CRITCAL CARE PHARMACY GUIDELINE
2010
CLINICAL PHARMACY WORKING COMMITTEE (CRITICAL CARE SUBSPECIALTY)
PHARMACEUTICAL SERVICES DIVISION, MINISTRY OF HEALTH
LIST OF CONTENTS
Page
CHAPTER 1 : THE ROLE OF PHARMACIST IN CRITICAL CARE FIELD
CHAPTER 2 : PROTOCOLS
2.1 Dilution Protocols
2.2 DVT Prophylaxis
2.3 Stress Ulcer Prophylaxis
2.4 Antibiotic Guideline for Infections in Intensive Care Unit
2.5 Neuromuscular Blocking Agents in Critically Ill Patients
2.6 Sedative Agents in Critically Ill Patients
2.7 Fluid Management in Critically Ill Patients
2.8 Medication Administration in Enteral Feeding Tubes
CHAPTER 3 : DOSING
3.1 Renal Dosing
3.2 Liver Dosing
3.3 Special Dosing in Obese Patients
CHAPTER 4 : NUTRITION
4.2 Parenteral Nutrition in Critically Ill Patients
CHAPTER 5 : OTHERS
5.1 Drug Causing Haematological Disorder
5.2 Poisoning
APPENDICES:
Appendix 1: Drugs that may unmask/exacerbate Myastenia Gravis
Appendix 2: Categories of Safe & Unsafe Drugs in the Acute Poryphyrias
Appendix 3: Drugs and Chemicals in Glucose-6-Phosphate Dehydrogenase Deficiency
Appendix 4 : Drug-Disease Interaction
2
CHAPTER 1
THE ROLE OF PHARMACIST IN CRITICAL CARE FIELD
3
CHAPTER 2
PROTOCOLS
2.1 Dilution Protocols
2.1.1 Antiarrhythmic Agents
DRUG a. Digoxin b. Adenosine
STRENGTH/UNIT 500mcg/2ml ( Lanoxin ) 6mg/2ml ( Adenocor )
STORAGE Below 25˚C, Protect from light Below 25ºC ( Do not refrigerate )
RECONSTITUITION Already in solution Already in solution.STABILITY AFTER RECONSTITUITION Immediate use is recommended NA
DILUENTS FOR INFUSION
D5%
NA
NSFor direct IV injection can be administered undiluted or diluted with a 4 fold or greater
volume of diluents. The use of less than a 4 fold volume of diluents could lead to precipitation of
digoxin.( eg. 2ml ampoule with 500mcg in 500ml of
diluents for infusion)
METHOD OF ADMINISTRATION
IV infusion (over 10-20 mins or longer-Product Information Lanoxin Injection). ( To be given at
least 2 hours - BNF) IV bolus (2 seconds )
REMARKS
Intramuscular route are not recommended. The IM route is painful and associate with muscle
necrosis.
IV bolus into central or large peripheral vein.
Rapid injection is not recommended; it may cause systemic and coronary arteriolar
constriction.
If given into an IV line, it should be injected as proximally as possible, and followed by a
rapid saline flush (5ml of NS ).Mixing digoxin with other drugs in the same
container or simultaneous administration in the same intravenous line is not recommended.
Administer with cardiac monitoring.
REFERENCES:
1. Product information ( Lanoxin Injection). 2. Micromedex Healthcare series. 3. Pocket Guide to Injectable Drugs. Companion
to the handbook on Injectable Drugs.13 th edition. Lawrence A. Trissel. 2005.
4. British National Formulary (BNF). 55 edition. March 2008.
1. Product information Adenocor.2. Micromedex Healthcare series.3. Lexi-Comp's Drug
Information Handbook, 13th Edition, Charles F, Lacy, et al.2005
4. BNF 50, September 2005.
4
DRUG c. Amiodarone d. Isoproterenol Hydrochloride
STRENGTH/UNIT 150mg/3ml ( Cordarone ) 1mg/5ml ( Isuprel )
STORAGE Below 25ºC. 20ºC - 25ºC. Protect from light.
RECONSTITUITION Already in solution. Already in solution.
STABILITY AFTER RECONSTITUITION NA NA
DILUENTS FOR INFUSION D5% NS ( for IV bolus only )
D5% ( for IV bolus and IV infusion )
METHOD OF ADMINISTRATION
IV ( Central line )
Loading Dose : Dilute 300mg in 50 mL D5%, run over 1 hour.
Maintenance Dose : Dilute 600mg in 500mL D5% run over 23 hours.
IV bolus : dilute 0.2mg ( 1ml ) to 10 ml NS or D5%.
IV infusion : dilute 2mg ( 10ml ) in 500 ml D5%.
IM : use undiluted ( 0.2mg )
SC : use undiluted ( 0.2mg )
Intracardiac : use undiluted ( 0.02mg )
REMARKS
Do not use concentrations of less than 2 ampoules ( 300mg) in 500 ml.
Incompatible with NS.Do not add any other products to the
infusion solution.
Must be administered via the central venous route.
Concentration up to 10 times greater have been used when limitation of
volume is essential
Rate over 30mcg/min have been used in advanced stages of shock.
If heart rate exceed 110 beats /min,decrease or temporarily
discontinue the infusion.
Do not use if is pinkish or darker than slightly yellow or contain precipitate.
REFERENCES:
1. Product information Cordarone. 2. Micromedex Healthcare series. 3. Lexi-Comp's Drug Information Handbook, 13th Edition, Charles F, Lacy, et al.20054. BNF 50, September 2005.
1. Product information Isuprel.2. Micromedex Healthcare series.3. Lexi-Comp's Drug Information
Handbook, 13th Edition, Charles F, Lacy, et al.2005
4. BNF 50, September 2005.
DRUG a. Streptokinase
STRENGTH/UNIT 1 500 000 IU ( Streptase )
STORAGE 2ºC - 25ºC.
RECONSTITUITION 5ml NS.
STABILITY AFTER RECONSTITUITION 24 hours at 2ºC - 8ºC.
DILUENTS FOR INFUSION
NS
D5%
METHOD OF ADMINISTRATION
IV infusion : dilute up to 20 - 250mL NS or D5% over 60 mins.
REMARKS Avoid IM use.
REFERENCES: 1. Product information Streptase.2. Micromedex Healthcare series.3. Lexi-Comp's Drug Information Handbook, 13th
Edition, Charles F, Lacy, et al.20054. BNF 50, September 2005.
5
2.1.2 Antibiotics
6
DRUG a. Amikacin b. Ampicilin c. Azithromycin
STRENGTH/UNIT 250mg/2ml
500mg/2ml
500mg 500mg (Zithromax)
STORAGE Below 25˚C, Protect from light, Do not freeze
Below 25˚C 15ºC - 30ºC
RECONSTITUITION Already in solution 5ml Water for Injection 4.8ml Water for Injection
STABILITY AFTER RECONSTITUITION NA use within 1 hour
24 hours at room temperature
1 week in refrigerator
DILUENTS FOR INFUSION
D5% NS
D5% 1/2 NS D5% 1/4 NS
Lactated Ringer's Injection
NSInfusion concentration
should not exceed 30mg/ml.
NS1/2NSD5%
Lactated Ringer's InjectionInfusion
concentration: 1mg/ml - 2mg/ml
METHOD OF ADMINISTRATION
IV infusion : Adults and paed over 30 to 60 minutes. Infant over
1 to 2 hours.
IM injection in large muscle mass.
IV Bolus : 3 - 5 min
IV Infusion : 30 - 60 min
IM (Dissolve 500mg in 1.8ml Water for
Injection)
IV infusion 1mg/ml over 3 hours
IV infusion 2mg/ml over 1 hour
REMARKS Amikacin should not be mixed
with other antibiotics in the same solution and must be
administered separately.
Rapid infusion may cause seizures.
Should not be given as IV bolus or IM
REFERENCES
1. Product information Amikozit.2. Micromedex Healthcare
series.3. Lexi-Comp's Drug Information
Handbook, 13th Edition, Charles F, Lacy, et al.2005
4. BNF 50, September 2005.
1. Product information Pamecil.
2. Micromedex Healthcare series.
3. BNF 50, September 2005.
1. Product information Zithromax.
2. Micromedex Healthcare series.
3. Lexi-Comp's Drug Information Handbook, 13th Edition, Charles F, Lacy, et al.2005
4. BNF 50, September 2005.
DRUG d. Cefepime e. Cefotaxime f. Ceftazidime
7
STRENGTH/UNIT 1gm (Maxipime) 1gm 1gm , 2gm ( Fortum )
STORAGE 15ºC - 30ºC15ºC - 30ºC , Protect
from lightBelow 25ºC, Protect
from light
RECONSTITUITION 10ml Water for Injection, D5%, NS
10ml Water for Injection 10ml Water for Injection ( both 1gm
and 2gm)
STABILITY AFTER RECONSTITUITION
24 hours at room temperature
1 week in refrigerator
Not to be stored above 25ºC
Not longer than 24 hours
18 hours at below 25ºC
1 week in refrigerator
DILUENTS FOR INFUSION
NS
D5%
Infusion concentration: 1mg/ml - 40mg/ml
NS
D5%
NS
D5%
METHOD OF ADMINISTRATION
IV infusion over 30 minutes
IM ( Dissolve 1gm in 3ml Water for Injection, D5%, 1%
Lidocaine )
IV bolus over 3-5 minutes.
IV infusion: 100ml over 50 - 60 minutes.
IM ( Dissolve 1gm in 4ml Water for Injection )
IV bolus over 3-5 minutes.
IV infusion: diluent up to 50ml over 30
minutes.
IM ( Dissolve 1gm in 3ml Water for Injection
)
REMARKSIV preferable for patient with
severe or life-threatening infection.
IV preferable for dose exceed 1gm
IV preferable for dose exceeds1gm.
May be used in peritoneal dialysis and
CAPD.
Concentration : 125 - 250mg for 2L of
dialysis fluid
REFERENCES
1. Product information Maxipime.
2. Micromedex Healthcare series.
3. Lexi-Comp's Drug Information Handbook, 13th Edition, Charles F, Lacy, et al.2005
4. BNF 50, September 2005.
1. Product information Rekaxime.
2. Micromedex Healthcare series.
3. Lexi-Comp's Drug Information Handbook, 13th Edition, Charles F, Lacy, et al.2005
4. BNF 50, September 2005.
1. Product information Fortum.
2. Micromedex Healthcare series.
3. Lexi-Comp's Drug Information Handbook, 13th Edition, Charles F, Lacy, et al.2005
4. BNF 50, September 2005.
8
DRUG g. Ceftriaxone h. Cefuroxime i. Ciprofloxacin
STRENGTH/UNIT 500mg ( Rocephin )750mg, 1.5gm (Zinacef ) 100mg/50ml, 200mg/
100ml ( Ciprobay )
STORAGE Below 30ºC 25ºC Below 25ºC, Do not freeze
RECONSTITUITION 5ml of solvent
6ml Water for Injection for 750mg
15ml Water for Injection for 1.5gm
Already in solution
STABILITY AFTER RECONSTITUITION
6 hours at room temperature
24 hours in refrigerator
5 hours at room temperature
48 hours in refrigerator
NA
DILUENTS FOR INFUSION
NS
D5%
NS
0.45%NS
D5%
NS
D5%
Ringer lactate
METHOD OF ADMINISTRATION
IV bolus over 2-4 minutes.
IV infusion: 50 to 100ml over at least 30 minutes.
IM ( Dissolve 500mg in 2ml 1% Lidocaine )
IV bolus over 3-5 minutes.
IV infusion : 50 to 100ml over 30 minutes.
IM ( Dissolve 750mg in 3ml Water for
Injection )
IV Infusion over 60 minutes
REMARKS
Neonates : IV infusion should at least 60 minutes.
Dose exceed 1gm not be given by IM.
Only use Calcium-free infusion solutions.
Slow infusion into a large vein minimize
local IV site reactions
Ciprofloxacin solution can be infused directly or mixing with compatible infusion diluents.
REFERENCES
1. Product information Rocephin.
2. Micromedex Healthcare series.
3. Lexi-Comp's Drug Information Handbook, 13th Edition, Charles F, Lacy, et al.2005
4. BNF 50, September 2005.
1. Product information Zinacef.
2. Micromedex Healthcare series.
3. Lexi-Comp's Drug Information Handbook, 13th Edition, Charles F, Lacy, et al.2005
4. BNF 50, September 2005.
1. Product information Ciprobay
2. Micromedex Healthcare series.
3. Lexi-Comp's Drug Information Handbook, 13th Edition, Charles F, Lacy, et al.2005
4. BNF 50, September 2005.
9
DRUGj. Amoxicillin and Clavulanate Potassium
k. Cloxacillin l. Sulfamethoxazole and Trimethoprim
STRENGTH/UNIT 1.2gm 500mg 480mg/5ml
STORAGE Below 25ºC.Below 25ºC. Below 30ºC, Do not
refrigerate. Protect from light.
RECONSTITUITION WFI10ml Water for
Injection.Already in solution
STABILITY AFTER RECONSTITUITION
Solution should be made up to full infusion volume,
immediately after reconstitution.
30 minutes after reconstitution.
NA
DILUENTS FOR INFUSION
WFI
NS
NS
D5%
NS
D5%
METHOD OF ADMINISTRATION
IV Infusion: 50-100ml over 30-40 minutes
IV Infusion complete within 4 hours of reconstitution.
IV bolus over 3-5 minutes.
IV Infusion over 20-30 minutes
IM ( Dissolve 500mg in 2.5ml Water for
Injection )
IV Infusion over 60-90 minutes
REMARKSLess stable in infusions
containing glucose, dextran or bicarbonate.
1 amp(5ml) to 125ml, 2amp(10ml) to 250ml, 3amp(15ml) to 500ml
diluent.
Fluid restriction required, 1amp(5ml) to 75ml diluent.
Infusion commenced within 30 minutes after
preparation.
Duration of infusion not exceed 1.5 hours.
REFERENCES1. Product information
Moxied-CLV2. 2. BNF 50, September
2005.
1. Product information Monoclox
1. Product information DBL2. Micromedex Healthcare
series.3. Lexi-Comp's Drug
Information Handbook, 13th Edition, Charles F, Lacy, et al.2005
4. BNF 50, September 2005.
10
DRUG m. Fusidic Acid n. Gentamicin o. Imipenem with cilastatin
STRENGTH/UNIT 500mg ( Fucidin) 80mg/2ml 500mg
STORAGE 15 - 20ºC Below 25ºC 15 - 30ºC
RECONSTITUITION 10ml of buffer solution provided.
Already in solution. 10ml of diluent for infusion
STABILITY AFTER RECONSTITUITION NA
NA 4 hours at room temperature
24 hours in refrigerator
DILUENTS FOR INFUSION
NS
D5% **
NS
D5%
NS
D5%
D10%
D5%NS
Mannitol 5% and 10%
METHOD OF ADMINISTRATION
IV Infusion: 250 -500ml over 2-4 hours
IV infusion : 100-200ml over 30 minutes.
IV infusion : 500mg in 100m diluent for infusion. Rate depend
on dose.
Dose ≤ 500mg over 20 - 30 minutes , ≥ 500mg over 40 -60
minutes.
REMARKS
Give through central venous line to minimize venospams
and thrombophlebitis.
If superficial vein used, infusion over 6 hours.
Never be injected undiluted.
Must not be given intramuscularly or subcutaneously.
** Precipitation may occur in infusion solution pH below 7.4
( more acidic samples of dextrose 5% )
For extended-interval doses, an infusion period of 60 minutes recommended.
Administer other antibiotic at least 1 hour before or after gentamycin.
Must use the same diluent for reconstitution and as infusion
solution.
Reconstitution of Tienam : add ≈ 10 ml of appropriate infusion
solution to vial. Shake well and transfer the suspension to infusion solution container. Repeat with additional 10ml infusion solution to ensure
complete transfer of vial contents to infusion solution. Resulting
mixture should be agitated until clear.
REFERENCES
1. Product information Fucidin.
2. Micromedex Healthcare series.
3. BNF 50, September 2005.
1. Product information Garasent.
2. Micromedex Healthcare series.
3. Lexi-Comp's Drug Information Handbook, 13th Edition, Charles F, Lacy, et al.2005
4. BNF 50, September 2005.
1. Product information Tienam.
2. 2. Micromedex Healthcare series.
3. Lexi-Comp's Drug Information Handbook, 13th Edition, Charles F, Lacy, et al.2005
4. BNF 50, September 2005.
11
DRUG p. Meropenemq. Metronidazole r. Linezolid
STRENGTH/UNIT 500mg , 1gm ( Meronem ) 500mg/100ml 600mg/300ml ( Zyvox)
STORAGE Below 30ºC15 - 30ºC. Protect from light 15 - 30ºC. Protect from
light.Keep in overwrap until ready to use.
RECONSTITUITION 500mg - 10ml , 1gm - 20ml of NS or D5%
Already in solution Already in solution
STABILITY AFTER RECONSTITUITION
NS : 2 hours at RT, 18 hours in refrigerator.
D5% : 1 hours at RT, 8 hours in refrigerator.
NA NA
DILUENTS FOR INFUSION
NS
D5%
NA NA
METHOD OF ADMINISTRATION
IV bolus : 10ml of WFI per 500mg over 5 minutes.
IV infusion : 50-200ml over 15 - 30 minutes.
IV infusion : 100ml over 20 - 30 minutes.
IV infusion : 30 -120 minutes.
REMARKSRecommended to use freshly
prepared solution of Meropenem.
Avoid contact between drug and aluminium in infusion set.
Do not mix or infuse with other medications.
Yellow color of the injection may intensify over time without
affecting potency.
REFERENCES
1. Product information Meronem.
2. Micromedex Healthcare series.
3. Lexi-Comp's Drug Information Handbook, 13th Edition, Charles F, Lacy, et al.2005
4. BNF 50, September 2005.
1. Product information .2. Micromedex
Healthcare series.3. Lexi-Comp's Drug
Information Handbook, 13th Edition, Charles F, Lacy, et al.2005
1. Micromedex Healthcare series.
2. Lexi-Comp's Drug Information Handbook, 13th Edition, Charles F, Lacy, et al.2005
12
DRUG s. Polymixin Bt. Sulbactam Sodium/Ampicilin
Sodium
u. Sulbactam Sodium/Cefoperazone
Sodium
STRENGTH/UNIT 500,000 units 1.5gm 1gm ( Sulperazon)
STORAGE 15 - 30ºC Below 25ºC Below 25ºC
RECONSTITUITION 500mg - 10ml , 1gm - 20ml of NS or D5%
3.2ml Water for Injection 3.4ml Water for Injection, NS, D5%
STABILITY AFTER RECONSTITUITION 72 hours in refrigerator.
