Tiffany Bihis, PharmD Candidate Class of 2020

Creighton University

School of Pharmacy and Health Professions

Aemcolo

Learning Assessment

Aemcolo® is indicated for which of the following:

A. Acute diarrheaB. Chronic diarrheaC. Traveler’s diarrheaD. All of the above

Speaker Disclosure

Tiffany Bihis has no relevant financial relationships that would be considered a conflict of interest for the purposes of this program. This information will not include a discussion of non-FDA approved (off-label) medication use.

Indication

• Aemcolo® is indicated for the treatment of traveler’s diarrhea caused by non-invasive strains of Escherichia coli in adults.• Limitations of use: Not indicated in patients

with diarrhea complicated by fever, bloody stool, or pathogens other than non-invasive strains of Escherchia coli.

• Initial U.S. Approval: 2018

• There are currently no unapproved uses.

Traveler’s Diarrhea

Traveler’s diarrhea is a self-limiting digestive tract disorder that commonly develops in persons traveling to locations where the climate or sanitary practices are different than that of the patient’s home.

Most common cause is a bacterial pathogen acquired in local food or water supply.

Symptoms include the passing 3 or more unformed stools (usually watery) in 1 day and at least 1 other symptom: nausea, vomiting, fever, abdominal cramping, dysentery (e.g. fever and bloody stools).

Mechanism of Action

• Inhibits a step of DNA transcription by blocking the beta-subunit of bacterial DNA-dependent RNA polymerase.

•Results in inhibition of bacterial synthesis and consequently the growth of bacteria.

Pharmacokinetics

AbsorptionLimited systemic exposure following oral

administration of the recommended dosage.Based on total urinary excretion data,

bioavailability was <0.1% under fasting conditions.

DistributionPlasma protein binding ~80% in vitro.Binding primarily to albumin and inversely

proportional to concentration.

Pharmacokinetics (cont’d)

•Metabolism•Cytochrome P450 based metabolism not observed in vitro.

•Excretion•Fecal

Dosing

•388 mg (two tablets) orally twice daily for three days.•Available as 194 mg delayed-release tablets

•Maximum dose: 776 mg/day

Special Populations• Pregnancy

• No available data in humans, only animal data available

• No malformations observed in pregnant rats or rabbits

• Decreased risk of fetal exposure

• Lactation• Risk vs. benefit

• Pediatric• Safety and efficacy not established

Special Populations (cont’d)•Geriatric• Insufficient data•Other reported clinical experiences did

not identify differences between elderly and younger patients

•Hepatic Impairment•Unaffected

•Renal Impairment•Unaffected

Contraindications

•Patients with a known hypersensitivity to: •Rifamycin •Other Rifamycin class antimicrobial agents (e.g. Rifaximin)•Any other components in Aemcolo®

Warnings & Precautions

Presence of fever and/or bloody stoolNot shown to be effective

Diarrhea due to pathogens other than non-invasive strains of Escherichia coli Not shown to be effective

Clostridium difficile-associated diarrhea (CDAD)Evaluate if diarrhea occurs after therapy, does not improve, or worsens during therapy

Adverse Reactions

•Most common (incidence >2%):•Headache•Constipation

•Most severe:•None reported

Drug-Drug Interactions

•Clinical drug-drug interaction studies of Aemcolo® have not been conducted.

Price

•Wholesale acquisition cost (WAC): $144 for full 3-day course

Place in therapy

•Last line agent•Traveler’s diarrhea is self-limiting.•Aemcolo® only works on non-invasive Escherchia coli strains and without the presence of fever and/or bloody stool.

Patient Counseling

Persistent diarrheaDiscontinue Aemcolo® if diarrhea persists >48 hours or worsens and seek medical care.

Administration instructions:Take each dose with a full glass of liquid (6-8 ounces).Do not take concomitantly with alcohol.May be taken with or without food.Swallow tablets whole. Do not crush, break, or chew.

Learning Assessment

Aemcolo® is indicated for which of the following:

A. Acute diarrheaB. Chronic diarrheaC. Traveler’s diarrheaD. All of the above

References

AEMCOLO Highlights of Prescribing Information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210910s000lbl.pdf. Accessed May 16, 2019.

Rifamycin Drug Monograph. ClinicalKey. https://www-clinicalkey-com.cuhsl.creighton.edu/#!/content/drug_monograph/6-s2.0-5115. Accessed May 16, 2019.

Traveler's diarrhea. Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/travelers-diarrhea/symptoms-causes/syc-20352182. Published May 16, 2019. Accessed May 29, 2019.

Traveler’s Diarrhea Clinical Overview. ClinicalKey. https://www-clinicalkey-com.cuhsl.creighton.edu/#!/content/clinical_overview/67-s2.0-10b8c627-6b3c-46d0-a93f-ba6d5f2f1593. Accessed May 16, 2019.

Melissa Borsh, PharmD Candidate Class of 2020

University of Nebraska Medical Center

College of Pharmacy

Asparlas

Asparlas is indicated for which of the following:

A. Acute Lymphoblastic Leukemia in pediatric and young adults aged 1 month to 21 years old

B. Acute Myeloid Leukemia in both pediatric and adult populations

C. Chronic Lymphoblastic Leukemia in pediatric and young adults aged 1 month to 21 years old

D. Chronic Myeloid Leukemia in both pediatric and adult populations

Speaker Disclosure

Melissa Borsh has no relevant financial relationships that would be considered a conflict of interest for the purposes of this program. This information will not include a discussion of non-FDA approved (off-label) medication use.

