clofazimine
Brand: Lamprene
Prototype Drug
Drug Class: riminophenazine antibiotic
Drug Family: antibiotic
Subclass: anti-leprosy and anti-NTM agent
Organ Systems: infectious-disease
Mechanism of Action
Binds mycobacterial DNA and generates reactive oxygen species; also disrupts the bacterial electron transport chain by acting as a lipophilic electron acceptor; exhibits slow bactericidal activity against M. leprae and is active against M. abscessus and NTM.
mycobacterial DNA and membrane
Indications
- leprosy (part of multidrug therapy — WHO regimen)
- Mycobacterium avium complex (MAC) — treatment in non-HIV patients
- M. abscessus infections
- MDR-TB (second-line)
Contraindications
- clofazimine hypersensitivity
Adverse Effects
Common
- red-brown to black skin discoloration (universal — dose- and duration-dependent)
- ichthyosis and dry skin
- GI upset
Serious
- QTc prolongation
- crystalline enteropathy (deposition in intestinal wall — abdominal pain)
- hepatotoxicity
- phototoxicity
Pharmacokinetics (ADME)
| Absorption | 45–62% oral; must be taken with food (fat increases absorption) |
| Distribution | highly lipophilic; accumulates in fatty tissues, skin, reticuloendothelial system; Vd >1000 L |
| Metabolism | not significantly metabolized |
| Excretion | primarily fecal; minimal renal excretion; extremely slow elimination |
| Half-life | 70 days (terminal, due to tissue accumulation) |
| Onset | days (slow accumulation) |
| Peak | 8 hours |
| Duration | months (due to tissue stores) |
| Protein Binding | >99% |
| Vd | extremely large (>1000 L) |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| QTc-prolonging drugs | additive QTc prolongation | major |
| bedaquiline/delamanid | combination increases QTc prolongation risk in MDR-TB regimens | major |
Nursing Considerations
- Counsel patients thoroughly about inevitable skin discoloration — red-brown to black pigmentation of skin, conjunctivae, and body fluids (tears, urine, sweat) develops in all patients; it fades gradually over months to years after stopping therapy.
- Administer with food or fatty meals to maximize absorption.
- Monitor ECG periodically for QTc prolongation, especially when combined with bedaquiline or other QTc-prolonging drugs in MDR-TB regimens.
- Abdominal pain or intestinal obstruction symptoms may indicate crystalline enteropathy; report to prescriber.
Clinical Pearls
- Clofazimine's skin discoloration is so reliable that patients in leprosy clinical trials who developed characteristic skin pigmentation were unblinded by their discoloration — an important consideration in study design.
- The WHO multidrug therapy (MDT) for leprosy consists of rifampin + dapsone + clofazimine (for multibacillary disease) or rifampin + dapsone (for paucibacillary disease) for 6–12 months.
Safety Profile
Pregnancy use-with-caution
Lactation use-with-caution
Renal Adjustment Not required
Hepatic Adjustment Required
TDM Not required
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.