Version May 2024
Erythema nodosum leprosum: Oral:100 mg 3 times daily for a maximum of 12 weeks; taper to 100 mg twice daily for 12 weeks, and then to 100 mg once daily for 12 to 24 weeks. May be used with concomitant prednisolone (≤1 mg/kg/day) (WHO 2012).
Leprosy, lepromatous (multibacillary): Oral:
National Hansen Disease Program: 50 mg once daily, in combination with dapsone and rifampin, for 24 months (NHDP [HRSA 2016]).
World Health Organization: 50 mg once daily and 300 mg once a month (directly observed), in combination with dapsone and rifampin, for 12 months (WHO 2012).
Mycobacterial (nontuberculous) (eg, M. abscessus) infection (off-label use): Oral: 100 to 200 mg once daily as part of an appropriate combination regimen (ATS/ERS/ESCMID/IDSA [Daley 2020]).
Tuberculosis, drug-resistant (off- label use): Oral: 100 mg once daily as part of an appropriate combination regimen (AST/CDC/ERS/IDSA [Nahid 2019]); some experts recommend up to 200 mg once daily (Schluger 2020).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Mild to moderate impairment: No dosage adjustment necessary.
Severe impairment: Use with caution.
Avoid in patients with hepatic impairment (Child-Pugh classes A, B, and C) unless benefit outweighs risk.
Refer to adult dosing.
(For additional information see "Clofazimine (United States: Available via expanded access program and FDA investigational drug [IND] protocol only): Pediatric drug information")
Note: Clofazimine is not commercially available in the United States. Refer to "Prescribing and Access Restrictions" for additional information.
Leprosy, lepromatous (multibacillary): Limited data available: Note: In the United States, it is strongly recommended to contact the National Hansen's Disease Program for management of leprosy in children (NHDP/HRSA 2018a). Use in combination with dapsone and rifampin.
National Hansen Disease Program dosing: Children and Adolescents: Oral: 1 mg/kg/dose once daily for 24 months; maximum dose: 50 mg/dose (NHDP/HRSA 2018a). Note: Lowest available capsule size is 50 mg, and capsule should not be opened; doses of 2 mg/kg/dose every other day are acceptable if needed based on dosage form constraints (NHDP/HRSA 2018b).
World Health Organization dosing (WHO 2018):
Children <10 years: Oral: 50 mg twice weekly and 100 mg once monthly for 12 months.
Children ≥10 years and Adolescents <15 years:
<40 kg: Oral: 50 mg twice weekly and 100 mg once monthly for 12 months.
≥40 kg: Oral: 50 mg once every other day and 150 mg once monthly for 12 months.
Adolescents ≥15 years: Oral: 50 mg once daily and 300 mg once monthly for 12 months.
Mycobacterial (nontuberculous) infection (eg, Mycobacterium abscessus):
Odontogenic infection, osteomyelitis: Very limited data available: Oral: Children 3 to 9 years: Oral: 1 mg/kg/dose once daily as part of an appropriate combination regimen. Dosing from a retrospective case series of 27 children who received clofazimine as part of combination therapy for treatment of jaw osteomyelitis due to M. abscessus after an outbreak at a dental office. Due to dosage form limitations (smallest available capsule is 50 mg, which cannot be opened), the dose was adjusted and administered 2 to 6 times per week to achieve an average dose of ~1 mg/kg/day (Adler-Shohet 2020).
Pulmonary infection in patients without cystic fibrosis: Limited data available: Children and Adolescents: Oral: 3 to 5 mg/kg/dose once daily as part of an appropriate combination regimen; maximum dose: 100 mg/dose; doses up to 200 mg are recommended in adults (BTS [Haworth 2017]).
Pulmonary infection in patients with cystic fibrosis: Limited data available: Children and Adolescents: Oral: 1 to 2 mg/kg/dose once daily as part of an appropriate combination regimen; maximum dose: 100 mg/dose. Due to dosage form limitations (smallest available capsule is 50 mg, which cannot be opened), higher doses may be administered less frequently (3 to 7 days per week) to achieve an average dose of 1 to 2 mg/kg/day (Cameron 2021; CFF/ECFS [Floto 2016]).
