Abacavir Sulfate/Lamivudine Atlanta Medicare Drug Interactions

The fixed-dose combination Abacavir 600 mg / Lamivudine 300 mg tablets contains abacavir and lamivudine, therefore any interactions identified for these individually are relevant to the fixed-dose combination Abacavir 600 mg / Lamivudine 300 mg tablets. Clinical studies have shown that there are no clinically significant interactions between abacavir and lamivudine.
Abacavir and lamivudine are not significantly metabolised by cytochrome P450 enzymes (such as CYP 3A4, CYP 2C9 or CYP 2D6) nor do they inhibit or induce this enzyme system. Therefore, there is little potential for interactions with antiretroviral protease inhibitors, non-nucleosides and other medicinal products metabolised by major P450 enzymes. The interactions listed below should not be considered exhaustive but are representative of the classes of medicinal products where caution should be exercised.
Interactions relevant to abacavir: Potent enzymatic inducers such as rifampicin, phenobarbital and phenytoin may via their action on UDP-glucuronyltransferases slightly decrease the plasma concentrations of abacavir.
The metabolism of abacavir is altered by concomitant consumption of ethanol resulting in an increase in AUC of abacavir of about 41%. These findings are not considered clinically significant. Abacavir has no effect on the metabolism of ethanol.
Retinoid compounds are eliminated via alcohol dehydrogenase. Interaction with abacavir is possible but has not been studied.
In a pharmacokinetic study, co-administration of 600 mg abacavir twice daily with methadone showed a 35% reduction in abacavir C_max and a 1 hour delay in t_max, but the AUC was unchanged. The changes in abacavir pharmacokinetics are not considered clinically relevant. In this study, abacavir increased the mean methadone systemic clearance by 22%. The induction of metabolizing enzymes cannot therefore be excluded. Patients being treated with methadone and abacavir should be monitored for evidence of withdrawal symptoms indicating under dosing, as occasionally methadone re-titration may be required.
Interactions relevant to lamivudine: The likelihood of metabolic interactions with lamivudine is low due to limited metabolism and plasma protein binding, and almost complete renal clearance. The possibility of interactions with other medicinal products administered concurrently with the fixed-dose combination Abacavir 600 mg / Lamivudine 300 mg tablets should be considered, particularly when the main route of elimination is active renal secretion, especially via the cationic transport system e.g. trimethoprim. Other medicinal products (e.g. ranitidine, cimetidine) are eliminated only in part by this mechanism and were shown not to interact with lamivudine. The nucleoside analogues (e.g. zidovudine and didanosine) are not metabolised by this mechanism and are unlikely to interact with lamivudine.
Administration of trimethoprim/sulfamethoxazole 160 mg/800 mg results in a 40% increase in lamivudine exposure, because of the trimethoprim component. However, unless the patient has renal impairment, no dosage adjustment of lamivudine is necessary. The pharmacokinetics of trimethoprim or sulfamethoxazole are not affected. When concomitant administration with cotrimoxazole is warranted, patients should be monitored clinically. Co-administration of the fixed-dose combination Abacavir 600 mg / Lamivudine 300 mg tablets with high doses of co-trimoxazole for the treatment of Pneumocystis carinii pneumonia (PCP) and toxoplasmosis should be avoided.
Co-administration of lamivudine with intravenous ganciclovir or foscarnet is not recommended until further information is available.
Lamivudine may inhibit the intracellular phosphorylation of zalcitabine when the two medicinal products are used concurrently. The fixed-dose combination Abacavir 600 mg / Lamivudine 300 mg tablets is therefore not recommended to be used in combination with zalcitabine.