pretomanid
Brand: Dovprela
Prototype: delamanid
Drug Class: nitroimidazole antimycobacterial
Drug Family: antibiotic
Subclass: BPaL regimen component
Organ Systems: infectious-disease
Mechanism of Action
Aerobically: inhibits mycobacterial cell wall lipid biosynthesis (mycolic acid and arabinogalactan); anaerobically: generates reactive nitrogen intermediates that are toxic to dormant bacteria; active against extensively drug-resistant TB.
mycobacterial cell envelope (aerobic and anaerobic mechanisms)
Indications
- extensively drug-resistant tuberculosis (XDR-TB) or treatment-intolerant/non-responsive MDR-TB — as part of the BPaL regimen (Bedaquiline + Pretomanid + Linezolid)
Contraindications
- nitroimidazole hypersensitivity
Adverse Effects
Common
- peripheral neuropathy (primarily from linezolid in BPaL)
- myelosuppression (from linezolid)
- nausea
- hepatotoxicity
Serious
- QTc prolongation
- visual disturbances
- psychiatric effects
- lactic acidosis (from linezolid)
Pharmacokinetics (ADME)
| Absorption | increased ~2-fold with moderate-fat meal; administer with food |
| Distribution | large Vd |
| Metabolism | hepatic; multiple metabolic pathways |
| Excretion | fecal (primarily) |
| Half-life | 16–18 hours |
| Onset | 4–5 hours |
| Peak | 4–5 hours |
| Duration | 6-month BPaL course |
| Protein Binding | >96% |
| Vd | large |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| QTc-prolonging drugs | additive QTc prolongation | major |
| serotonergic drugs (with linezolid in BPaL) | linezolid component can cause serotonin syndrome | major |
Nursing Considerations
- Administer pretomanid only as part of the BPaL regimen (bedaquiline + pretomanid + linezolid) for XDR-TB or treatment-intolerant MDR-TB under specialist supervision.
- Monitor CBC twice monthly due to linezolid-induced myelosuppression in the BPaL regimen; linezolid dose reductions are often required.
- Obtain baseline ECG and repeat every 4 weeks; bedaquiline and pretomanid both prolong QTc.
- Monitor LFTs, complete neurological assessment, and screen for psychiatric symptoms monthly throughout the 6-month course.
Clinical Pearls
- The BPaL regimen (bedaquiline, pretomanid, linezolid) represents a 6-month all-oral treatment option for XDR-TB that demonstrated 89% success in the ZeNix trial, transforming the treatment landscape for previously nearly untreatable TB.
- Pretomanid received accelerated FDA approval in 2019, becoming the third new anti-TB drug in 50 years; its approval was specifically for XDR-TB and treatment-intolerant MDR-TB rather than standard MDR-TB.
Safety Profile
Pregnancy insufficient-data
Lactation avoid
Renal Adjustment Not required
Hepatic Adjustment Required
TDM Not required
Guideline Update pending
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.