Indication

• FDA approved to treat acute lymphoblastic leukemia as a part of a multi-agent chemotherapy regimen in pediatric and young adult patients aged 1 month to 21 years

• Approved December 20, 2018

• Currently no unapproved uses

Acute Lymphoblastic Leukemia

• Progresses quickly and affects immature lymphocytes

• It begins in the bone marrow• B or T cells

Acute Lymphoblastic Leukemia continued

• Treatment typically consists of three phases • Induction • Consolidation• Maintenance

• Length of treatment around 2 years with a combination of chemotherapy, targeted therapy, immunotherapy, surgery, radiation, and potentially stem cell transplant

Mechanism of Action•Selective killing of leukemic cells through

depletion of plasma L-asparagine

• L-asparaginase enzyme catalyzes the conversion of L-asparagine into aspartic acid and ammonia

Pharmacokinetics

•Absorption•Peak plasma time: 1.17 h •Peak plasma concentration: 1.62 units/mL

•Distribution•Vd (ss): 2.96 L

Pharmacokinetics continued

•Metabolism•unknown

•Excretion•Half-life: 16.1 days•Clearance: 0.147 L/day

Dosing•Recommended dose is 2,500 units/m2 IV

no more frequently than every 21 days

•3,750 units/5 mL in a single dose vial for injection

• Infused over 1 hour

Special Populations

• Pregnant/Nursing: no available data in pregnant population. Women should not breastfeed during and for 3 months after treatment

• Males and Females of reproductive potential: pregnancy testing should occur prior to start of treatment; avoid pregnancy while on Asparlas, use means of contraception including a barrier method continued for at least 3 months after end of treatment

Special Populations continued

Pediatric: safety and effectiveness established in those 1 month to <17 years old

Geriatric: has not been studied in geriatric population

Hepatic Impairment: unknown effects

Renal Impairment: unknown effects

Contraindications

History of severe hypersensitivity reactions to pegylated L-asparaginase therapy

History of serious thrombosis during previous L-asparaginase therapy

History of serious pancreatitis during previous L-asparaginase therapy

History of serious hemorrhagic events during previous L-asparaginase therapy

Severe hepatic impairment

Precautions

Hypersensitivity: patients need to be observed for 1 hour after administration

Pancreatitis: monitor blood glucose

Thrombosis: provide anticoagulation as necessary

Hemorrhage: evaluate etiology and treat

Hepatotoxicity: monitor for toxicity throughout recovery period from cycle

Adverse Reactions

• The most common: • Hypersensitivity: 7-21%• Thrombotic events: 9-12%• Pancreatitis: 12-16%• Elevated LFTs• Hemorrhage

• The more severe: • Grade 3 or 4 hypersensitivity and infusion

reactions, clinical pancreatitis, life-threatening thrombotic event

Drug-Drug Interactions

•Potential interaction with oral contraceptive pills

Price

•As of July 2, 2019, the manufacturer has not yet released pricing information

Place in therapy

•As part of a multi-agent chemotherapy regimen in the treatment of acute lymphoblastic leukemia usually during induction phase

•Dosed less frequently than pegaspargase (Oncaspar) with similar safety profile •Every 21 days vs. every 14 days

Additional information

•Patients should be aware of the risk for serious adverse effects associated with the drug and report any concerns to their doctors

Asparlas is indicated for which of the following:

A. Acute Lymphoblastic Leukemia in pediatric and young adults aged 1 month to 21 years old

B. Acute Myeloid Leukemia in both pediatric and adult populations

C. Chronic Lymphoblastic Leukemia in pediatric and young adults aged 1 month to 21 years old

D. Chronic Myeloid Leukemia in both pediatric and adult populations

ReferencesAngiolillo AL, Schore RJ, Devidas M, Borowitz MJ, Carroll AJ, Gastier-Foster JM, et. al. Pharmacokinetic and

pharmacodynamic properties of calaspargase pegol Escherichia coli L-asparaginase in the treatment of patients with acute lymphoblastic leukemia: results from Children’s Oncology Group Study AALL07P4. Journal of Clinical Oncology. 2014; 32 (34): 3874-82. doi: 10.1200/JCO.2014.55.5763

Drug Information Portal. Calaspargase pegol image. https://druginfo.nlm.nih.gov/drugportal/name/calaspargase%20pegol Accessed May 9, 2019.

ASPARLAS-calaspargase pegol injection, solution [package insert]. Boston, MA: Servier Pharmaceuticals LLC. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=6585bd0d-bd78-4341-9e87-0f7664821f05. 2018. Accessed May 9, 2019.

Brumano LP, Santos da Silva FV, Costa-Silva TA, Apolinario AC, Santos JH, Kleingesinds EK, et. al. Development of L-Asparaginase Biobetters: Current Research Status and Review of the Desirable Quality Profiles. Frontiers in Bioengineering and Biotechnology. 2019; 6 (212): 1-22. doi: 10.3389/fbioe.2018.00212

American Cancer Society. What is Acute Lymphocytic Leukemia (ALL)? 2018. https://www.cancer.org/cancer/acute-lymphocytic-leukemia/about/what-is-all.html. Accessed May 9, 2019.

American Cancer Society. Treatment of Children with Acute Lymphocytic Leukemia (ALL). 2019. https://www.cancer.org/cancer/leukemia-in-children/treating/children-with-all.html. Accessed May 9, 2019.

The ASCO Post. FDA Approves Calaspargase Pegol-mknl for Pediatric and Young Adult Patients with ALL. 2018. https://www.ascopost.com/News/59598?utm_source=TrendMD&utm_medium=cpc&utm_campaign=The_ASCO_Post_TrendMD_0. Accessed May 9, 2019.

EGATEN (triclabendazole)

Anthony Donovan, PharmD Candidate Class of 2020

University of Nebraska Medical Center

College of Pharmacy

Learning Assessment

What is the most important counseling point on the administration of triclabendazole?

A. GI Upset

B. QTc Prolongation

C. Must be taken with food

D. Biliary Colic

Speaker Disclosure

Anthony Donovan has no relevant financial relationships that would be considered a conflict of interest for the purposes of this program. This information will not include a discussion of non-FDA approved (off-label) medication use.

Indication

For the treatment of fascioliasis in patients 6 years and older

Fascioliasis

• Infection caused by liver flukes (trematodes or flatworms) Fasciola hepatica and F. gigantica

•Neglected tropical disease •Similar to Schistosomiasis

•Worms become lodged in gallbladder and biliary tract

Photos of liver flukes

Drug Formulation

Available in 250 mg scored tablets

Available in veterinary practice since the 80’sFasinex for cattle and sheep

Mechanism of Action

•Benzimidazole class anthelminthic agent

•Not entirely understood•Uptake of metabolites to tegument leading to

decrease in resting membrane potential and inhibition of tubulin function•Metabolic disturbances and inhibition of motility

leads to death •Active against adult and immature worms

Pharmacokinetics• Absorption

• When taken with meals increases AUC and Cmax 3-fold

• Distribution• Vd approximately 1L/kg and highly protein bound(~96%

active and metabolites)

