rifampin and Abnormalities--Drug-Induced

To review the pharmacokinetics, efficacy, adverse effects, and cost of the newest antitubercular drug, rifapentine.. A MEDLINE search using key terms such as rifapentine, rifampin, isoniazid, Mycobacterium tuberculosis, and pyrazinamide was conducted for the time period 1966-November 1998.. Animal data were used for basic information and human studies were selected for inclusion if they were randomized, controlled studies assessing efficacy, or if they were single- or multiple-dose studies assessing the pharmacokinetics of rifapentine. Background articles on the pathophysiology of tuberculosis and cost of care and noncontrolled studies assessing drug interactions were also included.. Compared with an oral solution, the relative bioavailability of rifapentine is 70% following oral admninistration of tablets. Food increased bioavailability by 55%. Rifapentine accumulated significantly in human macrophages and its elimination half-life was longer than that of rifampin. Comparative studies of rifapentine and rifampin in humans during intensive- and continuation-phase treatment of tuberculosis suggest that at currently accepted doses, rifapentine was slightly less effective than rifampin. The most significant drug interaction with rifapentine involves indinavir: the maximum concentration and AUC of indinavir are reduced by 55% and 70%, respectively, when rifapentine is coadministered with indinavir. Adverse events of rifapentine may occur less frequently at the currently recommended 600-mg dose as compared with rifampin; however, the difference was not statistically significant. If only drug costs were evaluated during the six-month treatment of tuberculosis, rifapentine is more expensive than rifampin.. Rifapentine can be administered twice weekly during the intensive phase of tuberculosis treatment and then once weekly during the continuation phase of treatment. This may improve patient adherence over some other treatments and possibly reduce costs of treatment by preventing development of resistant tubercular strains due to nonadherence. Rifapentine is well tolerated, with most patients experiencing adverse effects at a similar rate as rifampin. Rifapentine induces cytochrome P450 somewhat less than rifampin, although few drug interaction studies have been done with rifapentine. Its efficacy at the currently approved dosage of 600 mg may be slightly lower than that of rifampin. Studies are needed to determine if equal or greater efficacy can be achieved with higher doses of rifapentine. Rifampin is less expensive than rifapentine. Further pharmacoeconomic studies are needed to evaluate costs of relapse and failure in patients receiving these agents.

Topics: Abnormalities, Drug-Induced; Animals; Antibiotics, Antitubercular; Drug Interactions; Female; Humans; Lactation; Mycobacterium tuberculosis; Pregnancy; Pregnancy Complications; Rifampin; Tuberculosis

The teratogenic effects of twelve antituberculosis drugs in animal models and man are reviewed. A number of congenital malformations have been associated with the use of these agents; however, for the most part, the birth defect rate is not above that expected for the normal population. Isoniazid and ethambutol are considered the safest for maternal use. Although rifampicin appears to be more problematic, if the disease is severe or extensive, it may be added, preferably after the first trimester. Streptomycin and kanamycin are associated with eighth cranial nerve damage and should be avoided if possible during cyesis. At least five of these compounds have documented evidence of transplacental passage. In consideration of the number of drugs that are available for treatment, routine therapeutic abortions in pregnant females with tuberculosis is not medically indicated.

Topics: Abnormalities, Drug-Induced; Animals; Antitubercular Agents; Female; Humans; Isoniazid; Pregnancy; Rifampin; Risk; Streptomycin; Teratogens

The pregnant woman with tuberculosis who requires treatment presents a therapeutic dilemma; therefore, we reviewed all available literature on pregnant women treated with isoniazid (INH), ethambutol (EMB), rifampin (RMP), or streptomycin (SM) and report here on the relative safety of these drugs and whether the risk of teratogenesis justifies abortion on medical grounds. Other than the ototoxicity of SM, none of these drugs in normal dosages are proved teratogens to human fetuses. We recommend the use of INH in combination with EMB for a pregnant woman with tuberculosis, if the disease is not extensive. If a third drug is warranted, then RMP could be added. Because of its ototoxicity, SM should not be used, unless RMP is contraindicated or proves unsatisfactory. Routine therapeutic abortion is not medically indicated for a pregnant woman who is taking first-line antituberculosis drugs.