Stability at 25ºC and 4ºC depends on concentration of
solution prepared. For IM administration, used within 1
hour of reconstitution.
Stability at 25ºC and 4ºC depends on concentration of
solution prepared. For IM administration, used within 1
hour of reconstitution.
DILUENTS FOR INFUSION
D5% Water for Injection
NS
D5%
Lactated ringer
Water for InjectionNS
D5%
METHOD OF ADMINISTRATION
IV infusion : 300-500ml over 60 - 90 minutes.
IM : 2ml Water for Injection, NS, 1% procaine solution.
Intrathecal : 10ml physiological solution
IV bolus : slowly over 10 -15 minutes
IV infusion : 50-100ml over 15 - 30 minutes.
IM : 3.2ml Water for Injection or 2% Lidocaine
IV bolus : over minimum 3 minutes
IV infusion : 20ml over 15 - 60 minutes.
IM : 3.2ml Water for Injection, and further diluted with 2%
Lidocaine.
REMARKS
Intrathecal is for meningeal infection.
May cause extravasation. Monitor the IV site, rotate infusion site frequently.
IV infusion : dilute using diluents (NS,Water for Injection, Lactated ringer) to a maximum concentration of 45mg/ml.
IV infusion : dilute using D5% to a maximum concentration of 30mg/ml. Administer within 2 hours.
Must use the same diluent for reconstitution and as infusion
solution.
REFERENCES
1. Micromedex Healthcare series.
2. Lexi-Comp's Drug Information Handbook, 13th Edition, Charles F, Lacy, et al.2005
1. Product information Easyn.
2. Micromedex Healthcare series.
3. Lexi-Comp's Drug Information Handbook, 13th Edition, Charles F, Lacy, et al.2005
1. Product information Easyn.2. Micromedex Healthcare
series
13
DRUG v. Piperacillin / Tazobactomw. Vancomycin
STRENGTH/UNIT 4.5gm ( Tazocin ) 500mg
STORAGE Below 25ºC Below 25ºC. Protect from light.
RECONSTITUITION 20ml of Water for Injection, NS10ml Water for Injection.
STABILITY AFTER RECONSTITUITION
24 hours at room temperature
48 hours in refrigerator
Freshly prepared prior to use.
DILUENTS FOR INFUSION
Water for Injection
NS
D5%
NS
D5%
METHOD OF ADMINISTRATION
Slow Iv injection : 3 - 5 mins
IV Infusion :- 50 ml - 150ml for 20 - 30 mins.
IM : 2.25g with 4ml WFI
IV Infusion : dilute with infusion fluid up to 5mg/ml over 1 hour.
REMARKS
IV infusion : maximum infusion volume with WFI is 50ml.
During IV infusion, discontinue primary infusion solution.
IV infusion concentration can increased to 10mg/ml in fluid restriction, but increased risk of infusion-related effects.
Rate of administration not exceed 10mg/min for doses over 500mg.
Use continuous infusion if intermittent not feasible.
If Red-man syndrome appears, slow infusion rate to 1½ - 2 hours and increase dilution volume.
REFERENCES
1. Product information Tazocin.2. Micromedex Healthcare series.3. Lexi-Comp's Drug Information
Handbook, 13th Edition, Charles F, Lacy, et al.2005
4. BNF 50, September 2005.
1. Product information Vancotex.2. Micromedex Healthcare series.3. Lexi-Comp's Drug Information
Handbook, 13th Edition, Charles F, Lacy, et al.2005
4. BNF 50, September 2005
14
2.1.3 Antifungal
DRUG a. Amphotericin Bb. Fluconazole c. Voriconazole
STRENGTH/UNIT 500mg ( Fungizone) 100mg/50ml ( Diflucan ) 200mg ( Vfend)
STORAGEStored in refrigerator
Protected against exposure to light
Below 30ºC, Do not refrigerate.
15-30ºC
RECONSTITUITION 10ml Water for InjectionAlready in solution 19ml Water for Injection.
STABILITY AFTER RECONSTITUITION
24 hours at room temperature
1 week in refrigerator
NA 24 hours at 2- 8ºC
DILUENTS FOR INFUSION
D5%
Infusion concentration is 0.1mg/ml
NS
Ringer's Solution
Hartmann's solution
D20%
NS
D5%
Compound Sodium Lactate
METHOD OF ADMINISTRATION
Slow Intravenous infusion : 2 - 6 hours
IV Infusion over 1-2 hours IV infusion: dilute to concentration of 0.5-5mg/ml
over 1 -2 hours.
REMARKS
Test dose : 1mg in 20ml D5% , administer over 20-30 minutes
Do not reconstitute with NS
Begin infusion immediately after dilution and protect from light.
Infusion rate do not exceed 200mg/hr
Fluconazole is formulated in 0.9% sodium
chloride solution, each 100mg containing 7.5mmol
of sodium.
Patient requiring sodium or fluid restriction, consideration given to rate
of fluid administration.
Maximum rate :3mg/kg/hour.
REFERENCES
1. Product information Fungizone.
2. Micromedex Healthcare series.
3. Lexi-Comp's Drug Information Handbook, 13th Edition, Charles F, Lacy, et al.2005
4. BNF 50, September 2005.
1. Product information Diflucan.
2. Micromedex Healthcare series.
3. Lexi-Comp's Drug Information Handbook, 13th Edition, Charles F, Lacy, et al.2005
4. BNF 50, September 2005.
1. Product information Vfend.
2. 2. Micromedex Healthcare series.
3. Lexi-Comp's Drug Information Handbook, 13th Edition, Charles F, Lacy, et al.2005
4. BNF 50, September 2005.
15
2.1.4 Antiviral
DRUG Acyclovir
STRENGTH/UNIT 250mg
STORAGE Below 25˚C, Protect from light
RECONSTITUITION 10ml Water for Injection
STABILITY AFTER RECONSTITUITION12 hours at room temperature
Do not refrigerate
DILUENTS FOR INFUSION
D5%
NS
Infusion concentration should be approximately 7mg/ml or less.
METHOD OF ADMINISTRATION
IV infusion (over 1 hour)
REMARKS
Should not be given intramuscularly, subcutaneously, locally or intra-ocularly.
Rapid infusion is not recommended to avoid possible renal tubular damage.
REFERENCES
1. Product information Klovireks-L.2. Micromedex Healthcare series.3. Lexi-Comp's Drug Information Handbook, 13th Edition,
Charles F, Lacy, et al.20054. BNF 50, September 2005.
16
2.1.5 Anticoagulants
DRUG HeparinFondaparinux ( Arixtra ) Enoxaparin Sodium
( Clexane )
STRENGTH/UNIT 1000 IU/ml , 5000 IU/ml.2.5mg/0.5ml 40mg/0.4ml ,
60mg/0.6ml
STORAGE 15ºC - 30 ºC. Protect from light.
Below 25ºC. Do not freeze. Below 25ºC.
RECONSTITUITION Already in solution.Already in solution. Already in solution.
STABILITY AFTER RECONSTITUITION NA NA
NA
DILUENTS FOR INFUSION
NS
D5%
NA NA
METHOD OF ADMINISTRATION
IV infusion : minimum volume 250ml D5%.
Subcutaneous.
Subcutaneous. Subcutaneous.
REMARKS
Should be avoided in children below 2 years old and not
used in neonates.
Do not administer IM due to pain, irritation and hematoma
formation.
Must not be administered by IM.
Do not mix with other injections or infusions.
Prefilled syringe is designed with an automatic needle protection system to
prevent needle stick injuries.
Do not administer by IM route.
Pre-filled syringes are ready-to-use.
REFERENCES
1. Product information Heparinol.
2. Micromedex Healthcare series.
3. Lexi-Comp's Drug Information Handbook, 13th Edition, Charles F, Lacy, et al.2005
4. BNF 50, September 2005.
1. Product information Arixtra.
2. Micromedex Healthcare series.
3. Lexi-Comp's Drug Information Handbook, 13th Edition, Charles F, Lacy, et al.2005
4. BNF 50, September 2005.
1. Product information Clexane.
2. Micromedex Healthcare series.
3. Lexi-Comp's Drug Information Handbook, 13th Edition, Charles F, Lacy, et al.2005
4. BNF 50, September 2005.
17
2.1.6 Antiepileptics
DRUG PhenytoinPhenobarbitone Sodium Valproate
STRENGTH/UNIT 250mg/ Dilantin 200mg/ml 400mg (Epilim)
STORAGE Between 15°C to 30°C (Do not freeze)
Protect from light Below 25°C
RECONSTITUITION Already in solutionAlready in solution Reconstitute with solvent
provided
STABILITY AFTER RECONSTITUITION NA NA
24 hours at 2°C to 8°C
DILUENTS FOR INFUSION
NS
Dilute with 50-100ml NS to make a 1mg/ml solution. Max
concentration is 10mg/ml.
NS
D5%
IV infusion: Dilute with at least an equal volume of
fluid.
NS
D5%
Dilute with at least 50ml of NS or D5%
METHOD OF ADMINISTRATION
IV: Rate not exceeding 50mg/minute. Sensitive patient eg. Elderly with cardiovascular condition should receive more
slowly (eg. 20mg/minute)
Recommended to give through a 0.22-0.5 micron in-line filter
due to high potential of precipitation.
Finish infusion within 1 hour after mixing the solution.
IV: Over 3 to 5 minutes. Not to exceed 60mg/min.
IV infusion: eg. Emergency in status epilepticus
IM
S/C
IV infusion: Administer as 60 minutes infusion. Not to
exceed 20mg/min
IV: (Loading dose) single doses up to 15mg/kg has
been administered as rapid infusion over 5-10 minutes.
REMARKS
IM administration is approved but not recommended due to
erratic absorption
The solution is vesicant. Avoid extravasation.
Avoid intra-arterial injection Divide total daily dose if exceeds 250 mg/day
REFERENCES
1. Product information (Dilantin Injection).2. Micromedex Healthcare
series.3. Britisn National Formulary
564. Lexi-Comp's Drug
Information Handbook, 13th Edition, Charles F, Lacy, et al.2005
1. Product information (Phenobarbital Sodium Injection).
2. Micromedex Healthcare series.
3. Lexi-Comp's Drug Information Handbook, 13th Edition, Charles F, Lacy, et al.2005
1. Product information (Epilim Injection).
2. Micromedex Healthcare series.
3. Lexi-Comp's Drug Information Handbook, 13th Edition, Charles F, Lacy, et al.2005
18
DRUG DiazepamThiopentone (Thiopental)
STRENGTH/UNIT 10mg/2ml (Valium) 500 mg (Pentotex)
STORAGE Room temperatureBelow 25°C
RECONSTITUITION Already in solution
STABILITY AFTER RECONSTITUITION NA
Use immediately. Discard any unused portion after 24 hours.
DILUENTS FOR INFUSION
Recommended to give alone
But stable in NS, D5%. Use immediately after mixing.
Dilute 10 mg with 200-250ml NS or D5%
WFI
NS
D5%
METHOD OF ADMINISTRATION
IM
IV injection: Rate not exceeding 5mg/min
IV infusion: Rate not exceeding 5mg/min
IV slow: Over 20 to 40 seconds of 2.5% solution. (occasionally as 0.5%
solution)
IV infusion: as 0.2-0.4% solution.
REMARKS
Infusion rate exceeding 5mg/ min may cause apnea, venous thrombosis,
thrombophlebitis and hypotension. Avoid extravasation.
Thiopental sodium preparation may be given rectally as solution or
suspension
REFERENCES
1. Product information ( Diazepam Injection).
2. Micromedex Healthcare series.3. Britisn National Formulary 564. Lexi-Comp's Drug Information
Handbook, 13th Edition, Charles F, Lacy, et al.2005
1. Product information ( Pentotex Injection).
2. Micromedex Healthcare series.3. Lexi-Comp's Drug Information
Handbook, 13th Edition, Charles F, Lacy, et al.2005
19
2.1.7 Antihypertensive
DRUG a. Frusemideb. Isosorbide Dinitrate
STRENGTH/UNIT 20mg/2ml 10mg/10ml
STORAGE
Below 25˚C. Protect from light. Do not use if solutions yellow in colour. Refrigeration
may result in precipitation. However, resolubilization at room temperature or
warming may be performed without affecting the stability of frusemide.
Below 30˚C.
RECONSTITUITION Already in solutionAlready in solution
STABILITY AFTER RECONSTITUITION
24 hours. Protect from light.24 hours.
DILUENTS FOR INFUSION
NSLactated Ringer's
D5%
.
NS
D5%
Recommended concentration: 0.1mg/ml ( 10mg/amp in 100 ml
diluents for infusion) OR 0.2 mg/ml ( 10mg/amp in 50 ml diluents for
infusion).
METHOD OF ADMINISTRATION
IM
Direct IV injection (slowly over 1-2 mins)- for doses<120mg
IV infusion or continuous IV infusion: rate of infusion should not exceed 4mg/min.
Continuous IV infusion.
It should always be administered as an intravenous admixture and should
never be injected directly.
1-10mg/hr
REMARKS
Unstable in acidic media but very stable in basic media.
Isosorbide dinitrate adsorbed to some extent by PVC infusion containers.
Preferably use glass or polyethylene container.
REFERENCES
1. Micromedex Healthcare series.2. Pocket Guide to Injectable Drugs.
Companion to the handbook on Injectable Drugs.
3. British National Formulary (BNF). 55 edition. March 2008.
4. Drug Information Handbook. 13th edition. 2005-2006. Lexi-comps.
5. Product information Frusemide Injection - AKOSET®. (Duopharma).
1. Micromedex Healthcare series.2. British National Formulary (BNF).
55 edition. March 2008.3. Product information Isosorbide
Injection - Isoket®. (Schwardz Pharma).
20
DRUG c. Labetalold. Hydralazine
STRENGTH/UNIT 25mg/5ml 20mg
STORAGE Below 30˚C. Protected from light.Below 30˚C. Protected from light.
RECONSTITUITION Already in solutionDissolve with 1ml water for injection
STABILITY AFTER RECONSTITUITION Within 24 hours.
Within 24 hours.
DILUENTS FOR INFUSION
NS
D5%
Recommended concentration: 1mg/ml. Suggested volume: 200ml (200mg/40ml
labetalol injection into 160ml of compatible diluent )
Slow IV Injection: 10ml NS
IV Infusion: 500ml NS or Ringer's solution
METHOD OF ADMINISTRATION
IV bolus injection - slowly over 2 minutes. May repeat 40-80mg at 10 min intervals, up
to 300mg total dose.
Continuous IV infusion - initial rate of 2mg/min, titrate to response up to 300mg
total dose.
IM, Slow IV Injection over 1 min. 10-20mg 4-6 hours as needed.
IV Infusion: Initially 200mcg-300mcg/min; maintenance 50-
150mcg/min
REMARKS
Incompatible with Sodium Bicarbonate and alkaline solution. Precipitation may occur.
D5% decrease stability of Hydralazine
REFERENCES
1. Micromedex Healthcare series.2. Pocket Guide to Injectable Drugs.
Companion to the handbook on Injectable Drugs.
3. British National Formulary (BNF). 55 edition. March 2008.
4. Product information Labetalol Injection (Trandate®).
5. Drug Information Handbook. 13th edition. 2005-2006. Lexi-comps.
1. Micromedex Healthcare series.2. British National Formulary (BNF).
55 edition. March 2008.3. Product information Hydralazine
Injection (Apresoline®).4. Drug Information Handbook. 13th
edition. 2005-2006. Lexi-comps.
21
2.1.8 Gastrointestinal
DRUG a. Ranitidine b. Esomeprazole
STRENGTH/UNIT 50mg/2ml
STORAGEBelow 30˚C, Protect from light. Solution is a clear,
colorless to yellow solution; slight darkening does not affect potency.
Below 30˚C. Protect from light. However, can be stored exposed to normal in door light outside the box for up to 24 hours.
RECONSTITUITION Already in solution
5ml of NS (The degradation of reconstituted solution is highly pH
dependent. It must only be reconstituted in the specified volume of NS).
STABILITY AFTER RECONSTITUITION Within 48 hours at room temperature.
Reconstituted solution for injection: With 5ml of NS and store within 12 hours at room temperature. Refrigeration is not
required.
Reconstitution solution for infusion: With 5ml of NS, Lactate Ringer's, D5% then
further dilute to final volume of 50ml solution. Storage for 6hours (D5%) and 12 hours (NS and Lactate Ringer's) in room
temperature. Refrigeration is not required.
DILUENTS FOR INFUSION
- D5%- NS- Intermittent bolus injection: dilute to maximum
of 2.5mg/ml- Intermittent infusion: dilute to maximum of
0.5mg/ml
- NS- Lactate Ringer's- D5%
METHOD OF ADMINISTRATION
- IM: Injection is administered undiluted.- IV: must be diluted. May be administered IVP or
IVPB or continuous IV infusion.- Direct IV injection/IVP: 50mg diluted to a total of 20
ml with compatible infusion solution and given over at least 5 mins. (Administration not greater than 4ml/min.)
- Intermittent infusion/ IV PB : 50mg added to 100ml of compatible solution and administer over 15-20 mins. (Administration not greater than 5-7ml/min).
- Continuous IV infusion: 150mg diluted in 250ml of compatible IV solution and infused at 6.25mg/hr for 24hrs
IV injection: over a period of at least 3 mins.
IV infusion: over a period of 10-30 mins.
REMARKSThe stability of esomeprazole in aqueous solution is strongly dependent upon pH. The rate of degradation increase in response of decreasing pH.
REFERENCES
1. Product information Gastril Injection. (Duopharma).2. Micromedex Healthcare series3. Pocket Guide to Injectable Drugs. Companion to
the handbook on Injectable Drugs. 13 th edition. Lawrence A. Trissel. 2005.
