Cytochrome CYP3A4 inducer

Carbamazepine is an enzyme inducer, and its own metabolism can be induced or inhibited by other drugs, particularly those affecting cytochrome CYP3A4. 

HIV-1 infection. Like indinavir, atazanavir frequently causes unconjugated hyperbilirubinemia, although this is mainly a cosmetic side effect and is not associated with other hepatotoxicity. Because atazanavir is metabolized by cytochrome (CYP3A4), concomitant administration of agents that induce this enzyme (e.g., rifampin) is contraindicated. 

Rimonabant is partly metabolised by the cytochrome P450 isoenzyme C YP3A4. Ketoconazole, a potent CYKIA4 inhibitor, doubles the AUC of rimonabant. The manufacturers therefore expect that other potent CYP3A4 inhibitors (they name clarithromycin, itraconazole, nefazo-done, ritonavir, and teUthromycin) will also raise rimonabant levels, and they therefore advise caution on concurrent use. They similarly suggest that potent CYP3A4 inducers (such as carbamazepine, phenobarbital, phenytoin, rifampicin (rifampin) and St John s wort) may lower rimonabant levels. If concurrent use is necessary monitor to ensure that rimonabant remains effective. See Table 1.4 , (p.6), for a list of clinically relevant CYE 3A4 inducers and inhibitors. 

Pretreatment with rifampicin 600 mg once daily for 7 days reduced the AUC of erlotinib by about 66%. In another study, the AUC of a single 450-mg dose of erlotinib, taken after 11 days treatment with rifampicin was about 57% of that of erlotinib 150 mg taken without rifampicin. The manufacturers advise that alternative treatments with no cytochrome P450 enzyme-inducing activity should be considered. If this is not possible, the starting dose of erlotinib should be adjusted to 300 mg (UK) with close monitoring, and, if tolerated, further increased after 2 weeks, in 50 mg increments, to 450 mg. They also advise caution with other CYP3A4 inducers, and specifically name barbiturates, carbamazepine, phenobarbital, phenytoin, rifabutin, rifapentine, and St John s wort. 

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). 

Jushchyshyn MI, Hutzler JM, Schrag ML, Wien-kers LC (2005) Catalytic turnover of pyrene by CYP3A4 evidence that cytochrome directly induces positive cooperativity. Arch Biochem Biophys 438 21-28... 

By using in vitro preparations of human enzymes it is possible to predict those antibiotics that will adversely affect the metabolism of other drugs [110]. Such studies have shown that rifaximin, at concentrations ranging from 2 to 200 ng/ml, did not inhibit human hepatic cytochrome P450 isoenzymes 1A2, 2A6, 2B6, 2C9, 2C19, 2D6, 2E1 and 3A4 [34], In an in vitro hepatocyte induction model, rifaximin was shown to induce cytochrome P450 3A4 (CYP3A4) [34], an isoenzyme which rifampicin is known to induce [109],... 

Pharmacokinetic interactions Preliminary evidence suggests that Saint-John s-wort induces the cytochrome oxidase enzyme isoform CYP3A4 (Ernst 1999). This raises the potential for pharmacokinetic interactions with drugs metabolized by the same enzyme. A few cases have been reported of reduced warfarin levels (Yue et al. 2000). Similar interactions have also been reported for concurrent use with digoxin, theophylline, and cyclosporin (Nebel et al. 1999 Ruschitzka et al. 2000 Johne et al. 1999). As with any other medication, potential interactions should be considered when taking a combination of drugs. 

CYP3A4 7q21.1 Cytochrome P450, P450-III, steroid inducible Alprazolam, anthracychne, cisapride. Breast neoplasms. CP33 CP34 ... 

CYP 450 Drugs that induce liver enzymes (eg, phenytoin, carbamazepine, phenobarbital) increase the metabolism and clearance of zonisamide and decrease its half-life. Concurrent medication with drugs that induce or inhibit CYP3A4 would be expected to alter serum concentrations of zonisamide. Zonisamide is not expected to interfere with the metabolism of other drugs that are metabolized by cytochrome P450 isozymes. 

Amprenavir is metabolized by the cytochrome P450 enzyme system and inhibits CYP3A4. Use caution when coadministering medications that are substrates, inhibitors, or inducers of CYP3A4, or potentially toxic medications that are metabolized by CYP3A4. 

A. Diazepam is metabolized in the liver by CYP3A4 and CYP2C19 efavirenz inhibits both of these isozymes and is likely to increase plasma levels of diazepam. Diazepam is almost completely converted to inactive metabolites therefore, renal elimination is not much of a concern. Lamivudine may produce fatigue as a side effect but does not potentiate the depressant activity of diazepam. Zidovudine does not induce cytochrome P450 activity, and diazepam does not have to be converted to an active form for sedative activity. 

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