• Metabolism

• Primarily metabolized by CYP1A2 and 2C9

• Excretion

• In animals, largely excreted via biliary tract in feces

Dosing

•10 mg/kg every 12 hours for two doses•Supplied in #4 blister packs

•Round dose upwards if unable to adjust dose exactly

Special Populations

•Pregnant/Nursing- not studied

•Pediatric- approved only in 6 years and older

•Geriatric – not studied

•Hepatic Impairment – not studied

•Renal Impairment – not studied

Contraindications

•Known hypersensitivity to triclabendazole or other benzimidazole derivatives

Precautions

•QTc Prolongation•Those with known history of QTc prolongation should be monitored

Adverse Reactions

•Common: abdominal pain, hyperhidrosis, nausea, and urticaria

•Severe: transient liver enzyme elevations•Short therapy duration

Drug-Drug Interactions

•No specific drug interactions studies have been done

•Due to in vitro evidence of CYP2C19 inhibition, drugs metabolized by 2C19 should be monitored •Short duration of therapy

Price

•Currently not available except through CDC and Novartis*

•US physicians must go through CDC and FDA to get access through the CDC Drug Service

Place in therapy

•Triclabendazole recommended by the WHO for treatment of fascioliasis

•Other active treatments are longer duration and have more severe toxicities associated with their use

•Other benzimidazole agents are inactive against F. hepaticas and F. gigantica

Additional information

•Has been supplied to endemic areas since 2005 by Novartis

•Approved through Priority Review program

Learning Assessment

What is the most important counseling point on the administration of triclabendazole?

A. GI Upset

B. QTc Prolongation

C. Must be taken with food

D. Biliary Colic

References

1.Novartis receives FDA approval for egaten® for the treatment of fascioliasis, a neglected tropical disease Novartis Global. https://www.novartis.com/news/media-releases/novartis-receives-fda-approval-egaten-treatment-fascioliasis-neglected-tropical-disease. Updated Feb 13, 2019. Updated 2019 .

2.Martin J, Rosa BA, Ozersky P, Hallsworth-Pepin K, Zhang X, Bhonagiri-Palsikar V, Tyagi R, Wang Q, Choi Y, Gao X, McNulty S, Brindley PJ and Mitreva M (2014) Helminth.net: expansions to Nematode.net and an introduction to Trematode.net Nucleic Acids Research first published online November 12, 2014 doi: 10.1093/nar/gku1128

3.EGATEN™-triclabendazole tablet [Package insert]. East Hanover, NJ: Novartis. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/208711s000lbl.pdf. Published February 2019. Accessed May 15, 2019.

Kelsey Haywood, PharmD Candidate Class of 2020

University of Nebraska Medical Center

College of Pharmacy

Motegrity

Learning Assessment

When and how should Motegrity be taken?

A. With or without food B. Any time throughout the dayC. Once daily D. All of the above E. None of the above

Speaker Disclosure

Kelsey Haywood has no relevant financial relationships that would be considered a conflict of interest for the purposes of this program. This information will include a discussion of non-FDA approved (off-label) medication use.

Indication

•FDA approved indication:•approved in December 2018 for

the treatment of chronic idiopathic constipation in adults

•Off-label uses:•opioid induced constipation in

patients with chronic, non-cancer, pain

Disease State• Constipation is a common complaint that can be

a result of many different causes• Must rule out secondary causes (i.e. drugs

and secondary disorders) in order to identify idiopathic constipation (CIC)

• Idiopathic constipation can be the result of:• Normal or slow colonic transit• Defecatory dysfunction (i.e. pelvic floor)

Mechanism of Action•5-HT4 receptor agonist

•GI prokinetic agent that stimulates colonic peristalsis, result in increased motility •Via high amplitude propagating contractions

(HAPCs)

• In animal studies:•Acetylcholine release

Pharmacokinetics

•Absorption•Rapid oral absorption•Time to peak: 2-3 hours•Bioavailability > 90%•Not effected by food

•Distribution•567 L (via IV—which is not available)

Pharmacokinetics (con’t)

•Metabolism•Minor route of elimination, 7

metabolites•Substrate of CYP450

•Excretion•T1/2: 24 hours•Unchanged in urine (84.2%) and feces

(13.3%)•Passive and active secretion

Dosing

•Normal adult dose: 2 mg daily•With or without food•Any time of day •Setting a time (i.e. “every morning”) is best

Special Populations• Pregnant/Nursing• Information limited, consider use of

contraception in those with reproductive potential •Do not breastfeed

• Pediatric•Not indicated

•Geriatric• Refer to adult dosing•Use cautiously

Special Populations (con’t)

Contraindications

Hypersensitivity to prucalopride/components of formulation

Intestinal perforation or obstruction due to a structural/functional problem with the: Gut wallObstructive ileus Crohn’s, UC, Megacolon/rectum

Precautions

CNS effects including drowsiness

DiarrheaTypically resolved during 1st

week of therapy

Suicidal ideation/behavior

Elderly

Adverse Reactions• The most common:

• Headache (19%)• Abdominal Pain (16%)• Nausea (14%)• Diarrhea (13%)

• The more severe:

• Diarrhea, therapy should be discontinued if resolution of this side effect doesn’t occur in the first two weeks of therapy

Drug-Drug Interactions• No major drug-drug interactions have been

documented.

• Minor interactions that require monitoring include:• Fosfomycin

• Lowers serum levels of Fosfomycin

• P-GP Inhibitors• Increases concentration of prucalopride

Price

•Wholesale Acquisition Cost: •$423.90 per 30 tablets

Place in therapy

•Should be used after adequate trials of OTC options •Dietary Changes•Fiber supplementation•Laxatives

•Trial of more cost effective prescription options, first

Additional Information

There are cost savings available at:www.motegrity.comCo-pays as low as $15/month

Must be dispensed in original container

In clinical trials, results of a CSBM were noticed between 1.4 and 4.7 days and were maintained throughout the duration of therapy (12 weeks)

Learning Assessment

When and how should Motegrity be taken? A. With or without food B. Any time throughout the dayC. Once daily D. All of the above E. None of the above

Motegrity is a once daily solution for CIC in those that have failed other therapies, it can be taken without regard to food/meals and at any time of the day.

References

1. Prucalopride. Lexi-Drugs. Lexicomp. Wolters Kluwer Health, Inc. Riverwoods, IL. Available at: http://online.lexi.com. Accessed May 1st, 2019.

