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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 )


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


DRUG a. Streptokinase

STRENGTH/UNIT 1 500 000 IU ( Streptase )

STORAGE 2ºC - 25ºC.

RECONSTITUITION 5ml NS.

STABILITY AFTER RECONSTITUITION 24 hours at 2ºC - 8ºC.


NS

D5%


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


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


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



1. Product information Pamecil.

2. Micromedex Healthcare series.


1. Product information Zithromax.


3. Lexi-Comp's Drug Information Handbook, 13th Edition, Charles F, Lacy, et al.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



Not to be stored above 25ºC

Not longer than 24 hours

18 hours at below 25ºC



NS

D5%

Infusion concentration: 1mg/ml - 40mg/ml

NS

D5%

NS

D5%


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 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.




1. Product information Rekaxime.




1. Product information Fortum.




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



24 hours in refrigerator



NA


NS

D5%

NS

0.45%NS

D5%

NS

D5%

Ringer lactate



IV infusion: 50 to 100ml over at least 30 minutes.

IM ( Dissolve 500mg in 2ml 1% Lidocaine )


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.




1. Product information Zinacef.




1. Product information Ciprobay




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


Solution should be made up to full infusion volume,

immediately after reconstitution.

30 minutes after reconstitution.

NA


WFI

NS

NS

D5%

NS

D5%


IV Infusion: 50-100ml over 30-40 minutes

IV Infusion complete within 4 hours of reconstitution.


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



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



NS

D5% **

NS

D5%

NS

D5%

D10%

D5%NS

Mannitol 5% and 10%


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.



1. Product information Garasent.




1. Product information Tienam.

2. 2. Micromedex Healthcare series.



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


NS : 2 hours at RT, 18 hours in refrigerator.

D5% : 1 hours at RT, 8 hours in refrigerator.

NA NA


NS

D5%

NA NA


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.




1. Product information .2. Micromedex

Healthcare series.3. Lexi-Comp's Drug




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.


D5% Water for Injection

NS

D5%

Lactated ringer

Water for InjectionNS

D5%



IM : 2ml Water for Injection, NS, 1% procaine solution.

Intrathecal : 10ml physiological solution

IV bolus : slowly over 10 -15 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. Product information Easyn.



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.




Freshly prepared prior to use.


Water for Injection

NS

D5%

NS

D5%


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



1. Product information Vancotex.2. Micromedex Healthcare series.3. Lexi-Comp's Drug Information


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.




NA 24 hours at 2- 8ºC


D5%

Infusion concentration is 0.1mg/ml

NS

Ringer's Solution

Hartmann's solution

D20%

NS

D5%

Compound Sodium Lactate


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.




1. Product information Diflucan.




1. Product information Vfend.

2. 2. Micromedex Healthcare series.



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


D5%

NS

Infusion concentration should be approximately 7mg/ml or less.


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.


NA


NS

D5%

NA NA


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.




1. Product information Arixtra.




1. Product information Clexane.




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


24 hours at 2°C to 8°C


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%


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


1. Product information (Phenobarbital Sodium Injection).



1. Product information (Epilim Injection).



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.


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%


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


1. Product information ( Pentotex Injection).

2. Micromedex Healthcare series.3. Lexi-Comp's Drug Information


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


24 hours. Protect from light.24 hours.


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).


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.


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.


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


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


Companion to the handbook on Injectable Drugs.


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.


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.


- 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%


- 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


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



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.


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)


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.



1. Product information Mobitil Injection. (Duopharma)


Companion to the handbook on Injectable Drugs. 13 th edition. Lawrence A. Trissel. 2005.



23

DRUG c. Dopamine d. Noradrenaline

STRENGTH/UNIT 200mg/5ml 4mg/4ml

STORAGE Below 25˚C. Protected from lightBelow 25˚C, Protect from light



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.


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)



Do not add dopamine in any alkaline solution. It is inactivated in alkaline solution. Incompatible with

bicarbonate


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.



1. Product information Loxin Injection (Duopharma)


Companion to the handbook on Injectable Drugs. 13 th edition. Lawrence A. Trissel. 2005.



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


N/A NA NA


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


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



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


1. Product information (Pampara injection).


3. British National Formulary 56.


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


NA NA NA


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


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).


3. Britisn National Formulary 56


1. Product information (Nootropil Injection).


1. Product information ( Minirin injection).


3. Micromedex Healthcare series


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.


NA NA Use within 6 hours at room temperature.


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.


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)




1. Product information (Calcium gluconate injection)




1. Product information (Dantrium Intravenous)


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


NA NA NA


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%


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. Product information (Potassium Dihydrogen Phosphate injection)


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


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


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


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


NA NA NA


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%


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



1. Product information ( Tren Injection)

2. British National Formulary 563. Lexi-Comp's Drug Information


4. Micromedex Healthcare series5. Martindale 32nd Edition

1. Product information ( Sodium Bicarbonate 8.4% injection)



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


NA N/A


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


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)



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.


NA NA N/A


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%


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).




1. Product information (Rocuronium bromide

Injection - Esmeron).2. British National

Formulary 563. Lexi-Comp's Drug



1. Product information (Pavulon).



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.


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)


NA12 hours at 15°C to 25°C. But product

leaflet recommends to discard any unused portion.


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.


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



1. Product information (Norcuron).2. British National Formulary 563. Lexi-Comp's Drug Information


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


NA NA NA


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 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.


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).




1. Product information (Pampara injection).




1. Product information (Ventolin injection).



34

DRUG TerbutalineAminophylline

STRENGTH/UNIT 0.5mg/ml250mg/5ml

STORAGE Below 25°CBelow 25°C

RECONSTITUITION Already in solution Already in solution


N/A NA


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


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).


3. British National Formulary 56.4. Lexi-Comp's Drug Information


1. Product information (Aminophyllin IV-Fresenius injection).

2. Micromedex Healthcare series.3. British National Formulary 56.4. Lexi-Comp's Drug Information


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


NAAfter dilution, store at 2-8°C

and use within 24 hours.NA


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)


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).




1. Product information (Precedex)



1. Product information (Fresofol 1% MCT/LCT emulsion).



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.


NA NA


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


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


1. Product information (Dormicum).2. Britisn National Formulary 523. Micromedex Healthcare series.4. Lexi-Comp's Drug Information


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


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


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




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




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




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


Antagonists



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,


Antagonists



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




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




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


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


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


Paraquat Poisoning

Prevention of absorption


Adult : 25 – 100 gm

Child : 25 – 50 gm

< 1 yr : 0.5 – 1 gm/kg

Tx : Cont until pt clinical condition improve




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


1. Prevention of absorption- Activated

Charcoal

Adult : 25 – 100 gm

Child : 25 – 50 gm

< 1 yr : 0.5 – 1 gm/kg





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


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



Adult : 25 – 100 gm

Child : 25 – 50 gm

< 1 yr : 0.5 – 1 gm/kg






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



Adult : 25 – 100 gm

Child : 25 – 50 gm

< 1 yr : 0.5 – 1 gm/kg






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


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


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


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


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


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


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


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

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