THE APhA COMPLETE REVIEW FOR PHARMACY, 7th Ed

Appendix C: Drugs in Hepatic Failure

Drug

Trade name

Dose

Abacavir

Ziagen

For mild impairment, use 200 mg bid; abacavir is contraindicated in patients with moderate to severe impairment.

Acetaminophen

Cetafen, FeverAll, Silapap, Tylenol

Use with caution; avoid chronic use in patients with impairment.

Amiodarone

Cordarone, Pacerone

Dose adjustment may be necessary in patients with hepatic dysfunction.

Amitriptyline

Elavil

Begin with low initial doses, and increase dose as tolerated and needed.

Amlodipine

Norvasc

Start dose at 2.5 mg po daily.

Amoxicillin-clavulanic acid

Augmentin

Use with caution in patients with impairment, and monitor hepatic function with prolonged use.

Aspirin

 

Avoid in patients with severe hepatic dysfunction.

Atomoxetine

Strattera

Decrease dose by 50% in patients with moderate hepatic dysfunction; give 25% of normal dose if hepatic dysfunction is severe.

Azathioprine

Imuran

Monitor hepatic transaminases every 2 weeks for 4 weeks, then monthly thereafter.

Azithromycin

Zithromax

Use with caution in patients with impairment because of potential for hepatotoxicity.

Azole antifungals:

   
 

Fluconazole

Diflucan

No adjustments are necessary.

 

Itraconazole

Sporanox

Adjustments may be necessary, but no guidelines are available.

 

Ketoconazole

Nizoral

Dose reduction should be considered in patients with severe liver disease.

 

Posaconazole

Noxafil

Use with caution.

 

Voriconazole

VFEND

For patients with mild to moderate hepatic dysfunction, use standard loading dose; reduce maintenance dosage by 50% for patients with severe hepatic impairment; use only when benefit outweighs risk; monitor closely for toxicity.

Benzodiazepines:

   
 

Alprazolam

Xanax

Reduce by 50-60% or avoid in patients with cirrhosis.

 

Chlordiazepoxide

Librium

Avoid or decrease dose in patients with cirrhosis or hepatitis (5 mg po bid-qid).

 

Diazepam

Valium

Decrease dose by 50% in patients with liver disease.

 

Lorazepam

Ativan

Use with caution.

 

Midazolam

Versed

Dose reduction of 50% may be necessary.

 

Oxazepam

Serax

No dose adjustments are necessary.

 

Temazepam

Restoril

No dose adjustments are necessary.

 

Triazolam

Halcion

Dose reduction of 50% may be necessary (0.125 mg po at night).

Bicalutamide

Casodex

No adjustment is needed; use with caution in patients with moderate to severe hepatic dysfunction; discontinue if alanine transaminase > 2 times upper limit of normal or jaundice develops.

Bisoprolol

Zebeta

Decrease initial dose to 2.5 mg in patients with hepatic insufficiency; do not exceed a dose of 10 mg daily.

Bosentan

Tracleer

Liver function should be tested monthly; adjust or discontinue accordingly.

Buspirone

Buspar

Avoid in patients with severe hepatic dysfunction; use lower initial doses, and increase gradually as needed and tolerated.

Bupivacaine

Marcaine, Sensorcaine

Dose adjustment is recommended in patients with severe disease; use with caution.

Carbamazepine

Tegretol

Avoid in patients with hepatic disease.

Celecoxib

Celebrex

Decrease dose by 50% in patients with moderate hepatic dysfunction; avoid in patients with severe hepatic dysfunction.

Chlorambucil

Leukeran

Adjustment may be necessary in patients with impairment.

Chloramphenicol

 

Use with caution; monitor serum concentrations; dose may be decreased in patients with hepatic impairment.

Chlorpromazine

Thorazine

Use doses in the lower ranges with frequent monitoring and gradual dose adjustment.

Cimetidine

Tagamet

Decrease dose by 50% in patients with severe hepatic dysfunction.

Clindamycin

Cleocin

Decrease dose in patients with severe hepatic dysfunction.

Clomiphene

Clomid, Serophene

Clomiphene is contraindicated in patients with liver disease.

Codeine

 

Dose adjustment may be necessary; use with caution in patients with severe impairment.

Cyclosporin

Gengraf, Neoral, Restasis, Sandimmune

Dose adjustment may be necessary; monitor levels closely.

Cytarabine

Cytosar

Dose reduction may be necessary; use with caution in patients with hepatic impairment.

Dacarbazine

DTIC

Dacarbazine may cause hepatotoxicity; monitor closely for signs.

