Pretomanid !

A nitroimidazole prodrug for drug-resistant TB, the P in the 6-month BPaLM regimen. It kills both dividing and dormant bacilli; the liver is watched.

Updated 2026-11-01

Class: Antituberculosis drugs
Enzyme: Deazaflavin-dependent nitroreductase Ddn (activating enzyme)
ATC code: J04AK08
WHO Model List of Essential Medicines

Also called: Pa, PA-824

Mechanism of action

Pretomanid is a bicyclic nitroimidazole prodrug activated by the bacterial nitroreductase Ddn with the cofactor F420. In dividing bacilli it blocks mycolic acid production; in dormant, non-replicating bacilli it releases reactive nitrogen species such as nitric oxide that poison respiration and deplete ATP.

Ddn and F420 activate pretomanid inside the bacillus
Dividing bacilli: mycolic acid production is blocked
Dormant bacilli: nitric oxide poisons respiration

Pharmacokinetics

Absorption: Food increases exposure
Metabolism: Partly by CYP3A; inducers such as rifampicin lower its levels

Indications

Multidrug- or rifampicin-resistant tuberculosis and pre-XDR-TB, within BPaLM or BPaL Tuberculosis →
Drug-resistant pulmonary tuberculosis Pulmonary tuberculosis →

Adverse effects

Common

Rise in liver enzymes
In BPaLM, linezolid adds myelosuppression and peripheral or optic neuropathy

Contraindications

Use with strong or moderate CYP3A inducers (such as rifampicin)
Hypersensitivity to pretomanid

Key interactions

Rifampicin and other CYP3A inducers: Lower pretomanid levels: avoided
Efavirenz: Markedly lowers pretomanid: dolutegravir-based ART is preferred

What is monitored

Liver tests and symptoms of hepatitis
Blood counts, vision and neuropathy symptoms (linezolid in the regimen)
ECG (bedaquiline and moxifloxacin in the regimen)

Administration and safety

By mouth with food
Only as part of the BPaLM or BPaL combination, never alone

Nursing care

Teach the signs of hepatitis
Ask about tingling, numbness or vision changes (linezolid)
Review antiretrovirals: efavirenz is not combined
Support adherence: the regimen lasts only 6 months but every dose counts

Test yourself

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

Which regimen does pretomanid belong to?

BPaLM (or BPaL): bedaquiline, pretomanid, linezolid and moxifloxacin, for 6 months.

How does pretomanid kill dormant bacilli?

After activation it releases nitric oxide and other reactive nitrogen species that poison respiration.

Which antiretroviral is avoided with pretomanid?

Efavirenz, which lowers pretomanid levels; dolutegravir-based ART is preferred.

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

Sources: WHO consolidated guidelines on tuberculosis: module 4: treatment and care (World Health Organization (WHO), 2025); Tuberculosis (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).

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Representative model, for educational purposes only.