4. Drug Information Handbook. 13th edition. 2005-2006. Lexi-comps
5. British National Formulary (BNF). 55 edition. March 2008.
1. Product information Nexium Injection. (AstraZeneca).
2. Micromedex Healthcare series.3. British National Formulary (BNF). 55
edition. March 2008.
22
DRUG a. Adrenaline b. Dobutamine
STRENGTH/UNIT 1.8mg/1ml 250mg/20ml
STORAGE 15˚C - 30˚C. Protect from light.Below 25˚C, Protect from light
RECONSTITUITION Already in solutionAlready in solution
STABILITY AFTER RECONSTITUITION
Within 24hrs at room temperature and refrigerate. Oxidation turns drug pink, then a brown color; solution should not be used if they are discoloured or contain a
precipitate.
Within 24 hours. A pink discoloration may form due to slight oxidation of the drug but
no significant drug loss within recommended times. If refrigerated,
solution can be stored up to 48 hours.
DILUENTS FOR INFUSION
IV: NSIV:D5%
Recommended: IV infusion: 1mg in 250ml of NS
Intratracheal: dilute in NS or WFI. Absorption is greater with distilled water, but causes
more adverse effects on PaO2.
D5%NS
Must be diluted to a concentration of not more than 5mg/ml before use. If higher
concentration is used eg 500mg dobutamine in 50 cc diluents of infusion. It
should be protected from light.
Recommended: ( eg. 250mg-500mg of dobutamine in 500 cc diluents of infusion)
METHOD OF ADMINISTRATION
SC, IM, slow IV injection, IV infusion, intracardiac injection, intratracheal injection.
IM injection into the buttocks should be avoided.
IV infusion (mcg/min): 1-10mcg/min
IV infusion (mcg/kg/min)
REMARKS
Central line administration if IV infusion. Avoid extravasation.
Incompatible with bicarbonate solution and other alkaline solutions.
Do not add to 5% sodium bicarbonate or other strongly alkaline solution.
Should not be used in conjunction with other agents or diluent containing sodium
bisulphites and ethanol.
REFERENCES
1. Product information Adrenaline Injection BP. (Duopharma)
2. Micromedex Healthcare series.3. Pocket Guide to Injectable Drugs. Companion to
the handbook on Injectable Drugs. 13 th edition. Lawrence A. Trissel. 2005.
4. Drug Information Handbook. 13th edition. 2005-2006. Lexi-comps
5. British National Formulary (BNF). 55 edition. March 2008.
1. Product information Mobitil Injection. (Duopharma)
2. Micromedex Healthcare series.3. Pocket Guide to Injectable Drugs.
Companion to the handbook on Injectable Drugs. 13 th edition. Lawrence A. Trissel. 2005.
4. Drug Information Handbook. 13th edition. 2005-2006. Lexi-comps
5. British National Formulary (BNF). 55 edition. March 2008.
23
DRUG c. Dopamine d. Noradrenaline
STRENGTH/UNIT 200mg/5ml 4mg/4ml
STORAGE Below 25˚C. Protected from lightBelow 25˚C, Protect from light
RECONSTITUITION Already in solutionAlready in solution
STABILITY AFTER RECONSTITUITION
Within 24 hours. Do not use the injection if it is darker than slightly yellow or discoloured in any
other way.
Within 24 hours with protection from light. Solution gradually darkens with exposure to light or air. Do not use if it is discoloured or
contains a precipitate.
DILUENTS FOR INFUSION
D5%
NS
Injection should be diluted before administration.
Recommended: 200mg or 400mg of dopamine in 250ml or 500ml diluents for infusion. (Micromedex, Handbook of Injectable Drugs). Max concentration:
3.2mg/ml (BNF)
D5%
D5%in NS
NS alone is not recommended.(Product Information Levophed Injection). (Lack of
oxidation protection).
Must be diluted before infusion. Recommended:
a. 4-8mg in 250-1000ml of diluents for infusion. ( Micromedex). (Handbook of
Injectable drugs). b. 4mg in 50ml of diluents for infusion. (BNF)
METHOD OF ADMINISTRATION
IV infusion (mcg/kg/min)
Do not add dopamine in any alkaline solution. It is inactivated in alkaline solution. Incompatible with
bicarbonate
IV infusion (mcg/kg/min)
REMARKS
It is also sensitive to oxidizing agent and iron salts.
Avoid extravasation. Administer into the large vein.
IV infusion must be given into a large vein. Avoid extravasation.
Avoid contact with iron salts, alkalis, or oxidizing agents.(Product Information
Levophed).
Incompatible with bicarbonate solution.
REFERENCES
1. Product information Loxin Injection (Duopharma)
2. Micromedex Healthcare series.3. Pocket Guide to Injectable Drugs. Companion
to the handbook on Injectable Drugs. 13 th edition. Lawrence A. Trissel. 2005.
4. Drug Information Handbook. 13th edition. 2005-2006. Lexi-comps
5. British National Formulary (BNF). 55 edition. March 2008.
1. Product information Loxin Injection (Duopharma)
2. Micromedex Healthcare series.3. Pocket Guide to Injectable Drugs.
Companion to the handbook on Injectable Drugs. 13 th edition. Lawrence A. Trissel. 2005.
4. Drug Information Handbook. 13th edition. 2005-2006. Lexi-comps
5. British National Formulary (BNF). 55 edition. March 2008.
24
2.1.9 Miscellaneous
DRUG ParentrovitePotassium chloride Pralidoxime
STRENGTH/UNIT5ml x 2 ampoules (1 pair)
(P-Trovite)10% W/V, 10ml 500mg/20ml (Pampara)
STORAGE Protect from light Below 25˚C Below 28˚C, Protect from light,
RECONSTITUITION Already in solution Already in solution Already in solution
STABILITY AFTER RECONSTITUITION
N/A NA NA
DILUENTS FOR INFUSION
Compatible with commonly used
intravenous solutions
NS (for the treatment of hypokalemia)
Maximum concentration recommended for peripheral
line is 6g/L. (can dilute up to 3 gm KCL in 500ml NS).
For fluid restricted patient with central line, maximum
concentration recommended is 11g/L.
For IV intermittent: as 5% to 10% solution (the
product is 2.5% in strenght, so can be
readily administered)
For IV infusion: Dilute in 100ml NS
METHOD OF ADMINISTRATION
The content of each ampoule (No 1 and No 2) should be mixed prior to
injection.
Although compatible with commonly used
intravenous solutions, it is recommended
parentrovite is given by slow injection
For fluid restricted patient with central line, maximum
concentration recommended is 11g/L.
IV intermittent : over 5 to 10 minutes.
IIV infusion: over 15 to 30 minutes
S/C
IM
REMARKS
Use with caution in patients with cardiac disease
Maximum recommended daily
dose is 12 gm
REFERENCES
Product information (P-trovitel).
1. Product information (Potassium chloride 10%
W/v 10ml).2. Micromedex Healthcare
series.3. British National
Formulary 56.4. Lexi-Comp's Drug
Information Handbook, 12th Edition, Charles F, Lacy, et al.2003
1. Product information (Pampara injection).
2. Micromedex Healthcare series.
3. British National Formulary 56.
4. Lexi-Comp's Drug Information Handbook, 12th Edition, Charles F, Lacy, et al.2003
25
DRUG N-AcetylcysteinePiracetam Desmopressin
STRENGTH/UNIT
2gm/10ml
5gm/25ml
1gm/5ml 4mcg/ml (Minirin)
STORAGE Below 25˚C, 15°C to 25°C 2°C to 8°C
RECONSTITUITION Already in solution Already in solution Already in solution
STABILITY AFTER RECONSTITUITION
NA NA NA
DILUENTS FOR INFUSION
D5% (Preferable)
NS
PCM poisoning: 150mg/kg in 200ml, then 50mg/kg in
500ml followed by 100mg/kg in 1000ml.
NS
IV infusion: Dilute in 50ml NS
METHOD OF ADMINISTRATION
PCM poisoning: IV infusion of 150mg/kg over 15 to 60 minutes, then IV infusion of
50mg/kg over 4 hours followed by IV infusion of 100mg/kg over 16 hours.
Prevention of radiocontrast-induced renal dysfunction
(unlabeled use): IV infusion
S/C
IM
IV infusion over 15 to 30 minutes
REMARKS
For PCM poisoning patient less than 40kg and those
requiring fluid restriction, the volume of diluent could be
adjusted as needed to avoid fluid overload.
NA
REFERENCES
1. Product information (Hidonac N-Acetylcysteine).
2. Micromedex Healthcare series.
3. Britisn National Formulary 56
4. Lexi-Comp's Drug Information Handbook, 12th Edition, Charles F, Lacy, et al.2003
1. Product information (Nootropil Injection).
2. Micromedex Healthcare series.
1. Product information ( Minirin injection).
2. Britisn National Formulary 56
3. Micromedex Healthcare series
4. Lexi-Comp's Drug Information Handbook, 13th Edition, Charles F, Lacy, et al.2005
26
DRUG HaloperidolCalcium gluconate Dantrolene
STRENGTH/UNIT 5mg/ml 10ml 20 mg (Dantrium)
STORAGEBelow 25°C. Protect from
light.Below 30°C. Below 30 °C. Do not
refrigerate. Protect from light.
RECONSTITUITION Already in solution Already in solution
60ml WFI (shake until solution is clear)
If necessary transfer individual vials into a
larger volume sterile IV plastic bag. Do not transfer into glass
bottle. Precipitation may occur.
STABILITY AFTER RECONSTITUITION
NA NA Use within 6 hours at room temperature.
DILUENTS FOR INFUSION
D5%
IV infusion : Dose of 0.5mg-100mg in 50ml-100ml D5%
D5%
NS
IV infusion: Dilute to a maximum concentration of 50mg/ml (eg. 1gm in 20ml)
NOT to be mixed with other intravenous
infusions.
METHOD OF ADMINISTRATION
IM
IV bolus
IV infusion of 50ml-100ml diluted solution with the rate
of 3-25mg/hour
IV slow bolus: Maximum rate of 50mg/minute
IV infusion: The diluted solution of 50mg/ml to be
infused over 1 hour
IV push: In malignant hyperthemia crisis
IV infusion: Over 1 hour in prevention of
malignant hyperthemia
REMARKS
Decanoate form should never be administered IV
(IM only)
Has rarely been given by IM and S/C, but not
recommended because the risk of tissue necrosis.
Solution is high pH and there is possibility for tissue necrosis, avoid
extravasation.
REFERENCES
1. Product information (Manace injection 5mg)
2. Britisn National Formulary 56
3. Micromedex Healthcare series.
4. Lexi-Comp's Drug Information Handbook, 12th Edition, Charles F, Lacy, et al.2003
1. Product information (Calcium gluconate injection)
2. Britisn National Formulary 56
3. Micromedex Healthcare series.
4. Lexi-Comp's Drug Information Handbook, 12th Edition, Charles F, Lacy, et al.2003
1. Product information (Dantrium Intravenous)
2. Micromedex Healthcare series.
3. Lexi-Comp's Drug Information Handbook,
27
DRUG MannitolPotassium dihydrogen
phosphateHuman Normal Immunoglobulin
STRENGTH/UNIT 20% (100gm/500ml) 10mmol/10ml (1.361g) Intragam 3g (50ml)
STORAGEBetween 15°C to 30°C. Do
not freeze.
Below 25°C. 2°C to 8°C. Do not freeze. Once removed from
refrigeration, store below 25°C and use within 3
months
RECONSTITUITION Already in solution. Already in solution Already in solution
STABILITY AFTER RECONSTITUITION
NA NA NA
DILUENTS FOR INFUSION
NA
D5%
NS
Must be diluted before use
IV doses should be incorporated into patient's
maintenance IV fluid. Intermittent IV infusion should
be reserved for severe depletion patient under ECG
monitoring.
Can be administered undiluted
Or can be diluted with up to 2 parts of NS or D5%
METHOD OF ADMINISTRATION
Test dose (to assess adequate renal function): IV
over 3-5 minutes
IV infusion (eg. Cerebral edema or increased
intraocular pressure): over more than 30 minutes
IV infusion, slow: administer over 6 to 12 hours. Minimum
infusion time is 4 hours.
IV infusion: can be given undiluted. Start infusion at the
rate of 1ml/minute. After 15 minutes, the rate can be gradually increased to a
maximum of 3 to 4ml/minute. Reducing the rate in elderly
and in patients with pre-existing renal disease should
be considered.
REMARKS
Use a filter when infuse mannitol solution of
concentration of 20% or more.
Incompatible with calcium or magnesium containing
solutions.
Infusion which is too rapid may cause flushing and
changes in heart rate and blood pressure. Prolonged
administration (over 6 hours) using larger dose (greater than 0.4g/kg) may result in
thrombophlebitis at the infusion site.
REFERENCES
1. Micromedex Healthcare series.
2. Lexi-Comp's Drug Information Handbook, 12th Edition, Charles F, Lacy, et al.2003
1. Product information (Potassium Dihydrogen Phosphate injection)
2. Lexi-Comp's Drug Information Handbook, 12th Edition, Charles F, Lacy, et al.2003
Product information (Intragam).
28
DRUG Hydrocortisone Methylprednisolone Dexamethasone sodium phosphate
STRENGTH/UNIT
100mg 1gm (Solu-Medrol) 8mg/2ml
STORAGE Below 25˚C Below 25°C Below 25˚C, Protect from light.
RECONSTITUITION
2ml WFI Reconstitute with the diluent (15.6ml
WFI+ Benzyl alcohol) providedAlready in solution
STABILITY AFTER RECON-
STITUITION
Use immediately after reconstitute
48 hours at temperature below 25°CNA
DILUENTS FOR INFUSION
D5%
NS
IV infusion: Reconstituted solution is then further
diluted to 1mg/ml
D5%
NS
D5%
NS
IV infusion: Dilute content of vial with 50-100ml of diluents
Diluted solution is stable for 24 hours in room temperature or 2
days in fridge
METHOD OF ADMINISTRATI
ON
IM
IV injection: Over 30 seconds to several
minutes depending on the dose
IV infusion: Over 20 to 30 minutes
IM
IV bolus: The reconstitued solution can be given undiluted. Preferred for
emergency. Only for low dose (<125mg) - over 5 to 15 minutes and moderate dose (below 250mg) - over
15 to 30 minutes. Maximum concentration: 125mg/ml
IV infusion : Dilute the reconstitued solution with D5% or NS. For high dose (more than 250mg) - over at
least 30 minutes. Dose of more than 1 gm - over 1 hour
Special notes: For acute spinal cord injury, start with IV bolus. After 45
minutes pause, followed by IV infusion of 5.4mg/kg/hour for 23
hours.
IM
IV injection: Administer as IV bolus over 5-10 minutes or can be administered through tubing
IV infusion: Of diluted solution
REMARKS none Rapid IV bolus injection is associated with high incidence of
perianal discomfort
REFERENCES
1.Product information ( Stricort 100mg)
2.Lexi-Comp's Drug Information Handbook, 12th Edition, Charles F, Lacy, et al.2003
3.British National Formulary 56
1. Product information (Solumedrol)2. Lexi-Comp's Drug Information
Handbook, 12th Edition, Charles F, Lacy, et al.2003
3. Britisn National Formulary 564. Micromedex Healthcare series.
1. Product information (Penatone Injection).2. British National Formulary 563. Micromedex Healthcare series.4. Lexi-Comp's Drug Information
Handbook, 13th Edition, Charles F, Lacy, et al.2005
29
DRUG Vitamin K (Phytomenadione)Tranexamic acid Sodium bicarbonate
STRENGTH/UNIT 10mg/ml (Kisan) 1g/10ml 8.4% (10mmol/10ml)
STORAGE Below 25˚C. Protect from light. Between 15˚C to 30˚C. Protect from light.
Below 25˚C. Protect from light.
RECONSTITUITION Aiready in solution Aiready in solutionAiready in solution
STABILITY AFTER RECONSTITUITION
NA NA NA
DILUENTS FOR INFUSION
NS
D5%
NS
D5%
WFI
NS
D5%
S/C: Dilute to isotonicity (1.5%) by adding 1ml of 8.4% solution into 4.6ml WFI or NS
or D5%
METHOD OF ADMINISTRATION
IM
Slow IV: Reserved for potentially fatal haemorrhage. Maximum per dose-20 mg and maximum total doses - 40mg.
IV injection at rate not exceeding 1mg/minute.
IV infusion
S/C
Slow IV: Do not inject more rapidly than 1ml/min
IV continous infusion: eg. Local fibrinolysis - 25 to 50mg/kg over 24 hours or post operation on heart -1mg/kg/hour for 5 to 6
hours.
IV: of undiluted solution. Rate not exceeding 10mEq/minute (equivalent to 10ml/minute)
IV: of diluted solution
S/C: Of diluted to 1.5% solution.
REMARKS
Injectable solution may be given orally, undiluted.
Sodium bicarbonate solution 8.4% contains 1 mEq/ml
bicarbonate (and sodium)
REFERENCES
1. Product information ( Kisan 10mg/ml)
2. British National Formulary 56
3. Lexi-Comp's Drug Information Handbook, 12th Edition, Charles F, Lacy, et al.2003
4. Micromedex Healthcare series
1. Product information ( Tren Injection)
2. British National Formulary 563. Lexi-Comp's Drug Information
Handbook, 12th Edition, Charles F, Lacy, et al.2003
4. Micromedex Healthcare series5. Martindale 32nd Edition
1. Product information ( Sodium Bicarbonate 8.4% injection)
2. Lexi-Comp's Drug Information Handbook, 12th Edition, Charles F, Lacy, et al.2003
3. Micromedex Healthcare series
30
DRUG Magnesium SulphateNimodipine
STRENGTH/UNIT 2.465 g/ 5ml 10mg/50ml (Nimotop)
STORAGE Below 25˚C. Below 30˚C.
RECONSTITUITION Aiready in solution Already in solution
STABILITY AFTER RECONSTITUITION
NA N/A
DILUENTS FOR INFUSION
NS
D5%
Lactated Ringer
IV: 1 ampoule (5ml) diluted with at least 7.5ml of compatible solution
IM: dilution is not required but each ampoule (5ml) can be diluted with 5ml of
compatible solution.
Solution is for direct infusion. See Method Of Administration
METHOD OF ADMINISTRATION
IM: of undiluted or diluted solution.
