreg LARreg The only adverse event reported was hot flushes
Cancer patients receiving doses of Sandostatinreg LARreg up to 60 mgmonth and up to 90 mg2 weeks have been reported These doses were in general well tolerated however the following adverse events have been reported frequent urination fatigue depression anxiety and lack of concentration
The management of overdosage is symptomatic
List of excipients
Vial
Poly (DL-lactide-co-glycolide) 7835 of nominal1048790ll weight sterile mannitol 170 of nominal fill weight
Prefilled syringe
Kit without vial adaptersafety needle
One prefilled syringe (solvent for parenteral use) containing sodium carboxymethylcellulose 125 mg mannitol 15 mg water for injection qs ad 25 mL
Kit with vial adaptersafety needle
One prefilled syringe (solvent for parenteral use) containing sodium carboxymethylcellulose (14 mg) mannitol (12 mg) poloxamer 188 (4 mg) water for injection qs ad 2 mL
Pharmaceutical formulations may vary between countries
Please see the Summary of Product Characteristics
SANDOSTATINreg LARreg IMPORTANT SAFETY INFORMATION (cont)
Please see Important Safety Information on pages 8-13
14G-SAS-1157173317copy Novartis 2017
Novartis Pharma AG CH-4002 Basel Switzerland
References 1 Kunz PL Reidy-Lagunes D Anthony LB et al Consensus guidelines for the management and treatment of neuroendocrine tumors Pancreas 201342(4)557-577 2 Veenendaal LM Rinkes IHMB Lips CJM Hillegersberg RV Liver metastases of neuroendocrine tumours early reduction of tumour load to improve life expectancy World J Surg Oncol 2006435 3 Lee E Pachter HL Sarpel U Hepatic arterial embolization for the treatment of metastatic neuroendocrine tumors Int J Hepatol 20122012471203 4 Vinik AI Woltering EA OrsquoDorisio TM Go VLW Mamikunian G Diagnosing and treating gastroenteropancreatic tumors including ICD-9 codes In Neuroendocrine Tumors A Comprehensive Guide to Diagnosis and Management 5th ed Inglewood CA Inter Science Institute 20121-56 5 Grozinsky-Glasberg S Grossman AB Gross DJ Carcinoid heart disease from pathophysiology to treatmentndashlsquoSomething in the way it movesrsquo Neuroendocrinology 2015101(4)263- 273 6 Sandostatin LAR [Summary of Product Characteristics] Novartis 2016 7 Warner ME The Carcinoid Cancer Foundation Nutritional concerns for the carcinoid patient developing nutritional guidelines for persons with carcinoid disease httpwwwcarcinoidorgfor-patientsgeneral -informationnutritionnutritional-concerns-for-the-carcinoid-patient-developing-nutrition-guidelines -for-persons-with-carcinoid-disease Accessed January 30 2017 8 Cancer Research UK Tips on coping with diarrhea httpwwwcancerresearchukorgabout-cancercoping-with-cancercoping -physicallyboweltypesdiarrhoeamanagingtips-on-how-to-cope-with-diarrhoea Accessed January 30 2017 9 CancerNet Carcinoid tumor symptoms and signs httpwwwcancernetcancertypes carcinoidtumorsymptomsandsigns Accessed February 1 2017 10 Powell B Mukhtar AA Mills GH Carcinoid the disease and its implications for anaesthesia Continuing Education in Anaesthesia Critical Care amp Pain 201111(1)9-13 11 Rinke A Muumlller HH Schade-Brittinger C et al Placebo-controlled double-blind prospective randomized study on the effect of octreotide LAR in the control of tumor growth in patients with metastatic neuroendocrine midgut tumors a report from the PROMID study group J Clin Oncol 200927(28)4656-4663 12 Greenberger NJ Merck Manual Diarrhea httpwww merckmanualscomprofessionalgastrointestinal-disorderssymptoms-of-gi-disordersdiarrhea Accessed January 30 2017 13 Anthony L Freda PU From somatostatin to octreotide LAR evolution of a somatostatin analogue Curr Med Res Opin 200925(12)2989-2999 14 Litchford MD Dorner B Posthauer ME Malnutrition as a precursor of pressure ulcers Adv Wound Care 20143(1)54-63
Please see Important Safety Information on pages 8-13
12
Table 2 Adverse drug reactions derived from spontaneous reports
Post-marketing
Spontaneously reported adverse reactions presented in Table 2 are reported voluntarily and it is not always possible to reliably establish frequency or a causal relationship to drug exposure
Description of selected adverse reactionsGastrointestinal disorders
In rare instances gastrointestinal side effects may resemble acute intestinal obstruction with progressive abdominal distension severe epigastric pain abdominal tenderness and guarding
The frequency of gastrointestinal adverse events is known to decrease over time with continued treatment