2. Motegrity.com. (2019). Motegrity™ (prucalopride) Patients. Available at: www.motegrity.com. Accessed 21 May 2019.

3. MOTEGRITY- prucalopride tablet [package insert]. Lexington, MA. Shire US Manufacturing Inc. 2018.

4. Prucalopride. Clinical Pharmacology [Internet]. Tampa (FL): Elsevier. 2018. [Cited 2018 Dec 18]. Available from: http://www.clinicalpharmacology.com

Ryan Kano, PharmD Candidate Class of 2020

Creighton University

School of Pharmacy and Health Professions

Nuzyra

Learning Assessment

What is the major drug-drug interaction with Nuzyra:

A. AmiodaroneB. WarfarinC. SimvastatinD. St John’s Wort

Speaker Disclosure

Ryan Kano has no relevant financial relationships that would be considered a conflict of interest for the purposes of this program. This information will not include a discussion of non-FDA approved (off-label) medication use.

Indication•Nuzyra is indicated for the treatment

of adults with:•Community acquired bacterial pneumonia (CABP)•Acute Bacterial Skin and Skin Structure Infections (ABSSSI)

•FDA approved October 2, 2018.•There are currently no unapproved uses.

Community Acquired Bacterial Pneumonia

Diagnosis:Infection of the lower respiratory tract

Clinical Features:

cough

fever

sputum production

infiltrate on chest x-ray or other imaging required for diagnosis

Common Pathogens:Strep pneumonia

Haemophilius Influenza

Mycoplasma pneumonia

• pleuritic chest pain

• rales or bronchial breath sounds on lung

examination

Drug Formulation

Single Dose vial 100mg/10mlReconstituted w/ Sterile

Water then, further diluted for Injection under aseptic conditions

Oral Tablet:150mg

Mechanism of Action

•Nuzyra is an aminomethylcycline falling within the tetracycline class of antibacterial drugs.

•It blocks protein synthesis by binding to the 30S ribosomal subunit.

Pharmacokinetics cont.•Absorption•Bioavailability, oral: 34.5%•Effects of Food: Administration 2 hours after high-

fat meal decreased Cmax and AUC

•Distribution•Protein binding: 20%•Vd, IV: 190 L (steady state)•Vd, Oral: 794 L (single 300-mg dose)

Pharmacokinetics

•Metabolism•Not metabolized•Substrate of P-gp

•Excretion•Elimination Half-life -16 hours

CABP Dosing

• IV loading dose: (Day 1) 200 mg on as a single dose OR 100 mg twice daily

• Maintenance dose (once a day) : IV - 100 mg or PO 300 mg

• Duration of therapy 7 to 14 days

ABSSSI Dosing

IV Loading dose: (Day 1) 200 mg once a day or 100 mg twice a day

Oral Loading dose: 450 mg once a day on days 1 and 2

Maintenance dose: IV – 100 mg once daily or 300 mg once a day

Duration of therapy 7 to 14 days

Special PopulationsPregnant/NursingFetal risk cannot be ruled out. (TH)

PediatricGeneral Dosage InformationSafety and efficacy have not been established in patients younger

than 18 years .

GeriatricNo dose adjustment is required.

Hepatic and Renal ImpairmentNo dose adjustment is required.

Contraindications

•Those who have a known hypersensitivity to the tetracycline-class of antibacterial drugs, or to any of the components of Nuzyra

Precautions

•Photosensitivity

•Permanent discoloration of the teeth (yellow-gray-brown)•Especially in children <18 yo.

Adverse Reactions

Common:GastrointestinalNausea (2% to 22%), vomiting (3% to 11%).

Severe:Dermatologic: Photosensitivity

Endocrine metabolic: Acidosis, Hyperphosphatemia

Immunologic: Anaphylaxis

Drug-Drug Interactions

•Concurrent use of Anticoagulants may result in increased risk of bleeding.

•Antacids containing metal ions

•Bismuth

• WAC of Nuzyra is $345 per vial

Price

Course of therapy Cost

14 day course of therapy $5,175

Place in Therapy

Used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria.CAPB Proven non-inferior when compared to Moxifloxacin

ABSSSIProven non-inferior when compared to Linezolid

Additional Information

•Patient Counseling:•Pregnancy status•N/V•Protect exposed skin and sunscreen use•Separate from food•2 hours prior OR 4 hours post prandial

Learning Assessment

What is the major drug-drug interaction with Nuzyra:

A. AmiodaroneB. WarfarinC. SimvastatinD. St John’s Wort

References

1.A MODERNIZED TETRACYCLINE. NUZYRA™ (omadacycline) | About. https://www.nuzyra.com/hcp/about. Accessed May 20, 2019.

2.Creighton University Libraries - EZProxy Login. https://fco-factsandcomparisonscom.cuhsl.creighton.edu/lco/action/doc/retrieve/docid/fc_dfc/6708610#adr-nested-0. Accessed May 20, 2019.

3.Creighton University Libraries - EZProxy Login. http://www.dynamed.com.cuhsl.creighton.edu/topics/dmp~AN~T115170/Community-acquired-pneumonia-in-adults#Making-the-diagnosis. Accessed May 20, 2019.

Natasha Konfrst, PharmD Candidate Class of 2020

University of Nebraska Medical Center

College of Pharmacy

Spravato

Learning Assessment

Spravato is indicated for which of the following:

A. As an anesthetic agent

B. In conjunction with an oral antidepressant, for the treatment of treatment-resistant depression in adults

C. Monotherapy for the treatment of resistant-depression in adult

D. In conjunction with an oral antidepressant for the treatment of treatment-resistant depression in adolescents and adults

Speaker Disclosure

Natasha has no relevant financial relationships that would be considered a conflict of interest for the purposes of this program. This information will not include a discussion of non-FDA approved (off-label) medication use.

Indication

•Spravato is indicated for use in conjunction with an oral antidepressant for the treatment of treatment-resistant depression in adults.

•FDA approved March 5, 2019.

•There are currently no unapproved uses.

Treatment-Resistant Depression

•There is no agreed-upon clinical definition of TRD

•The definition of TRD as used for the approval of Spravato is: nonresponse (<25% response) to 2 or more oral antidepressants at appropriate doses and for adequate duration.

Drug Formulation

•Pre-filled nasal spray•2 sprays that total 28 mg in each device•Each device can only be used for the 2 sprays (28 mg) •Room temperature storage

Mechanism of Action

•Non-selective, non-competitive human N-methyl-D-asparte (NMDA) antagonist

•NMDA is an ionotropic glutamate receptor, and inhibition of NMDA decreases excessive excitatory cell activity

•The exact mechanism of Spravato on depression is unknown.