IV bolus: of diluted solution at rate not exceeding 150mg/minute
IV infusion: rate not exceeding 2g/hour
500mg MgSO4 = 4.06 mEq Mg = 49.3 mg elemental Magnesium
IV infusion: administer as continous IV infusion via CENTRAL catheter using infusion pump. It
should be given via three-way stopcock together with 40ml/hr of either NS or D5% or
Lactated Ringer.
Solution must not be added to an infusion bag or bottle.
Nimodipine is absorbed by PVC so the PE tube provided must be used.
REMARKSMannitol, human albumin or blood are suitable
for co-infusion
REFERENCES
1. Product information ( Magnesium Sulphate Concentrated Injection)
2. British National Formulary 563. Lexi-Comp's Drug Information
Handbook, 12th Edition, Charles F, Lacy, et al.2003
4. Micromedex Healthcare series5. Martindale 32nd Edition
1. Product information (Nimotop)2. British National Formulary 56.
31
2.1.10 Muscle Relaxant
DRUG SuxamethoniumRocuronium Pancuronium
STRENGTH/UNIT 100mg/ 2ml25mg/ 2.5 ml (Esmeron)
50mg/ 5ml
4mg/ 2ml (Pavulon)
STORAGE
Between 2°C to 8°C. Protect from light
Multiple-dose vial solution are stable at room temperature for 14
days
Between 2°C to 8°C. Protect from light.
Between 2°C to 8°C.
RECONSTITUITION Already in solution Already in solutionAlready in solution.
STABILITY AFTER RECONSTITUITION
NA NA N/A
DILUENTS FOR INFUSION
NS
D5%
Normally prepared as 1-2mg/ ml solution
NS
D5%
WFI
Dilute to a concentration of 0.5mg/ ml or 2mg/ml. Up to
5mg/ml.
NS
D5%
METHOD OF ADMINISTRATION
IM: Total dose not exceeding 150mg
IV injection: over 10 to 30 seconds. Without dilution
IV infusion: Ranged from 0.5 mg-10mg/ minute. Normally at the rate
of 2.5-4.3mg/ minute.
IV bolus: of indiluted
IV infusion
IV bolus: of the undiluted solution.
Can be administered through the line of a
running infusion.
IV infusion.
REMARKSSuxamethonium Chloride =
Succinylcholine chlorideIf stored at room temperature,
rocuronium should be used within 60 days
REFERENCES
1. Product information ( Suxamethonium Chloride - Fresinius Injection).
2. British National Formulary 563. Lexi-Comp's Drug Information
Handbook, 12th Edition, Charles F, Lacy, et al.2003
4. Micromedex Healthcare series
1. Product information (Rocuronium bromide
Injection - Esmeron).2. British National
Formulary 563. Lexi-Comp's Drug
Information Handbook, 12th Edition, Charles F, Lacy, et al.2003
4. Micromedex Healthcare series
1. Product information (Pavulon).
2. Lexi-Comp's Drug Information Handbook, 12th Edition, Charles F, Lacy, et al.2003
3. Micromedex Healthcare series
32
DRUG AtracuriumVecuronium
STRENGTH/UNIT
25mg/ 2.5ml
50mg/ 5ml
4mg (Norcuron)
10mg
STORAGE Between 2°C to 8°C. Protect from light. Below 25°C. Protect from light.
RECONSTITUITION Already in solution
Norcuron 4mg: with 1ml WFI (to make 4mg/ml solution) or with 4ml WFI (to
make1mg/ml solution)
Norcuron 10mg: with 5ml WFI (to make 2mg/ml solution) or with 10ml WFI (to make
1mg/ml solution)
STABILITY AFTER RECONSTITUITION
NA12 hours at 15°C to 25°C. But product
leaflet recommends to discard any unused portion.
DILUENTS FOR INFUSION
NS
D5%
Solution may be prepared in a range of 0.2mg/ml to 5mg/ml. Common as 0.2mg/ml
and 0.5mg/ml.
Stability: 24 hrs in NS, 8 hrs in D5% at 30°C
D5%
NS
Dilute reconstituted vial to 0.1-0.2mg/ml.
METHOD OF ADMINISTRATION
IV injection: of indiluted
IV infusion
IV bolus: of reconstituted solution
IV infusion: of diluted solution. Concentration of 1mg/ml may be used for
IV infusion in fluid-restricted patient
REMARKSNot for IM due to tissue irritation.
REFERENCES
1. Product information ( Atralex Injection).2. British National Formulary 563. Lexi-Comp's Drug Information
Handbook, 12th Edition, Charles F, Lacy, et al.2003
4. Micromedex Healthcare series
1. Product information (Norcuron).2. British National Formulary 563. Lexi-Comp's Drug Information
Handbook, 12th Edition, Charles F, Lacy, et al.2003
33
2.1.11 Respiratory
DRUG Potassium chloridePralidoxime Salbutamol
STRENGTH/UNIT 10% W/V, 10ml500mg/20ml (Pampara) 0.5mg/ml
5mg/5ml
STORAGE Below 25˚CBelow 28˚C, Protect from light,
Below 30˚C, Protect form light
RECONSTITUITION Already in solution Already in solutionAlready in solution
STABILITY AFTER RECONSTITUITION
NA NA NA
DILUENTS FOR INFUSION
NS (for the treatment of hypokalemia)
Maximum concentration recommended for peripheral
line is 6g/L. (can dilute up to 3 gm KCL in 500ml NS).
For fluid restricted patient with central line, maximum
concentration recommended is 11g/L.
For IV intermittent: as 5% to 10% solution (the product is 2.5% in strenght, so can be
readily administered)
For IV infusion: Dilute in 100ml NS
NS
D5%
WFI
WFI can be used to dilute Ventolin 0.5mg/ml
to facilitate injection
IV infusion: Dilute 5mg/5ml salbutamol in 500ml Ns or D5% to produce 10mcg/ml
solution.
METHOD OF ADMINISTRATION
IV infusion (Maximum rate is 3 gm/hour)
IV intermittent : over 5 to 10 minutes.
IIV infusion: over 15 to 30 minutes
S/C
IM
S/C
IM
IV slow bolus
IV infusion
REMARKSUse with caution in patients
with cardiac diseaseMaximum recommended daily
dose is 12 gm
REFERENCES
1. Product information ( Potassium chloride 10% W/v 10ml).
2. Micromedex Healthcare series.
3. British National Formulary 56.
4. Lexi-Comp's Drug Information Handbook, 12th Edition, Charles F, Lacy, et al.2003
1. Product information (Pampara injection).
2. Micromedex Healthcare series.
3. British National Formulary 56.
4. Lexi-Comp's Drug Information Handbook, 12th Edition, Charles F, Lacy, et al.2003
1. Product information (Ventolin injection).
2. Micromedex Healthcare series.
3. British National Formulary 56.
34
DRUG TerbutalineAminophylline
STRENGTH/UNIT 0.5mg/ml250mg/5ml
STORAGE Below 25°CBelow 25°C
RECONSTITUITION Already in solution Already in solution
STABILITY AFTER RECONSTITUITION
N/A NA
DILUENTS FOR INFUSION
D5%
NS
For premature labour: Dilute in D5% to a concentration 100mcg/ml and give
via syringe pump. If pump not available, dilute to a concentration of
10mcg/ml.
NS
D5%
Dilute with NS to a concentration of 1mg/ml. Max concentration is 25mg/ml
METHOD OF ADMINISTRATION
S/C: For bronchodilation.
IV infusion: For tocolysis acute (unlabeled used), duration of infusion is
at least 12 hours.
IV slow injection
IV infusion: LD: Over 20-30 minutes. Rate not exceeding 25mg/minute.
REMARKSDose of aminophylline = dose of
theophylline/ 0.8
REFERENCES
1. Product information (Terbutaline injection- Baltic).
2. Micromedex Healthcare series.
3. British National Formulary 56.4. Lexi-Comp's Drug Information
Handbook, 12th Edition, Charles F, Lacy, et al.2003
1. Product information (Aminophyllin IV-Fresenius injection).
2. Micromedex Healthcare series.3. British National Formulary 56.4. Lexi-Comp's Drug Information
Handbook, 12th Edition, Charles F, Lacy, et al.2003
35
2.1.12 Sedative
DRUG FentanylDexmedetomidine
HydrochloridePropofol
STRENGTH/UNIT 0.1mg/2ml200mg/2ml (Precedex) 200mg/20ml (Fresofol 1%
emulsion)
STORAGE
Below 25°C. Protect from light.
Between 15°C to 30°C . Below 25°C. Do not freeze. Shake before use.
RECONSTITUITION Already in solution Already in solutionAlready in solution
STABILITY AFTER RECONSTITUITION
NAAfter dilution, store at 2-8°C
and use within 24 hours.NA
DILUENTS FOR INFUSION
NS
D5%
NS
Must be diluted before use for both LD and maintenance
dose. Dilution is the same for LD and MD: 2ml of
dexmedetomidine add into 48ml NS.
NS
D5%
Minimum concentration is 2mg propofol /1ml diluent. Do not dilute less than 2mg/ml. Dilute in glass bottle. Shake
before use
Also compatible with lidocaine 1% (not exceeding
20mg lidocaine /200mg propofol)
METHOD OF ADMINISTRATION
IV slow over 1-2 minutes
IV infusion
IM
IV infusion (using a controlled infusion device)
LD: 1mcg/kg over 10 minutes followed by infusion of 0.2-
0.7mcg/kg/hr (titrate accordingly)
IV bolus
IV infusion
For IV infusion, both diluted or undiluted solution can be
used.
REMARKS
Muscle rigidity may occur with rapid IV
administration
Contious infusion not to exceed 24 hours. Safety and effectiveness have not been
evaluated in infusions over 24 hours.
Duration of administration must not exceed 7 days.
REFERENCES
1. Product information (Fentanyl Citrate Injection).
2. Britisn National Formulary 52
3. Micromedex Healthcare series.
4. Lexi-Comp's Drug Information Handbook, 12th Edition, Charles F, Lacy, et al.2003
1. Product information (Precedex)
2. Micromedex Healthcare series.
3. Lexi-Comp's Drug Information Handbook, 13th Edition, Charles F, Lacy, et al.2005
1. Product information (Fresofol 1% MCT/LCT emulsion).
2. Britisn National Formulary 52
3. Micromedex Healthcare series.
36
DRUG MidazolamMorphine
STRENGTH/UNIT 5mg/ml , 15mg/3ml (Dormicum)10mg/ml
STORAGE Room temperatureBelow 25°C. Protect from light.
RECONSTITUITION Already in solution Already in solution.
STABILITY AFTER RECONSTITUITION
NA NA
DILUENTS FOR INFUSION
NS
D5%
Concentration of dilution: 15mg midazolam per 100-1000ml diluent (source: Dormicum product insert)
Concentration of dilution: The 5mg/ml formulation should be
diluted to a concentration 0.5mg/ml (source: Micromedex)
D5%
Usual concentration for IV infusion is 0.1-1mg/ml
For IV slow, a strenght of 2.5 to 15mg may be diluted in 4-5ml WFI
METHOD OF ADMINISTRATION
IV bolus (at a rate of 1mg over 30 seconds. Elderly: dose of 2-2.5mg
over 5-10 minutes)
IV infusion
IM
IV slow (over 2-5 minutes)
IV infusion
IM
S/C
REMARKSNone Rapid S/C administration may cause local
tissue irritation
REFERENCES
1. Product information (Dormicum).2. Britisn National Formulary 523. Micromedex Healthcare series.4. Lexi-Comp's Drug Information
Handbook, 12th Edition, Charles F, Lacy, et al.2003
1. Product information (Dormicum).2. Britisn National Formulary 523. Micromedex Healthcare series.4. Lexi-Comp's Drug Information
Handbook, 12th Edition, Charles F, Lacy, et al.2003
37
2.2 Deep Vein Thrombosis Prophylaxis
2.2.1 INTRODUCTION
The occurrence of deep vein thrombosis in hospitalised patients is depending upon various risk factors. In orthopaedic patients undergoing surgery, up to 76.5% incidence of DVT has been reported.1 Meanwhile approximately 10 to 40% among medical or general surgical patients and 40 to 60% following major orthopedic surgery in patient without the prophylaxis confirm has hospital-acquired DVT.2 One quarter to one third of these thrombi involve the proximal deep veins, and these thrombi are much more likely to produce symptoms and result in pulmonary embolism (PE). 3In a study of 51,645 hospitalized patients, the prevalence of acute PE was 1%, and PE was believed to have caused or contributed to death in 37% of these cases4.
To prevent the occurrence of DVT and subsequent pulmonary embolism which can be fatal, thromboprophylaxis is recommended. The 2 methods of prophylaxis are either pharmacological or mechanical and is describe under method prophylaxis.
2.2.2 DEFINITION
Deep vein thrombosis (DVT) is defined as a clot that occurs in the deep veins of the extremities. Further subclassifications include symptomatic versus asymptomatic and proximal (above the knee) versus distal (below the knee). 5
Pulmonary embolism is defined as being a clot usually originating from a DVT that travels to the pulmonary vasculature where it becomes an embolism and thereby impedes gas exchange distal to embolism. 5
Venous thromboembolism (VTE) is defined as as event due to thrombosis of a vein and includes DVT or PE. 5
Thrombophlebitis is the inflammation of a vein around which a DVT has occurred. This condition can be painful and chronic. This term is synonymous with postphlebitic or postthrombotic syndrome. 5
Immobilized : restricted to bed or chair with no instruction or ability to ambulate. 5
38
2.2.3 INDICATION OF PROPHYLAXIS
All adult inpatient will be assessed for their risk of VTE that include the background history and acute or subacute precipitating factors which shown in table 1. Clinicians will need to use their own judgment in addition to the guideline to determine the best method of reducing the risk of VTE in each individual patient. It is combined responsibility of the physician and other healthcare staff including clinical pharmacist and nursing staff to ensure all patients at risk for VTE have received appropriate prophylaxis when needed.1
Table 1 : Venous Thromboembolism – Risk Factors 6
Background Factors Age
Marked obesity ( BMI >30 )
Immobility ( bed rest longer than 4 days. )
Pregnancy
Puerperium
High dose estrogens
Previous DVT or PE
Thrombophilia - Deficiency of antithrombin, protein-C or protein-S - activated protein-C resistance - antiphospholipid antibody or
Lupus anticoagulant.
Precipitating Factors Trauma or surgery, especially of pelvis, hip, lower limb.
Malignancy , especially pelvic , abdominal , metastatic
Heart failure
Recent myocardial infarction
Paralysis of lower limb(s)
Severe infection
Inflammatory bowel disease
Nephrotic syndrome
Polycythemia
Paraproteinemia
39
Paroxysmal nocturnal hemoglobinurea
Bechet’s disease.
Burns
a. Low-risk groups 1
patients with minor trauma or minor medical illness at any age, in the absence of thrombophilia, previous DVT or PE.
patients undergoing minor surgery (duration under 30 minutes) at any age, in the absence of other risk factors.
patients undergoing major surgery (duration over 30 minutes) who are aged under 40 years and have no additional risk factors.
b. Moderate risk groups 1
patients undergoing major general, urological, gynaecological, cardiothoracic, vascular, or neurological surgery who are aged > 39 years or with other risk factors.
patients immobilised with acute medical illness. major trauma minor surgery or trauma or illness in patients with previous deep
vein thrombosis, pulmonary embolism, or thrombophilia.
c. High-risk groups1
fracture or major orthopaedic surgery of pelvis, hip, or lower limb. major pelvic or abdominal surgery for cancer. major surgery, trauma, or illness in patients with previous deep vein
thrombosis, pulmonary embolism, or thrombophilia. lower limb paralysis (for example, hemiplegic stroke, paraplegia). critical lower limb ischaemia or major lower limb amputation.
2.2.4 METHODS OF PROPHYLAXIS
There are two method of prophylaxis of DVT, which are 1
a. Pharmacological methods :
40
- Standard heparin (usually in low dosage)- Low molecular weight heparins- Oral anticoagulant such as warfarin- Aspirin
b. Mechanical methods - increase venous outflow and/or reduce stasis within the leg veins :
- Graduated compression stockings (GCS) - Intermittent pneumatic compression (IPC) devices - Venous foot pump (VFP)
* Below show the summary table for recommendation of method prophylaxis regarding the type of risk and procedure.
Table 2: Recommended DVT prophylaxis for surgical procedures and medical conditions 8
Surgery/Condition Recommended Prophylaxis
Comments
General Surgery—low-risk: minor procedures, <40 years old, no additional risks
None Early ambulation
General Surgery—moderate risk: minor procedure but with risk factor, nonmajor surgery age 40-60 with no risks, or major surgery <40 years with no risks
Heparin , LMWH , ES, or IPC
Heparin 5000 – 7500 iu bd
OR
LMWH (daily dose according to manufacturer) with IPC or ES.
* LMWH and heparin has comparible efficacy for DVT prophylaxis.8,9 The clinical advantages of LMWH over LDUH is its once-daily administration and the lower risk of heparin-induced thrombocytopenia (HIT), BUT LMWH is more costly.10
General Surgery—high risk: non-major surgery over age 60 or over age 40 with risks.
Heparin , LMWH Heparin 5000 – 7500 iu tds
OR
LMWH (daily dose according to manufacturer)
41
Surgery/Condition Recommended Prophylaxis
Comments
*In high-risk general surgery patients, higher doses of LMWH provide greater protection than lower doses.3
General Surgery—very high risk: major surgery over age 40 plus prior VTE, cancer or hypercoagulable state
LMWH combined with ES or IPC
LMWH (daily dose according to manufacturer
*May consider postdischarge LMWH or perioperative warfarin
Elective Hip Replacement
LMWH or warfarin May combine with ES or IPC; start LMWH 12 hours before surgery, 12-24 hours after surgery, or 4-6 hours after surgery at half the dose for initial dose for at least 10 days. Start warfarin preoperatively or immediately after surgery, target INR 2. 0-3. 0. Extended prophylaxis is recommended for up to 28 to 35 days after surgery. 8
Elective Knee Replacement
LMWH or warfarin Both LMWH and warfarin resulted in significantly fewer proximal DVTs compared with LDUH or IPC (p<0.006 for each comparison).11 Pooled data from 5 trials that directly compared LMWH with warfarin showed rates of proximal DVT of 3.4% and 4.8%, respectively.8
Hip Fracture Surgery LMWH or warfarin
Neurosurgery IPC, LDUH or LMWH
Start LMWH post-surgery
Trauma LMWH with ES or IPC
If high risk of bleeding, may use ES and/or IPC alone.
