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Rifampin: Drugs
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Rifampin is a potent inducer of cytochrome P-450 oxidative enzymes. A few examples of well-documented clinically significant interactions include interactions with warfarin, oral contraceptives, cyclosporine, glucocorticoids, ketoconazole or itraconazole, theophylline, quinidine sulfate, digitoxin or digoxin, verapamil hydrochloride, human immunodeficiency virus–related protease inhibitors, zidovudine, delavirdine mesylate, nifedipine, and midazolam. Recent reports have demonstrated clinically relevant interactions with numerous other drugs, such as buspirone hydrochloride, zolpidem tartrate, simvastatin, propafenone hydrochloride, tacrolimus, ondansetron hydrochloride, and opiates. Rifabutin reduces serum concentrations of antiretroviral agents, but less so than rifampin. To avoid a reduced therapeutic response, therapeutic failure, or toxic reactions when rifampin is added to or discontinued from medication regimens, clinicians need to be cognizant of these interactions. Enhanced knowledge of known interactions will continue to develop, including research on the induction of specific cytochrome P-450 isoenzymes and on the importance of the P-glycoprotein transport system.
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Rifampin is a rifamycin antibiotic used to treat tuberculosis (TB), as well as to treat those who have been exposed to meningitis-causing bacteria before they become sick. This drug does not treat acute meningitis. Rifampin may ... be used to treat other conditions as determined by your doctor.
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Rifampin comes in pill and injectable forms. The drug is usually taken orally. Dosage is 600 mg per day or 450 mg per day for people weighing less than 50 kg. Rifampin interacts with ketoconazole in the body and can reduce the effectiveness of both drugs. Rifampin reduces the effectiveness of methadone and may lead to withdrawal symptoms. Rifampin lowers serum dapsone levels, so the two drugs should not be used together. Rifampin can decrease the effectiveness of oral contraceptives.
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Rifampin acts by disrupting protein synthesis through inhibiting DNA-dependent RNA polymerase in susceptible bacteria. It is generally well tolerated for short-term use, but has the potential for significant adverse effects, and many drug interactions (rifampin can reduce serum concentrations of other medications) are documented.
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Rifampin is heavily metabolized in the liver. Rifampin's tendency to "dominate" the liver's metabolism may cause other drugs to be "shunted" aside, and eventually eliminated through the urine before they are completely absorbed. In other cases, rifampin may interact with other drugs, reducing the effectiveness of one or both drugs. Some common AIDS treatment drugs (e.g. ketoconazole, dapsone) may have reduced effectiveness when they are taken with rifampin. In such cases, the dosages of drugs may need to be increased or alternate drugs used.
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MECHANISM OF ACTION — Rifampin is thought to inhibit bacterial DNA-dependent RNA polymerase, which is not a mechanism of action shared with other antibiotics. This effect on RNA polymerase appears to result from drug binding in the polymerase subunit deep within the DNA/RNA channel where direct blocking of the elongating RNA can occur [2].
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