Abacavir Sulphate 120 mg, Lamivudine 60 mg Tablets

Abacavir and lamivudine is an antiretroviral agent with activity against HIV-1 [see Microbiology (12.4)].

Pharmacokinetics in Adults — In a single-dose, 3-way crossover bioavailability trial of 1 abacavir and lamivudine tablet versus 2 ZIAGEN tablets (2 x 300 mg) and 2 EPIVIR tablets (2 x 150 mg) administered simultaneously in healthy subjects (n = 25), there was no difference in the extent of absorption, as measured by the area under the plasma concentration-time curve (AUC) and maximal peak concentration (C max), of each component.

Abacavir:Following oral administration, abacavir is rapidly absorbed and extensively distributed. After oral administration of a single dose of 600 mg of abacavir in 20 subjects, C maxwas 4.26 ± 1.19 mcg per mL (mean ± SD) and AUC∞ was 11.95 ± 2.51 mcg·hour per mL. Binding of abacavir to human plasma proteins is approximately 50% and was independent of concentration. Total blood and plasma drug-related radioactivity concentrations are identical, demonstrating that abacavir readily distributes into erythrocytes. The primary routes of elimination of abacavir are metabolism by alcohol dehydrogenase to form the 5’-carboxylic acid and glucuronyl transferase to form the 5’-glucuronide.

Lamivudine:Following oral administration, lamivudine is rapidly absorbed and extensively distributed. After multiple-dose oral administration of lamivudine 300 mg once daily for 7 days to 60 healthy subjects, steady-state C max(C max,ss) was 2.04 ± 0.54 mcg per mL (mean ± SD) and the 24-hour steady-state AUC (AUC 24,ss) was 8.87 ± 1.83 mcg·hour per mL. Binding to plasma protein is low. Approximately 70% of an intravenous dose of lamivudine is recovered as unchanged drug in the urine. Metabolism of lamivudine is a minor route of elimination. In humans, the only known metabolite is the trans-sulfoxide metabolite (approximately 5% of an oral dose after 12 hours).

In humans, abacavir and lamivudine are not significantly metabolized by cytochrome P450 (CYP) enzymes.

The pharmacokinetic properties of abacavir and lamivudine in fasting subjects are summarized in Table 2.

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

Specific Populations — Patients with Renal Impairment:The pharmacokinetics for the individual lamivudine component of abacavir and lamivudine has been evaluated in patients with renal impairment (see the U.S. prescribing information for the individual lamivudine component).

Patients with Hepatic Impairment:The pharmacokinetics for the individual components of abacavir and lamivudine have been evaluated in patients with varying degrees of hepatic impairment (see the U.S. prescribing information for the individual abacavir and lamivudine components).

Pregnant Women: Abacavir: Abacavir pharmacokinetics were studied in 25 pregnant women during the last trimester of pregnancy receiving abacavir 300 mg twice daily. Abacavir exposure (AUC) during pregnancy was similar to those in postpartum and in HIV-infected non-pregnant historical controls. Consistent with passive diffusion of abacavir across the placenta, abacavir concentrations in neonatal plasma cord samples at birth were essentially equal to those in maternal plasma at delivery.

Lamivudine:Lamivudine pharmacokinetics were studied in 36 pregnant women during 2 clinical trials conducted in South Africa. Lamivudine pharmacokinetics in pregnant women were similar to those seen in non-pregnant adults and in postpartum women. Lamivudine concentrations were generally similar in maternal, neonatal, and umbilical cord serum samples.