Maraviroc Rifampicin

Efavirenz reduces the plasma levels of maraviroc by about 50% and rifampicin reduces them by about two-thirds. A regimen containing nevirapine appeared to have little effect on the levels of a single dose of maraviroc. 

In a placebo-controlled study in healthy subjects, rifampicin 600 mg once daily for 14 days reduced the steady-state AUC and maximum and minimum plasma levels of maraviroc 100 mg twice daily by about two-thirds. Doubling the dose of maraviroc to 200 mg twice daily overcame this increased metabolism, resulting in an AUC comparable to that of maraviroc 100 mg twice daily alone. ... 

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). 

The pharmacokinetic interactions with efavirenz and rifampicin are likely to be clinically important. The reduction in maraviroc plasma levels seen could result in decreased efficacy and the development of viral resistance. Doubling the dose of maraviroc overcame this interaction, and this is the suggested approach of the manufacturer when maraviroc is used in the absence of protease inhibitors. Efavirenz appears to halve the increase in maraviroc levels seen with ritonavir-boosted protease inhibitors. 

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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