Injection site reactions
Injection site related reactions including pain burning redness hematoma hemorrhage pruritus or swelling were commonly reported in patients receiving Sandostatinreg LARreg however these events did not require any clinical intervention in the majority of the cases
Metabolism and nutrition disorders
Although measured fecal fat excretion may increase there is no evidence to date that long-term treatment with octreotide has led to nutritional deficiency due to malabsorption
Pancreatic enzymes
In very rare instances acute pancreatitis has been reported within the first hours or days of Sandostatinreg sc treatment and resolved on withdrawal of the drug In addition cholelithiasis induced pancreatitis has been reported for patients on long term Sandostatinreg sc treatment
Immune system disorders Anaphylaxis allergyhypersensitivity reactions
Skin and subcutaneous tissue disorders
Urticaria
Hepatobiliary disorders Acute pancreatitis acute hepatitis without cholestasis cholestatic hepatitis cholestasis jaundice cholestatic jaundice
Cardiac disorders Arrhythmias
Investigations Increased alkaline phosphatase levels increased gamma glutamyl transferase levels
SANDOSTATINreg LARreg IMPORTANT SAFETY INFORMATION (cont)
Please see Important Safety Information on pages 8-13
13
Cardiac disorders
In both acromegalic and carcinoid syndrome patients ECG changes were observed such as QT prolongation axis shifts early repolarization low voltage RS transition early R wave progression and nonspecific ST-T wave changes The relationship of these events to octreotide acetate is not established because many of these patients have underlying cardiac diseases (see Special warnings and precautions)
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorization of the medicinal product is important It allows continued monitoring of the benefitrisk balance of the medicinal product Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system
Overdose
A limited number of accidental overdoses of Sandostatinreg LARreg have been reported The doses ranged from 100 mg to 163 mgmonth of Sandostatinreg LARreg The only adverse event reported was hot flushes
Cancer patients receiving doses of Sandostatinreg LARreg up to 60 mgmonth and up to 90 mg2 weeks have been reported These doses were in general well tolerated however the following adverse events have been reported frequent urination fatigue depression anxiety and lack of concentration
The management of overdosage is symptomatic
List of excipients
Vial
Poly (DL-lactide-co-glycolide) 7835 of nominal1048790ll weight sterile mannitol 170 of nominal fill weight
Prefilled syringe
Kit without vial adaptersafety needle
One prefilled syringe (solvent for parenteral use) containing sodium carboxymethylcellulose 125 mg mannitol 15 mg water for injection qs ad 25 mL
Kit with vial adaptersafety needle
One prefilled syringe (solvent for parenteral use) containing sodium carboxymethylcellulose (14 mg) mannitol (12 mg) poloxamer 188 (4 mg) water for injection qs ad 2 mL
Pharmaceutical formulations may vary between countries
Please see the Summary of Product Characteristics
SANDOSTATINreg LARreg IMPORTANT SAFETY INFORMATION (cont)
Please see Important Safety Information on pages 8-13
14G-SAS-1157173317copy Novartis 2017
Novartis Pharma AG CH-4002 Basel Switzerland
References 1 Kunz PL Reidy-Lagunes D Anthony LB et al Consensus guidelines for the management and treatment of neuroendocrine tumors Pancreas 201342(4)557-577 2 Veenendaal LM Rinkes IHMB Lips CJM Hillegersberg RV Liver metastases of neuroendocrine tumours early reduction of tumour load to improve life expectancy World J Surg Oncol 2006435 3 Lee E Pachter HL Sarpel U Hepatic arterial embolization for the treatment of metastatic neuroendocrine tumors Int J Hepatol 20122012471203 4 Vinik AI Woltering EA OrsquoDorisio TM Go VLW Mamikunian G Diagnosing and treating gastroenteropancreatic tumors including ICD-9 codes In Neuroendocrine Tumors A Comprehensive Guide to Diagnosis and Management 5th ed Inglewood CA Inter Science Institute 20121-56 5 Grozinsky-Glasberg S Grossman AB Gross DJ Carcinoid heart disease from pathophysiology to treatmentndashlsquoSomething in the way it movesrsquo Neuroendocrinology 2015101(4)263- 273 6 Sandostatin LAR [Summary of Product Characteristics] Novartis 2016 7 Warner ME The Carcinoid Cancer Foundation Nutritional concerns for the carcinoid patient