Clofazimine

Indications

Clofazimine is used for: Leprosy

Adult Dose

Dapsone-sensitive multibacillary leprosy 50 mg PO qDay in combination with dapsone 100 mg/day and rifampicin 600 mg/day Administer for at least 2 years and continued, if possible, until negative skin smears are obtained At this time, monotherapy with an appropriate antileprosy drug can be instituted Dapsone-resistant leprosy 100 mg PO qDay in combination with 1 or more other antileprosy drugs for 3 years, followed by monotherapy with 100 mg of clofazimine daily

Child Dose

Renal Dose

Administration

Should be taken with food.

Contra Indications

Hypersensitivity. Lactation.

Precautions

Pregnancy. Patients with GI symptoms. Lactation: Distributed in human breast milk; do not administer to breastfeeding women unless clearly indicated

Pregnancy-Lactation

Pregnancy Category: C Crosses the human placenta; the skin of infants born to women who had received the drug during pregnancy was found to be deeply pigmented at birth Lactation: Distributed in human breast milk; do not administer to breastfeeding women unless clearly indicated

Interactions

Dapsone Concomitant use of dapsone and clofazimine does not have a clinically important effect on dapsone pharmacokinetics. Some evidence suggests dapsone may decrease or nullify some anti-inflammatory effects of clofazimine and theoretically might adversely affect clofazimine’s efficacy in patients with ENL reactions; several borderline leprosy and lepromatous leprosy patients with severe, recurrent ENL reactions reportedly required higher clofazimine dosage to control these reactions when dapsone therapy was given concomitantly than when clofazimine was given alone. Isoniazid Possible increased clofazimine plasma and urine concentrations and decreased clofazimine skin concentrations. Rifampin Although one study indicated that concomitant use of clofazimine in leprosy patients receiving rifampin alone or in conjunction with dapsone may decrease plasma concentrations and AUC of rifampin, concomitant use of clofazimine in another study in lepromatous leprosy patients receiving dapsone (100 mg daily) and rifampin (600 mg daily) did not affect rifampin pharmacokinetics.

Adverse Effects

Side effects of Clofazimine : Well tolerated when dose does not exceed 100 mg/day >10% Skin discoloration (75-100%) Gastrointestinal: Abdominal and epigastric pain, diarrhea, nausea, vomiting, GI intolerance (40%-50%) Ichthyosis and dry skin (8-28%) 1-10% Rash and pruritus (1-5%) Ocular: Conjunctival and corneal pigmentation due to crystal deposits, dryness, burning, itching, irritation (>1%) Discoloration of urine, feces, sputum, sweat (>1%) Increased blood glucose (>1%) Increased ESR (>1%) <1% Skin: Phototoxicity, erythroderma, acneiform eruptions, monilial cheilosis Body fluid discoloration and other skin reactions Gastrointestinal: Bowel obstruction, GI bleeding, anorexia, constipation, weight loss, hepatitis, jaundice, eosinophilic enteritis, enlarged liver Ocular: Diminished vision Nervous: Dizziness, drowsiness, fatigue, headache, giddiness, neuralgia, taste disorder Psychiatric: Depression secondary to skin discoloration Laboratory: Elevated levels of albumin, serum bilirubin, and AST (SGOT), eosinophilia, hypokalemia Ocular: Addition of maculopathy (bull’s eye retinopathy) Other: Splenic infarction, thromboembolism, anemia, cystitis, bone pain, edema, fever, lymphadenopathy, vascular pain Potentially Fatal: Crystal depletion in the wall of small bowel mesenteric lymph nodes, liver and spleen. Severe abdominal symptoms including bowel obstruction, GI bleeding and splenic infarction.

Mechanism of Action

Clofazamine inhibits mycobacterial growth by binding preferentially to mycobacterial DNA. It also has some anti-inflammatory activity.