Topics: Abnormalities, Drug-Induced; Adolescent; Adult; Antitubercular Agents; Ethambutol; Female; Hearing Disorders; Humans; Isoniazid; Limb Deformities, Congenital; Pregnancy; Pregnancy Complications, Infectious; Rifampin; Streptomycin; Tuberculosis, Pulmonary

Topics: Abnormalities, Drug-Induced; Anti-Bacterial Agents; Anti-Infective Agents; Bacterial Infections; Chemical and Drug Induced Liver Injury; Drug Interactions; Drug Resistance, Microbial; Endocarditis, Bacterial; Gonorrhea; Humans; Intestinal Absorption; Leprosy; Meningococcal Infections; Mycobacterium; Respiratory Tract Infections; Rifampin; Thrombocytosis; Tuberculosis; Tuberculosis, Pulmonary; Urologic Diseases; Viruses

Topics: Abnormalities, Drug-Induced; Adolescent; Adult; Animals; Clofazimine; Dapsone; Drug Therapy, Combination; Female; Humans; Infant, Newborn; Leprostatic Agents; Leprosy; Mice; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Outcome; Rats; Retrospective Studies; Rifampin

Topics: Abnormalities, Drug-Induced; Female; Humans; Infant, Newborn; Lactation; Leprosy; Pregnancy; Pregnancy Complications, Infectious; Rifampin

Topics: Abnormalities, Drug-Induced; Animals; Antitubercular Agents; Female; Humans; Infant, Newborn; Maternal-Fetal Exchange; Pregnancy; Pregnancy Complications, Infectious; Rats; Rifampin; Risk; Tuberculosis

Topics: Abnormalities, Drug-Induced; Antitubercular Agents; Dihydrostreptomycin Sulfate; Ethambutol; Ethionamide; Female; Fetus; Hearing Disorders; Humans; Infant, Newborn; Isoniazid; Pregnancy; Pregnancy Complications, Infectious; Rifampin; Streptomycin; Tuberculosis, Pulmonary

Topics: Abnormalities, Drug-Induced; Abortion, Spontaneous; Animals; Female; Fetal Death; Hemorrhagic Disorders; Humans; Infant; Infant, Newborn; Pregnancy; Rabbits; Rats; Rifampin; Teratogens

Topics: Abnormalities, Drug-Induced; Adult; Antitubercular Agents; Drug Therapy, Combination; Ethambutol; Female; Humans; Infant, Newborn; Pregnancy; Pregnancy Complications, Infectious; Rifampin; Tuberculosis

Topics: Abnormalities, Drug-Induced; DNA-Directed RNA Polymerases; Electron Transport Complex IV; Embryo, Mammalian; Embryo, Nonmammalian; Embryonic and Fetal Development; Growth; Mitochondria; Protein Biosynthesis; Rifampin

Topics: Abnormalities, Drug-Induced; Animals; Child; Child, Preschool; Chronic Disease; Drug Therapy, Combination; Ethambutol; Female; Fetus; Follow-Up Studies; Growth; Humans; Infant; Infant, Newborn; Isoniazid; Mice; Pregnancy; Pregnancy Complications, Infectious; Rabbits; Rats; Rifampin; Tuberculosis, Pulmonary

Topics: Abnormalities, Drug-Induced; Animals; Cephalothin; Chick Embryo; Chloramphenicol; Embryo, Mammalian; Rats; Rifampin

Topics: Abnormalities, Drug-Induced; Adult; Contraceptives, Oral; Drug Antagonism; False Negative Reactions; Female; Fetus; Humans; Pregnancy; Pregnancy Complications, Infectious; Rifampin; Tuberculosis, Pulmonary

Topics: Abnormalities, Drug-Induced; Animals; Body Weight; Female; Fetus; Maternal-Fetal Exchange; Pregnancy; Rabbits; Rats; Rifampin

Topics: Abnormalities, Drug-Induced; Animals; Cleft Palate; Embryo, Mammalian; Female; Mice; Pregnancy; Rabbits; Rats; Rifampin; Spinal Dysraphism; Tooth Abnormalities

Topics: Abnormalities, Drug-Induced; Animals; Chick Embryo; Rifampin

Topics: Abnormalities, Drug-Induced; Animals; Female; Mice; Pregnancy; Pregnancy, Animal; Rats; Rifampin