Acute Spinal Cord Injury
LMWH Continue LMWH during rehabilitation or convert to warfarin (target INR 2.5)
Ischemic Stroke LDUH, LMWH If contraindication to anticoagulant, use ES or IPC.
Two studies directly comparing LDUH (5000 U three times daily) to LMWH (enoxaparin 40 mg once daily), using venography for diagnosis, found greater reduction in DVT with LMWH.8
A meta-analysis of studies of hospitalized patients with conditions other than myocardial infarction or ischemic stroke given VTE prophylaxis with unfractionated or low molecular weight heparin
42
Surgery/Condition Recommended Prophylaxis
Comments
showed no significant difference was found between LMWH and LDUH in incidence of DVT, PE, or mortality; however, major hemorrhage was lower with LMWH than with LDUH (RR 0.48, 95% CI: 0.23-1.00).12
ES : elastic stockings LDUH: low-dose unfractionated heparin
INR : international normalized ratio LMWH: low molecular weight heparin
IPC : intermittent pneumatic compression VTE : venous thromboembolis.
* warfarin is hardly use in critical care due to administration problem, thus it is not recommended as first line
43
Table 3: MEDICATIONS USED TO PREVENT DVT
Medication Class Unfractionated heparin
Low molecular weight heparin
Medication Heparin Enoxaparin Fondaparinux
Dosage Moderate risk
SC Heparin 5000units twice daily
High risk
SC Heparin 5000units 8 hourly
20 mg SC daily
(moderate risk surgery) OR
40 mg SC daily
(can go up to 30 mg SC q12h for high risk general surgery, major trauma or acute spinal cord injury) 14
Morbid obese (> 150 kg): can increase to SC 60 mg 12 hourly 13
Dose renal adjustment ( CrCL < 30 ml/min )14
Prophylaxis dose :
SC 20 mg daily
Therapeutic dose : 1 mg/kg daily
Adult (>50 kg)
2.5 mg SC once daily
Initiate dose after hemostasis has been established, 6 – 8 hours postoperatively. 16
Duration 5 days OR until hospital discharge if this is earlier than 5 days.
Surgical case14
7 – 10 days or longer if there is a risk of DVT and until patient ambulatory.
Medical case14
6 – 14 days
Orthopedic and abdominal surgery15
5 – 9 days after surgery.
In patient undergoing hip fracture surgery 9 – 24 days ( consider the risk )
Medical patients with DVT risk
Duration of 6 to 14 days .
Monitoring Platelet count
Recommendation : the platelet count is monitored in patients receiving heparin for more than five days,
Platelet count
Risk of thrombocytopenia (happen between 5th and the 21st day following the beginning of enoxaparin therapy.) If it significant decrease (30 to 50% of initial count),
Full blood count, serum creatinine, and occult blood testing of stools are recommended. PT and APTT are insensitive measures. 16
Medication Class Unfractionated heparin
Low molecular weight heparin
Medication Heparin Enoxaparin Fondaparinux
and that heparin is stopped immediately if thrombocytopenia occurs.
the treatment should be discontinued and switch to other alternative.
Contraindication16 - bleeding disorders - a history of allergy either to enoxaparin, heparin or other low molecular
weight heparin 1
- Hypersensitivity to fondaparinux
- severe renal impairment (CLCr < 30 mL/min)
- body weight < 50 kg (prophylaxis)
- active major bleeding
- bacterial endocarditis
- thrombocytopenia
Precaution16 Hypersensitivity to drug.
May cause thrombocytopenia. Discontinue and consider alternative if platelet are < 100,000/mm3 or /and thrombosis develop.
In neonate suggest use preservative free as some preparation content large amount benzyl alcohol (> 100 mg/kg/day) that can cause fatal toxicity (gasping syndrome).
Recent or anticipated neuraxial anesthesia (epidural or spinal anesthesia) are at risk of spinal or epidural hematoma and subsequent paralysis. Consider risk versus benefit.
Risk of thrombocytopenia
Caution in patient with renal failure; dosage adjustment need for ClCr < 30 mL/min.
Same with enoxaparin
Not to be use interchangeable (unit-for-unit) with heparin, LMWH or heparinoids.
Use caution in patient with moderate renal dysfunction
Patient with severe hepatic impairment with elevation in prothrombin time.
Not recommended prior to and during percutaneous coronary prevention (PCI) for reperfusion in STEMI patients, due to
Medication Class Unfractionated heparin
Low molecular weight heparin
Medication Heparin Enoxaparin Fondaparinux
increasesd risk for guiding catheter thrombosis.
Avoid administration 24 hours before and 48 hours after coronary artery bypass graft (CABG) surgery.
Side effect Thrombocytopenia occurs in about 3-4% of patients given prophylactic heparin.
Allergic reactions (including skin necrosis), raised serum transaminase concentrations, and osteoporosis with long term use (especially in pregnancy) 1
1 to 10% risk16
CNS : fever, confusion, pain
Dermatology : erythema, bruising, hematoma at site of injection
GI : nausea, diarrhea
Hematologic : hemorrhage, thrombocytopenia
Hepatic : ALT/ALP increase
> 10%
- Fever, nausea, anemia16
1- 10%
Edema, hypotension, insomnia, dizziness, headache, confusion, rash, purpura, bullous eruption, hypokalemia, constipation, vomiting, diarrhea, dyspepsia, moderate thrombocytopenia, increase in liver enzyme. 16
Drug interaction Increased effect/toxicity if use with anticoagulant, thrombolytics, dextran and drug affect platelet function ( eg aspirin, NSAIDs, dipyridamole, ticlopidine, clopidogrel), cephalosporins which contain MTT chain and parenteral penicillins (may inhibit platelet aggregation). 16
Decreased effect if use with Nitroglycerin (IV) that may occur in high dosages. 16
Increased effect/toxicity if use with anticoagulant, thrombolytics, dextran and drug affect platelet function ( eg aspirin, NSAIDs, dipyridamole, ticlopidine, clopidogrel), cephalosporins which conatain MTT chain and parenteral penicillins (may inhibit platelet aggregation). 16
Increased effect/toxicity if use with anicoagulants, antiplatelet agents, drotecogin alfa, NSAIDs, salicylates and thrombolytic agents. 16
Medication Class Unfractionated heparin
Low molecular weight heparin
Medication Heparin Enoxaparin Fondaparinux
Special instruction
There is an increased risk of wound haematomas, which can be minimised by avoiding injections close to wounds. 1
To avoid loss of medicinal product when using prefill syringe do not expel the air bubble from the syringe before the injection. 15
IV administration (first dose in STEMI patients only) either directly or use small volume (25-50 ml) 0.9% saline minibag and administer through existing IV line over 1 -2 minute. Then flush with saline after injection to ensure all medicinal product is administered.15
References
1. College of surgeons Malaysia. 1999 . Consensus On Prophylaxis Of Venous Thromboembolism. Academy of medicine Malaysia.
2. Wiig, JN, Solhaug, JH, Bilberg, T, et al 1995. Prophylaxis of venographically diagnosed deep vein thrombosis in gastrointestinal surgery: multicentre trials 20 mg and 40 mg enoxaparin versus dextran. Eur J Surg 161,663-668
3. Geerts WH, GP, Pineo Heit JA, Bergqvist D, Lassen MR, Colwell CW, & Ray JGl. 2009. Prevention of venous thromboembolism. Chest seventh ACCP Consensus Conference on Antithrombotic Therapy.
4. Stein PD, Henry JW. 1995. Prevalence of acute pulmonary embolism among patients in a general hospital and at autopsy. Chest 108,978-981
5. Thambi M, Galanter B. 2006. VTE/Deep vein thrombosis prophylaxis. University of Illinios Medical Centre.
6. Thromboembolic Risk Factors ( THRIFT ) Consensus Group. Risk of and prophylaxis for venous thromboembolism in hospital patients. BMJ 1992; 305: 567 - 74.
7. Kleinbart J, Williams MV and Rask KR. Chapter 31. Prevention of Venous Thromboembolism Emory University Schools of Medicine and Public Health. www.ahrg.gov.
8. Geerts WH, Heit JA, Clagett GP, Pineo GF, Colwell CW, Anderson FA, et al. 2001. Prevention of venous thromboembolism. 156S-158S. Chest Sixth ACCP Consensus Conference on Antithrombotic Therapy.
9. Palmer AJ, Schramm W, Kirchhof B, Bergemann R. 1997.Low molecular weight heparin and unfractionated heparin for prevention of thrombo-embolism in general surgery: a meta-analysis of randomised clinical trials. Haemostasis 27:65-74.
10. Warkentin, TE, Levine, MN, Hirsh, J, et al 1995 Heparin-induced thrombocytopenia in patients treated with low-molecular-weight heparin or unfractionated heparin. N Engl J Med 332,1330-1335
11. Freedman KB, Brookenthal KR, Fitzgerald RH, Jr. , Williams S, Lonner JH. 2000. A meta-analysis of thromboembolic prophylaxis following elective total hip arthroplasty. J Bone Joint Surg 82-A:929-938.
12. Mismetti P, Laporte-Simitsidis S, Tardy B, Cucherat M, Buchmuller A, Juillard-Delsart D, et al. 2000. Prevention of venous thromboembolism in internal medicine with unfractionated or low-molecular-weight heparins: a meta-analysis of randomised clinical trials. Thromb Haemost 83:14-19.
13. Duplaga BA, Rivers CW, Nutescu E. 2001. Dosing and monitoring of low-molecular-weight heparins in special populations. Pharmacotherapy 21:218-34.
14. Enoxaparin (Clexane) product leaflet, Sanofi-Aventis15. Fondaparinux (Arixtra) product leaflet, GloxiSmithKline16. Drug Information Handbook 17th Edition. 2008. Lexi Comp. United States
Author
1. Dr Arbayah Rais, Head of Dept Anesthetist, Selayang Hospital2. Fadilah Othman, Chief Pharmacist (Senior Clinical Pharmacist), Pharmacy Dept. Selayang Hospital3. Dr Haslinda Anesthetist ICU, Selayang Hospital4. Norliza Mat Ariffin, Pharmacist, Pharmacy Dept. Selayang Hospital5. Masrahayu Moydin, Clinical Pharmacist, Pharmacy Dept. Selayang Hospital
2.3 STRESS ULCER PROPHYLAXIS
2.3.1 INTRODUCTION
Stress-related mucosal disease (SRMD) is an acute condition which erosion of the gastric mucosa occur secondary to a physiologic stress.1 It can be manifestation by bleeding which can be considered equivalent to overt gastroduodenal bleeding that result in hemodynamic instability (measured through a drop in blood pressure or an increase in heart rate) and subsequent need for red blood cell transfusions or surgical intervention of the gastric ulcers.2,
3
The etiology of stress-related mucosal disease (SRMD) or stress related ulcer is multifactorial and complex. Patients with head injury or burns represent those at highest risk of SRMD, likely due to gastric acid secretion resulting from vagal stimulation. Other critically ill patients appear to develop SRMD as a result of diminishes mucosal defenses and hypoperfusion. 4 The longer the gastric pH remains below 4 the greater the risk of hemorrhage. Clinical trials have estimates clinically important bleeding occur in 3% to 6% of intensive care unit (ICU) patients with the most common risk factors ( ie those who are ventilated or have coagulopathy). 5, 6 Work by Cook and colleagues ascribed the risk of overt bleeding to be 4.4 % and clinically significant bleeding to be 1.5%.5 There is a strong relationship between duration of mechanical ventilation, duration of intensive care stay and incidence of ulceration: patient without coagulopathy and mechanical ventilation had an incidence of bleeding of 0.1%. 5
2.3.2 INDICATION OF PROPHYLAXIS
a. High risk patient - All patients to receive prophylaxis- mechanical ventilation > 48 hours- coagulopathy- History of previous GI hemorrhage- Current outpatient PUD treatment or prophylaxis- Central nervous system (CNS) injury ( subarachnoid hemorrhage (SAH) /
cardiovascular attack (CVA) – hemorrhagic or ischemic)- Sepsis with or without organ dysfunction- Vasopressor/inotropic prescription
b. Moderate risk patient - consider prophylaxis- Chronic non steroidal antiinflamatory drug (NSAID) or aspirin use- High dose prolonged steroid treatment- ICU stay > 10 days
c. Low risk patient or tolerating per oral diet/Full gastric enteral feeds – No prophylaxis or discontinue prophylaxis
2.3.3 NUTRITIONAL GUIDELINE AND STRESS ULCERS
The administration of gastric nutrition reduces, but does not eliminate the risk of GI hemorrhage. Any patient predicted to be mechanically ventilated > 48 hours and without a contraindication to gastric enteral nutrition, is encouraged to have nasogastric nutrition initiated within 72 hours of admission when a nasoenteric tube is in situ.
2.3.4 PROPHYLAXIS SMRD AGENT
Many agents are available for use in patients at risk for stress-related mucosal disease. These agents include histamine type 2 receptor antagonists (H2RAs), proton pump inhibitors (PPIs), sucralfate, antacids, and prostaglandin analogs. Common products, usual dosage ranges, and considerations are shown in the Table 1.
Current studies reveal that histamine type 2 receptor antagonists are the most widely used first-line agents; however proton pump inhibitors are widely used and their diverse routes of administration and favorable side effect profile are desirable features.13
The largest randomized controlled trial to date involved 1200 mechanically ventilated patients and determined that ranitidine was significant better than sucralfate for reducing clinically important SRMD bleeding ( odds ration [ OR]: 0.44; 95% confidence interval [CI] : 0.21-0.92). 7
Multiple studies have examined the effects of proton inhibitors (PPIs) in ICU patients, but all have been small and many measured intermediate endpoints. 7
Some studies have been observational with PPI therapy alone, whereas others have compared PPI therapy with placebo or histamine-2 receptor antagonis (H2RA) therapy. Conclusions that can be gathered currently are that acid suppression achieved with PPI therapy is, on average, superior to that achieved with H2RAs, and that the clinical benefit of PPIs for reducing SRMD bleeding appears to be at least similar to that achieved with H2RAs. Current trends indicate increasing awareness and use of acid suppression in the population, with H2RAs representing first-line agents and PPIs gaining use.
The most common complication of stress ulcer prophylaxis is pneumonia. 10 The hypothesis is based upon the concept that higher pH relates to overgrowth of gastric microbes and leads to upper tracheal colonization. This concept partnered with microspiration of intubated patients lying supine may increase the nosocomial pneumonia rate. The ability to reliably maintain a pH < 4 will decrease the rate of pneumonia. Several studies comparing the pneumonia rate when comparing sucralfate, antacids and H2RA show ether improvement or insignificant trends toward decreasing rate with sucralfate. 10 However, due to the
current incidence of outpatient ulcer and reflux reduction therapy and the complexity of administering sucralfate, overall benefit appears to be small.
Table 1: MEDICATION USED TO PREVENT SRMD 14
Medication class Histamine Type 2 Receptor
Antagonists
Proton pump inhibitors
Medication Ranitidine Esomeprazole Omeprazole Pantoprazole
Dosage Adult
Oral : 150 mg bd
IV : 50 mg Q8H
Adjust for creatinine clearance
(CrCl) < 50 ml/min.
Oral : 150 mg every 24 hour
IV : 50 mg every 18-24 hours; adjust dose cautiously if needed
Hemodialysis : Adjust dosing schedule so that dose coincides with the end of hemodialysis.
40 mg daily (IV, nasogastric tube, PO)
20-40 mg daily (PO, nasogastric/jejunal, duodenal tube)
40 mg daily (IV,nasogastric tube, PO)
Patient who develops significant GI hemorrhage receiving prophylaxis :
IV Omeprazole / Pantoprazole / Esomeprazole
80 mg loading dose followed by 8 mg/hr for 3 days
- consider endoscopic evaluation
- When no evidence of bleeding for 24 hours, convert to intermittent dosing schedule.
*Defined as bleeding that requires transfusion, causes hemodynamic changes and/or decrease in Hmeoglobin (Hgb) ≥ 1 gram
The result of 16 randomized, controlled trials involving a total of > 3,800 patients (1,892 receiving PPIs and 1,911 controls) suggest that bolus administration plus continuous infusion of PPIs is a more effective pharmacotherapy than bolus infusion alone in decreasing both rebleeding and the need for surgery. 11
Medication class Histamine Type 2 Receptor
Antagonists
Proton pump inhibitors
Medication Ranitidine Esomeprazole Omeprazole Pantoprazole
Monitoring AST, ALT, serum creatinine, sign and symptoms of PUD, occult blood with GI bleeding, renal function
Hypersecretory disorders
Contraindication Hypersensitivity to the component of the formulation
Precaution Use in caution in patient with hepatic impairment and renal impairment
Severe liver dysfunction may require dose adjustment
Bioavailability may increase in the elderly, Asian population, and with hepatic dysfunction
IV preparation contain edentate sodium (EDTA); use caution in patient who are at risk for zinc deficiency if other EDTA containing solution are co-administered
Side effect Arrythmias, dizziness, headache, mental confusion, rash, anemia, thrombocytopenia, leucopenia, hepatic failure and pneumonia
Headache, hypertension, pain, dizziness, flatulence, diarrhesa, constipation, urinary tract infection, anemia, pneumonia
Headache, dizziness, diarrhea, abdominal pain, pneumonia
Headache, diarrhea, flatulence, abdominal pain, abnormal liver function test
Drug interaction CYP450 effect
Increase the effect : Cyclosporine
Decrease effect
Warfarin, ketoconazole, itraconazole, cephalosporin, cycanocobalamin
CYP450 effect
Increase the effect : HMG-CoA reductase inhibitor, methotrexate, benzodiazepine, phenytoin
Decrease effect
ketoconazole, itraconazole,
CYP450 effect
Increase the effect :
HMG-CoA reductase inhibitor, Montelukast, phenytoin, warfarin, methotrexate
Decrease effect
ketoconazole, itraconazole,
Medication class Histamine Type 2 Receptor
Antagonists
Proton pump inhibitors
Medication Ranitidine Esomeprazole Omeprazole Pantoprazole
Special instruction
First line in treatment of SRMD
If patient on PPI for chronic disease (PUD treatment or prophylaxis) requiring this medication
Stability of PPIs after reconstitution
After reconstitution with 10 ml of isotonic sodium chloride solution, intravenous omeprazole / pantoprazole can be administers as a rapid injection over 2 minutes or it can be stores for up to 2 hours at room temperature.
