Rifampicin Efavirenz

EFAVIRENZ RIFAMPICIN Possible 1 efficacy of efavirenz Uncertain t dose of efavirenz from 600 mg to 800 mg... 

Fig. 8.29 Structures of known clinical CYP3A4 inducers nevirapine (A), troglitazone (B), phenobarbitone (C), efavirenz (D), probenicid (E), phenytoin (F), moricizine (G), felbamate (H), rifampicin (I) and carba-mazepine (J).

Rifampicin modestly reduces the trough levels of caspofungin after 2 weeks of concurrent use, but this is not thought to be due to increased metabolism. One case of caspofungin treatment failure has been reported in a patient taking rifampicin. Other enzyme inducers (carbamazepine, dexamethasone, efavirenz, nevirapine, and phenytoin) also appeared to reduce caspofungin levels. Rifampicin and other unnamed enzyme inducers did not appear to alter anidulafungin clearance. 

The manufacturers report that carbamazepine reduced the mean maximum plasma concentration and AUC of aripiprazole 30 mg by 68% and 73%, respectively. They recommend that the dose of aripiprazole is doubled when taken with carbamazepine. Other potent inducers of CYP3A4, such as efavirenz, nevirapine, phenytoin, phenobarbital, primidone, rifabutin, rifampicin and St John s wort are expected to have similar effects and an increase in the dose of aripiprazole may also be necessary if these drugs are given. ... 

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. 

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. 

Rifabutin and rifampicin (rifampin) cause a very marked fall in delavirdine plasma levels rifabutin levels are raised when the delavirdine dose is increased to compensate for this. Rifabutin does not affect efavirenz levels, whereas efavirenz decreases rifabutin levels. There is usually no important interaction between rifabutin and nevirapine, although some patients may have a higher risk of rifabutin adverse effects. 

Neither efavirenz nor nevirapine affect rifampicin levels, but rifampicin modestly reduces the levels of these NNRTIs, and there is some debate about whether it is necessary to increase their dose. 

Rifampicin (Rifampin). In patients with HIV and tuberculosis the concurrent use of HAART including efavirenz 600 mg once daily with antituber-cular therapy including rifampicin 480 to 720 mg daily decreased the AUC of efavirenz by 22% and decreased the trough concentration by 25% (although large interpatient variability was observed). Overall the pharmacokinetics of efavirenz 800 mg daily with rifampicin were similar to those... 

Lopez-Cort s LF, Ruiz-Valderas R, VicianaP, Alarcon-Gonzalez A, Gomez-Mateos J, Leon-Jimenez E, Sarasa-Nacenta L6pez-Pua Y, Pachon J. Pharmacokinetic interactions between efavirenz and rifampicin in HIV-infected patients with tuberculosis. Clin Pharmacok-inet 2002) 41,681-90,... 

Brerinan-Benson P, Lyus R, Harrison T, Pakianathan M, Macallan D. Pharmacokinetic interactions between efavirenz and rifampicin in the treatment of HIV and tuberculosis one size does not fit all. (2005) 19, 1541-3. 

Manosuthi W, Kiertiburanakul S, Sungkanuparph S, Ruxrungtham K, Vibhagool A, Rattan-asiri S, Thakkinstian A. Efavirenz 600 mg/day versus efavirenz 800 mg/day in HIV-infected patients with tuberculosis receiving rifampicin 48 weeks results. AIDS (2006) 20, 131-2. 

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... 

In a prospective randomized comparison of standard doses of efavirenz-based and nevirapine-based antiretroviral drug therapy, 142 patients with concurrent HIV-1 infection and tuberculosis who were taking rifampicin were randomized to antiretroviral drug therapy that included either efavirenz 600 mg/day or nevirapine 400 mg/day [40 ]. Efavirenz and nevirapine concentrations at 12 hours after dosing were monitored at weeks 6 and 12. CD4+ cell counts and HlV-1 RNA concentrations were assessed every 12 weeks. At weeks 6 and 12, the mean efavirenz concentrations were 4.3 and 3.5 mg/l respectively, and the mean nevirapine concentrations were 5.6 and 5.6 mg/l respectively. At week 12, 3.1% of patients taking efavirenz group and 21 % of those taking nevirapine had concentrations that were less than the recommended minimum concentrations (OR = 8.4 95% Cl = 1.8, 39). Intention-to-treat analysis... 

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