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Clofazimine
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NOTE: Clofazimine is no longer commercially available in the United States. It is available via Investigational New Drug (IND) application; the National Hansen's Disease Program holds the IND for the use of clofazimine in treating Hansen's Disease.[53390]
50 mg PO once daily plus 300 mg PO once monthly in combination with rifampin and dapsone for 6 months.[63942]
50 mg PO once daily plus 300 mg PO once monthly in combination with rifampin and dapsone for 6 months.[63942]
50 mg PO every other day plus 150 mg PO once monthly in combination with rifampin and dapsone for 6 months.[63942]
50 mg PO twice weekly plus 100 mg PO once monthly in combination with rifampin and dapsone for 6 months.[63942]
50 mg PO twice weekly plus 100 mg PO once monthly in combination with rifampin and dapsone for 6 months.[63942]
50 mg PO once daily in combination with rifampin and dapsone for 24 months.[53390] Alternatively, 50 mg PO once daily plus 300 mg PO once monthly in combination with rifampin and dapsone for 12 months.[63942] The shorter duration of therapy recommendation is mainly due to WHO's considerations for developing countries; longer duration of treatment is preferred.[53390] [63942] The FDA-labeled dosage is 100 mg PO once daily with 2 other antileprosy agents for at least 2 years.[63936]
1 mg/kg/dose (Max: 50 mg/dose) PO once daily or 2 mg/kg/dose (Max: 50 mg/dose) PO every other day in combination with rifampin and dapsone for 24 months. Round dose to nearest 50 mg as there is no formulation less than 50 mg and the capsule may not be opened.[53390] Alternatively, 50 mg PO once daily plus 300 mg PO once monthly in combination with rifampin and dapsone for 12 months.[63942] The shorter duration of therapy recommendation is mainly due to WHO's considerations for developing countries; longer duration of treatment is preferred.[53390] [63942]
1 mg/kg/dose (Max: 50 mg/dose) PO once daily or 2 mg/kg/dose (Max: 50 mg/dose) PO every other day in combination with rifampin and dapsone for 24 months. Round dose to nearest 50 mg as there is no formulation less than 50 mg and the capsule may not be opened.[53390] Alternatively, 50 mg PO every other day plus 150 mg PO once monthly in combination with rifampin and dapsone for 12 months.[63942] The shorter duration of therapy recommendation is mainly due to WHO's considerations for developing countries; longer duration of treatment is preferred.[53390] [63942]
1 mg/kg/dose (Max: 50 mg/dose) PO once daily or 2 mg/kg/dose (Max: 50 mg/dose) PO every other day in combination with rifampin and dapsone for 24 months. Round dose to nearest 50 mg as there is no formulation less than 50 mg and the capsule may not be opened.[53390] Alternatively, 50 mg PO twice weekly plus 100 mg PO once monthly in combination with rifampin and dapsone for 12 months.[63942] The shorter duration of therapy recommendation is mainly due to WHO's considerations for developing countries; longer duration of treatment is preferred.[53390] [63942]
1 mg/kg/dose (Max: 50 mg/dose) PO once daily or 2 mg/kg/dose (Max: 50 mg/dose) PO every other day in combination with rifampin and dapsone for 24 months. Round dose to nearest 50 mg as there is no formulation less than 50 mg and the capsule may not be opened.[53390] Alternatively, 50 mg PO twice weekly plus 100 mg PO once monthly in combination with rifampin and dapsone for 12 months for multibacillary disease is recommended by the WHO.[63942] The shorter duration of therapy recommendation is mainly due to WHO's considerations for developing countries; longer duration of treatment is preferred.[53390] [63942]
100 mg PO once daily in combination with 1 or more other antileprosy agents for 3 years, followed by clofazimine 100 mg PO once daily as monotherapy.[63936]
50 mg PO once daily in combination with ofloxacin and minocycline for 6 months, followed by clofazimine in combination with ofloxacin or minocycline for 18 months or ofloxacin and clarithromycin for 6 months, followed by clofazimine in combination with ofloxacin for 18 months. Levofloxacin or moxifloxacin may replace ofloxacin.[63942]
50 mg PO once daily in combination with clarithromycin and minocycline for 6 months, followed by clofazimine in combination with clarithromycin or minocycline for 18 months.[63942]
100 mg PO once daily.[65465] [65744] [69584] [69587]
2 to 5 mg/kg/dose (Max: 100 mg/dose) PO once daily.[65465] [65744] [69584] [69586] [69587]
300 mg PO once daily for up to 3 months. If effective, reduce the dose to 200 mg for 3 months, followed by 100 mg for 6 to 12 months.[53390]
300 mg/day PO divided 1 to 3 times daily for 6 weeks, followed by 200 mg PO once daily for 2 to 6 months, then 100 mg PO once daily for up to 1 to 2 years. When no steroids are required for 3 months, reduce the dose to 50 mg PO once daily and discontinue when no steroids are required for an additional 3 months.[53390] The FDA-labeled dosage is 100 to 200 mg PO once daily as clinically necessary; taper to 100 mg PO once daily as soon as the reaction is controlled.[63936]
200 mg/day PO; 300 mg PO once monthly plus daily dosing has also been used.
