rifabutin, pyrazinamide and protionamide

J04AM11

Forms & Strengths

Fixed-dose combination capsule: Rifabutin 150 mg / Pyrazinamide 400 mg / Protionamide 150 mg (exact proprietary ratios may vary globally)

Adult Dosing

Pulmonary Tuberculosis: Dosing is determined by patient weight and regional treatment guidelines, typically administered as multiple capsules daily. Consult specific national TB control program guidelines for exact milligram-per-kilogram dosing of the individual components.

Pediatric Dosing

Not generally recommended for pediatric use as a fixed-dose combination due to the difficulty in adjusting individual component doses based on changing pediatric body weight.

Indications

Treatment of pulmonary tuberculosis caused by Mycobacterium tuberculosis susceptible to rifabutin, pyrazinamide, and protionamide, particularly in multi-drug resistant regimens or when simplification of multi-drug therapy is indicated.

Mechanism of Action

Rifabutin inhibits bacterial DNA-dependent RNA polymerase, suppressing initiation of RNA synthesis.
Pyrazinamide is converted to pyrazoic acid in M. tuberculosis, disrupting membrane potential and inhibiting membrane transport.
Protionamide is a thioisonicotinamide derivative that inhibits mycolic acid synthesis, disrupting the mycobacterial cell wall.

Contraindications

Hypersensitivity to rifamycins, pyrazinamide, or thioisonicotinamide derivatives (such as ethionamide)
Severe hepatic impairment or active acute liver disease
Concomitant administration with certain antiretroviral agents (e.g., protease inhibitors) contraindicating rifabutin
Severe renal impairment (for pyrazinamide/protionamide components, depending on clinical status)

Adverse Reactions

Hepatotoxicity (elevated transaminases, clinical hepatitis)
Gastrointestinal disturbances (nausea, vomiting, anorexia, abdominal pain)
Hematologic abnormalities (thrombocytopenia, leukopenia, neutropenia, anemia)
Uveitis (associated with rifabutin, especially at higher doses)
Hyperuricemia and arthralgia (due to pyrazinamide)
Neurological effects (peripheral neuropathy, headache, drowsiness, psychiatric disturbances due to protionamide)
Red-orange discoloration of body fluids (urine, sweat, tears, saliva)

Drug Interactions

Rifabutin is a potent inducer of hepatic CYP3A enzymes, significantly lowering plasma concentrations of co-administered CYP3A substrates (e.g., certain antiretrovirals, antifungals, oral anticoagulants, oral contraceptives).
Concurrent use with other hepatotoxic drugs increases the risk of severe liver injury.
Protionamide and pyrazinamide may enhance the neurotoxic or hepatotoxic effects of other concurrent medications.

Curated Content: Needs Vetting Before Put to Clinical Use