Effect of Food on Absorption of EPZICOM: EPZICOM may be administered with or without food. Administration with a high-fat meal in a single-dose bioavailability study resulted in no change in AUClast, AUC∞, and Cmax for lamivudine. Food did not alter the extent of systemic exposure to abacavir (AUC∞), but the rate of absorption (Cmax) was decreased approximately 24% compared to fasted conditions (n = 25). These results are similar to those from previous studies of the effect of food on abacavir and lamivudine tablets administered separately.

Special Populations: Impaired Renal Function:

EPZICOM: Because lamivudine requires dose adjustment in the presence of renal insufficiency, EPZICOM is not recommended for use in patients with creatinine clearance <50 mL/min (see PRECAUTIONS).

Impaired Hepatic Function: EPZICOM: Abacavir is contraindicated in patients with moderate to severe hepatic impairment and dose reduction is required in patients with mild hepatic impairment. Because EPZICOM is a fixed-dose combination and cannot be dose adjusted, EPZICOM is contraindicated for patients with hepatic impairment.

Pregnancy: See PRECAUTIONS: Pregnancy.

Abacavir and Lamivudine: No data are available on the pharmacokinetics of abacavir or lamivudine during pregnancy.

Nursing Mothers: See PRECAUTIONS: Nursing Mothers.

Abacavir: No data are available on the pharmacokinetics of abacavir in nursing mothers. Lamivudine: Samples of breast milk obtained from 20 mothers receiving lamivudine monotherapy (300 mg twice daily) or combination therapy (150 mg lamivudine twice daily and 300 mg zidovudine twice daily) had measurable concentrations of lamivudine.

Pediatric Patients: EPZICOM: The pharmacokinetics of EPZICOM in pediatric patients are under investigation. There are insufficient data at this time to recommend a dose (see PRECAUTIONS: Pediatric Use).

Geriatric Patients: The pharmacokinetics of abacavir and lamivudine have not been studied in patients over 65 years of age.

Gender: Abacavir: A population pharmacokinetic analysis in HIV-infected male (n = 304) and female (n = 67) patients showed no gender differences in abacavir AUC normalized for lean body weight.

Lamivudine: A pharmacokinetic study in healthy male (n = 12) and female (n = 12) subjects showed no gender differences in lamivudine AUC∞ normalized for body weight.

Race: Abacavir: There are no significant differences between blacks and Caucasians in abacavir pharmacokinetics.

Lamivudine: There are no significant racial differences in lamivudine pharmacokinetics.

Drug Interactions: See PRECAUTIONS: DRUG INTERACTIONS: The drug interactions described are based on studies conducted with the individual nucleoside analogues. In humans, abacavir and lamivudine are not significantly metabolized by cytochrome P450 enzymes nor do they inhibit or induce this enzyme system; therefore, it is unlikely that clinically significant drug interactions will occur with drugs metabolized through these pathways.

Abacavir: Fifteen HIV-infected patients were enrolled in a crossover-designed drug interaction study evaluating single doses of abacavir (600 mg), lamivudine (150 mg), and zidovudine (300 mg) alone or in combination. Analysis showed no clinically relevant changes in the pharmacokinetics of abacavir with the addition of lamivudine or zidovudine or the combination of lamivudine and zidovudine. Lamivudine exposure (AUC decreased 15%) and zidovudine exposure (AUC increased 10%) did not show clinically relevant changes with concurrent abacavir.

In a study of 11 HIV-infected patients receiving methadone-maintenance therapy (40 mg and 90 mg daily), with 600 mg of ZIAGEN twice daily (twice the currently recommended dose), oral methadone clearance increased 22% (90% CI 6% to 42%). This alteration will not result in a methadone dose modification in the majority of patients; however, an increased methadone dose may be required in a small number of patients.

Lamivudine: No clinically significant alterations in lamivudine or zidovudine pharmacokinetics were observed in 12 asymptomatic HIV-infected adult patients given a single dose of zidovudine (200 mg) in combination with multiple doses of lamivudine (300 mg q 12 hr). Lamivudine pharmacokinetics are not significantly affected by abacavir.

Table 2. Effect of Coadministered Drugs on Abacavir and Lamivudine AUC*
Note: ROUTINE DOSE MODIFICATION OF ABACAVIR AND LAMIVUDINE IS NOT WARRANTED WITH COADMINISTRATION OF THE FOLLOWING DRUGS.

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