200 mg/day PO; 300 mg PO once monthly plus daily dosing has also been used.
15 to 17 years: 50 mg/day PO, with or without 300 mg PO once monthly, has been used.
13 to 14 years weighing 40 kg or more: 50 mg/day PO, with or without 150 mg PO once monthly, has been used.
13 to 14 years weighing less than 40 kg: 50 mg/day PO, with or without 100 mg PO once monthly, has been used.
10 to 12 years weighing 40 kg or more: 50 mg/day PO, with or without 150 mg PO once monthly, has been used.
10 to 12 years weighing less than 40 kg: 50 mg/day PO, with or without 100 mg PO once monthly, has been used.
1 to 9 years: 50 mg/day PO, with or without 100 mg PO once monthly, has been used.
Safety and efficacy have not been established.
Safety and efficacy have not been established.
Avoid clofazimine in patients with hepatic impairment (Child-Pugh class A, B, or C) unless the benefit outweighs the risk.[63936]
No dosage adjustment needed. Use clofazimine with caution in patients with severe renal impairment.[32569][63936]
† Off-label indicationClofazimine is an oral antimycobacterial agent indicated for dapsone-sensitive or dapsone-resistant lepromatous leprosy as part of a combination regimen as well as lepromatous leprosy complicated by erythema nodosum leprosum. Because of resistance, clofazimine is not used alone for leprosy. Clofazimine exerts a slow bactericidal effect on Mycobacterium leprae and possesses anti-inflammatory properties in treating erythema nodosum leprosum reactions. Cases of QT prolongation with torsade de pointes have been reported with clofazimine; ECG monitoring is recommended. Other significant adverse reactions associated with clofazimine include skin discoloration that has been reported to result in depression and suicide and intestinal obstruction.[63936]
For storage information, see the specific product information within the How Supplied section.
Tuberculosis patients
Directly observed therapy (DOT) is recommended for all children as well as adolescents and adults living with HIV.[34361] [34362] [61094]
Clofazimine may accumulate in various organs as crystals, including the mesenteric lymph nodes and histiocytes at the lamina propria of the intestinal mucosa, spleen, and liver. Deposition in the intestinal mucosa may lead to intestinal obstruction that may necessitate exploratory laparotomy. Splenic infarction, GI bleeding, and death have been reported. Gastrointestinal intolerance was reported in 40% to 50% of patients. Other GI adverse reactions reported in more than 1% of patients include epigastric and abdominal pain, diarrhea, nausea, and vomiting. GI adverse reactions reported in less than 1% of patients include splenic infarction, GI obstruction, GI bleeding, anorexia, constipation, weight loss, hepatitis, jaundice, eosinophilic enteritis, enlarged liver (hepatomegaly), elevated hepatic enzymes (i.e., AST), and elevated bilirubin (hyperbilirubinemia). If patients complain of pain in the abdomen, nausea, vomiting, or diarrhea, initiate appropriate medical investigations, and reduce the daily dose, increase the dosing interval, or discontinue clofazimine.[63936]
Conjunctival and corneal deposits (crystal deposits) and pigmentation have been reported in more than 1% of patients. Other ophthalmic adverse effects reported in more than 1% of patients include visual impairment, ocular dryness, ocular burning, ocular pruritus, and ocular irritation. Maculopathy (bull's eye retinopathy) was reported in less than 1% of patients.[63936]
Central nervous system adverse reactions reported in less than 1% of clofazimine-treated patients include dizziness, drowsiness, fatigue, giddiness, headache, dysgeusia (taste disorder), and neuralgia.[63936]
Miscellaneous and laboratory adverse reported in more than 1% of clofazimine treated patients include elevated blood glucose (hyperglycemia) and elevated erythrocyte sedimentation rate (ESR). Anemia, bone pain, cystitis, edema, fever, lymphadenopathy, thromboembolism, and vascular pain were reported in less than 1% of patients. Other laboratory value alterations included eosinophilia, hypokalemia, and elevated albumin were reported in less than 1% of patients.[63936]
Cases of torsade de pointes with QT prolongation have been reported in patients receiving more than clofazimine 100 mg/day or in combination with QT-prolonging medications. Monitor ECGs for QT prolongation and cardiac rhythm disturbances. For QT prolongation and torsade de pointes cases, patients must remain under medical surveillance.[63936]