Pharmacokinetics

AbsorptionNasal sprayMean absolute bioavailability ~ 48%Time to peak concentration is 20-40

minutes after the last spray of a treatment session

DistributionVd: 709 LProtein binding ~43-45%

Pharmacokinetics •Metabolism•Primarily metabolized by CYP3A4 and 2B6 to

noresketamine

•Excretion•Elimination of both esketamine and noresketamine

is biphasic •Terminal half-life 7-12 hours •Terminal half-life of major metabolites,

noresketamine is 8 hours •Mostly excreted in the urine

DosingInduction: 56 mg twice weekly, may increase after first dose up to 84 mg twice weekly, evaluate after 4 weeks.Maintenance: On week 5, using previously established dose (56 or 84 mg) decrease to once weekly. At week 9, adjust the dosing frequency to maintain remission or response to once weekly or every 2 weeks.

A 5 minute rest must occur between each device usedPatients should be monitored for 2 hours after each

dose administration

Special Populations

•Pregnant/Nursing•Not recommended for use during

pregnancy or nursing

•Pediatric•Not been studied in pediatric patients

•Geriatric•No difference from adults

Special Populations

• Hepatic and Renal dose adjustments• There are no dose adjustments recommended

for mild or moderate renal or hepatic impairment • Patients with mild-moderate hepatic

impairment may need to be monitored for adverse reactions for longer periods of time

• Not recommended in patients with severe hepatic or renal impairment

Contraindications

•History of aneurysmal vascular disease or arteriovenous malformation•Thoracic and abdominal aorta,

intracrainial and peripheral arterial vessels

•History of intracerebral hemorrhage

•Serious hypersensitivity reaction of esketamine or ketamine

Boxed Warnings

•Risk of sedation

•Risk of dissociative or perceptual changes after administration

•Abuse and Misuse

•Suicidal Thoughts and Behaviors

REMSSpravato is intended for patient administration

under the direct observation of a healthcare provider

Patients are required to be monitored by a healthcare provider for at least 2 hours post dose.

Has limited distribution

To order, dispense, prescribe, and/or supervise administration the healthcare setting and/or pharmacy must be registered and certified through the Spravato REMS.

Patients must also be enrolled in the REMS program

Adverse ReactionsOccurred in ≥ 5% of

patients:VertigoNausea/VomitingDiarrheaDry mouthFeeling drunkIncreased blood

pressureDizzinessDysgeusiaHeadacheHypoesthesia

LethargySedationAnxietyDissociation

InsomniaNasal DiscomfortThroat irritation

Adverse Reactions

• The most common: • Sedation: 49-61% • Dissocation/perceptual changes,

derealization, and depersonalization: 61-75% • Increases in blood pressure: 8-17%

• The more severe: • Dissocation and other cognitive changes • Suicidal thoughts or behaviors

Drug-Drug Interactions

•There are no clinically significant drug-drug interactions.

Price• The WAC price for each device of Spravato is $295

• Cost of 56 mg dose: $590

• Cost of 84 mg dose: $885

• Cost of induction for 56 mg: $4,720

• First 4 weeks, used twice weekly

• Cost of induction for 84 mg: $6,785• First 4 weeks,

• Cost of maintenance for 56 mg: $2,360

• Cost of maintenance for 84 mg: $3,540

Place in therapy

•Third or fourth line, used as an adjunct to an oral antidepressant

•Only indicated for TRD

Additional information

• Careful consideration is advised prior to treating patients with a history of substance use disorder

• Monitoring for signs of abuse and dependence is highly recommended

• Given only in healthcare settings that have registered with the Spravato REMS program.

• Administered under the direct observation of a healthcare provider

• Patient must be monitored by at least 2 hours prior last nasal administration

Additional Information

Patient Counseling tipsAfter treatment with Spravato, do not drive,

operate heavy machinery, or do anything that requires full and complete focus and concentration until after getting restful sleep

Learning AssessmentSpravato is indicated for which of the following:

A. As an anesthetic agent

B. In conjunction with an oral antidepressant, for the treatment of treatment-resistant depression in adults

C. Monotherapy for the treatment of resistant-depression in adult

D. In conjunction with an oral antidepressant for the treatment of treatment-resistant depression in adolescents and adults

References

• Available at: Janssen: Pharmaceutical Companies of Johnson&Johnson. Spravato. https://www.spravatohcp.com/. Accessed May 18th, 2020.

• Available at FDA: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211243lbl.pdf. Accessed May 18, 2020.

• Available at Clinical Pharmacology: https://www-clinicalkey-com.library1.unmc.edu/pharmacology/monograph/5130?sec=monindi&n=SPRAVATO. Accessed May 18, 2020

• Fava M. Diagnosis and definition of treatment-resistant depression. Biological Psychiatry. 2003; 53(8): 649-659. https://www.sciencedirect.com/science/article/pii/S0006322303002312. May 18, 2020.

• Available at: CMS https://www.cms.gov/Medicare/Coverage/DeterminationProcess/downloads/id105TA.pdf. Accessed May 18, 2020.

Mackenzie Moritz, PharmD Candidate Class of 2020

Creighton University

School of Pharmacy and Health Professions

Ultomiris

Learning Assessment

Ultomiris has a boxed warning for which of the following conditions?

A. Cardiovascular events

B. Stevens-Johnson syndrome

C. Meningococcal infections

D. Major bleeding events

Speaker Disclosure

•Mackenzie Moritz has no relevant financial relationships that would be considered a conflict of interest for the purposes of this program. This information will not include a discussion of non-FDA approved (off-label) medication use.

Indication

Ultomiris is indicated for the treatment of adults with paroxysmal nocturnal hemoglobinuria (PNH).

FDA approved December 21, 2018.

There are currently no unapproved uses.

Paroxysmal Nocturnal Hemoglobinuria

•Per Alexion (manufacturer), PNH is a rare, chronic blood disorder that causes destruction of red blood cells.

•The most severe complications of PNH include fatal thrombotic events and renal failure.

Mechanism of Action

•Humanized monoclonal antibody binds to the complement protein C5 and inhibits its cleavage into C5a and C5b.

•This prevents the generation of the C5b9 complex, therefore prohibiting the complement-mediated hemolysis in patients with PNH.