Darunavir

Prezista

No dose adjustment is needed for patients with mild to moderate hepatic impairment; avoid in patients with severe impairment; monitor liver function tests at baseline, then periodically thereafter.

Daunorubicin

Cerubidine

If bilirubin is 1.2-3 mg/dL, reduce dose by 25%; if > 3 mg/dL, reduce dose by 50%.

Delavirdine

Rescriptor

Use with caution in patients with hepatic impairment.

Didanosine

Videx

Consider dose adjustment; monitor for toxicity.

Diltiazem

Cardizem, Cartia, Dilacor, Tiazac

Use with caution because diltiazem is extensively metabolized by the liver.

Disulfiram

Antabuse

Use with caution in patients with hepatic cirrhosis or hepatic insufficiency; avoid in patients with advanced or severe hepatic disease.

Doxorubicin

Adriamycin, Rubex

If bilirubin is 1.2-3 mg/dL, reduce dose by 50%; if bilirubin is 3.1-5 mg/dL, reduce dose by 75%.

Efavirenz

Sustiva

Use with caution in patients with hepatic impairment.

Erythromycin

E-Mycin

Dose reduction may be necessary in patients with hepatic dysfunction.

Esomeprazole

Nexium

Do not exceed a dose of 20 mg in patients with severe hepatic dysfunction.

Estrogens

 

Use with caution in patients with impaired liver function.

Felodipine

Plendil

Initial dose is 2.5 mg/day; monitor blood pressure.

Flecainide

Tambocor

Flecainide has an increased half-life in patients with hepatic impairment; monitor plasma levels; avoid use in patients with significant impairment.

Flumazenil

Romazicon

Use caution with initial and repeated doses in patients with liver disease.

Fluorouracil

Adrucil, Carac, Efudex, Fluoroplex

Use with extreme caution.

Fluphenazine

Prolixin

Use with caution.

Furosemide

Lasix

Furosemide has a diminished natriuretic effect with increased sensitivity to hypokalemia and volume depletion in patients with cirrhosis; monitor effects, especially with high doses.

Griseofulvin

Grifulvin, Gris-PEG

Griseofulvin is contraindicated in patients with severe liver disease.

Haloperidol

Haldol

Use with caution in patients with hepatic impairment.

3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors

 

Avoid in patients with elevated serum transaminases.

Ibuprofen

Addaprin, Advil, Genpril, I-Prin, Midol, Motrin, NeoProfin, Proprinal, Ultraprin

Use with caution in patients with hepatic impairment; avoid in patients with severe impairment.

Indinavir

Crixivan

Decrease dose to 600 mg q8h in patients with mild to moderate hepatic dysfunction.

Interferon beta-1a

Avonex

Consider a dose reduction if serum glutamic pyruvic transaminase > 5 times upper limit of normal; discontinue if jaundice or other symptoms of liver disease develop.

Interferon beta-1b

Betaseron

Test liver function at months 1, 3, and 6, then periodically thereafter.

Isoniazid

Laniazid, Nydrazid

Lower doses may be necessary; defer therapy for treatment of latent tuberculosis infection in patients with acute hepatic disease.

Isotretinoin

Accutane

Empiric dose reductions are recommended in patients with hepatitis; monitor liver function tests at baseline, then at weekly or biweekly intervals until a response to the treatment is established.

Lamivudine-zidovudine

Combivir

Fixed-dose combinations should not be used in patients with impaired hepatic function; lamivudine-zidovudine is contraindicated in patients with hepatic impairment.

Lamotrigine

Lamictal

Reduce initial, escalation, and maintenance doses by 25% in patients with moderate to severe hepatic impairment without ascites; decrease doses by 50% in patients with severe hepatic dysfunction with ascites.

Lansoprazole

Prevacid

Decrease dose in patients with severe hepatic dysfunction.

Leflunomide

Arava

Avoid in patients with moderate to severe hepatic dysfunction; decrease dose to 10 mg/d if liver enzymes are elevated to 2 times the upper limit of normal; discontinue if liver enzymes are elevated to 3 times the upper limit of normal.

Levonorgestrel

Mirena, Plan B

Levonorgestrel is contraindicated in patients with acute liver disease.

Lidocaine

Xylocaine

Dose adjustments may be required.

Losartan

Cozaar

Initiation of therapy at a reduced dosage may be advisable in patients with hepatic impairment.

Medroxyprogesterone

Depo-Provera, Provera

Medroxyprogesterone is contraindicated in patients with severe hepatic impairment.

Mefloquine

Lariam

Mefloquine may have increased half-life and plasma levels.

Mercaptopurine

Purinethol

Dose reduction may be necessary in patients with hepatic impairment.

