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Dosage adjustment in patients with hepatic disease Return to Top

Dosage adjustment may be required in the presence of hepatic disease for the following medications (consult FDA package insert for details):

Antimicrobial Agent	Drug Category	Dosing Recommendation
Abacavir	Antiviral agent	A dose of 200 mg abacavir administered twice daily is recommended for patients with mild liver disease. The safety, efficacy, and pharmacokinetics of abacavir have not been studied in patients with moderate or severe hepatic impairment; therefore, abacavir is contraindicated in these patients.
Atazanavir	Antiviral agent	Mild hepatic impairment (Child-Pugh class A): 400 mg once daily Moderate hepatic impairment (Child-Pugh class B): 300 mg once daily Severe hepatic impairment (Child-Pugh class C): not recommended
Caspofungin	Antifungal agent	Mild hepatic impairment (Child-Pugh score 5–6): no dosage adjustment is required Moderate hepatic impairment (Child-Pugh score 7–9): 35 mg once daily following a 70-mg loading dose on day 1 Severe hepatic impairment (Child-Pugh score 10–15): no clinical experience available Pediatric patients with any degree of hepatic impairment: dosing recommendations are not available
Chloramphenicol	Antibacterial agent	Adults with impairment of hepatic function may have reduced ability to metabolize and excrete the drug. In instances of impaired metabolic processes, dosages should be adjusted accordingly. Precise control of concentration of the drug in the blood should be carefully followed in patients with impaired metabolic processes by the available microtechniques.
Clindamycin	Antibacterial agent	This product contains benzyl alcohol as a preservative and has been associated with gasping syndrome in pediatric patients. The risk of benzyl alcohol toxicity depends on the quantity administered and the hepatic capacity to detoxify the chemical.
Darunavir-Ritonavir	Antiviral agent	No dose adjustment of Darunavir/ritonavir is necessary for patients with either mild or moderate hepatic impairment. No pharmacokinetic or safety data are available regarding the use of Darunavir/ritonavir in subjects with severe hepatic impairment; therefore, Darunavir/ritonavir is not recommended for use in patients with severe hepatic impairment.
Delavirdine	Antiretroviral agent	Delavirdine is metabolized primarily by the liver. Caution should be exercised when administering delavirdine to patients with impaired hepatic function.
Efavirenz	Antiretroviral agent	Patients with mild hepatic impairment may be treated with efavirenz without any adjustment in dose. Because of the extensive cytochrome P450-mediated metabolism of efavirenz and limited clinical experience in patients with hepatic impairment, caution should be exercised in administering efavirenz to these patients. Efavirenz is not recommended for patients with moderate or severe hepatic impairment because there are insufficient data to determine whether dose adjustment is necessary.
Fosamprenavir	Antiretroviral agent	Mild Hepatic Impairment (Child-Pugh score 5–6): 700 mg twice daily without ritonavir (therapy-naive) or 700 mg twice daily plus ritonavir 100 mg once daily (therapy-naive or protease inhibitor-experienced) Moderate Hepatic Impairment (Child-Pugh score 7–9): 700 mg twice daily without ritonavir (therapy-naive), or 450 mg twice daily plus ritonavir 100 mg once daily (therapy-naive or protease inhibitor-experienced) Severe Hepatic Impairment (Child-Pugh score 10–15): 350 mg twice daily without ritonavir (therapy-naive) or 300 mg twice daily plus ritonavir 100 mg once daily (therapy-naive or protease inhibitor-experienced) Pediatric patients with any degree of hepatic impairment: dosing recommendations are not available
Indinavir	Antiretroviral agent	Patients with mild to moderate hepatic insufficiency and clinical evidence of cirrhosis had evidence of decreased metabolism of indinavir. Indinavir pharmacokinetics have not been studied in patients with severe hepatic insufficiency.