developing nutritional guidelines for persons with carcinoid disease httpwwwcarcinoidorgfor-patientsgeneral -informationnutritionnutritional-concerns-for-the-carcinoid-patient-developing-nutrition-guidelines -for-persons-with-carcinoid-disease Accessed January 30 2017 8 Cancer Research UK Tips on coping with diarrhea httpwwwcancerresearchukorgabout-cancercoping-with-cancercoping -physicallyboweltypesdiarrhoeamanagingtips-on-how-to-cope-with-diarrhoea Accessed January 30 2017 9 CancerNet Carcinoid tumor symptoms and signs httpwwwcancernetcancertypes carcinoidtumorsymptomsandsigns Accessed February 1 2017 10 Powell B Mukhtar AA Mills GH Carcinoid the disease and its implications for anaesthesia Continuing Education in Anaesthesia Critical Care amp Pain 201111(1)9-13 11 Rinke A Muumlller HH Schade-Brittinger C et al Placebo-controlled double-blind prospective randomized study on the effect of octreotide LAR in the control of tumor growth in patients with metastatic neuroendocrine midgut tumors a report from the PROMID study group J Clin Oncol 200927(28)4656-4663 12 Greenberger NJ Merck Manual Diarrhea httpwww merckmanualscomprofessionalgastrointestinal-disorderssymptoms-of-gi-disordersdiarrhea Accessed January 30 2017 13 Anthony L Freda PU From somatostatin to octreotide LAR evolution of a somatostatin analogue Curr Med Res Opin 200925(12)2989-2999 14 Litchford MD Dorner B Posthauer ME Malnutrition as a precursor of pressure ulcers Adv Wound Care 20143(1)54-63
Please see Important Safety Information on pages 8-13
13
Cardiac disorders
In both acromegalic and carcinoid syndrome patients ECG changes were observed such as QT prolongation axis shifts early repolarization low voltage RS transition early R wave progression and nonspecific ST-T wave changes The relationship of these events to octreotide acetate is not established because many of these patients have underlying cardiac diseases (see Special warnings and precautions)
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorization of the medicinal product is important It allows continued monitoring of the benefitrisk balance of the medicinal product Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system
Overdose
A limited number of accidental overdoses of Sandostatinreg LARreg have been reported The doses ranged from 100 mg to 163 mgmonth of Sandostatinreg LARreg The only adverse event reported was hot flushes
Cancer patients receiving doses of Sandostatinreg LARreg up to 60 mgmonth and up to 90 mg2 weeks have been reported These doses were in general well tolerated however the following adverse events have been reported frequent urination fatigue depression anxiety and lack of concentration
The management of overdosage is symptomatic
List of excipients
Vial
Poly (DL-lactide-co-glycolide) 7835 of nominal1048790ll weight sterile mannitol 170 of nominal fill weight
Prefilled syringe
Kit without vial adaptersafety needle
One prefilled syringe (solvent for parenteral use) containing sodium carboxymethylcellulose 125 mg mannitol 15 mg water for injection qs ad 25 mL
Kit with vial adaptersafety needle
One prefilled syringe (solvent for parenteral use) containing sodium carboxymethylcellulose (14 mg) mannitol (12 mg) poloxamer 188 (4 mg) water for injection qs ad 2 mL
Pharmaceutical formulations may vary between countries
Please see the Summary of Product Characteristics
SANDOSTATINreg LARreg IMPORTANT SAFETY INFORMATION (cont)
Please see Important Safety Information on pages 8-13
14G-SAS-1157173317copy Novartis 2017
Novartis Pharma AG CH-4002 Basel Switzerland
References 1 Kunz PL Reidy-Lagunes D Anthony LB et al Consensus guidelines for the management and treatment of neuroendocrine tumors Pancreas 201342(4)557-577 2 Veenendaal LM Rinkes IHMB Lips CJM Hillegersberg RV Liver metastases of neuroendocrine tumours early reduction of tumour load to improve life expectancy World J Surg Oncol 2006435 3 Lee E Pachter HL Sarpel U Hepatic arterial embolization for the treatment of metastatic neuroendocrine tumors Int J Hepatol 20122012471203 4 Vinik AI Woltering EA OrsquoDorisio TM Go VLW Mamikunian G Diagnosing and treating gastroenteropancreatic tumors including ICD-9 codes In Neuroendocrine Tumors A Comprehensive Guide to Diagnosis and Management 5th ed Inglewood CA Inter Science Institute 20121-56 5 Grozinsky-Glasberg S Grossman AB Gross DJ Carcinoid heart disease from pathophysiology to treatmentndashlsquoSomething in the way