Metformin

Glucophage

Avoid; liver disease is a risk factor for developing lactic acidosis during therapy.

Methadone

Dolophine

Adjust dose in patients with impairment because of risk of accumulation; avoid in patients with severe disease.

Methotrexate

Folex, Rheumatrex

Decrease dose by 25% when bilirubin is 3.1-5 mg/dL or aspartate transaminase is > 180 IU; avoid if bilirubin is > 5 mg/dL.

Methyldopa

Aldomet

Methyldopa is contraindicated in patients with liver disease.

Metoprolol

Lopressor

Dose adjustment may be necessary in patients with hepatic insufficiency; no recommendations are available.

Metronidazole

Flagyl

Decrease dose in patients with severe disease; no recommendations are available.

Mexiletine

Mexitil

Decrease dose to 25-30% of normal dose.

Morphine

Avinza, DepoDur, Duramorph, Infumorph, Kadian, MS Contin, Oramorph SR, Roxanol

Decrease dose in patients with cirrhosis.

Nabumetone

Relafen

Use with caution in patients with severe hepatic insufficiency; reduce dose if necessary.

Nefazodone

Serzone

Avoid in patients with elevated transaminases.

Nelfinavir

Viracept

No adjustment is necessary for patients with mild impairment; use is not recommended in patients with moderate to severe impairment.

Nevirapine

Viramune

Nevirapine is contraindicated in patients with moderate to severe impairment.

Nifedipine

Adalat, Procardia

Decrease dose by 50-60% in patients with cirrhosis.

Nisoldipine

Sular

Starting dose is not to exceed 8.5 mg/d in patients with liver impairment.

Ofloxacin

Floxin

Do not exceed 400 mg/d in patients with severe liver dysfunction.

Omeprazole

Prilosec

Decrease dose in patients with hepatic dysfunction.

Ondansetron

Zofran

Do not exceed 8 mg/d in patients with severe hepatic insufficiency.

Oxycodone

Oxycontin

Dose should be decreased in patients with severe liver disease.

Pantoprazole

Protonix

Adjustment is not required.

Pioglitazone

Actos

For alanine aminotransferase < 2.5 upper limit of normal, use caution; for active liver disease (alanine aminotransferase > 2.5 upper limit of normal), avoid use.

Phenobarbital

Barbita, Luminal, Solfoton

Dose reduction may be necessary in patients with hepatic dysfunction.

Phenytoin

Dilantin

Monitor levels frequently because dose reduction may be necessary in patients with hepatic insufficiency; increased unbound concentrations may occur.

Prednisolone

Econopred, Orapred, Pediapred, Pred Forte, Pred Mild, Prelone

Prednisolone is contraindicated in patients with cirrhosis; use with caution in patients with severe hepatic impairment.

Procainamide

Procanbid, Promine, Pronestyl, Rhythmin

Lower doses or longer dosing intervals may be required in patients with hepatic failure.

Procarbazine

Matulane

Use with caution in patients with impairment.

Propranolol

Betachron, Inderal

Marked slowing of heart rate may occur in patients with chronic liver disease with conventional doses; low initial dose and slow titration are suggested. Monitor more frequently in patients with hepatic dysfunction; regular heart rate monitoring is recommended.

Pyrazinamide

 

Pyrazinamide is contraindicated in patients with severe dysfunction.

Quinidine

Cardioquin, Quinaglute, Quinalan, Quinidex, Quinora

Reduction of maintenance doses by 50% may be necessary in patients with hepatic impairment; monitor serum levels closely.

Ranitidine

Zantac

Ranitidine may have minor changes in half-life, distribution, clearance, and bioavailability; no adjustment is necessary; monitor serum levels and liver function tests.

Ribavirin

Copegus, Rebetol, Ribasphere, Virazole

Ribavirin is contraindicated in patients with hepatic decompensation.

Rifampin

Rifadin, Rimactane

Dose reductions may be necessary to reduce hepatotoxicity; use with caution or avoid in patients with hepatic impairment.

Risperidone

Risperdal

Decrease dose in patients with hepatic dysfunction. For IM, administer titrated oral doses prior to starting IM. For po, start at 0.5 mg bid and titrate.

Ritonavir

Norvir

No adjustments are needed; monitor closely. Decrease dose about 40% in steady state in patients with mild to moderate impairment. No data are available for patients with severe impairment; monitor closely.

Saquinavir

Fortovase, Invirase

Use with caution in patients with mild to moderate hepatic impairment; saquinavir is contraindicated in patients with severe impairment.

Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors:

 

Dose should be decreased or dosing interval increased in patients with hepatic insufficiency.

 

Citalopram

Celexa

A 20-mg dose is recommended for patients with decreased hepatic function; dosage may be increased to 40 mg/d only in nonresponsive patients.

 

Fluoxetine

Prozac

A lower or less frequent dose is recommended in patients with hepatic impairment because of a prolonged elimination half-life.

 

Fluvoxamine

Luvox

Decrease the dose or frequency, and titrate slowly in patients with hepatic insufficiency.

 

Paroxetine

Paxil

Dose initially at 10 mg qd or at 12.5 mg qd of the controlled-release product; doses should not exceed 40 mg qd or 50 mg qd of the controlled-release product.

 

Sertraline

Zoloft

Decrease the dose, or increase the interval.

 

Venlafaxine

Effexor

Decrease the dose by 50% in patients with mild to moderate hepatic impairment.

Sodium nitroprusside

Nipride, Nitropress

Use with caution in patients with hepatic impairment.

Succinylcholine

Anectine, Quelicin

Decrease dose in patients with severe disease.

Sulfamethoxazole-trimethoprim

Bactrim, Setpra, Sulfatrim

Sulfamethoxazole-trimethoprim is contraindicated in patients with marked hepatic damage if not monitored.

Sulfonylureas:

 

Dose reduction may be necessary in patients with hepatic disease.

 

Chlorpropamide

Diabinese

Use conservative initial and maintenance doses.

 

Glimepiride

Amaryl

Use conservative initial and maintenance doses.

 

Glipizide

Glucotrol

Start dose at 2.5 mg po qd.

 

Glyburide

Diabeta, Glynase, Micronase

Use conservative initial and maintenance doses; avoid use in patients with severe disease.

 

Tolazamide

Tolinase

Use conservative initial and maintenance doses.

 

Tolbutamide

Orinase

Use conservative initial and maintenance doses.

Tacrolimus

Prograf

Dose at the low end of the dosing range in patients with hepatic impairment; consider dose adjustment; monitor closely.

Testosterone

Androderm, Androgel, Delatestryl, Depo-Testosterone, First-Testosterone MC, Striant, Testim, Testopel

Decrease dose in patients with impairment; testosterone is contraindicated in patients with severe hepatic impairment.

Tetracycline

Sumycin

Use with caution in patients with impairment.

Theophylline

Aerolate, Aminophyllin, Aquaphyllin, Asmalix, Bronkodyl, Choledyl, Duraphyl, Respbid, Slo-bid, Slo-Phyllin, Sustaire, Theo-24, Theobid, Theochron, Theoclear, Theo-Dur, Theolair, Theon, Theospan, Theovent, Truphylline

Dose reduction may be necessary in patients with hepatic insufficiency; monitor serum levels frequently.

Tiagabine

Gabitril

Dose adjustments may be necessary in patients with impairment caused by decreased clearance.

Tipranavir

Aptivus

No dose adjustment is necessary for patients with mild impairment. Tipranavir is contraindicated in patients with moderate to severe hepatotoxicity; monitor liver functions at baseline, then periodically thereafter.

Tramadol

Ultram

Immediate release: Dose 50 mg po q12h in patients with cirrhosis. Extended release: This form is not recommended.

Tricyclic antidepressants:

 

Start low dose initially, and increase as needed and tolerated.

 

Amitriptyline

Elavil

 
 

Clomipramine

Anafranil

 
 

Desipramine

Norpramin

 
 

Doxepin

Sinequan

 
 

Imipramine

Tofranil

 
 

Nortriptyline

Pamelor

 
 

Protriptyline

Vivactil

 

Valproic acid

Depakene, Depakote

Avoid in patients with hepatic disease or significant hepatic insufficiency.

Verapamil

Calan, Covera, Isoptin, Verelan

Decrease dose by 20-50% in patients with impairment.

Vinblastine

Velban

If bilirubin is > 3 mg/100mL, reduce dose by 50%.

Vincristine

Vincasar PFS

If bilirubin is > 3 mg/100mL, reduce dose by 50%.

Warfarin

Coumadin

Use initial dose of 5 mg or less, with adjustments based on international normalized ratio.

Zafirlukast

Accolate

Consider a decreased dose in patients with impairment; monitor for adverse effects.

Zalcitabine

Hivid

Avoid in patients with liver function tests > 5 times the upper limit of normal.

Zidovudine

Retrovir

Decrease daily dose or extend dosing interval.

Reference

Micromedex Healthcare Series. Greenwood Village, Colo.: Thomson Healthcare. Available at: www.thomsonhc.com. Updated periodically.