Interactions : אינטראקציות

4.5   Interaction with other medicinal products and other forms of interaction

Based on the results of in vitro experiments and the known major metabolic pathways of abacavir, the potential for P450 mediated interactions with other medicinal products involving abacavir is low.
P450 does not play a major role in the metabolism of abacavir, and abacavir does not inhibit metabolism mediated by CYP 3A4. Abacavir has also been shown in vitro not to inhibit CYP 3A4, CYP2C9 or CYP2D6 enzymes at clinically relevant concentrations. Induction of hepatic metabolism has not been observed in clinical studies. Therefore, there is little potential for interactions with antiretroviral PIs and other medicinal products metabolised by major P450 enzymes. Clinical studies have shown that there are no clinically significant interactions between abacavir, zidovudine, and lamivudine.

Potent enzymatic inducers such as rifampicin, phenobarbital and phenytoin may via their action on UDP-glucuronyltransferases slightly decrease the plasma concentrations of abacavir.

Ethanol: the metabolism of abacavir is altered by concomitant 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.

Methadone: in a pharmacokinetic study, co-administration of 600 mg abacavir twice daily with methadone showed a 35% reduction in abacavir Cmax and a one hour delay in tmax 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 drug metabolising 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.

Retinoids: retinoid compounds are eliminated via alcohol dehydrogenase. Interaction with abacavir is possible but has not been studied.