Pharmacokinetics•Distribution•Mean Vd: 5.34 L

•Metabolism•Unknown interaction with CYP450

enzymes or drug transporters

•Excretion•Mean clearance: 0.08 L/day •Mean half-life: 49.7 days

Dosing• IV infusion

• Loading dose

• Maintenance dose

Special PopulationsPregnancyAnimal studies No data in humans available

Nursing No data on drug transfer to breastmilk or effect on milk

production

PediatricSafety/efficacy has not been established

Special Populations

GeriatricClinical trials did not include enough subjects over 65 years

old to determine a difference in response

Hepatic ImpairmentAppears that no dose adjustment is needed

Renal ImpairmentAppears that no dose adjustment is needed

Contraindications

•Contraindicated in patients with unresolved Neisseria Meningitidis infection

Precautions

•Caution administering in patients with any other active systemic infection

•Boxed warning for serious meningococcal infections

•Prescribers are required to register with the Ultomiris REMS program

Adverse Reactions

•The most common (>10%):•Headache – 32% •Upper respiratory tract infections –

39%

•The more severe:•Meningococcal infection

• Infusion related reaction also possible

Drug-Drug Interactions

•No information currently available regarding drug interactions with Ultomiris

Price

•WAC for one 300mg (30mL) vial is $213.46

•A 3,000 mg maintenance dose would cost $2,134.60 every 8 weeks

Place in therapy

•Primary treatment of PNH

•Offers less frequent dosing compared to eculizumab •Every 8 weeks vs every 2 weeks for maintenance therapy

Additional information

• Any patient without a history of meningococcal vaccinations should receive them at least 2 weeks prior to starting Ultomiris

• If urgent initiation of Ultomiris is needed or if vaccinated less than 2 weeks prior to initiation, antibiotic prophylaxis should be considered

Learning Assessment

Ultomiris has a boxed warning for which of the following conditions?

A. Cardiovascular events

B. Stevens-Johnson syndrome

C. Meningococcal infections

D. Major bleeding events

References

Available at: FDA.

https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/761108s000lbl.pdf. Accessed May 14th, 2019.

Available at: Clinical Pharmacology.

https://www-clinicalkey-com.cuhsl.creighton.edu/pharmacology/monograph/5121. Accessed May 14th, 2019.

Available at: Alexion.

https://alexion.com/products/Ultomiris. Accessed May 14, 2019.

Kateri Petto, PharmD Candidate Class of 2020

Creighton University

School of Pharmacy and Health Professions

Vitrakvi

Learning Assessment

Use of Vitrakvi is appropriate in which of the following:

A. NTRK gene fusion positive solid tumors

B. Metastatic cancer or where surgical resection is not possible

C. Patients with no satisfactory alternative treatment options

D. All of the above

Speaker Disclosure

Kateri Petto has no relevant financial relationships that would be considered a conflict of interest for the purposes of this program. This information will not include a discussion of non-FDA approved (off-label) medication use.

Indication

•Vitrakvi is indicated for the treatment of adult and pediatric neurotrophic receptor tyrosine kinase (NTRK) gene fusion-positive solid tumors. •FDA approved on November 26th, 2018 •Orphan drug with no unapproved uses.

NTRK Gene Fusion-Positive Solid Tumors

• Neurotrophic receptor tyrosine kinase (NTRK) genes encode tropomyosin receptor kinase (TRK) proteins, growth factors essential for cell differentiation and proliferation

• Fusion of NTRK genes results in constitutively active TRK proteins, acting as oncogenic drivers promoting proliferation and survival of tumor cell lines

Drug Formulation

•Oral Capsule •25 mg •100 mg

•Oral Solution •20 mg/mL

Mechanism of Action

•Potent and highly specific small-molecule inhibitor of three tropomyosin receptor kinase proteins—TRKa, TRKb, TRKc

• Inhibition of TRK proteins prevents the differentiation and proliferation of tumor cells, resulting in targeted anti-tumor activity

Pharmacokinetics

•Absorption•Administered orally•32-37% oral bioavailability

•Time to peak: ~ 1 hour

•Distribution•70% protein bound•Volume of distribution: 48 L

Pharmacokinetics

•Metabolism•Hepatic •Primarily CYP3A4

•Excretion•Clearance: 98 L/hr•Half-life: 2.9 hours •Feces: 58% (5% unchanged)•Urine: 39% (20% unchanged)

Dosing

•Normal dose/ Maintenance Dose•For BSA of 1 m2 or greater: 100 mg PO twice daily•For BSA less than 1 m2: 100 mg/m2 PO twice daily

•Maximum dose•100 mg PO twice daily until disease progression or

unacceptable toxicity

Special Populations

•Pregnancy •Avoid use due to teratogenic potential•Effective contraception needed for both men and

women of reproductive potential

• Lactation •Discontinue breastfeeding during therapy and for 1

week following last dose

Special Populations

• Pediatric• Dosing based on BSA

• 100 mg/m2 per dose twice daily• continue until disease progression or unacceptable toxicity

• Higher incidence of neutropenia and weight gain • Propylene glycol toxicity

• Geriatric • Insufficient data to determine differences in safety or efficacy

Special Populations •Hepatic Impairment •Child-Pugh Class A (Mild) •No dosage adjustment necessary

•Child-Pugh Classes B & C (Moderate to Severe)• reduce dose by 50%

•Renal Impairment •No dosage adjustment necessary

Contraindications

•There are no contraindications listed in the manufacturer’s labeling.

Precautions

•Hepatotoxicity •LFT monitoring

•Neurotoxicity •Most common within first three months of therapy

•Hypersensitivity Reactions

Adverse Reactions

• The most common:

• Increased ALT/AST (45%) ─ Cough (26%) • Anemia (42%) ─ Vomiting (26%) • Fatigue (37%) ─ Constipation (23%) • Nausea (29%) ─ Diarrhea (22%) • Dizziness (28%) ─ Hypoalbuminemia (35%)• Increased ALP (30%) ─ Neutropenia (23%)

Recommended Dose Modifications for Adverse Reactions

For Grade 3 or 4 adverse reactions:Withhold Vitrakvi until adverse reaction resolves or improves to

baseline/Grade 1. Resume at next dosage modification if resolution occurs within 4 weeks

Permanently discontinue if adverse reaction does not resolve within 4 weeks

Permanently discontinue in patients who are unable to tolerate after 3 dose modifications

Drug-Drug Interactions

• Vitrakvi is a weak CYP3A4 inhibitor

• Avoid use with:

• Strong CYP3A4 Inhibitors

• If concomitant use cannot be avoided, reduce Vitrakvi dose by 50%

• Strong CYP3A4 Inducers

• If concomitant use cannot be avoided, double Vitrakvi dose

Strong CYP3A4 Inducers Strong CYP3A4 Inhibitors

PhenobarbitalPhenytoin St. John’s Wort Glucocorticoids

Clarithromycin/Erythromycin Diltiazem, VerapamilItraconazole/Ketoconazole RitonavirGrapefruit/Grapefruit Juice

