Rifapentine !

A longer-acting rifamycin used in short preventive treatment with isoniazid and in a 4-month regimen for drug-susceptible pulmonary TB.

Updated 2026-11-01

Class: Antituberculosis drugs
Enzyme: DNA-dependent RNA polymerase, β subunit
ATC code: J04AB05
WHO Model List of Essential Medicines

DNA-dependent RNA polymerase, β subunitRifapentine

The figure shows rifapentine bound to the RNA polymerase of Thermus thermophilus, in the same rifamycin pocket of the β subunit as in M. tuberculosis.

Target in 3D: DNA-dependent RNA polymerase, β subunit. PDB structure 2A69 (RCSB PDB, public domain). View the structure at RCSB PDB

Mechanism of action

A cyclopentyl rifamycin that blocks bacterial DNA-dependent RNA polymerase and kills intracellular and extracellular M. tuberculosis; its 25-desacetyl metabolite is also active. Its longer half-life allows spaced dosing in preventive regimens.

Rifapentine binds the β subunit of RNA polymerase
Bacterial transcription stops
Its long half-life allows spaced doses

Pharmacokinetics

Absorption: Food, especially fatty food, increases absorption
Distribution: Highly bound to albumin
Metabolism: Hydrolysis to an active 25-desacetyl metabolite; it induces CYP3A4 and CYP2C8/9
Half-life: About 13 hours

Indications

TB infection: short preventive treatment with isoniazid Tuberculosis →
Drug-susceptible pulmonary TB from age 12: 4-month regimen with isoniazid, moxifloxacin and pyrazinamide Pulmonary tuberculosis →

Adverse effects

Common

Red-orange colour of body fluids; can stain contact lenses and dentures
Flu-like symptoms
Rise in liver enzymes

Contraindications

Hypersensitivity to any rifamycin
Porphyria (avoided)
Rifampicin-resistant tuberculosis (it would not work)

Key interactions

HIV protease inhibitors and some reverse transcriptase inhibitors: Their levels can fall markedly
Hormonal contraceptives: Less effective: a non-hormonal or barrier method is used
Warfarin, azole antifungals, methadone, immunosuppressants: Faster breakdown; induction lasts about two weeks after stopping

What is monitored

Liver tests at baseline and during treatment in people with liver disease
Symptoms of hepatitis and hypersensitivity
Adherence to every scheduled dose

Administration and safety

By mouth with food
Tablets can be crushed into semi-solid food
Preventive regimens are often directly observed
Look-alike names: rifapentine is not rifampicin or rifabutin

Nursing care

Warn about orange-red body fluids and stained lenses or dentures
Teach flu-like or allergic symptoms to report
Review antiretrovirals and contraceptives
Track each dose in the preventive schedule

Pregnancy and breastfeeding

Human data are limited; use in the last weeks of pregnancy may increase bleeding in mother and newborn, so vitamin K may be indicated.

Test yourself

Think of the answer, then tap the question to see it.

With which drug is rifapentine combined for short preventive treatment?

Isoniazid.

Which WHO 4-month regimen contains rifapentine?

Isoniazid, rifapentine, moxifloxacin and pyrazinamide (2HPMZ/2HPM), from age 12 with drug-susceptible pulmonary TB.

Does food help or hinder rifapentine?

They help: food, especially fatty food, increases its absorption.

Add to my cards (3)

← Back to the class: Antituberculosis drugs

Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.

Sources: DailyMed - RIFAPENTINE tablet, film coated (DailyMed (U.S. National Library of Medicine), 2026); WHO consolidated guidelines on tuberculosis: module 4: treatment and care (World Health Organization (WHO), 2025); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026); Goodman & Gilman's The Pharmacological Basis of Therapeutics, 14th ed., ch. 65 (McGraw Hill, 2023).

Spotted a mistake?We are always improving for the community. Tell us what is wrong and our team will review it.Report a mistake

Representative model, for educational purposes only.