Depression and suicide secondary to skin discoloration were reported in less than 1% of clofazimine-treated patients. Advise patients about skin discoloration, and monitor patients for depression or suicidal ideation during clofazimine therapy.[63936]
Clofazimine is contraindicated in any patient with known hypersensitivity to clofazimine or any of the excipients of clofazimine.[63936]
Clofazimine causes orange-pink to brownish skin discoloration, as well as discoloration of the conjunctivae, tears, sweat, sputum, and feces. Advise patients that skin discoloration is likely to occur and that it may take several months or years to reverse after cessation of therapy.[63936]
Avoid clofazimine in patients with hepatic disease or impairment (Child-Pugh Class A, B, or C) unless the benefit outweighs the risk.[63936]
Carefully select dose, starting at the lower end of the dosage range, in geriatric patients, reflecting the greater frequency of decreased renal, hepatic, or cardiac function, and concomitant disease or drug therapy.[63936]
Cases of torsade de pointes with QT prolongation have been reported in patients receiving clofazimine at doses more than 100 mg/day or in combination with medications that prolong the QT interval. Use clofazimine with caution in patients with conditions that may increase the risk of QT prolongation including congenital long QT syndrome, bradycardia, AV block, heart failure, stress-related cardiomyopathy, myocardial infarction, stroke, hypomagnesemia, hypokalemia, hypocalcemia, or in patients receiving medications known to prolong the QT interval or cause electrolyte imbalances. Females, people 65 years and older, patients with sleep deprivation, pheochromocytoma, sickle cell disease, hypothyroidism, hyperparathyroidism, hypothermia, systemic inflammation (e.g., human immunodeficiency virus (HIV) infection, fever, and some autoimmune diseases including rheumatoid arthritis, systemic lupus erythematosus (SLE), and celiac disease) and patients undergoing apheresis procedures (e.g., plasmapheresis [plasma exchange], cytapheresis) may also be at increased risk for QT prolongation.[28432] [28457] [56592] [63936] [65180]
Use clofazimine during pregnancy only if the potential benefit justifies the potential risk to the fetus. There are no studies of clofazimine use in pregnant women to inform drug-associated risk. A few cases reported in the literature describe the skin of infants born to pregnant mothers who received clofazimine during pregnancy as deeply pigmented at birth. Limited data are available regarding the reversibility of discoloration. Based on previous observations, discoloration gradually faded over the first year. Advise pregnant women of the potential risk to the fetus. In animal studies, embryotoxicity and fetotoxicity were evident. Retardation of fetal skull ossification, increased incidences of abortions and stillbirths, and impaired neonatal survival were observed with animal prenatal exposure of 25 mg/kg (equivalent to 0.6 times the maximum recommended human daily dose of 200 mg, based on body surface area comparisons).[63936]
Clofazimine is excreted in human breast milk. Skin discoloration has been observed in breast-fed neonates of mothers receiving clofazimine. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for clofazimine and any potential adverse effects on the breast-fed infant from clofazimine or the underlying maternal condition.[63936]
Clofazimine may be associated with reproductive risk. Conduct pregnancy testing for sexually-active females of reproductive potential before starting treatment with clofazimine. Discuss contraception requirements with the patient. Advise sexually-active females of reproductive potential to use effective contraception (methods that result in less than 1% pregnancy rates) during clofazimine treatment and for at least 4 months after stopping clofazimine treatment. Advise males taking clofazimine to use a condom during intercourse while on clofazimine treatment and for at least 4 months after stopping clofazimine treatment. Female infertility or impaired fertility (i.e., reduced number of offspring and a lower proportion of implantation) was observed in an animal study. There are no non-clinical data on male fertility.[63936]