Price

•WAC for Vitrakvi

Formulation Quantity WAC

25 mg Capsules 60 $10,933

100 mg Capsules 60 $32,800

20 mg/mL solution 100 mL $14,578

Place in therapy

Vitrakvi is indicated for the treatment of adult nad pediatric patients with solid tumors that:are neurotrophic receptor tyrosine kinase

(NTRK) gene fusion positive without known resistance mutations are metastatic or where surgical resection

may result in severe morbidity have no alternative treatments available or

have progressed following treatment

Additional information•Patient counseling points:•May be taken with or without food •Do not crush or chew oral capsules •Oral solution and capsules may be

used interchangeably •Use of effective contraception in both

men and women with reproductive potential •Drug-drug interactions

Learning Assessment

Use of Vitrakvi is appropriate in which of the following:

A. NTRK gene fusion positive solid tumors

B. Metastatic cancer or where surgical resection is not possible

C. Patients with no satisfactory alternative treatment options

D. All of the above

References

Available at: Bayer and Loxo Oncology. Vitrakvi. https://www.hcp.vitrakvi-us.com/. Accessed May 14th, 2019.

Available at: FDA. https://www.fda.gov/drugs/fda-approves-larotrectinib-solid-tumors-ntrk-gene-fusions-0. Accessed May 14th, 2019.

Available at: Clinical Pharmacology. https://www-clinicalkey-com.cuhsl.creighton.edu/pharmacology/monograph/5118?sec=monpreg&n=VITRAKVI. Accessed May 15th, 2019.

Available at: Lexicomp. http://online.lexi.com.cuhsl.creighton.edu/lco/action/doc/retrieve/docid/patch_f/6727995?searchUrl=%2Flco%2Faction%2Fsearch%3Fq%3DVitrakvi%26t%3Dname%26va%3Dvitra#dora. Accessed May 15th, 2019.

Xiaoxiao Qi (Monica) PharmD Candidate Class of 2020

University of Nebraska Medical Center

College of Pharmacy

Xofluza

Learning Assessment

What is the difference between indications of Tamiflu and Xofluza?

A. Tamiflu is only indicated for prophylaxis of influenza.

B. Xofluza is indicated for treatment and prophylaxis of influenza.

C. Tamiflu is only indicated for treatment of influenza.

D. Xofluza is only indicated for treatment of influenza.

Speaker Disclosure

Xiaoxiao Qi has no relevant financial relationships that would be considered a conflict of interest for the purposes of this program. This information will not include a discussion of non-FDA approved (off-label) medication use.

Indication

•XOFLUZA is indicated for the treatment of acute uncomplicated influenza in patients 12 years of age and older who have been symptomatic for no more than 48 hours.

•There are currently no unapproved uses.

Influenza •A contagious, infectious disease caused by

influenza virus that impacts people of all ages.

•Symptoms arise within as little as 24 hours from infection:•Fever, aches, chills, fatigue, weakness, chest

discomfort, cough, headache

• results in 140,000 to 960,000 hospitalizations and is associated with 12,000 to 79,000 deaths in the United States each year.

Drug Formulation

• XOFLUZA 20 mg Tablets

• XOFLUZA 40 mg Tablets

Mechanism of Action• It is a prodrug that is converted by

hydrolysis to baloxavir, the active form.

•Baloxavir inhibits influenza-specific polymerase acidic endonuclease to prevent viral replication.• an enzyme in the viral RNA

polymerase complex required for viral gene transcription

Pharmacokinetics•Absorption: •Administered orally. •The peak concentration is achieved 4

hours after.

•Distribution:• It is 92.9% to 93.9% bound to human

plasma proteins and has a volume of distribution of 1,180 L.

Pharmacokinetics• Metabolism:

• The major route of elimination is via metabolism, primarily by uridine diphosphate glucuronosyl transferase (UGT1A3) with minor contributions from CYP3A4.

• The drug's terminal elimination half-life is 79.1 hours.

• Excretion:• 14.7% of total dose excreted through urine,

80.1% excreted through feces.

Dosing•The recommended dose of XOFLUZA in

patients 12 years of age or older with acute uncomplicated influenza is a single weight-based dose as follows: •Body Weight (kg) 40 kg to less than 80

kg : Single Dose of 40 mg •>=80 kg: Single Dose of 80 mg •Within 48 hours of symptoms onset

Special Populations• Pregnant/Nursing

• Consider if at higher risk of complications from flu in pregnant patient.

• Not recommended in breastfeeding.

• Pediatric• No use in patients under age 12.

• Geriatric• No clinical studies have been done in elderly

(>65 years old).

Special Populations

Hepatic ImpairmentNo difference in pharmacokinetics

Renal ImpairmentCrCl > 50ml/min: no meaningful effect

of renal function on pharmacokinetics has been established. Severe renal impairment, no data.

Contraindications

•XOFLUZA is contraindicated in patients with a history of hypersensitivity to baloxavir marboxil or any of its ingredients.

Precautions

•Potential secondary bacterial infections

•Serious bacterial infections may begin with influenza-like symptoms, may coexist with, or occur as a complication of influenza.

•XOFLUZA has not been shown to prevent such complications.

Adverse Reactions

•The most common: diarrhea (3%), bronchitis (2%), nasopharyngitis (1%), headache (1%) and nausea (1%).

Drug-Drug Interactions

•Avoid co-administration of XOFLUZA with polyvalent cation-containing laxatives, antacids, or oral supplements (e.g., calcium, iron, magnesium, selenium, or zinc).

•Live attenuated influenza vaccines may be affected.

Price

•Wholesale acquisition cost (WAC)

•$150.00 for both available strengths (40 mg/dose and 80 mg/dose).

Place in therapyXofluza and Tamiflu have similar efficacy

in reducing the length of flu symptoms.(median time to the alleviation was 23.4-28.2 hours shorter than placebo group in the phase 2 trial)

Xofluza was superior to both Tamiflu and placebo in reducing the viral load 1 day after initiation of the trial regimen in patients with uncomplicated influenza.

Place in therapy Tamiflu is indicated for the treatment of

the flu and for prophylaxis for individuals coming in close contact with infected individuals.

Xofluza is only indicated for the treatment of the acute uncomplicated influenza.

Tamiflu has a broader range of use, e.g. use in infants and pregnancy.

