Clofazimine

Leprosy

For dapsone-sensitive lepromatous leprosy 100 mg daily with meals as a part of a combination regimen for at least 2 years is recommended. For dapsone-resistant lepromatous leprosy 100 mg daily with meals in combination with one or more other agents for 3 years. For lepromatous leprosy complicated by erythema nodosum leprosum 100 mg to 200 mg daily for up to 3 months. Taper dose to 100 mg as quickly as possible.

Renal Impairment No Clofazimine dosage adjustments are recommended in patients with mild to moderate renal impairment. Use caution in patients with severe renal impairment.

Clinical studies of Clofazimine did not include sufficient numbers of subjects aged 65 and older to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Hepatic Impairment Avoid Clofazimine in patients with hepatic impairment (Child-Pugh Class A, B, and C) unless the benefit outweighs the risk.

Should be taken with food.

Contraindicated in patients with known hypersensitivity to clofazimine or any of the excipients of clofazimine

Abdominal obstruction and other gastrointestinal adverse reactions: Clofazimine may deposit in intestinal mucosa causing intestinal disturbances, including abdominal obstruction, bleeding, splenic infarction and death. Reduce dose or discontinue Clofazimine if patient complains of pain in abdomen or other gastrointestinal symptoms. QT prolongation: QT prolongation and Torsade de Pointes may occur with Clofazimine. Concomitant use with other QT prolonging drugs or bedaquiline may cause additive QT prolongation. Monitor ECGs and discontinue Clofazimine if significant ventricular arrhythmia or QTcF interval greater than or equal to 500 ms develop. Skin and body fluid discoloration and other skin reactions: Advise patients that skin and body fluid discoloration frequently occur with use of Clofazimine. Depression and suicide due to skin discoloration. Monitor patients for psychological effects of skin discoloration.

Not Classi Pregnancy There are no data with use in pregnant women to inform associated risk; there are no studies in pregnant women; few cases of use during pregnancy reported in the literature; these reports indicate that the skin of infants born to women who had received this drug during pregnancy was deeply pigmented at birth; this drug should be used during pregnancy only if potential benefit justifies risk to fetus; advise pregnant women of potential risk to fetus; the background risk of major birth defects and miscarriage for indicated population is unknown The skin of infants born to pregnant mothers who had received therapy during pregnancy is pigmented at birth; limited data is available regarding reversibility of discoloration; based on previous observations, discoloration gradually faded over the first year Limited data is available regarding the reversibility of discoloration; based on previous observations, discoloration gradually faded over first year Females and males of reproductive potential Sexually-active females of reproductive potential should have a pregnancy test prior to starting treatment Animal studies have shown this drug to be harmful to developing fetus; advise sexually active females of reproductive potential to use effective contraception (methods that result in less than 1% pregnancy rates) when using this drug during treatment and for at least 4 months after stopping treatment Advise males taking this drug to use a condom during intercourse while on treatment and for at least 4 months after stopping treatment with this drug Impaired female fertility (reduced number of offspring and lower proportion of implantations) was observed in one study in rats receiving; there are no non-clinical data on male fertility Animal data Embryofetal toxicity studies were conducted in rats, rabbits and mice. In mice, drug-induced embryotoxicity and fetotoxicity was evident; retardation of fetal skull ossification, increased incidences of abortions and stillbirths, and impaired neonatal survival were observed in mice following prenatal exposure to this drug at 25 mg/kg, equivalent to 0.6 times maximum recommended human daily dose (200 mg), based on body surface area comparisons The skin and fatty tissue of offspring became discolored approximately 3 days after birth, which was attributed to presence of clofazimine in maternal milk; no developmental effects were observed in rat or rabbits drug orally administered during organogenesis at doses up to 50 mg/kg and 15 mg/kg, (equivalent to about 2.4 and 1.5 times the MRHD of 200 mg based on body surface area) respectively; these animal studies were conducted according to standards at time of initial drug approval and not under current regulatory standards Lactation This drug is excreted in human milk; skin discoloration has been observed in breastfed neonates of mothers receiving this drug The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for therapy and any potential adverse effects on breastfed infant from therapy or from underlying maternal condition

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. Contraindicated (2) ceritinib clarithromycin Serious (12) adagrasib entrectinib fexinidazole gepotidacin givinostat glasdegib hydroxychloroquine sulfate ivosidenib lefamulin macimorelin pitolisant ribociclib

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.

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