Ansamycin - General Information
A broad-spectrum antibiotic that is being used as prophylaxis against disseminated Mycobacterium avium complex infection in HIV-positive patients.
Pharmacology of Ansamycin
Ansamycin is an antibiotic that inhibits DNA-dependent RNA polymerase activity in susceptible cells. Specifically, it interacts with bacterial RNA polymerase but does not inhibit the mammalian enzyme. It is bactericidal and has a very broad spectrum of activity against most gram-positive and gram-negative organisms (including Pseudomonas aeruginosa) and specifically Mycobacterium tuberculosis. Because of rapid emergence of resistant bacteria, use is restricted to treatment of mycobacterial infections and a few other indications. Ansamycin is well absorbed when taken orally and is distributed widely in body tissues and fluids, including the CSF. It is metabolized in the liver and eliminated in bile and, to a much lesser extent, in urine, but dose adjustments are unnecessary with renal insufficiency.
Ansamycin for patients
Patients should be advised of the signs and symptoms of both MAC and tuberculosis, and should be instructed to consult their physicians if they develop new complaints consistent with either of these diseases. In addition, since MYCOBUTIN may rarely be associated with myositis and uveitis, patients should be advised to notify their physicians if they develop signs or symptoms suggesting either of these disorders.
Urine, feces, saliva, sputum, perspiration, tears, and skin may be colored brown-orange with rifabutin and some of its metabolites. Soft contact lenses may be permanently stained. Patients to be treated with MYCOBUTIN should be made aware of these possibilities.
Effects on Other Drugs: Rifabutin induces CYP3A enzymes and therefore may reduce the plasma concentrations of drugs metabolized by those enzymes. This effect may reduce the efficacy of standard doses of such drugs, which include itraconazole, clarithromycin, and saquinavir.
Effects on Rifabutin: Some drugs that inhibit CYP3A may significantly increase the plasma concentration of rifabutin. Because high plasma levels of rifabutin may increase the risk of adverse reactions, carefully monitor patients receiving coadministration of such drugs, which include fluconazole and clarithromycin. In some cases, the dosage of MYCOBUTIN may need to be reduced when it is coadministered with such a drug.
Delavirdine: Coadministration of rifabutin and delavirdine is not recommended because rifabutin substantially decreases the plasma concentrations of delavirdine, and delavirdine increases the plasma concentrations of rifabutin.
Indinavir: Coadministration of indinavir and rifabutin increases the plasma concentration of rifabutin. In patients receiving coadministration of indinavir, reduce the dosage of MYCOBUTIN by half.
Nelfinavir: Coadministration of nelfinavir increases the plasma concentration of rifabutin. In patients receiving nelfinavir, reduce the dosage of MYCOBUTIN by half.
Ritonavir: Coadministration of ritonavir is not recommended because it substantially increases the plasma concentration of rifabutin. High plasma concentrations of rifabutin may increase the risk of adverse reactions, including uveitis.
Oral contraceptives: Rifabutin may decrease the efficacy of oral contraceptives by inducing drug metabolism of ethinylestradiol and norethindrone. Women using oral contraceptives should be advised to change to or supplement with nonhormonal methods of birth control during treatment with MYCOBUTIN.
Other drugs: The structurally similar drug, rifampin, is known to reduce the plasma concentrations of a number of other drugs. Although rifabutin is a weaker enzyme inducer than rifampin, it may be expected to have some effect on those drugs as well.
MYCOBUTIN Capsules are contraindicated in patients who have had clinically significant hypersensitivity to rifabutin or to any other rifamycins.
Additional information about Ansamycin
Ansamycin Indication: For the prevention of disseminated Mycobacterium avium complex (MAC) disease in patients with advanced HIV infection.
Mechanism Of Action: Ansamycin acts via the inhibition of DNA-dependent RNA polymerase, leading to a suppression of RNA synthesis and cell death.
Drug Interactions: Not Available
Food Interactions: Not Available
Generic Name: Rifabutin
Synonyms: Rifabutinum [Latin]; Rifabutine [French]; Rifabutina [Spanish]; RBT; Antibiotic LM 427; Ansatipine; Ansatipin
Drug Category: Anti-Bacterial Agents; Antibiotics, Antitubercular
Drug Type: Small Molecule; Approved
Other Brand Names containing Rifabutin: Ansamycin; Alfacid; Mycobutin;
Absorption: Rifabutin is readily absorbed from the gastrointestinal tract, with an absolute bioavailability averaging 20%.
Toxicity (Overdose): LD50 = 4.8 g/kg (mouse, male)
Protein Binding: 85%
Biotransformation: Hepatic. Of the five metabolites that have been identified, 25-O-desacetyl and 31-hydroxy are the most predominant. The former metabolite has an activity equal to the parent drug and contributes up to 10% to the total antimicrobial activity.
Half Life: 45 (± 17) hours
Dosage Forms of Ansamycin: Capsule Oral
Chemical IUPAC Name: (9S,12E,14S,15R,16S,17R,18R,19R,20S,21S,22E,24Z)-6,16,18,20-Tetrahydroxy-1'-isobutyl-14-methoxy-7,9,15,17,19,21,25-hepta-methyl-spiro[9,4-(epoxypentadeca[1,11,13]trienimino)-2H-furo-[2',3':7,8]-naphth[1,2-d]imidazol-2,4'-piperidin]-5,10,26-(3H,9H)-trione 16-acetate
Chemical Formula: C46H62N4O11
Rifabutin on Wikipedia: http://en.wikipedia.org/wiki/Rifabutin
Organisms Affected: Enteric bacteria and other eubacteria