rifabutin
Mycobutin

Available forms
Available by prescription only
Capsules: 150 mg

Indications and dosages
 Primary prevention of disseminated Mycobacterium avium complex (MAC) in patients with advanced HIV infection. Adults: 300 mg P.O. daily as a single dose or divided b.i.d. with food.

Pharmacodynamics
Antibiotic action: Rifabutin inhibits DNA-dependent RNA polymerase in susceptible strains of Escherichia coli and Bacillus subtilis, but not in mammal cells. It isn’t known if rifabutin inhibits this enzyme in M. avium or in M. intracellulare, which compose MAC.

Pharmacokinetics
Absorption: Readily absorbed from the GI tract.
Distribution: Because of its high lipophilicity, rifabutin has a high propensity for distribution and intracellular tissue uptake. About 85% of drug is bound to plasma proteins independent of concentration.
Metabolism: Metabolized in the liver to five metabolites. The 25-0-desacetyl metabolite has an activity equal to parent drug and contributes up to 10% of total antimicrobial activity.
Excretion: Less than 10% is excreted in urine as unchanged drug. About 53% of oral dose is excreted in urine, primarily as metabolites. About 30% is excreted in feces.

Contraindications and precautions
Contraindicated in patients hypersensitive to drug or other rifamycin derivatives (such as rifampin) and in patients with active tuberculosis because single-agent therapy with rifabutin increases the risk of inducing bacterial resistance to both rifabutin and rifampin.
  Use cautiously in patients with neutropenia and thrombocytopenia.

Interactions
Drug-drug. Drugs metabolized by the liver, zidovudine: Rifabutin may decrease serum levels of these drugs, although it doesn’t affect inhibition of HIV by zidovudine. Dosage adjustments may be needed.
Hormonal contraceptives: Decreases contraceptive effectiveness. Instruct patient to use nonhormonal forms of contraception.

Adverse reactions
CNS: headache, insomnia, fever.
GI: dyspepsia, eructation, flatulence, diarrhea, nausea, vomiting, abdominal pain, altered taste, anorexia.
GU: discolored urine (brown-orange).
Hematologic: neutropenia, leukopenia, thrombocytopenia, eosinophilia.
Musculoskeletal: myalgia.
Skin: rash.

Effects on lab test results
• May increase aminotransferase levels.
• May decrease neutrophil, eosinophil, WBC, and platelet counts.

Overdose and treatment
Although there’s no experience in treating rifabutin overdose, experience with rifamycins suggests that gastric lavage to evacuate gastric contents (within a few hours of overdose), followed by instillation of an activated charcoal slurry into the stomach, may help absorb any remaining drug from the GI tract. Hemodialysis or forced diuresis probably won’t enhance systemic elimination of unchanged rifabutin.

Special considerations
 ALERT Don’t confuse rifabutin with rifampin and rifapentine.
• High-fat meals slow the rate but not extent of drug absorption.
• Evaluate patient immediately if complaints develop that are consistent with active tuberculosis during rifabutin prophylaxis, so active disease may be given an effective combination regimen of antituberculotics. Administration of single-agent rifabutin to patients with active tuberculosis increases the risk of tuberculosis that’s resistant to rifabutin and rifampin.
• Because rifabutin may lead to neutropenia, and more rarely to thrombocytopenia, consider obtaining hematologic studies periodically in patients receiving rifabutin prophylaxis.
Breast-feeding patients
• It isn’t known if drug appears in breast milk. Because of risk for serious adverse effects in breast-fed infants, either breast-feeding or drug should be discontinued, depending on importance of drug to mother.
Pediatric patients
• Although safety and efficacy in children haven’t been fully established, several studies indicate that drug may be helpful in children at maximum daily dose of 5 mg/kg.
Geriatric patients
• No specific recommendations have been made for dosage adjustment or monitoring in these patients.

Patient education
• If patient has trouble swallowing, suggest mixing drug with soft foods such as applesauce.
• Advise patient with nausea, vomiting, or other GI upset to take drug with food, in two divided doses.
• Warn patient that urine and other body fluids may become discolored (brown-orange). Caution that clothes and soft contact lenses may become permanently discolored.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use