Intravenous admixtures of pantoprazole can be prepared by mixing with 100 ml of isotonic sodium chloride solution, 5% dextrose in water, or lactated Ringer’s solution to achieve a final concentration of 0.4 mg/ml. This solution can be stored for up to 24 hours at room temperature. This admixture can be administered over 15 minutes. 12
References
1. Sesler JM. Stress-related mucosal disease in the intensive care unit: an update on prophylaxis. AACN Adv Crit Care. 2007; 18:119-126.
2. Cook DJ, Fuller HD, Guyatt GH, et al. Risk factors for gastrointestinal bleeding in critically ill patients. Canadian Critical Care Trials Group. N Engl J Med. 1994; 330:377-381.
3. ASHP Therapeutic Guidelines on Stress Ulcer Prophylaxis. ASHP Commission on Therapeutics and approved by the ASHP Board of Directors on November 14, 1998. Am J Health Syst Pharm. 1999; 56:347-379.
4. Cho CH, Koo MWL, Garg GP, et al. Stress-induced gastric ulceration: Its aetiology and clinical implications, Scand J Gastroenterol. 1992;27:257-262.
5. Cook DJ, Fuller HD, Guyatt GH, et al. Risk factors for gastrointestinal bleeding in critically ill patients. N Eng J Med. 1994;330:337-381.
6. Brown RB, Klar J, Teres D, et al. Prospective study of clinical bleeding in intensive care unit patients. Crit Care Med. 1988;16:1171-1176.
7. Cook DJ, Guyatt G, Marshall J et al. A comparison of sucralfate and ranitidine for the prevention of upper gastrointestinal bleeding in patients requiring mechanical ventilation.
8. Jung R, Maclaren R. Proton pump inhibitor for stress ulcer prophylaxis in critically ill patients. Ann Pharmacother. 2002;36:1929-1937.
9. Redbuck JA, Welage LS et al. Prevention of stress ulceration: current trends in critical care. Crit care Med. 2004;32: 2008-2013.
10. Messori A, Trippoli S, Vaiani M, Gorini M, Corrado A. Bleeding and pneumonia in intensive care patients given ranitidine and sucralfate for prevention of stress ulcer : meta analysis of randomized controlled trials. BMJ 2202;321(7269):1103-1106.
11. Morgan D. Crit care Med. 2002;30:S369-S37212. Wyeth Pharmaceutical [package insert]. Philadelphia, Pa: Wyeth laboratories;200413. Daley RJ, Rebuck JA, Welage LS, Rogers FB. Prevention of stress ulceration: current trends in
critical care. Crit Care Med. 2004; 32:2008-2013.
14. Drug Information Handbook 17th Edition. 2008. Lexi Comp. United States
Author
6. Dr Anselm Suresh Rao, Intensivist ICU, Selayang Hospital7. Wong Kok Thong, Chief Pharmacist, Pharmacy Dept. Selayang Hospital8. Fadilah Othman, Clinical Pharmacist, Pharmacy Dept. Selayang Hospital9. Zainon Abudin, Pharmacist, Pharmacy Dept. Selayang Hospital10. Siti Hajar Abdul Jalil, Pharmacist, Pharmacy Dept. Selayang Hospital11. Masrahayu Moydin, Clinical Pharmacist, Pharmacy Dept. Selayang Hospital
2.4 ANTIBIOTIC GUIDELINE FROM INFECTIONS IN INTENSIVE CARE UNITS – Adapted from National Antibiotic Guideline 2008, MOH Malaysia
Infection/ condition & Likely Organism
Suggested Treatment Comments
Preferred Alternative
A. Severe Sepsis or Septic Shock Where Site Of Infection Is Not IdentifiedSevere sepsis or septic shock
(site of infection is unknown)
Gram-negative bacilli
Gram-positive cocci
Methicillin-resistant S.aureus
Penicillin-resistant
S. pneumoniae
Ampicillin-resistant Enterococci
Candida
Cefepime 2g IV q12h;
ORPiperacillin/Tazobactam 4.5g IV q8h
PLUS OPTIONALVancomycin1 1g IV q12h
PLUS OPTIONALFluconazole 400 - 800mg IV q24h
Meropenem 1g IV q8h;
ORImipenem 500mg IV q6h
PLUS OPTIONALAmphotericin B 0.6 -1.0mg/kg IV q24h
Current evidence suggests that carbapenems, 4th generation cephalosporins or Piperacillin/ Tazobactam are equally effective in treatment of septic shock.
If melioidosis cannot be ruled out, carbapenem should be used as the empirical agent.
Empirical use of Vancomycin1 is only justified in areas with high endemic levels of MRSA or high levels of penicillin-resistant S.pneumoniae
Empirical antifungal agents should not be used on a routine basis.
Reference 1,2
B. Severe Community-Acquired Pneumonia Requiring Mechanical Ventilation
Infection/ condition & Likely Organism
Suggested Treatment Comments
Preferred Alternative
Severe community-acquired pneumonia requiring mechanical ventilation
S. pneumoniae
H. influenzae
S. aureus
K. pneumoniae
M. pneumoniae
L. pneumophilia
C. pneumoniae
*B.pseudomallei
3rd gen. Cephalosporins, e.g;
Ceftriaxone 2g IV q24h
PLUSErythromycin 500mg IV q6h
ORAzithromycin 500mg IV q24h
* If risk factors present, consider Ceftazidime (Please Refer to Page 95(LRTI))
-lactam/-lactamase inhibitors, eg;
Amoxycillin/Clavulanate 1.2g IV q8h
PLUSErythromycin 500mg IV q6h
ORAzithromycin 500mg IV q24h
Reference 3,4,5
C. Severe Nosocomial Pneumonia Requiring Mechanical Ventilation (Including Ventilator-Associated Pneumonia)
Nosocomial pneumonia requiring mechanical ventilation (including VAP)
Low risk for infection with multi-drug resistant (MDR) organisms - < 5 days
S. pneumoniae H. influenzae
S. aureus E. coli
K. pneumoniae Enterobacter spp. Proteus spp. Serratia marcescens
3rd gen. Cephalosporins, e.g;
Ceftriaxone 2g IV q24h;
OR-lactam/-lactamase inhibitors, eg;
Ampicillin/Sulbactam 1.5g IV q6h
-lactam/-lactamase inhibitors, eg;
Amoxycillin/Clavulanate 1.2g IV q8h
S. aureus is more common in diabetes mellitus, head trauma.
Monotherapy is recommended for early onset HAP/VAP/HCAP.
Reference 6,7
Infection/ condition & Likely Organism
Suggested Treatment Comments
Preferred Alternative
High risk for infection with multi-drug resistant (MDR) organisms
P. aeruginosa
Acinetobacter spp.
K. pneumoniae (ESBL)
Methicillin-Resistant S. aureus
Piperacillin/Tazobactam 4.5g IV q6h OR Cefepime 2g IV q12h
PLUSAmikacin1 15mg/kg/24h IV ORCiprofloxacin 400mg IV q8h
Cefoperazone/Sulbactam 2g IV q12h
Meropenem 1g IV q8hORImipenem 500mg IV q6h
PLUS(if MRSA is suspected)Vancomycin1 1g IV q12h
Imipenem 500mg IV q6h ORMeropenem 1g IV q8h
PLUSAmikacin1 15mg/kg/24h IV ORCiprofloxacin 400mg IV q8h
-lactam/-lactamase inhibitors, eg; Ampicillin/Sulbactam 1.5g IV q6h
Use combination therapy if MDR pathogen is suspected.
Aminoglycoside can be stopped after 5-7 days in patients on combination therapy who are responding to treatment.
1Refer Appendix 1 (Clinical Pharmacokinetic Guidelines: Aminoglycosides & Vancomycin)
References:
1. Crit Care Med 2003; 31:1250-1256 3. Am J Respir Crit Care Med 2002, 166:717-723 6. Am J Respir Crit Care Med. 2005;171:388-4162. Crit Care Med 2004; 32(11)S495 S512 4. Clin Infect Dis 2003;37:1405-33 Curr Anaes and 7. Crit Care 2005;16:209-219 5. Curr Opin Crit Care 2004; 10:59-64
2.5 NEUROMUSCULAR BLOCKING AGENTS IN CRITICALLY ILL PATIENTS MAZNI
2.6 SEDATIVE AGENTS IN CRITICALLY ILL PATIENTS Mazni
2.7 FLUID MANAGEMENT IN CRITICALLY ILL PATIENTS Shafie
2.8 MEDICATION ADMINISTRATION IN ENTERAL FEEDING TUBES
2.8.1 Medication plan
Temporarily discontinue medications that are not immediately necessary Consider giving medications by an alternate route such as transdermal,
rectal, inhaled, intramuscular, subcutaneous, buccal, sublingual or intravenous whichever possible
2.8.2 . Enteral administration of medications
Evaluate tube type, tube location in the GI tract, site of drug action and absorption and effects of food on drug absorption (e.g. sucralfate is not suitable for intestinal feeding tubes administration as it acts on the stomach)
Drug that require administration on empty stomach, feeding should be stopped 30 minutes before and after dosing
Liquid dosage forms is preferred whenever possible Tablets that could be crushed into fine powder and the contents of capsules
can be mixed to a slurry in water and given through large-bore feeding tubes Feeding tubes should be flushed with at least 30 ml of water before and after
administration of medication via the tube Medication should not be added to enteral formula to reduce the risk of
microbial contamination and to avoid drug-nutrient incompatibilities
2.8.3 Medications that should not be crushed
2.8.4 Consideration with Liquid Medications
Medication dosage or frequency may need adjustment when switching from solid to liquid preparations (e.g. extended-release phenytoin capsules may be given once daily, however phenytoin suspension is an immediate-release product that need to be dosed 2 to 4 times daily)
Osmolality
Formulation Reason
Sustained-release Crushing destroys the sustained-release tablets and microencapsulated drugs, resulting in erratic blood levels
Enteric-coated Do not crush well but break into small chunks that bond together when moist and clogging the tube
Decreased the efficacy of the medication Increased stomach irritation
Teratogenic, carcinogenic or cytotoxic medication
Aerosolized particles may be harmful to the health-care provider
- Many commercial liquids have osmolalities over 1000 mOsm/kg, the osmolality of GI secretions ranges from 100 to 400 mOsm/kg
- Diarrhea, cramping, abdominal distension and vomiting may occur after administration of hyperosmolar products through the feeding tube – the effects may be reduced by diluting medication with 10-30 ml of sterile water before administration
- Osmolality of diluted mixture = (osmolality of drug / volume of drug) / total volume of mixture
Contents of sorbitol
- many sweeteners including mannitol, lactose, saccharin and sucrose may cause or worsen diarrhea, the most likely excipient to cause GI problems is sorbitol
- sorbitol may cause gas and bloating at total daily doses of 10 gram, cramping and diarrhea may occur a total daily dose of 20 gram
2.8.5 Drug interaction and incompatibility and special consideration
Interaction / Incompatibility Recommended intervention (s)
Syrups and other acidic medication (pH less than 4) may clump when mixed with enteral feeding formulas
Stopping the enteral feeding for 1 to 2 hours before and 2 hours after drug administration
To avoid nutritional status compromise:- minimize the time of feeding interruption by
using once daily or twice daily dosing regimen
Phenytoin absorption decreases by 50% to 75% when given with enteral feeding
Stopping the enteral feeding for 2 hours before and after each dose
Flushing the tube before and after each phenytoin dose
Phenytoin suspension given through feeding tube may be diluted with 20-60 ml of water
Close monitoring of serum concentrations is warranted
Carbamezepine absorption may decrease with enteral feeding
Carbamazepine suspension may be diluted with an equal volume of sterile water or normal saline
Close monitoring of serum concentrations is warranted
Warfarin effects may be decrease in patients receiving enteral feeding due to reduce absorption and vitamin K antagonism
Consider increasing the warfarin dose or using alternative anticoagulants
Monitor prothrombin time Consider vitamin K contents in enteral
formulas – vitamin K may directly block warfarin’s effects in doses of 140-500 mcg.day
Interaction / Incompatibility Recommended intervention (s)
Fluroquinolones antibtiotics may have an erratically changes in its pharmacokinetics in patients receiving enteral feeds
Fluroquinoloes should not be given within 2 hours before or 4 hours after enteral formulas
Avoid giving via enteral feeding tubes or concomitantly with enteral formulas – parenteral route is preferred
If to be given via entral tube – crush tablets and mix in 20 to 60 ml sterile water immediately before administration
Proton-pump inhibitors – these medications are acid labile and inactivated by gastric acid, specially formulated to maintain the acidity until it delivers to alkaline pH of the duodenum for absorption
Omeprazole and lansoprazole capsules (delayed-release) through large-bore nasogastric or gastrostomy tubes- may be mixed with juices (apple, orange)- mixing with water may cause clumping and
lead to occlusion Omeprazole and lansoprazole capsules
(delayed-release) through small-bore jejunostomy or gastrostomy tubes- Dissolve in sodium bicarbonate 8.4%
solution Esomeprazole granules (delayed-release)
should be mixed with water Commercial immediate-release omperazole
with sodium bicarbonate- Should only be mixed with water- Continuous enteral feeding should be held
for 3 hours before and 1 hour after medication administration
Lansoprazole disintegrating tablet (delayed-release)- Dissolves on tongue or may be mixed with
small amount of water in an oral syringe and injected through the NG tube
- Should not be given through feeding tube – increased viscosity, tube occlusion
Continuous enteral feeding should be held for 3 hours before and 1 hour after medication administration
Laxatives Bulk forming laxatives (e.g. methycellulose) - Should not be given via feeding tubes- Form semisolid mass that may occlude
feeding tube when mixed with less than 250 ml fluid (still potentially block feeding tube when mixed properly)
- Consider using fiber-containing enteral nutrition
References:
1. Silberman H. Parenteral and Enteral Nutrition. 2nd ed. Norwalk, CT: Appleton & Lange; 1989, 117–58.
2. Estoup M. Approaches and limitations of medication delivery in patients with enteral feeding tubes. Crit Care Nurse. 1994;14:68–72,79.
3. Gora ML, et al. Considerations of drug therapy in patients receiving enteral nutrition. Nutr Clin Pract. 1989; 4:105–10.
4. Thomson F.C., Naysmith, M.R. & Lindsay, A. Managing drug therapy in patients receiving enteral and parenteral nutrition. Hosp Pharmacist. 2000;7:155–64.
5. Gilbar PJ. A guide to enteral drug administration in palliative care. J Pain Symptom Manage. 1999;17:197–207.
6. Rombeau JL, Caldwell MD, eds. Clinical Nutrition: Enteral and Tube Feeding. 3rd ed. Philadelphia, PA: WB Saunders; 1997.
7. Janson DD, Chessman KH. Enteral nutrition. In: DiPiro JT et al, eds. Pharmacotherapy: A Pathophysiologic Approach. 5th ed. New York, NY: McGraw-Hill; 2002, 2495–517.
8. Mitchell JF. Oral dosage forms that should not be crushed or chewed. Hosp Pharm. 2002; 37:213–14.
9. Dickerson RN, Melnik G. Osmolality of oral drug solutions & suspensions. Am J Hosp Pharm. 1988;45:832–34.
10. Jew RK, et al. Osmolality of commonly used medications and formulas in the neonatal intensive care unit. Nutr Clin Pract. 1997;12:158–63.
11. Lutomski DM, et al. Sorbitol content of selected oral liquids. Ann Pharmacother. 1993;27:269–74.
12. Burns PE, et al. Physical compatibility of enteral formulas with various common medications. J Am Diet Assoc. 1988;88:1094–6.
13. Cutie AJ, et al. Compatibility of enteral products with commonly employed drug additives. JPEN J Parenter Enter Nutr. 1983;7:186–91.
14. Healy DP, et al. Ciprofloxacin absorption is impaired in patients given enteral feedings orally and via gastrostomy and jejunostomy tubes. Antimicrob Agents Chemother. 1996;40:6–10.
15. de Marie S, et al. Bioavailability of ciprofloxacin after multiple enteral and intravenous doses in ICU patients with severe gram-negative intra-abdominal infections. Intensive Care Med. 1998;24:343–6.
16. Wright DH, et al. Decreased in vitro fluoroquinolone concentrations after admixture with an enteral feeding formulation. JPEN J Parenter Enter Nutr. 2000;24:42–8.
17. Cohn SM, et al. Enteric absorption of ciprofloxacin during tube feeding in the critically ill. J Antimicrob Chemother. 1996;38:871–6.
18. Mueller BA, et al. Effect of enteral feeding with Ensure on oral bioavailabilities of ofloxacin and ciprofloxacin. Antimicrob Agents Chemother. 1994;38:2101–5.
19. Mimoz O, et al. Pharmacokinetics and absolute bioavailability of ciprofloxacin administered through a nasogastric tube with continuous enteral feeding to critically ill patients. Intensive Care Med. 1998;24:1047–51.
20. Cacek, A.T., DeVito, J.M. & Koonce, J.R. 1986. In vitro evaluation of nasogastric administration methods for phenytoin. Am. J. Hosp. Pharm. 43: 689-692.
21. Clark-Schmidt, A.L., Garnett, W.R., Lowe, DR et al. 1990. Loss of carbamazepine suspension through nasogastric feeding tubes. Am. J. Hosp. Pharm. 47: 2034-2037.
22. Williams, N.E. 2008. Medication administration through enteral feeding tubes. Am. J. Hosp. Pharm. 65(24): 2347-2357.
23. Beckwith, M.C., Feddema, S.S., Barton, R.G. & Graves, C. 2004. A guide to drug therapy in patients with enteral feeding tubes: dosage form selection and administration method. Hospital Pharmacy. 39(3): 225-237.
CHAPTER 3: DOSING
3.1 RENAL DOSING Siti Normiyah
3.2 LIVER DOSING Hasni
3.3 SPECIAL DOSING IN OBESE PATIENTS
Obesity is defined by the CDC as a BMI of >30kg/m2, and morbid obesity is defined as a BMI of >40kg/m2.