Additional information• Patient Counseling tips

• begin treatment with XOFLUZA as soon as possible at the first appearance of influenza symptoms, within 48 hours of onset of symptoms.

• can be taken with or without food.• Do not take with dairy products, calcium-fortified

beverages, polyvalent cation containing laxatives, antacids or oral supplements (e.g., calcium, iron, magnesium, selenium, or zinc).

• consult their healthcare provider prior to receiving a live attenuated influenza vaccine.

Learning Assessment

What is the difference between indications of Tamiflu and Xofluza?

A. Tamiflu is only indicated for prophylaxis of influenza.

B. Xofluza is indicated for treatment and prophylaxis of influenza.

C. Tamiflu is only indicated for treatment of influenza.

D. Xofluza is only indicated for treatment of influenza.

References

Available at: Genentech a member of the Roche Group. Xofluza. https://www.Xofluza.com/. Accessed May 2nd , 2019.

Available at: DAILYMED. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e49e1a61-1b7c-4be5-ac84-af6240b511e7. Accessed May 2nd, 2019.

Available at: Clinical Pharmacology. https://www-clinicalkey-com.library1.unmc.edu/pharmacology/monograph/5109?type=1&sec=monadve&n=XOFLUZA. Accessed May 2nd , 2019.

Hayden FG, Sugaya N, Hirotsu N, et al; Baloxavir Marboxil Investigators Group. Baloxavir marboxil for uncomplicated influenza in adults and adolescents. N Engl J Med. 2018;379(10):913-923. Supplement available at: https://www.nejm.org/doi/full/10.1056/NEJMoa1716197. Accessed May 2nd, 2019.

Laura Yacinthe, PharmD Candidate Class of 2020

Creighton University

School of Pharmacy and Health Professions

Yupelri

Learning Assessment

Yupelri is a _______?

A. Long-acting Beta Agonist

B. Long-acting Muscarinic Antagonist

C. LABA/LAMA combination

D. Inhaled Corticosteroid

Speaker Disclosure

Laura Yacinthe has no relevant financial relationships that would be considered a conflict of interest for the purposes of this program. This information will not include a discussion of non-FDA approved (off-label) medication use.

Indication

•Yulpelri is indicated as maintenance treatment for patients with chronic obstructive pulmonary disease (COPD)

•FDA Approved in November 9, 2018

•There are no known off-label uses for Yupelri

Chronic Obstructive Pulmonary Disorder

•COPD is a lung disease caused by exposure to gases such as cigarette smoke

•COPD patient’s tend to have •persistent and progressive respiratory symptoms•airflow limitation •destruction of cells of the lung

Drug Formulation (if needed)

•Yulperi is an inhaled solution to be nebulized.•175 mcg /3 mL vial •May be stored at room temperature

Mechanism of ActionYupelri is a long-acting muscarinic

antagonist also called an anticholinergic.It has affinity to the muscarinic receptors

M1 to M5. In the airways, it exhibits pharmacological

effects through inhibition of M3 receptor at the smooth muscle leading to bronchodilation. Prevention of methacholine- and

acetylcholine-induced bronchoconstrictiveeffects was dose-dependent and lasted longer than 24 hours.

Pharmacokinetics

•Absorption• Inhaled administration•Maximum concentration achieved between 14 to

41 minutes

•Distribution•Volume of distribution is 218 liters

Pharmacokinetics

•Metabolism• metabolized via hydrolysis of the

primary amide to a carboxylic acid forming its major active metabolite•The active metabolite is formed by

hepatic metabolism

•Excretion•Half-life is 22-70 hours

Dosing

•Normal dose•175mcg/3mL nebulized once daily

Special Populations

•Yupleri has shown no evidence of a clinically significant effect of age 44 to 79 years, gender, smoking status or weight on systemic exposure

•Pregnant/Nursing•Not studied in this population

•Pediatric•Not studied in this population

Special Populations•Pregnant/Nursing•No clinically relevant studies have

been completed in this population•Pediatric•Not indicated in this population

•Geriatric•No adjustment is necessary

•Healthcare teams should weigh benefits vs risk

Special Populations

•Hepatic Impairment•Not recommended for any patients that have any

hepatic deficiencies

•Renal Impairment•No dose adjustment is necessary in patients with

renal impairment

Contraindications

•The only known contraindication for Yupelri is hypersensitivity to revefenacin

Precautions

•Yupelri should not be used during an acute COPD episode

•May worsen narrow angle glaucoma and benign prostate hyperplasia

Adverse Reactions

The most common:coughnasopharyngitisupper respiratory tract infection headache back pain

Drug-Drug Interactions

•Avoid co-administration of Yupelri with other anti-cholinergic medications

•OATP1B1 and OATP1B3 inhibitors could lead to an increase in systemic exposure of Yupelri

Price

•The wholesale acquisition cost (WAC) for Yupelri is $34.33 for the 175 mcg/3 ml vial.

Place in therapy

•Yupelri can be used as monotherapy for patients in all stages of COPD

Additional information

•Yupelri is not for acute symptoms

•Yupelri can cause paradoxical broncospasms

•Yupelri may worsen glaucoma and benign prostate hyperplasia

Learning Assessment

Yupelri is a _______?

A. Long-acting Beta Agonist

B. Long-acting Muscarinic Antagonist

C. LABA/LAMA combination

D. Inhaled Corticosteroid

References• Available at: University Libraries - EZProxy Login. https://www-clinicalkey-

com.cuhsl.creighton.edu/pharmacology/monograph/5112?sec=mondesc&n=YUPELRI. Accessed May 20, 2019.

• Available at: Creighton University Libraries - EZProxy Login. http://www.dynamed.com.cuhsl.creighton.edu/topics/dmp~AN~T901285/Bronchodilators-for-COPD. Accessed May 20, 2019.

• Available at: These highlights do not include all the information needed to use YUPELRI™ (revefenacin) inhalation solution safely and effectively. See full prescribing information for Available at: YUPELRI (revefenacin) inhalation solution.YUPELRI (revefenacin) inhalation solution, for oral inhalation Initial U.S. Approval: 2018. U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?type=display&setid=6dfebf04-7c90-436a-9b16-750d3c1ee0a6. Accessed May 15, 2019.

• Available at: YUPELRIhcp.com/about.yupelri. Learn more about once-daily YUPELRI® (revefenacin). https://www.yupelrihcp.com/en/key-highlights. Accessed May 15, 2019.

Questions?