Clofazimine is an antimycobacterial agent that exerts a slow bactericidal effect on Mycobacterium leprae. Clofazimine binds preferentially to mycobacterial DNA and inhibits growth. The mechanism of action is postulated through its membrane-directed activity including the bacterial respiratory chain and ion transporters. Intracellular redox cycling, involving oxidation of reduced clofazimine, leads to the generation of antimicrobial reactive oxygen species (ROS), superoxide-hydrogen peroxide (H202). Interaction of clofazimine with membrane phospholipids results in the generation of antimicrobial lysophospholipids, which promote membrane dysfunction, resulting in interference with potassium uptake. Both mechanisms cause interference with cellular energy metabolism by disrupting ATP production. Clofazimine also exerts anti-inflammatory properties in treating erythema nodosum leprosum reactions. Anti-inflammatory activity is likely primarily through inhibition of T lymphocyte activation and proliferation. Clofazimine may indirectly interfere with the proliferation of T cells by promoting the release of ROS and E-series prostaglandins (PGs), especially PGE2 from neutrophils and monocytes.[63936]
Revision Date: 12/05/2024, 02:07:00 AMClofazimine is administered orally. The highly lipophilic drug is distributed mainly to fatty tissue and the reticuloendothelial system. It is taken up by macrophages throughout the body. Clofazimine is bound to alpha- and primarily beta-lipoproteins in serum, and the binding is saturable at plasma concentrations of approximately 10 mcg/mL. Binding to gamma-globulin and albumin is negligible. At autopsy, clofazimine crystals have been found in mesenteric lymph nodes, adrenals, subcutaneous fat, liver, bile, gallbladder, spleen, small intestine, muscles, bones, and skin.[63936]
Information on the metabolism of clofazimine is limited; however, 3 metabolites were found in urine after repeated oral doses. After a single 300 mg dose, elimination of unchanged clofazimine and its metabolites was negligible in a 24-hour urine collection. Part of the ingested drug recovered from feces may represent excretion via the bile. A small amount is also eliminated in the sputum, sebum, and sweat. The mean elimination half-life of clofazimine is approximately 25 days (range 6.5 to 160 days) after repeated oral doses of 50 or 100 mg in leprosy patients.[63936]
Affected cytochrome P450 isoenzymes and drug transporters: CYP2C8, CYP2D6, CYP3A4/5
Clofazimine inhibits the metabolism of CYP2C8, CYP2D6, and CYP3A4/5 in vitro. It may increase the concentration of CYP3A4/5 substrates if used concomitantly.[63936]
Clofazimine absorption ranges from 45% to 62% in leprosy patients. The average serum concentrations of clofazimine in leprosy patients treated with 100 and 300 mg daily were 0.7 mcg/mL and 1 mcg/mL, respectively. Time to reach peak plasma concentration (median Tmax) decreases from 12 hours to 8 hours under fed conditions relative to the fasted state.[63936]
Use clofazimine during pregnancy only if the potential benefit justifies the potential risk to the fetus. There are no studies of clofazimine use in pregnant women to inform drug-associated risk. A few cases reported in the literature describe the skin of infants born to pregnant mothers who received clofazimine during pregnancy as deeply pigmented at birth. Limited data are available regarding the reversibility of discoloration. Based on previous observations, discoloration gradually faded over the first year. Advise pregnant women of the potential risk to the fetus. In animal studies, embryotoxicity and fetotoxicity were evident. Retardation of fetal skull ossification, increased incidences of abortions and stillbirths, and impaired neonatal survival were observed with animal prenatal exposure of 25 mg/kg (equivalent to 0.6 times the maximum recommended human daily dose of 200 mg, based on body surface area comparisons).[63936]
Clofazimine is excreted in human breast milk. Skin discoloration has been observed in breast-fed neonates of mothers receiving clofazimine. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for clofazimine and any potential adverse effects on the breast-fed infant from clofazimine or the underlying maternal condition.[63936]
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