3.3.1 Physiological changes in obesity
Can alter pharmacodynamic and pharmacokinetic of a drug which includes:
Dramatically increased adipose tissue Slightly increased lean tissue mass Increased cardiac output Increased glomerular filtration rate Fatty infiltration of liver
A higher proportion of body tissue can influence drug with lipophilic properties whereas increased organ mass, lean body mass, and blood volume in obesity can affect hydrophilic medications.
Failure to adjust doses in obesity may result either in sub therapeutic failure or increased toxicity.
3.3.2 Reported dosing adjustment in obesity
Drugs Suggested dosing weight Additional dosing recommendation
AntimicrobialsAcyclovir IBW1
Aminoglycosides IBW + 0.4(ABW-IBW)1
Amphotericin B ABW for conventional preparation; IBW for lipid preparation1
Beta-lactams IBW + 0.3(ABW-IBW)2
Ciprofloxacin IBW + 0.45(ABW-IBW)2
Erythromycin IBW1
Fluconazole Consider higher doses in obese patient1
Ganciclovir ABW3
Mycobacterial antibiotics IBW2
Vancomycin ABW2
Muscle relaxantSuxamethonium IBW3
Atracurium IBW3
Pancuronium IBW3
SedativePropofol ABW5
ABW = actual body weight IBW = ideal body weight
Calculations:-IBW (Ideal body weight):Male IBW (kg) = 50 kg + 2.3 (height in inches over 60 inches)Female IBW (kg) = 45.5 kg + 2.3 (height in inches over 60 inches)
3.3.3 Creatinine clearance in obese patient4
Overestimation or underestimation of clearance can occur in obesity when considering actual body weight versus ideal body weight, respectively. The Cockcroft-Gault equation is commonly used to calculate glomerular filtration rate (GFR) in lean patients, however its use in obesity is questionable due to the disparity between muscle mass and body weight ratio observed in obesity.
The Salazar-Corcoran equation takes into account multiple factors to provide a better estimation of ClCr in obesity including serum creatinine, gender, actual weight, age, and height.
Salazar-Corcoran Equation 4 :
ClCr(Male) = (137-age)x[(0.285xWt)+(12.1xHt 2 )] (51xSCr)
ClCr(Female) = (146-age)x[(0.287xWt)+(9.74xHt 2 )] (60xSCr)
Wt= actual body weight in kgHt= height in metersSCr=serum creatinine in mg/dl
Although some drugs have established dosing adjustments for obesity, it remains unknown for the majority of drugs if dosing adjustment is warranted.
References:1. Optimal antibiotic dosing for obese patients a challenge for clinicians by Elizabeth Dodds Ashley,
PharmD, BCPS Infectious Disease News June 2007
2. Antimicrobial Dosing in Obesity Rebecca Wurtz, GailItokazu, and Keith Rodvold Clinical Infectious Diseases1997;25:112C
3. Uptodate 17.1
4. Pharmacokinetics Alterations in Obesity By Jane B. Lee, PharmD; P. Shane Winstead, PharmD;Aaron M. Cook, PharmD ORTHOPEDICS 2006; 29:984
5. MICROMEDEX(R) Healthcare Series Vol. 143
CHAPTER 4: NUTRITION
4.1 PARENTERAL NUTRITION IN CRITICALLY ILL PATIENTS
ESPEN Guidelines on Parenteral Nutrition: Intensive Care (Adapted from Singer et al., 2009)
Recommendations Grade
Indications
Starvation and underfeeding in ICU patients is aasociated with increased morbidity and mortality
Parenteral Nutrition (PN) should be initiated within 24 to 48 hours in all patients who are not expected to be on normal nutrition within 3 days when enteral nutrition (EN) is not feasible
All patients receiving less than their targeted enteral feeding after 2 days should be considered for supplementary PN
C
C
C
Requirements
A complete PN formulation should be given to ICU patients to cover their needs fully
The aim in acute illness is to provide energy as close as possible to the measured energy expenditure (to reduce negative energy balance)
ICU patients should receive 25 kcal/kg/day increasing to target over the next 2-3 days (in the absence of indirect calorimetry)
C
B
C
Carbohydrates
The minimal amount required is about 2g/kg of glucose per day Hyperglycemia (glucose >10 mmol/L) contributes to death in critically ill
patient and should be avoided to prevent infectious complications
B
B
Lipids
Lipids should be an integral part of PN for energy and to ensure essential fatty acid provision in long term ICU patients
Intravenous lipid emulsions can be administered safely at a rate of 0.7 g/kg up to 1.5 g/kg over 12 to 24 hours
The tolerance of mixed LCT/MCT lipid emulsions in standard use is sufficiently documented
Olive oil-based PN is well tolerated in critically ill patients EPA and DHA containing lipid emulsions had demonstrable effects on cell
membranes and inflammatory process. Fish oil-enriched lipid emulsions probably decrease length of stay in crtitically ill patients
B
B
C
B
B
Amino Acids
A balanced amino acid mixture should be infused at approximately 1.3-1.5 g/kg of ideal body weight per day in conjunction with an adequate energy supply
B
Recommendations Grade
In critically ill patients indicated for PN, the amino acid solution should contain 0.2-0.4 g/kg/day of L-glutamine (e.g. 0.3-0.6 g/kg/day alanyl-glutamine dipeptide) A
Micronutrients
All PN prescriptions should include a daily dose of multivitamins and of trace elements
C
Route
A central venous access is required to administer the high osmolarity PN mixture
Peripheral venous access may be considered for low osmolarity PN mixture (<850 mOsm/L)
If peripherally administered PN does not allow full provision of the patient’s need, then PN should be administered via the central venous access
C
C
C
Mode
PN admixtures should be administered as a complete all-in-one bag B
Reference:
Singer, P., Berger, M.M., Van den Berghe, G., Biolo, G., Calder, P., Forbes, A., Griffiths, R., Kreyman, G., Leverve, X. & Pichard, C. 2009. ESPEN guidelines on parenteral nutrition: intensive care. Clinical Nutrition. (28). 387-400.
CHAPTER 5: OTHERS
5.1 DRUG CAUSING HAEMATOLOGICAL DISORDER
Drugs may produce hematologic toxicity by one of three general mechanisms:
direct drug (or a metabolite) toxicity
toxicity due to a drug effect on a genetic abnormality in the bone marrow
toxicity involving immune mechanisms.
The four major blood dyscrasias attributable to drugs are:
agranulocytosis or leukopenia (loss of the white blood cells)
aplastic anemia (loss of all the formed elements of the blood)
thrombocytopenia (loss of the platelets)
hemolytic anemia (loss of the red blood cells).
The incidence of these adverse hematologic drug reactions, the relative importance of various etiologic chemicals, and their resultant morbidity and mortality vary.
5.1.1 Drugs Suspected of Inducing Agranulocytosis (Leukopenia)
Drug-induced agranulocytosis is classified as Type 1 (due to an immune mechanism) and Type II (drug effect on bone marrow DNA synthesis). In Type I reactions, blood immunoglobins are directed against drug-related antigens located on circulating leukocytes.
Allopurinol*
Aminopyrine
Chloramphenicol
Chlordiazepoxide
Chloroquine
Chlorpromazine
Indomethacin
Mefenamic acid
Penicillamine
Anticonvulsants
Antimalarials
Aspirin
Captopril
Cephalosporins
Chlorthalidone
Cimetidine
Clindamycin
Diazepam
Isotretinoin
L-dopa
Mercurial diuretics
Methyldopa
Naproxyn
Nitrofurantoin
Penicillins
Phenothiazines
Piroxicam
Phenylbutazone
Phenytoin
Quinidine
Rifampicin
Sulfonamides
Thiazides
Acetaminophen §
Acetazolamide
Diflunisal
Doxycycline
Fenoprofen
Gentamicin
Griseofulvin
Hydralazine
Ibuprofen
Isoniazid
Procainamide
Propranolol
Spironolactone
Streptomycin
Sulfonylureas
Sulindac
Tolmetin
Vancomycin
* Underlined drugs are most significant
§ Many of these other drugs have been implicated in only one or a few case reports
5.1.2 Drugs Suspected of Inducing Aplastic Anemia
Aplastic anemia is an unexpected peripheral-blood pancytopenia with variable bone marrow hypocellularity in the absence of underlying malignant or myeloproliferative disease.
Severe aplastic anemia is seen with a bone marrow of less than 25% of normal cellularity or a bone marrow of less than 50% of normal cellularity with less than 30% of the hematopoietic cells and at least two of the following peripheral blood values:
Granulocytes fewer than 500/mm3
Platelets fewer than 20,000/mm3
Anemia with reticulocytes fewer than 1%. 15 About 65% of people with aplastic anemia die within 4 months of diagnosis; few die after this 4-month period.'
Allopurinol*
Aminopyrine
Chloramphenicol
Sulfonamides
Acetaminophen §
Aspirin
Naproxyn
Organic solvents
Phenytoin
Chloroquine
Gold salts
Indomethacin
Mefenamic acid
Phenylbutazone
Propylthiouracil
Benzene
Captopril
Chlordiazepoxide
Chlorpromazine
Fenoprofen
Indoprofen
Piroxicam
Sulfonylureas
Sulindac
Thiazides
Thiocyanate
*Underlined drugs are most significant
§ Many of these other drugs have been implicated in only one or a few case reports
5.1.3 Drugs Suspected of Inducing Thrombocytopenia
Drug-induced immune thrombocytopenia is characterized by acute purpura, confluent petechiae or ecchy-moses- particularly after mild trauma-and gastrointestinal, central nervous system, or urinary tract bleeding,all associated with a mild or severe lack of blood platelets.
Drugs may induce marrow hypoplasia, destroy platelets directly, or be responsible for an immune reaction. Thrombocytopenia may be associated with several disease states (acute leukemia, Gaucher's disease, systemic lupus erythematosus, sarcoidosis); drug-induced thrombocytopenia usually remits 1 to 2 weeks after drug discontinuance.
Gold salts*
Indomethacin
Mefenamic acid
Quinidine
Quinine
Thiazides
Acetaminophen §
Aminopyrine
Aspirin
Codeine
Danazol
Diclofenac
Digitoxin
Fenoprofen
Heparin
Ibuprofen
Isotretinoin
Para-aminosalicyclic acid
Phenytoin
Piroxicam
Ranitidine
Sulindac
Tolmetin
Amiodarone
*Underlined drugs are most significant
§ Many of these other drugs have been implicated in only one or a few case reports
5.1.4 Drugs Suspected of Inducing Hemolytic Anemia
Aminopyrine*
Methyldopa
Quinidine
Acetaminophen §
Aspirin
Cephalosporins
Chlorpromazine
Phenytoin
Diclofenac
Ibuprofen
L-dopa
Mefenamic acid
Naproxyn
Penicillins
Phenylbutazone
Quinine
Rifampicin
Sulfonamides
Sulindac
Tetracyclines
Thiopental
Volatile nitrites
*Underlined drugs are most significant.
§ Many of these other drugs have been implicated in only one or a few case reports.
5.2 POISONING
Treatment Option Dose & Duration Dilution Side Effects Contraindications Monitoring
Organophosphate Poisoning
1. Prevention of absorption
- Activated Charcoal
Adult : 25 – 100 gm
Child : 25 – 50 gm
< 1 yr : 0.5 – 1 gm/kg
Tx : Cont until pt clinical condition improve.
Dilute 30 gm in 240 ml Impaired intestinal motility
Absence of bowel sounds, GI perforation, intestinal obstruction, recent surgery, GI haemorrhage
Serum electrolyes, ECG, serum amylase
2. Treatment- Atropine
Adult :
2 mg q5-10 min
(IV) until atropinisd
Child :
0.05 mg/kg (IV),
then 0.02-0.05
mg/kg q15-60 min
until atropinised
Tx : cont for 12 – 24 H
Given undiluted
I/Tracheal : Dilute dose in 1-2 ml of NS
Antimuscarinic effect e.g dry skin, dilated pupil, flushing, urinary retention,↓bronchial secretion, constipation, bradycardia etc
Hypersensivity, Myasthenia Gravis, paralytic ileus, pyloric stenosis and prostatic enlargement
Pulse rate, EKG, urine output, GI motility
- Pralidoxime Adult : 30mg/kg (bolus),repeat at 4-6 H, Inf : 8mg/kg/H(Max : 12 gm/day)Child : 20 – 50 mg/kg, 10 – 20 mg/kg/H(Max : 2gm/dose)Tx : until pt clinical condition improve
Dilute up to 20 mg/ml with WFI for IV inj. given over 5-10 min
Inf : dilute in 100ml NS over 15-30 min
Blurred vision, diplopis, dizziness, drowsiness,↑BP
headache,transcient ↑ LFT, impaired accommodation, N, tachycardia, laryngospasm
Hypersensitvity to any component of the product
Vital signs, ECG, urine output
Note : administer as soon as possible after exposure, however pt presenting late (2-6 days post exposure) may still benefit
Treatment Option Dose & Duration Dilution Side Effects Contraindications Monitoring
Paraquat Poisoning
Prevention of absorption
- Activated Charcoal
Adult : 25 – 100 gm
Child : 25 – 50 gm
< 1 yr : 0.5 – 1 gm/kg
Tx : Cont until pt clinical condition improve
Dilute 30 gm in 240 ml Impaired intestinal motility
Absence of bowel sounds, GI perforation, intestinal obstruction, recent surgery, GI haemorrhage
Serum electrolyes, ECG, serum amylase
Opiods Poisoning
1. Overdosage
- Naloxone
Adult :
0.4 – 2 mg q 2-3 min (bolus) (Max : 10 mg)
Child :
0.01 mg/kg, then 0.1 mg/kg if no response
Tx : up to 48H
Maybe given undiluted
Infusion :
4mg in 500ml in NS, D5 discrd inf after 24H
Hyperyension, N, V, sweating, tachycardia, elevated PTT
Hypersensitivity to naloxone
Vital Signs
2. Reversal of Opiod induced resp distress
- Naloxone 1.5 – 3 µg/kg (IV), if needed increment of 0.1mg q2min, further dose IM after 1-2H prn
Benzodiazepines Poisoning
Treatment Option Dose & Duration Dilution Side Effects Contraindications Monitoring
1. Prevention of absorption- Activated
Charcoal
Adult : 25 – 100 gm
Child : 25 – 50 gm
< 1 yr : 0.5 – 1 gm/kg
Tx : Cont until pt clinical condition improve.
Dilute 30 gm in 240 ml Impaired intestinal motility
Absence of bowel sounds, GI perforation, intestinal obstruction, recent surgery, GI haemorrhage
Serum electrolyes, ECG, serum amylase
2. Treatment- Flumazenil
Adult :
0.2 mg (15 sec), then 0.1mg q1min prn, usual 0.3-0.6mg (Slow IV),
Inf : 0.1-0.4 mg/H (Max : 2 mg)
Child :
5µg/kg every 60 sec, max 40 µg/kg
then 2-10 µ/kg/H
Tx : until desired level of consciousness with max dose achieved
Given undiluted or further dilute with D5,NS,½ NS
Discard solution after 24H
N, V, Flushing, agitation, anxiety, transcient ↑BP, HR
Life threatening condition controlled by BDZ (e.g ↑ intracranial pressure, status epilepticus)
Airway, breathing, circulation, vital signs, ECG
Treatment Option Dose & Duration Dilution Side Effects Contraindications Monitoring
Heparin and Derivatives Poisoning
Severe Haemorrhage- Protamine Sulfate
Adult :
1mg /100U hep,
(Max : 100 mg)
Child :
1mg/100U hep, 0.5mg/100U hep. If > 1H (slow IVstat), subs dose1mg/kg (Max : 50 mg)
Tx : any dose over 100mg in 2H should be justified by coagulation studies
Undiluted over 10 min
Maybe further dilute with NS or D5.Rate <5mg/min inf over 2-3H
Hypotension, bradycardia and dyspnoea
None when use as indicated
Airway, breathing, circulation, vital signs, Coagulation Profile, FBC
Warfarin Overdosage
1. Prevention of absorption
- Activated Charcoal
Adult : 25 – 100 gm
Child : 25 – 50 gm
< 1 yr : 0.5 – 1 gm/kg
Tx : Cont until pt clinical condition improve.
Dilute 30 gm in 240 ml Impaired intestinal motility
Absence of bowel sounds, GI perforation, intestinal obstruction, recent surgery, GI haemorrhage
Serum electrolyes, ECG, serum amylase
Treatment Option Dose & Duration Dilution Side Effects Contraindications Monitoring
2. Treatment- Vitamin K
Adult : 10 mg
(Max : 25 – 50 mg)
Child : 1-5 mg
(Max : 0.6 mg/kg)
Tx : may repeat in 6-8H if initial response is not adequate
Dilute 10mg in 50ml D5 over 30 min or into Y site of fast running D5
Max 40mg over 24H
Venous irritation, phlebitis, anaphylaxis
Hypersensitivity to components
Airway, breathing, circulation, vital signs, Coagulation Profile, FBC, INR
Paracetamol Poisoning
1. Prevention of absorption
- Activated Charcoal
Adult : 25 – 100 gm
Child : 25 – 50 gm
< 1 yr : 0.5 – 1 gm/kg
Tx : Cont until pt clinical condition improve.
Dilute 30 gm in 240 ml Impaired intestinal motility
Absence of bowel sounds, GI perforation, intestinal obstruction, recent surgery, GI haemorrhage
Serum electrolyes, ECG, serum amylase
Treatment Option Dose & Duration Dilution Side Effects Contraindications Monitoring
2. Treatment
- N-Acetylcysteine Adult :
150mg/kg over 15min, then 50mg/kg over 4H, then 100mg/kg over 16H
Child : Same as adult
Tx : usually total infusion time is 21H
Adult :
Initial dilute in 200ml D5% given over 15min, then in 500ml over 4H, then in 1L over 16 H
Child (<12y) :
Dilution ½ of adult given at the same rate of adult dose.
Child (<20 kg) :
Initial dilute as 3ml/kg over 15 min, then 7ml/kg over 4H, then 14/kg over 16H.
