Overview
DESCRIPTION Rifabutin capsules, USP for oral administration contain 150 mg of the rifamycin antimycobacterial agent rifabutin, USP, per capsule, along with the inactive ingredients, microcrystalline cellulose, sodium lauryl sulfate, colloidal silicon dioxide, magnesium stearate, gelatin, red iron oxide, titanium dioxide, shellac, and potassium hydroxide.
Mechanism of Action
CLINICAL PHARMACOLOGY Pharmacokinetics Absorption: Following a single oral dose of 300 mg to nine healthy adult volunteers, rifabutin was readily absorbed from the gastrointestinal tract with mean (±SD) peak plasma levels (C max ) of 375 (±267) ng/mL (range: 141 to 1033 ng/mL) attained in 3.3 (±0.9) hours (T max range: 2 to 4 hours). Absolute bioavailability assessed in five HIV-positive patients, who received both oral and intravenous doses, averaged 20%. Total recovery of radioactivity in the urine indicates that at least 53% of the orally administered rifabutin dose is absorbed from the gastrointestinal tract. The bioavailability of rifabutin from the capsule dosage form, relative to an oral solution, was 85% in 12 healthy adult volunteers.
Indications
- INDICATIONS AND USAGE Rifabutin capsules are indicated for the prevention of disseminated Mycobacterium avium complex (MAC) disease in patients with advanced HIV infection.
Common Doses
- 300 mg
- 150 mg
- 30 mL
Dosage
DOSAGE AND ADMINISTRATION It is recommended that rifabutin capsules be administered at a dose of 300 mg once daily. For those patients with propensity to nausea, vomiting, or other gastrointestinal upset, administration of rifabutin at doses of 150 mg twice daily taken with food may be useful. Doses of rifabutin may be administered mixed with foods such as applesauce. For patients with severe renal impairment (creatinine clearance less than 30 mL/min), consider reducing the dose of rifabutin by 50%, if toxicity is suspected.
Contraindications
- CONTRAINDICATIONS Rifabutin capsules are contraindicated in patients who have had clinically significant hypersensitivity to rifabutin or to any other rifamycins. Rifabutin capsules are contraindicated in patients being treated with cabotegravir/rilpivirine prolonged-release injectable suspension ( see PRECAUTIONS-Drug Interactions, Table 2 ).
Side Effects
- ADVERSE REACTIONS Adverse Reactions from Clinical Trials Rifabutin capsules were generally well tolerated in the controlled clinical trials. Discontinuation of therapy due to an adverse event was required in 16% of patients receiving rifabutin, compared to 8% of patients receiving placebo in these trials. Primary reasons for discontinuation of rifabutin were rash (4% of treated patients), gastrointestinal intolerance (3%), and neutropenia (2%).
Interactions
- Drug Interactions Effect of Rifabutin on the Pharmacokinetics of 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. Effect of Other Drugs on Rifabutin Pharmacokinetics: Some drugs that inhibit CYP3A may significantly increase the plasma concentration of rifabutin.