Isoniazid	Antimycobacterial agent	Patients with hepatitis attributed to isoniazid should be given appropriate treatment with alternative drugs. If isoniazid must be reinstituted, it should be administered only after symptoms and laboratory abnormalities have cleared. The drug should be restarted in very small and gradually increasing doses and should be withdrawn immediately if there is any indication of recurrent liver involvement. Preventive treatment with isoniazid should be deferred in patients with acute hepatic disease.
Itraconazole	Antifungal agent	Limited data are available on the use of itraconazole in patients with hepatic impairment. Caution should be exercised when this drug is administered in this patient population.
Lopinavir-Ritonavir	Antiretroviral agent	Lopinavir is principally metabolized and eliminated by the liver. Caution should be exercised when administering Lopinavir-Ritonavir to subjects with hepatic impairment. Lopinavir-Ritonavir has not been studied in patients with severe hepatic impairment.
Metronidazole	Antibacterial agent	Patients with hepatic impairment metabolize metronidazole slowly, with resultant accumulation of metronidazole in the plasma. For patients with mild to moderate hepatic impairment, no dosage adjustment is needed but these patients should be monitored for metronidazole associated adverse events. For patients with severe hepatic impairment (Child-Pugh class C), a reduction in metronidazole dosage by 50% is recommended.
Nafcillin	Antibacterial agent	For patients with hepatic insufficiency, measurement of nafcillin serum levels should be performed and dosage adjusted accordingly.
Nelfinavir	Antiretroviral agent	Nelfinavir may be used in patients with mild hepatic impairment without any dose adjustment. Nelfinavir should not be used in patients with either moderate or severe hepatic impairment.
Nevirapine	Antiretroviral agent	Nevirapine Nis contraindicated in patients with moderate (Child-Pugh class B) or severe (Child-Pugh class C) hepatic impairment.
Quinupristin-Dalfopristin	Antibacterial agent	The effect of dose reduction or increase in dosing interval on the pharmacokinetics of Quinupristin-Dalfopristin in patients with hepatic impairment has not been studied. No recommendations can be made regarding the appropriate dose modification.
Rifabutin	Antimycobacterial agent	Mild hepatic impairment does not require a dose modification.
Rimantadine	Antiviral agent	In patients with severe hepatic dysfunction, a dose reduction to 100 mg daily is recommended.
Ritonavir	Antiretroviral agent	No dose adjustment of ritonavir is necessary for patients with either mild (Child-Pugh class A) or moderate (Child-Pugh class B) hepatic impairment. No pharmacokinetic or safety data are available regarding the use of ritonavir in subjects with severe hepatic impairment (Child-Pugh class C); therefore, ritonavir is not recommended for use in patients with severe hepatic impairment.
Telithromycin	Antibacterial agent	Telithromycin may be administered without dosage adjustment in the presence of hepatic impairment. In the presence of severe renal impairment (CLCR < 30 mL/min) with coexisting hepatic impairment, the dose should be reduced to 400 mg once daily.
Tigecycline	Antibacterial agent	No dosage adjustment is warranted in patients with mild to moderate hepatic impairment (Child-Pugh class A and Child-Pugh class B). In patients with severe hepatic impairment (Child-Pugh class C), the initial dose should be 100 mg followed by a reduced maintenance dose of 25 mg every 12 hours.
Tinidazole	Antifungal agent	There are no data on tinidazole pharmacokinetics in patients with impaired hepatic function. Usual recommended doses of tinidazole should be administered cautiously in patients with hepatic dysfunction.
Voriconazole	Antifungal agent	Tablet: Voriconazole tablets have not been studied in patients with severe hepatic cirrhosis or in patients with chronic hepatitis B or chronic hepatitis C disease. Voriconazole tablets should only be used in patients with severe hepatic impairment if the benefit outweighs the potential risk. Patients with hepatic insufficiency must be carefully monitored for drug toxicity. Solution: The maintenance dose should be reduced in patients with mild to moderate hepatic impairment. There are no pharmacokinetic data to allow for dosage adjustment recommendations in patients with severe hepatic impairment.