Nevirapine Rifampicin

NEVIRAPINE RIFAMPICIN 1 efficacy of nevirapine Uncertain probable t metabolism of nevirapine Avoid concomitant use. FDA recommend use only if clearly indicated and monitored closely... 

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).

Nevirapine Possibly Data are insufficient to assess whether dose adjustments are necessary when rifampicin is co administered with nevirapine. Therefore, rifampicin and nevirapine should be used only in combination if clearly indicated and with careful monitoring... 

Selander HG, Jerina DM, Daly JW (1975) Metabolism of chlorobenzene with hepatic microsomes and solubilized cytochrome P-450 systems. Arch Biochem Biophys 168 309-321 Shaffer CL, Morton MD, Hanzlik RP (2001) N-dealkylation of an N-cyclopropylamine by horseradish peroxidase. Fate of the cyclopropyl group. J Am Chem Soc 123 8502-8508 Shen C, Meng Q, Zhang G et al (2008) Rifampicin exacerbates isoniazid-induced toxicity in human but not in rat hepatocytes in tissue-Uke cultures. Br J Pharmacol 153 784-791 Shenton J, Popovic M and Uetrecht J (2007) Nevirapine Hypersensitivity. In Pichler WJ (ed) Ehug Hypersensitivity. Karger AG, Basel, pp 115-128 Shin NY, Liu Q, Stamer SL et al (2007) Protein taigets of reactive electrophiles in human liver microsomes. Chem Res Toxicol 20 859-867... 

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. 

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). The manufacturer states that the AUC of nevirapine was reduced by 58% by rifampicin in 14 subjecls, when compared with historical data. There was no change in steady-state rifampicin pharmacokinetics. Based on these pharmacokinetic data, the manufacturer suggests that the concurrent use of rifampicin with nevirapine is not recommended, and that rifabutin may be considered instead, with close monitoring of adverse effects. ... 

Ribera E, Pou L, Lopez RM, Crespo M, Falco V, Ocana I, Ruiz I, Pahissa A. Phannacokinetic interaction between nevirapine and rifampicin in HIV-infected patients with tuberculosis. J AcquirImmune Defic Syndr (2001) 28, 450-3,... 

The compound piperine has been shown to increase the bioavailability of a number of drugs and other substances. Human studies have indicated that piperine generally increases the absorption and plasma concentrations and reduces the elimination rate of drugs including phenytoin (Bano et al. 1987 Pattanaik et al. 2006 Velpandian et al. 2001), carbamazepine (Pattanaik et al. 2009), propranolol (Bano et al. 1991), theophylline (Bano et al. 1991), rifampicin (Zutshi et al. 1985), nevirapine (Kasibhatta and Naidu 2007), and the supplements coenzyme Qjq (Badmaev et al. 2000) and curcumin (Shoba et al. 1998). Increases in the plasma levels of these substances have ranged from 30 to 120%. The standard dose of piperine used in human studies is 20... 

Time course Rifampicin induces CYP3A4 at about 15 days, and interaction studies have generally started treatment with protease inhibitors within 15 days of the start of rifampicin therapy. Furthermore, pharmacological tolerance to effects can occur. The problems of variations in pharmacokinetics with time have been illustrated by a study of the effects of rifampicin on the pharmacokinetics of nevirapine in 16 patients coinfected with HTV-1 and tuberculosis [39"]. They took standard antituberculosis therapy and a fixed-dose combination of stavudine, lamivudine, and nevirapine. The median AUC of nevirapine was reduced by rifampicin by 26% at 4 weeks, but by only 7.5% at 10 weeks. The median Crm was reduced by 20% at 4 weeks and by 7.1% at 10 weeks. The authors concluded that the effect of rifampicin on the pharmacokinetics of nevirapine substantially decreases over time. 

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... 

Matteelli A, Saleri N, Villani P, Bonkoungou V, Carvalho AC, Kouanda S, Sanou MJ, Simpor6 J, Monno L, Carosi G, Regazzi M, Dembele M. Reversible reduction of nevirapine plasma concentrations during rifampicin treatment in patients coinfected with HIV-1 and tuberculosis. J Acquir Immune Defic Syndr 2009 52(1) 64-9. 

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