Tuberculosis, active (drug-resistant); treatment: Limited data available: Children and Adolescents: Oral: 2 to 5 mg/kg/dose once daily as part of an appropriate combination regimen; maximum dose: 100 mg/dose (ATS/CDC/ERS/IDSA [Nahid 2019]; WHO 2020). Note: May administer higher dose every other day if needed based on dosage form constraints (WHO 2020).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no pediatric-specific recommendations; adult information suggests that no dosing adjustment is necessary for mild to moderate impairment; caution should be used in severe impairment.
There are no pediatric-specific recommendations; based on recommendations in adults, avoid use in any degree of hepatic impairment unless benefits outweigh risks.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Dermatologic: Skin discoloration (75% to 100%; orange-pink to brownish-black), ichthyosis (8% to 28%), xeroderma (8% to 28%)
Gastrointestinal: GI adverse effects (40% to 50%)
1% to 10%:
Dermatologic: Pruritus (1% to 5%), skin rash (1% to 5%), discoloration of sweat (1%)
Endocrine & metabolic: Increased serum glucose (>1%)
Gastrointestinal: Abdominal pain (>1%), diarrhea (>1%), fecal discoloration (>1%), nausea (>1%), vomiting (>1%)
Genitourinary: Urine discoloration (>1%)
Hematologic & oncologic: Increased erythrocyte sedimentation rate (>1%)
Ophthalmic: Burning sensation of eyes (>1%), conjunctival discoloration (>1%), corneal changes (pigmentation; >1%), dry eye syndrome (>1%), eye irritation (>1%), eye pruritus (>1%), vision loss (>1%)
Respiratory: Discoloration of sputum (>1%)
<1%, postmarketing, and/or case reports: Acneiform eruption, anemia, anorexia, cheilosis, constipation, cystitis, dizziness, drowsiness, edema, eosinophilia, erythroderma, fatigue, fever, gastroenteritis, gastrointestinal hemorrhage, headache, hepatitis, hepatomegaly, hypokalemia, increased serum albumin, increased serum aspartate aminotransferase, increased serum bilirubin, intestinal obstruction, jaundice, lymphadenopathy, maculopathy (bull’s eye retinopathy), neuralgia, ostealgia, pain (vascular), phototoxicity, prolonged QT Interval on ECG, splenic infarction, taste disorder, thromboembolism, torsades de pointes, weight loss
Hypersensitivity to clofazimine or any component of the formulation.
Concerns related to adverse effects:
• Cardiovascular effects: Cases of torsades de pointes (TdP) with QT prolongation have been reported in patients taking > 100 mg/day or in combination with other QT prolonging drugs. If TdP or QT prolongation occurs, patient must remain under medical surveillance while monitoring ECGs and cardiac rhythm.
• Dermatologic effects: May cause photosensitivity (Legendre 2012). Use skin protection and avoid prolonged exposure to sunlight; do not use tanning equipment. May cause skin dryness, pruritus, and ichthyosis; oil-based skin preparations may relieve symptoms.
• GI effects: May accumulate as crystals in organs including intestinal mucosa, spleen and liver. Intestinal mucosa deposition may lead to obstruction that may require exploratory laparotomies in some patients. Splenic infarction and GI bleeding (some fatal) have also been reported. May be dose related; dosages >100 mg/day should be used for the shortest duration possible (<3 months) and only under close supervision. If patient complains of abdominal pain (colicky or burning), nausea, vomiting, or diarrhea, initiate clinical investigations and decrease dose, increase dosing interval, or discontinue therapy.
• Skin and body fluid discoloration: Discoloration of the skin (red to brownish-black) or conjunctivae, lacrimal fluid, sweat, sputum, urine and feces may occur in 75% to 100% of patients. Skin discoloration is reversible after treatment discontinuation; however, disappearance of discoloration may take several months to years.
• Suicidal ideation: Suicide has been reported (rare); thought to be related to depression due to skin discoloration. Advise patients about potential for skin discoloration and monitor for suicidal ideation during therapy.