Rash, anaphylaxis, bronchospasm, hypocalcaemia and ECG changes
Hypersensitivity to acetylcysteine or any of its component
Airway, breathing, circulation, vital signs, Ca2+ level, LFT, ECG
Notes : NAC therapy should begin within 8H of ingestion if possible. NAC efficacy decrease progressively from 8-16H post ingestion
References :
1. BNF 51, March 20062. Drug Doses, 13th Ed 2005, Frank Shann3. Intravenous Medication 2008, 24th Ed, Betty LG, Adrienne RN4. Micromedex (R) Healthcare Series Vol. 13
APPENDICES
APPENDIX 1: DRUGS THAT MAY UNMASK/EXACERBATE MYASTHENIA GRAVIS
Anesthetic agentsChloroprocaine Diazepam Ether Halothane Ketamine Lidocaine
Neuromuscular blocking agents Propanidid Procaine
Antibiotics Aminoglycosides Amikacin Gentamicin Kanamycin Neomycin Netilmicin Paromomycin Spectinomycin Streptomycin Tobramycin
Fluoroquinolones Ciprofloxacin Levofloxacin Norfloxacin
Others Ampicillin Clarithromycin Clindamycin Colistin Erythromycin Lincomycin Quinine Telithromycin Tetracyclines Anticonvulsants Gabapentin Phenytoin Trimethadione
Antipsychotics Chlorpromazine
Lithium Phenothiazines
Antirheumatic drugs Chloroquine Penicillamine
Cardiovascular drugs Beta blockers Bretylium Procainamide Propafenone Quinidine Verapamil and calcium channel blockers
Glucocorticoids Corticotropin Methylprednisolone Prednisone
Neuromuscular blockers and muscle relaxants Botulinum toxin Magnesium sulfate and magnesium salts Methocarbamol
Ophthalmologic drugs Betaxolol Echothiophate Timolol Tropicamide Proparacaine
Other drugs Anticholinergics Carnitine Cholinesterase inhibitors Deferoxamine Diuretics Emetine (Ipecac syrup) Interferon alpha Iodinated contrast agents Narcotics Oral contraceptives Oxytocin Ritonavir and antiretroviral protease inhibitors Statins Thyroxine
* Drugs listed here should be used with caution in patients with myasthenia gravis. Aminoglycosides should be used only if absolutely necessary with close monitoring. Please refer to the text for further information.
Ref: Uptodate 17.1
APPENDIX 2: CATEGORIES OF SAFE & UNSAFE DRUGS IN THE ACUTE PORYPHYRIAS
Categories of safe drugs in the Acute Porphyrias
Drugs Which are SAFE to use: Drugs which are PROBABLY SAFE to use:
Drugs which are PROBABLY SAFE to use: (cont.)
Acetaminophen Acetazolamide Allopurinol Amiloridine Aspirin Atropine Bethanidine Bromides Bumetanide Chloral hydrate Cimetidine Corticosteroids Coumarins Fluoxetine Gabapentin Gentamycin Guanethidine Insulin Narcotic analgesics Ofloxacin Paracetamol Penicillins Phenothiazines Propranalol Streptomycin Succinylcholine Tetracycline
Adrenaline Amitriptyline Azathioprine Chloramphenicol Cisapride Colchicine Cyclosporin Cytarabine Dicumarol Chloroquine Digoxin Daunorubicin Doxazosin Estrogens (natural/endogenous) Ibuprophen Imipramine Indomethacin Labetalol Lithium Losartan
Methenamine Methylphenidate Naproxen Neostigmine Nortriptyline Nitrous oxide Penicillamine Procaine Propanidid Propofol Propoxyphene Rauwolfia alkaloids 6-Thioguanine Thiouracils Thyroxine Tricyclic antidepressants Tubocurarine Vigabatrin Vitamin B Vitamin C
This list is NOT comprehensive and does not reflect all information and opinions about drug safety in the acute porphyrias. There is considerable evidence for classification of drugs in the "Safe" category, but much less evidence, or conflicting evidence, for drugs in the "Probably Safe" category. Additional information concerning safe and unsafe drugs can be found in the text, including available websites. Reproduced with permission from Anderson, KE, et al. Disorders of heme synthesis: X-linked sidero-blastic anemia and the porphyrias. In: The metabolic and molecular bases of inherited disease (Scriver, CR, Beaudet, AL, Sly, WS, Valle, D, eds). McGraw-Hill Medical Publishing Division, New York. p 2991. Copyright © 2000 The McGraw-Hill Companies.
Categories of Unsafe drugs in the Acute Porphyrias
Drugs which are UNSAFE
Drugs which are UNSAFE (cont.)
Drugs which are POTENTIALLY UNSAFE
Drugs which are POTENTIALLY UNSAFE (cont.)
ACE inhibitors Antipyrine Aminopyrine (amidopyrine) Aminoglutethamide Barbiturates (all) N-butylscopolammonium bromide Calcium channel blockers Carbamazepine Chlorpropamide Danazol Dapsone Diclofenac Enalapril Diphenylhydantoin Ethosuximide Ergot preparations Ethchlorvynol Ethinamate Felbamate Glutethimide Griseofulvin Ketoconazole Lamotrigine
Mephenytoin Metoclopramide Meprobamate Methyprylon Nefazadone Nifedipine Novobiocin Phenazone Phenylbutazone Primidone Pargyline Progesterone (progestins) Rifampin Succinimides Sulfasalazine Sulfonamide antibiotics Sulfonmethane (sulfonal) Sulfonethylmethane (trional) Sulfonylureas Trimethadione Valproic acid Tranylcypromine
Alfadolone acetate Alfaxolone Alkylating agents* Altretamine (hexamethylmelamine) Benzodiazepines Busulfan Captopril Cephalosporins Chlorambucil Chlordiazepoxide Clonidine Cyclophosphamide Dacarbazine Deferoxamine Diazepam Diltiazem Colistin Dacarbazine Diphenhydramine EDTA Etomidate Estrogens (synthetic) Erythromycin 5-Fluorouracil Gold compounds Fluroxene
Heavy metals (eg, Gold) Hydralazine Hyoscine Ketamine Lisinopril Mefenamic acid Melphalan Mifepristone Methyldopa Metyrapone Nalidixic acid Nikethamide Nitrazepam Nitrofurantoin o,p'-DDD Pentazocine Phenoxybenzamine Procarbazine Pyrazinamide Spironolactone Theophylline Tiagabine Tramadol Tricyclic antidepressants Troglitazone
This list is NOT comprehensive and does not reflect all information and opinions about drug safety in the acute porphyrias. There is considerable evidence for classification of drugs in the "Unsafe" category, but much less evidence, or conflicting evidence, for drugs in the "Probably Unsafe" category. Additional information concerning safe and unsafe drugs can be found in the text, including available websites.
* Chlorambucil and Melphalan may be safer than the other alkylating agents listed here.
Reproduced with permission from Anderson, KE, et al. Disorders of heme synthesis: X-linked sidero-blastic anemia and the porphyrias. In: The metabolic and molecular bases of inherited disease (Scriver, CR, Beaudet, AL, Sly, WS, Valle, D, eds). McGraw-Hill Medical Publishing Division, New York. p 2991. Copyright © 2000 The McGraw-Hill Companies.
Ref: Uptodate 17.1
APPENDIX 3: DRUGS AND CHEMICALS IN GLUCOSE-6-PHOSPHATE DEHYDROGENASE
Unsafe for class I, II, and III variants Safe for class II and III variants*
Acetanilid Dapsone Furazolidone Methylene blue Nalidixic acid Naphthalene (mothballs, henna) Niridazole Nitrofurantoin Phenazopyridine Phenylhydrazine Primaquine Sulfacetamide Sulfamethoxazole Sulfanilamide Sulfapyridine Thiazosulfone Toluidine blue Trinitrotoluene
Acetaminophen Aminopyrine Ascorbic acid (except in very high doses) Aspirin Chloramphenicol Chloroquine Colchicine Diphenhydramine Isoniazid L-DOPA Menadione Paraaminobenzoic acid Phenacetin Phenytoin Probenecid Procainamide Pyrimethamine Quinidine Quinine Streptomycin Sulfamethoxpyridazine Sulfisoxazole Trimethoprim Tripelennamine Vitamin K
* Safety for class I variants is usually not known.
Data from Beutler, E, Blood 1994; 84:3613.
Reference: Uptodate 17.1
APPENDIX 4: DRUG-DISEASE INTERACTIONS
Drug Disease Remarks Management Ref
1 Aminoglycosides Myasthenia Gravis
Cause significant increase in weakness, respiratory depression. Aminoglycoside-related postoperative respiratory depression caused the greatest frequency of drug-induced neuromuscular blockade
Avoid or use only if absolutely necessary with close monitoring
www.uptodate.com
2 Androgens (testosterone)
HF Edema Endocrine Society Guideline (US) recommend not to use in NYHA III, IV
Uptodate vs 17.1
3 Amiodarone Thyroid disorders
the iodine-rich amiodarone affects the thyroid gland, causing overt hypothyroidism or thyrotoxicosis in 14%-18% of cases.
Thyroid function to be monitored.
Complex Drug-Drug-Disease Interactions Between Amiodarone, Warfarin, and the Thyroid GlandKurnik, Daniel MD; Loebstein, Ronen MD; Farfel, Zvi MD; Ezra, David MD; Halkin, Hillel MD; Olchovsky, David MD
4 Antiarrhythmic (sotalol, ibutilide)
HF Negative inotropic, precipitate HF, proarrhythmic
Amiodarone is the preferred choice in arrhythmias in HF
Uptodate vs 17.1
5 ACE inhibitors gold salts and interferon .
Psoriasis Occasional triggers of a psoriatic flare Use Cautiously Skin Therapy Letter • Editor: Dr. Stuart Maddin • Vol. 4 No. 3
6 Antimalarials Psoriasis Exacerbate Not contraindicated. Skin Therapy Letter • Editor: Dr. Stuart Maddin • Vol. 4 No. 3
7 Antipsychotics Parkinson’s disease
Parkinsonism Use with caution Neurology, Vol 66, Issue 6, March 2006
Drug Disease Remarks Management Ref
8 Beta Blockers COPD, Asthma Non selective beta blockers prevents bronchodilatation
-All beta blockers are contraindicated in severe disease
-Non selective ones to be avoided in mild to moderate disease. Selective or combined alpha/beta to be used cautiously at low dose
Uptodate vs 17.1
9 Beta Blockers Diabetes Facilitation of hypoglycaemia Use cautiously Uptodate vs 17.1
10 Beta Blockers Peripheral Vascular Disease, Raynaud’s phenomenon
Non selective beta blockers implicated. Reduction in cardiac output and blockade of beta-2-receptor-mediated skeletal muscle vasodilation contribute to the vascular insufficiency [
Selective agents can be used cautiously
Uptodate vs 17.1
11 Beta blockers Bradycardia, heart block
-ve Chronotropic effect.
-maintenance of cardiac output depends on sympathetic drive
Use cautiously Uptodate vs 17.1
12 Beta Blockers Psoriasis May aggravate existing disease Not contraindicated in psoriasis. However,
when there is a clear relationship between the exacerbation of
the psoriasis and the intake of a beta blocker, it sometimes help to switch from a non-cardioselective beta 2 blocker to
Skin Therapy Letter • Editor: Dr. Stuart Maddin • Vol. 4 No. 3
Drug Disease Remarks Management Ref
a cardioselective beta 1 blocker.
13 Beta Blockers Myasthenia gravis
Exacerbate Use with caution Uptodate vs 17.1
14 Chemotherapeutic agents (cyclophospha-mide, traztuzumab, bevacizumab, anthracycline-like chemo agents
HF Cardiotoxic Altenative administration schedule. Baseline and periodic monitoring of ECG and LVEF (with either ECHO) is recommended.
Uptodate vs 17.1
15 CNS depressants, opioids, muscle relaxants
Myasthenia Gravis
Increase symptoms when used together or at high doses
Use cautiously Uptodate vs 17.1
16 Corticosteroids Psoriasis Rebound that invariably follows their
use. The flare-up may be even worse than the original attack.
Avoid Skin Therapy Letter • Editor: Dr. Stuart Maddin • Vol. 4 No. 3
Drug Disease Remarks Management Ref
17 COX-2 selective inhibitosr
HF Exacerbation of HF Use with caution Uptodate vs17.1
18 Calcium Channel Blockers
CHF Negative Inotropic, increase sympathetic activity by short acting dihydropyridines. Longer acting ones appears safe
Avoid use of shorter acting dihydropyridines
Efficacy and safety of calcium channel blockers in heart failure: focus on recent trials with second-generation dihydropyridines.
AU de Vries RJ; van Veldhuisen DJ; Dunselman PH
SO Am Heart J 2000 Feb;139(2 Pt 1):185-94.
19 Calcium channel blockers (short acting –verapamil, diltiazem, nifedipine)
2nd-3rd degree heart block
Negative Inotropic. Avoid use of shorter acting dihydropyridines
20 Fluoroquinolones Myasthenia gravis
Exacerbate Use with caution Uptodate vs17.1
21 Lithium Psoriasis Well recognised cause of exacerbation.
It may even cause pustular or erythrodermic psoriasis in a significant proportion of
affected patients.
Lithium does not aggravate a pre-existing
psoriasis in all cases, and therefore is not contraindicated
Skin Therapy Letter • Editor: Dr. Stuart Maddin • Vol. 4 No. 3
Drug Disease Remarks Management Ref
in all patients with psoriasis.
22 Lignocaine and procaine may cause worsening if given iv
Myasthenia Gravis
Uptodate vs 17.1
23 Magnesium Sulfate Myasthenia Gravis
Relatively contraindicated since it has inhibitory effect on acetylcholine release
Relative contraindication Uptodate vs 17.1
24 Metformin HF Increased risk of lactic acidosis Use with caution Uptodate vs 17.1
25 NSAIDs, Aspirin Peptic Ulcers Gastrotoxicity Use with caution Uptodate vs 17.1
26 NSAIDs, Aspirin Asthma Acute exacerbation of airway inflammation. Less likely with COX-2 inhibitors
Avoid in aspirin sensitive asthma. Use with caution in others
Uptodate vs 17.1
27 NSAIDs HF Exacerbation and impaired response to ACE-I
Use with caution Uptodate vs 17.1
28 NSAIDs Psoriasis Anecdotal reports suggest adversely affecting psoriasis
Consider discontinuing a NSAID if the patient’s psoriasis worsened on starting, and
improved after stopping that drug
Uptodate vs 17.1
29 Neuromuscular Myasthenia Unmask or exacerbate MG Titrate judiciously Uptodate version 17.1
Drug Disease Remarks Management Ref
Blocking Agents Gravis
30 High Dose Prednisolone, glucocorticoids in high doses
Myasthenia Gravis
Exacerbation during early stages of treatment
During crisis, use only if patient’s airway is protected
Uptodate version 17.1
31 Penicillamine Myasthenia Gravis
Induces autoimmune Myasthenic syndrome. Reversible
Avoid Uptodate version 17.1
32 Phenytoin, Gabapentin
Myasthenia Gravis
Rare cases of exacerbation Use cautiously Uptodate version 17.1
33 Procainamide, quinidine, quinine,
List is comprehensive-Refer Appendix 1
Myasthenia Gravis
Cause significant increase in weakness Avoid Uptodate version 17.1
34 PDE-3 (Cilostazol) HF Increased mortality Contraindicated Uptodate vs 17.1
35 PDE-4 (Anagrelide) HF +inotropic, vasodilatory, leading to fluid retention and heart failure
Avoid Uptodate vs 17.1
36 PDE-5 (sildenafil, vardenafil, tadalafil)
HF Potentially hazardous in patients with HF with borderline BP. Avoid in IHD
Use with caution Lexicomp
37 Statins Myasthenia Gravis
Unmasking subclinical MG due to myotoxicity, new and worsening MG
Use cautiously Uptodate version 17.1
38 Sildenafil CHD Safety and efficacy has not been Use with caution Lexicomp Drugs
Drug Disease Remarks Management Ref
studied in these patients
39 Sulfonamide Antibiotics, Penicillin (but not the semi synthetic ones)
SLE Exacerbate SLE Avoid Uptodate vs 17.1
40 Theophylline Cardiac disease Can reduce theophylline clearance by as much as 50%
Monitor level closely Shannon: Haddad and Winchester's Clinical Management of Poisoning and Drug Overdose, 4th ed. Ch 65
41 Theophylline Primary Hepatic Disease
Can reduce theophylline clearance by as much as 50%
Monitor level closely Shannon: Haddad and Winchester's Clinical Management of Poisoning and Drug Overdose, 4th ed. Ch 65
42 Theophylline Cystic Fibrosis, Hyperthyroi-dism
Increase clearance May need to increase dose Shannon: Haddad and Winchester's Clinical Management of Poisoning and Drug Overdose, 4th ed. Ch 65
43 TNF blockers HF New onset or worsening pre-existing HF Use with caution in patients with HF or decreased left ventricular function; worsening and new-onset HF has been reported." In addition, infliximab is contraindicated at doses
Drug labels
Drug Disease Remarks Management Ref
higher than 5 mg/kg in patients with moderate or severe HF (NYHA class III/IV)
44 TNF blockers Psoriasis Possibility of emergence or worsening of psoriasis during treatment with TNF blockers, particularly pustular and palmoplantar forms of psoriasis.
Monitor FDA ALERT [8/4/2009]
45 Telithromycin Myasthenia Gravis
Black box warning on possibility of exacerbating or unmasking MG. Should not use.
Uptodate version 17.1
46 Warfarin Thyroid disorders
thyroid disorders may affect warfarin sensitivity, with hypothyroidism and thyrotoxicosis resulting in increased or decreased warfarin requirements, respectively
Thyroid function should be tested in any patient with otherwise unexplained changes in warfarin dose requirements, particularly if concomitantly treated with amiodarone.
Complex Drug-Drug-Disease Interactions Between Amiodarone, Warfarin, and the Thyroid GlandKurnik, Daniel MD; Loebstein, Ronen MD; Farfel, Zvi MD; Ezra, David MD; Halkin, Hillel MD; Olchovsky, David MD
47 Inexhaustive list (see Appendix 2, 3)
Acute Intermittent Porphyria
Can exacerbate disease Refer to Appendix 2 and 3 Uptodate 17.1
48 Inexhaustive list (see Appendix 4)
G6PD deficiency
Can cause hemolysis Refer to Appendix 4 Uptodate 17.1