Maraviroc CYP3A4 inducers

CCR5 antagonists are a new class of entry inhibitors currently under development. Maraviroc is the nearest to marketing, and is a substrate of CYP3A4. Because of this, CYP3A4 inducers (e.g. efavirenz) lower its levels and CYP3A4 inhibitors (e.g. protease inhibitors) increase its levels. 

Maraviroc is a substrate of the cytochrome P450 isoenzyme CYP3A4, and its levels would therefore be expected to be reduced by inducers of this enzyme, such as efavirenz and rifampicin. For a list of CYP3A4 inducers, see Table 1.4 , (p.6). 

In a placebo-controlled, crossover study in healthy subjects maraviroc 300 mg twice daily had no clinically relevant effect on the pharmacokinetics of zidovudine/lamivudine (Ctmbivir) 300/150 mg twice daily, when they were given together for one week. For the effect of other NRTIs in combination with protease inhibitors or NNRTIs on maraviroc, see CYP3A4 inhibitors , (p.780) and CYP3A4 inducers , (p.780), and for the effect of tenofovir, see Drugs that affect renal clearance , (above). 

Abel S, Jenkins TM, Whitlock LA, Ridgway CE, Muirhead GJ. Effects of CYP3A4 inducers with and without CYP3A4 inhibitors on the pharmacokinetics of maraviroc in healthy volunteers. Br J Clin Pharmacol 2008 65(Suppl 1) 38-46. 

Drug-drug interactions Maraviroc is a substrate of P glycoprotein and CYP3A4, by which it is about 65% metabolized. Maraviroc should therefore be used with caution when inhibitors of CYP3A4 are used concomitantly. Potent CYP 3A4 inhibitors, such as ketoconazole and protease inhibitors, except tipranavir + ritonavir, increase maraviroc exposure dosage reduction can compensate [246 ]. Conversely, enzyme inducers, such as rifampicin and efavirenz, reduce exposure [247 ]. In contrast, drugs... 

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