Disease-related concerns:
• Depression: Use with caution in patients with a history of depression; skin discoloration caused by clofazimine may result in depression. Advise patients about potential for skin discoloration and monitor for depressive symptoms during therapy.
• Gastrointestinal disease: Use with caution in patients with gastrointestinal disorders, including abdominal pain and diarrhea.
Other warnings/precautions:
• Contact lenses: Remove contact lenses during therapy; staining may occur (Legendre 2012).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral: 50 mg
Clofazimine is not commercially available in the United States. For the treatment of leprosy, information on how to access clofazimine is available from the National Hansen’s Disease Program (https://www.hrsa.gov/hansens-disease).
For the treatment of other nontuberculous mycobacterial (NTM) infections in adults contact the Novartis NTM program at 1-888-NOW-NOVA (1-888-669-6682). Eligibility criteria for the Novartis NTM program can be found at https://www.clinicaltrials.gov/study/NCT04334070. For patients not eligible for the Novartis expanded access program providers should contact the Food and Drug Administration (FDA) Division of Anti-Infective products at 301-796-1400 or visit https://www.fda.gov/about-fda/center-drug-evaluation-and-research-cder/expanded-access-clofazimine for information on single patient IND requests.
International: No longer available commercially. In nations where a national leprosy elimination program exists, the Ministries of Health make an official request to the World Health Organization (WHO) for clofazimine. In nations where no such program exists, doctors or pharmacists from individual institutions contact the WHO with a request. A request can be made to the WHO via a letter, fax, or email to verify that the drug will be used to treat a severe ENL reaction due to leprosy and how many patients need the drug. If these conditions are met, a free supply of clofazimine will then be made available. For treatment of MDR-TB, the WHO handles decisions regarding distribution on an individual case-by-case basis. For additional information: http://www.who.int/lep/mdt/clofazimine/en/.
Oral: Administer with meals; capsules must be swallowed whole and should not be opened.
Oral: Administer with meals; capsules must be swallowed whole and should not be opened.
Leprosy: Treatment of lepromatous (multibacillary) leprosy, in combination with other agents; treatment of erythema nodosum leprosum.
Mycobacterial (nontuberculous, rapidly growing) infection; Tuberculosis, drug-resistant
Clofazimine may be confused with cloZAPine
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Amisulpride (Oral): May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). Risk C: Monitor therapy
Bacillus clausii: Antibiotics may diminish the therapeutic effect of Bacillus clausii. Management: Bacillus clausii should be taken in between antibiotic doses during concomitant therapy. Risk D: Consider therapy modification
BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Risk C: Monitor therapy
Chloroquine: QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of Chloroquine. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Management: Avoid cholera vaccine in patients receiving systemic antibiotics, and within 14 days following the use of oral or parenteral antibiotics. Risk X: Avoid combination
CYP3A4 Substrates (High risk with Inhibitors): Clofazimine may increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
Dabrafenib: Clofazimine may enhance the QTc-prolonging effect of Dabrafenib. Clofazimine may increase the serum concentration of Dabrafenib. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Domperidone: QT-prolonging Agents (Moderate Risk) may enhance the QTc-prolonging effect of Domperidone. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Elexacaftor, Tezacaftor, and Ivacaftor: Clofazimine may increase the serum concentration of Elexacaftor, Tezacaftor, and Ivacaftor. Risk C: Monitor therapy
Encorafenib: May enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Fecal Microbiota (Live) (Oral): May diminish the therapeutic effect of Antibiotics. Risk X: Avoid combination
Fecal Microbiota (Live) (Rectal): Antibiotics may diminish the therapeutic effect of Fecal Microbiota (Live) (Rectal). Risk X: Avoid combination
Fluorouracil Products: QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of Fluorouracil Products. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Haloperidol: QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of Haloperidol. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies): Antibiotics may diminish the therapeutic effect of Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies). Risk C: Monitor therapy
Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Risk C: Monitor therapy
Levoketoconazole: QT-prolonging Agents (Moderate Risk) may enhance the QTc-prolonging effect of Levoketoconazole. Risk X: Avoid combination
