RIFAPENTINE

Indications

• Tuberculosis (TB)
• Latent tuberculosis infection
• Active pulmonary tuberculosis

Dosage

Children: Refer to the BNF for Children for appropriate dosing guidelines in paediatric patients.

Adults: Refer to the BNF for specific dosing recommendations based on the condition being treated, including the patient’s weight and renal function.

Mechanism of action

Rifapentine inhibits DNA-dependent RNA polymerase in susceptible strains of Mycobacterium tuberculosis. This inhibition leads to suppression of RNA synthesis, resulting in cell death. Its effectiveness is particularly noted against intracellular bacteria within human monocyte-derived macrophages.

Pharmacodynamics

Rifapentine acts as an antibiotic by inhibiting the activity of DNA-dependent RNA polymerase in bacterial cells, specifically targeting Mycobacterium tuberculosis. This mechanism disrupts RNA synthesis, contributing to its bactericidal effects. It has a broad spectrum of activity against various gram-positive and gram-negative organisms, although its primary use is restricted to mycobacterial infections due to the potential for rapid emergence of resistant strains.

Pharmacokinetics

Rifapentine is well absorbed when administered orally and achieves widespread distribution in body tissues and fluids, including the central nervous system. It is metabolized primarily in the liver and is excreted mainly in bile, with minimal excretion in urine. There is no need for dose adjustments in cases of renal insufficiency, making it a suitable option for patients with compromised renal function.

Contra-indications

• Hypersensitivity to rifapentine or any component of the formulation
• Severe hepatic impairment
• Concurrent use of certain drugs that can cause severe liver injury

Adverse effects

• Hepatotoxicity
• Rash
• Gastrointestinal disturbances (nausea, vomiting, diarrhea)
• Hematological effects (thrombocytopenia, leukopenia)
• Flu-like symptoms
• Discoloration of body fluids (urine, sweat, saliva)

Interactions

• May interact with anticoagulants (e.g., warfarin) leading to altered anticoagulant effect
• Reduced efficacy of hormonal contraceptives
• Potential interactions with antiretroviral drugs
• Inducer of cytochrome P450 enzymes, which can affect the metabolism of other drugs

Precautions

• Monitor liver function tests before and during therapy
• Assess for signs of allergic reaction
• Use caution in patients with a history of liver disease
• Evaluate for potential drug interactions prior to initiation

Pregnancy

Rifapentine is classified as Category C. Risk cannot be ruled out, and it should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Rifapentine is excreted in breast milk. Caution should be exercised when administering to nursing mothers.

Storage

Store in a cool, dry place away from light. Keep out of reach of children.

Formulations

• Tablets (150 mg, 300 mg)

Mechanism of action

Rifapentine has shown higher bacteriostatic and bactericidal activities especially against intracellular bacteria growing in human monocyte-derived macrophages. Rifapentine inhibits DNA-dependent RNA polymerase in susceptible strains of M. tuberculosis. Rifapentine acts via the inhibition of DNA-dependent RNA polymerase, leading to a suppression of RNA synthesis and cell death.

Pharmacodynamics

Rifapentine 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. Rifampin 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.