delamanid
Brand: Deltyba
Prototype: bedaquiline
Drug Class: nitroimidazole antimycobacterial
Drug Family: antibiotic
Subclass: mycobacterial cell wall synthesis inhibitor (second-in-class for MDR-TB)
Organ Systems: infectious-disease
Mechanism of Action
Prodrug converted by mycobacterial enzymes to reactive metabolites that inhibit mycolic acid biosynthesis, disrupting the mycobacterial cell wall; bactericidal against both replicating and dormant M. tuberculosis.
mycobacterial mycolic acid synthesis (via nitro group metabolites)
Indications
- multidrug-resistant tuberculosis (MDR-TB) as part of combination therapy (when other regimens cannot be constructed)
Contraindications
- QTc >500 ms
- severe albumin depletion (increases QTc risk from delamanid metabolite)
Adverse Effects
Common
- nausea
- dizziness
- insomnia
Serious
- QTc prolongation (dose-dependent; mediated by active metabolite DM-6705)
- hepatotoxicity
- psychiatric effects
Pharmacokinetics (ADME)
| Absorption | increased ~2.7-fold with high-fat meal; administer with food |
| Distribution | highly protein-bound; metabolized to multiple active and inactive metabolites |
| Metabolism | extensive albumin-mediated and CYP3A4-mediated metabolism |
| Excretion | fecal (primarily) |
| Half-life | 30–38 hours |
| Onset | 4 hours |
| Peak | 4 hours |
| Duration | 6-month course |
| Protein Binding | >99% (albumin-bound) |
| Vd | large |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| QTc-prolonging drugs | additive QTc prolongation | major |
| CYP3A4 inducers | reduce delamanid metabolite levels; efficacy concern | moderate |
Nursing Considerations
- Administer with food; obtain baseline ECG and repeat every 4–8 weeks throughout therapy.
- Monitor serum albumin — low albumin increases concentrations of QTc-prolonging metabolite DM-6705.
- Use only in combination with a WHO-recommended MDR-TB regimen under specialist supervision.
- Monitor for CNS and psychiatric symptoms; psychiatric monitoring is recommended during therapy.
Clinical Pearls
- Delamanid and bedaquiline represent the first new anti-TB drug classes approved in 40 years and have transformed the treatment landscape for MDR-TB.
- Combination of bedaquiline and delamanid may increase QTc risk, requiring careful ECG monitoring; evidence suggests the combination can be used safely in MDR-TB when needed.
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.