Rifabutin: profile and news

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Other information

Indication
Used to prevent mycobacterial infection in immunocompromised patients, as a therapy in non-tuberculous mycobacterial infection, and as a treatment in pulmonary tuberculous.

Pharmacology
Rifabutin 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. Rifabutin 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.

Mechanism Of Action
Rifabutin acts via the inhibition of DNA-dependent RNA polymerase, leading to a suppression of RNA synthesis and cell death.

Drug Category
Antibiotics; Anti-bacterial Agents; Antituberculosis Agents; ATC:J04AB04

Brand Names/Synonyms
ANSAMYCIN; Alfacid; Ansamycin; Ansatipin; Ansatipine; Antibiotic Lm 427; Mycobutin; RBT; RIFABUTIN; Rifabutin; Rifabutina [Spanish]; Rifabutine [French]; Rifabutinum [Latin]

Dosage Forms
CAPSULE

Absorption
Following a single oral dose of 300 mg to nine healthy adult volunteers, rifabutin was readily absorbed from the gastrointestinal tract. Absolute bioavailability averaged 20%.

Interactions
Interactions for Rifabutin:

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.

Antiretrovirals:

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.

Other Drugs:

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.

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

Half Life
45 (+/- 17) hours

Drug Type
Approved Drug

# Accession No
APRD00094

CAS Registry Number
72559-06-9