Rifampicin !

The key sterilising drug for tuberculosis and leprosy. It turns urine and tears orange-red and speeds up the breakdown of many other medicines.

Updated 2026-11-01

Class: Antituberculosis drugs
Enzyme: DNA-dependent RNA polymerase, β subunit (M. tuberculosis)
ATC code: J04AB02
WHO Model List of Essential Medicines

Also called: Rifampin, R, RIF

DNA-dependent RNA polymerase, β subunit (M. tuberculosis)Rifampicin

The figure shows rifampicin bound to the RNA polymerase transcription initiation complex of M. tuberculosis.

Target in 3D: DNA-dependent RNA polymerase, β subunit (M. tuberculosis). PDB structure 5UHB (RCSB PDB, public domain). View the structure at RCSB PDB

Mechanism of action

Rifampicin binds the β subunit of bacterial DNA-dependent RNA polymerase and blocks the growing RNA chain, so the bacillus cannot transcribe its genes; the human enzyme is not affected. It kills semi-dormant 'persister' bacilli, which is why it lets treatment be shortened. Resistance comes from mutations in rpoB, and rifampicin resistance defines RR-TB.

Rifampicin binds the β subunit of RNA polymerase
The new RNA chain cannot grow
Even semi-dormant bacilli die

Pharmacokinetics

Absorption: Good by mouth; food lowers absorption
Distribution: Wide, including cerebrospinal fluid when the meninges are inflamed
Metabolism: Liver deacetylation; enterohepatic circulation; it induces its own clearance
Elimination: Mainly bile and faeces; part in urine
Half-life: Short: about 2 to 3 hours with repeated dosing

Indications

Tuberculosis (backbone of the 6-month regimen) Tuberculosis →
Pulmonary tuberculosis Pulmonary tuberculosis →
Spinal tuberculosis (Pott disease) Spinal tuberculosis (Pott disease) →
Leprosy, within multidrug therapy; single dose as post-exposure prophylaxis for contacts Leprosy (Hansen disease) →

Adverse effects

Common

Harmless orange-red colour of urine, sweat, tears and sputum; stains soft contact lenses
Nausea, abdominal discomfort
Rash, itching
Rise in liver enzymes

Contraindications

Hypersensitivity to any rifamycin
Use with HIV protease inhibitors (atazanavir, darunavir, fosamprenavir, saquinavir, tipranavir)
Use with cabotegravir, fostemsavir or lenacapavir
Use with praziquantel or lurasidone

Key interactions

HIV protease inhibitors (darunavir, atazanavir, lopinavir/ritonavir): Rifampicin collapses their levels: not combined; rifabutin is used instead
Dolutegravir and raltegravir: Levels fall: the integrase inhibitor schedule is adjusted by the team
Rilpivirine and doravirine: Levels fall too much: not combined; efavirenz can be combined with rifampicin
Hormonal contraceptives: Lose reliability: a non-hormonal method is used
Warfarin, methadone, oral antidiabetics, digoxin, clopidogrel: Faster breakdown (CYP3A4 and P-glycoprotein induction): INR, withdrawal symptoms or glucose are watched

What is monitored

Liver enzymes, bilirubin, creatinine and blood count at baseline in adults
Symptoms of hepatitis at every visit
Full list of the person's medicines, including antiretrovirals
INR if on warfarin; glucose in diabetes

Administration and safety

By mouth on an empty stomach; an intravenous form exists
Often given as fixed-dose combinations with isoniazid, pyrazinamide and ethambutol
Look-alike names: rifampicin, rifabutin, rifapentine and rifaximin are different drugs
Daily dosing is preferred; thrombocytopenia is seen mainly with high-dose intermittent dosing

Nursing care

Warn that urine, sweat and tears turn orange-red and soft contact lenses can stain
Review every medicine, especially antiretrovirals, anticoagulants, methadone and contraceptives
Advise non-hormonal contraception during treatment
Teach signs of hepatitis and of bleeding or bruising
Support directly observed treatment and full adherence

Pregnancy and breastfeeding

It crosses the placenta; when used in the last weeks of pregnancy it can cause bleeding in mother and newborn, so vitamin K may be indicated.

Test yourself

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

What is rifampicin's target?

The β subunit (rpoB) of bacterial DNA-dependent RNA polymerase.

Why is rifampicin not combined with darunavir or atazanavir?

It strongly induces CYP3A4 and lowers protease inhibitor levels so much that HIV treatment would fail; rifabutin is used instead.

A patient on TB treatment worries about orange urine. What do you explain?

It is the expected, harmless colour from rifampicin; it can also stain tears and soft contact lenses.

What contraceptive advice goes with rifampicin?

Hormonal contraceptives become unreliable; a non-hormonal method is used.

Add to my cards (4)

← 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 - RIFAMPIN capsule (DailyMed (U.S. National Library of Medicine), 2025); WHO consolidated guidelines on tuberculosis: module 4: treatment and care (World Health Organization (WHO), 2025); Goodman & Gilman's The Pharmacological Basis of Therapeutics, 14th ed., ch. 64 (McGraw Hill, 2023); Leprosy (World Health Organization (WHO), 2025).

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.