it movesrsquo Neuroendocrinology 2015101(4)263- 273 6 Sandostatin LAR [Summary of Product Characteristics] Novartis 2016 7 Warner ME The Carcinoid Cancer Foundation Nutritional concerns for the carcinoid patient developing nutritional guidelines for persons with carcinoid disease httpwwwcarcinoidorgfor-patientsgeneral -informationnutritionnutritional-concerns-for-the-carcinoid-patient-developing-nutrition-guidelines -for-persons-with-carcinoid-disease Accessed January 30 2017 8 Cancer Research UK Tips on coping with diarrhea httpwwwcancerresearchukorgabout-cancercoping-with-cancercoping -physicallyboweltypesdiarrhoeamanagingtips-on-how-to-cope-with-diarrhoea Accessed January 30 2017 9 CancerNet Carcinoid tumor symptoms and signs httpwwwcancernetcancertypes carcinoidtumorsymptomsandsigns Accessed February 1 2017 10 Powell B Mukhtar AA Mills GH Carcinoid the disease and its implications for anaesthesia Continuing Education in Anaesthesia Critical Care amp Pain 201111(1)9-13 11 Rinke A Muumlller HH Schade-Brittinger C et al Placebo-controlled double-blind prospective randomized study on the effect of octreotide LAR in the control of tumor growth in patients with metastatic neuroendocrine midgut tumors a report from the PROMID study group J Clin Oncol 200927(28)4656-4663 12 Greenberger NJ Merck Manual Diarrhea httpwww merckmanualscomprofessionalgastrointestinal-disorderssymptoms-of-gi-disordersdiarrhea Accessed January 30 2017 13 Anthony L Freda PU From somatostatin to octreotide LAR evolution of a somatostatin analogue Curr Med Res Opin 200925(12)2989-2999 14 Litchford MD Dorner B Posthauer ME Malnutrition as a precursor of pressure ulcers Adv Wound Care 20143(1)54-63
Please see Important Safety Information on pages 8-13
14G-SAS-1157173317copy Novartis 2017
Novartis Pharma AG CH-4002 Basel Switzerland
References 1 Kunz PL Reidy-Lagunes D Anthony LB et al Consensus guidelines for the management and treatment of neuroendocrine tumors Pancreas 201342(4)557-577 2 Veenendaal LM Rinkes IHMB Lips CJM Hillegersberg RV Liver metastases of neuroendocrine tumours early reduction of tumour load to improve life expectancy World J Surg Oncol 2006435 3 Lee E Pachter HL Sarpel U Hepatic arterial embolization for the treatment of metastatic neuroendocrine tumors Int J Hepatol 20122012471203 4 Vinik AI Woltering EA OrsquoDorisio TM Go VLW Mamikunian G Diagnosing and treating gastroenteropancreatic tumors including ICD-9 codes In Neuroendocrine Tumors A Comprehensive Guide to Diagnosis and Management 5th ed Inglewood CA Inter Science Institute 20121-56 5 Grozinsky-Glasberg S Grossman AB Gross DJ Carcinoid heart disease from pathophysiology to treatmentndashlsquoSomething in the way it movesrsquo Neuroendocrinology 2015101(4)263- 273 6 Sandostatin LAR [Summary of Product Characteristics] Novartis 2016 7 Warner ME The Carcinoid Cancer Foundation Nutritional concerns for the carcinoid patient developing nutritional guidelines for persons with carcinoid disease httpwwwcarcinoidorgfor-patientsgeneral -informationnutritionnutritional-concerns-for-the-carcinoid-patient-developing-nutrition-guidelines -for-persons-with-carcinoid-disease Accessed January 30 2017 8 Cancer Research UK Tips on coping with diarrhea httpwwwcancerresearchukorgabout-cancercoping-with-cancercoping -physicallyboweltypesdiarrhoeamanagingtips-on-how-to-cope-with-diarrhoea Accessed January 30 2017 9 CancerNet Carcinoid tumor symptoms and signs httpwwwcancernetcancertypes carcinoidtumorsymptomsandsigns Accessed February 1 2017 10 Powell B Mukhtar AA Mills GH Carcinoid the disease and its implications for anaesthesia Continuing Education in Anaesthesia Critical Care amp Pain 201111(1)9-13 11 Rinke A Muumlller HH Schade-Brittinger C et al Placebo-controlled double-blind prospective randomized study on the effect of octreotide LAR in the control of tumor growth in patients with metastatic neuroendocrine midgut tumors a report from the PROMID study group J Clin Oncol 200927(28)4656-4663 12 Greenberger NJ Merck Manual Diarrhea httpwww merckmanualscomprofessionalgastrointestinal-disorderssymptoms-of-gi-disordersdiarrhea Accessed January 30 2017 13 Anthony L Freda PU From somatostatin to octreotide LAR evolution of a somatostatin analogue Curr Med Res Opin 200925(12)2989-2999 14 Litchford MD Dorner B Posthauer ME Malnutrition as a precursor of pressure ulcers Adv Wound Care 20143(1)54-63
Please see Important Safety Information on pages 8-13