Ondansetron: QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of Ondansetron. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Pentamidine (Systemic): QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of Pentamidine (Systemic). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Pimozide: May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). Risk X: Avoid combination
QT-prolonging Agents (Highest Risk): May enhance the QTc-prolonging effect of Clofazimine. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
QT-prolonging Antidepressants (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Antipsychotics (Moderate Risk): QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging Antipsychotics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Class IC Antiarrhythmics (Moderate Risk): QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging Class IC Antiarrhythmics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-Prolonging Inhalational Anesthetics (Moderate Risk): QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of QT-Prolonging Inhalational Anesthetics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Kinase Inhibitors (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Miscellaneous Agents (Moderate Risk): May enhance the QTc-prolonging effect of Clofazimine. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Moderate Risk). QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of QT-prolonging Miscellaneous Agents (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Quinolone Antibiotics (Moderate Risk): QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging Quinolone Antibiotics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Sertindole: May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). Risk X: Avoid combination
Sodium Picosulfate: Antibiotics may diminish the therapeutic effect of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. Risk D: Consider therapy modification
Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Avoid use of live attenuated typhoid vaccine (Ty21a) in patients being treated with systemic antibacterial agents. Postpone vaccination until 3 days after cessation of antibiotics and avoid starting antibiotics within 3 days of last vaccine dose. Risk D: Consider therapy modification
Evaluate pregnancy status prior to use in females of reproductive potential. Females of reproductive potential should use effective contraception during treatment for multidrug-resistant tuberculosis (Esmail 2018); the manufacturer recommends use of effective contraception during therapy and for ≥4 months after the last clofazimine dose.
Clofazimine crosses the placenta (Freerksen 1992; Holdiness 1989).
Infants born to women who have received clofazimine during pregnancy had deeply pigmented skin at birth with gradual fading over 1 year (Holdiness 1989).
Clofazimine is approved for the treatment of leprosy. Leprosy may be exacerbated during pregnancy. Untreated disease may cause permanent damage to the maternal skin, nerves, limbs, and eyes (Ozturk 2017). The risk of erythema nodosum leprosum is increased during pregnancy when the cell-mediated immune system is depressed. Clofazimine is recommended for the treatment of lepromatous (multibacillary) leprosy during pregnancy (HRSA 2016).
Clofazimine is used off label for the treatment of drug resistant tuberculosis. Tuberculosis (TB) disease (active TB) is associated with adverse fetal outcomes including intrauterine growth restriction, low birth weight, preterm birth, and perinatal death (Esmail 2018; Miele 2020) as well as adverse maternal outcomes, including increased risks for anemia and cesarean delivery. Placental transmission may rarely occur with active maternal disease (Miele 2020). Data are limited for use of second-line drugs in pregnancy (ie, clofazimine). Individualized regimens should be utilized to treat multidrug-resistant tuberculosis in pregnant patients; evidence to support a specific regimen is not available (ATS/CDC/ERS/IDSA [Nahid 2019]; WHO 2020).
Clofazimine is present in breast milk (Venkatesan 1997).
Breast milk discoloration (red tint) has been reported (Freerksen 1992). Skin discoloration has also been noted in breastfed infants exposed to clofazimine through breast milk, with gradual fading after breastfeeding is stopped (Holdiness 1989; Ozturk 2017). According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother.
GI symptoms (eg, abdominal pain, nausea, vomiting, diarrhea); skin for discoloration; periodically monitor liver function tests and serum creatinine (WHO 1998); pregnancy test prior to treatment (women of reproductive potential); ECG (with concomitant use of clofazimine and bedaquiline); depression or suicidal ideation
Exact mechanism unknown; antibacterial activity may be due to binding to DNA of Mycobacterium leprae.
Absorption: Variable and incomplete (45% to 62%); may be increased when administered with food (Legendre 2012)
Distribution: Highly lipophilic; deposits primarily in fatty tissues and cells of reticuloendothelial system
Half-life elimination: ~25 days (range: 6.5 to 160 days)
Excretion: Feces
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