Ziagen Drug Interactions

Based on the results of in vitro experiments and the known major metabolic pathways of abacavir, the potential for drug interactions involving abacavir is low. Abacavir shows no potential to inhibit metabolism mediated by the cytochrome P₄₅₀ 3A4 enzyme. It has also been shown in vitro not to interact with drugs that are metabolised by CYP 3A4, CYP2C9 or CYP2D6 enzymes. Induction of hepatic metabolism has not been observed in clinical studies. Therefore, there is little potential for drug interactions with antiretroviral protease inhibitors and other drugs metabolised by major P₄₅₀ enzymes. Clinical studies have shown that there are no clinically significant interactions between abacavir, zidovudine and lamivudine.
Effect of Abacavir on the Pharmacokinetics of Other Agents: In vitro, abacavir demonstrates no or weak inhibition of the drug transporters organic anion transporter 1B1 (OATP1B1), OATP1B3, breast cancer resistance protein (BCRP) or P-glycoprotein (Pgp) and minimal inhibition of organic cation transporter 1 (OCT1), OCT2 and multidrug and toxin extrusion protein 2-K (MATE2-K). Abacavir is therefore not expected to affect the plasma concentrations of drugs that are substrates of these drug transporters.
Abacavir is an inhibitor of MATE1 in vitro, however abacavir has low potential to affect the plasma concentrations of MATE1 substrates at therapeutic drug exposures (up to 600 mg).
Effect of Other Agents on the Pharmacokinetics of Abacavir: In vitro, abacavir is not a substrate of OATP1B1, OATP1B3, OCT1, OCT2, OAT1, MATE1, MATE2-K, Multidrug resistance-associated protein 2 (MRP2) or MRP4, therefore drugs that modulate these transporters are not expected to affect abacavir plasma concentrations.
Although abacavir is a substrate of BCRP and Pgp in vitro, clinical studies demonstrate no clinically significant changes in abacavir pharmacokinetics when co-administered with lopinavir/ritonavir (Pgp and BCRP inhibitors).
Interactions relevant to abacavir: Ethanol: The metabolism of abacavir is altered by concomitant ethanol resulting in an increase in AUC of abacavir of about 41%. Given the safety profile of abacavir these findings are not considered clinically significant. Abacavir has no effect on the metabolism of ethanol.
Methadone: In a pharmacokinetic study, coadministration of 600 mg ZIAGEN twice daily with methadone showed a 35% reduction in abacavir C_max and a 1 h 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 %. This change is not considered clinically relevant for the majority of patients, however, occasionally methadone re-titration may be required.
Retinoids: Retinoid compounds such as isotretinoin, are eliminated via alcohol dehydrogenase. Interaction with abacavir is possible but has not been studied.