Clofazimine is a riminophenazine dye derivative with potent anti-mycobacterial and anti-inflammatory properties. It is a cornerstone in the treatment of multibacillary leprosy (MBL) and is a critical component of the WHO-recommended multidrug therapy (MDT) regimen. It is also a key drug for the treatment of drug-resistant tuberculosis (DR-TB), particularly in cases of pre-extensively drug-resistant (pre-XDR) and extensively drug-resistant (XDR) TB, as per the Indian National TB Elimination Programme (NTEP) guidelines. Its unique mechanism involves binding to mycobacterial DNA, generating reactive oxygen species, and inhibiting mycobacterial phospholipase A2. It has a very long half-life and accumulates in tissues, particularly in the skin and reticuloendothelial system, leading to its characteristic skin pigmentation.
Adult: **Leprosy (MDT):** 50 mg daily, plus 300 mg once monthly under supervision. **ENL:** 100-300 mg daily in divided doses, tapered to 100 mg daily as reaction subsides. **DR-TB (NTEP):** 100 mg once daily (often given as two 50mg capsules).
Note: Administer with meals, preferably a fatty meal, to enhance absorption. Capsules should be swallowed whole with water. For monthly supervised doses in leprosy MDT, administer under direct observation. Advise patients that skin and body fluid discoloration is expected and reversible.
Clofazimine exerts its effects through multiple mechanisms: 1) It binds preferentially to guanine bases in mycobacterial DNA, inhibiting template function and replication. 2) It is a weak bactericidal agent that generates mycobactericidal reactive oxygen species (ROS) within macrophages. 3) It inhibits mycobacterial phospholipase A2, an enzyme crucial for bacterial survival within phagocytes. 4) It possesses potent immunomodulatory and anti-inflammatory properties by stabilizing lysosomal membranes, inhibiting neutrophil migration, and suppressing T-cell proliferation and cytokine production, which is particularly useful in managing ENL reactions.
Pregnancy: Pregnancy Category C (US FDA). Animal studies show fetal skin pigmentation. No adequate human studies. Use only if the potential benefit justifies the potential risk to the fetus, such as in life-threatening DR-TB or severe leprosy reactions. Can cross the placenta.
Driving: Unlikely to impair ability. However, if photosensitivity or eye irritation (keratopathy) occurs, it may temporarily affect vision.
| Rifampicin | Rifampicin induces metabolism and may decrease clofazimine levels, potentially reducing efficacy. Monitor clinical response. | Moderate |
| QTc-prolonging drugs (e.g., Fluoroquinolones, Macrolides, Tricyclic Antidepressants, Antipsychotics) | Additive risk of QTc prolongation and cardiac arrhythmias. ECG monitoring is essential. | Major |
| Dapsone | No significant PK interaction. Used together in MDT for leprosy. | Minor |
| Isoniazid, Pyrazinamide, Ethambutol | No clinically significant interactions reported. Used together in various TB/DR-TB regimens. | Minor |
| Antacids, H2 Blockers, PPIs | May alter gastric pH and potentially reduce absorption. Administer clofazimine 2 hours apart. | Moderate |