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LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-.

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LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet].

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Last Update: October 13, 2017.



Clofazimine is a fat soluble, brick red dye that is used in combination with other agents in the therapy of leprosy. Clofazimine, by itself, has not been associated with serum aminotransferase elevations during therapy or to instances of clinically apparent acute liver injury.


Clofazimine (kloe faz' i meen) is a fat soluble iminophenazine, brick red dye that has in vitro activity against several species of mycobacteria and was found to be very effective in the treatment of leprosy (Hansen disease). Clofazimine binds to mycobacterial DNA and was developed as a potential therapy of mycobacterium tuberculosis, but showed minimal activity. In contrast, it was found to be a valuable agent in treating leprosy; clinical trials demonstrating benefit both as monotherapy and when combined with dapsone and rifampin. Multidrug therapy using all three agents is now considered the first line of therapy for adults with leprosy and provides a high rate of ultimate cure after 1 to 3 years of therapy. Clofazimine was approved for use in the United States in 1986, but was withdrawn in 2016 and is now only available under the auspices of the National Hansen's Disease (Leprosy) Program (https://www.hrsa.gov/hansens-disease/index.html). In other countries, clofazimine is available under the commercial name Lamprene in tablets of 50 mg, the recommended dose being 100 mg daily. Clofazimine also has immunosuppressive activity and it has been used experimentally to treat discoid lupus erythematosus and psoriasis. More recently, it has shown some activity in treating infectious with drug resistant non-tuberculosis Mycobacterium species including Mycobaterium avian complex and abscessus. The major side effects of clofazimine include skin discoloration and gastrointestinal upset with pain, nausea and diarrhea. The skin discoloration is due to the reddish-orange color of clofazimine and results in a pinkish-brown discoloration of skin and bodily fluids in the majority of patients treated for more than a month. The discoloration fades with stopping the drug, but may persist for months or years. The gastrointestinal side effects of clofazimine can be severe and require dose modification or discontinuation. The symptoms appear to be due to crystallization of the clofazimine molecule in intestinal submucosa; these crystals can also be found in liver, lymph nodes and spleen. While clofazimine is rarely used in the United States, it is an important medication from a worldwide perspective and has played an essential role in public health efforts to eradicate leprosy.


Therapy with clofazimine has not been associated with elevations in serum enzymes during treatment and has not been linked to cases of clinically apparent liver injury. The multidrug therapy combination of clofazimine, rifampin and dapsone, however, is associated with instances of jaundice and hepatitis, which are most likely attributable to dapsone ("dapsone syndrome") and marked by fever, rash, eosinophilia and hepatic involvement (DRESS syndrome) typically arising within 8 weeks of starting the drug regimen. Dapsone induced liver injury can be severe and the mortality rate in cases with jaundice is as high as 25% to 33%. The liver injury usually resolves with stopping therapy and most patients have later tolerated restarting of clofazimine and rifampin. Thus, clinically apparent liver injury from clofazimine must be very rare, if it occurs at all.

Likelihood score: E (unlikely cause of clinically apparent liver injury).

Mechanism of Injury

The possible causes of liver injury from clofazimine therapy are not known and might relate to formation of drug-crystals in macrophages in the liver. While crystals of clofazimine can be found in liver and spleen in patients on prolonged therapy, they do not appear to be associated with appreciable liver damage. The hepatic metabolism of clofazimine is not well defined.

Outcome and Management

The serum aminotransferase and alkaline phosphatase elevations that occur during clofazimine therapy are self-limited and are generally due to other drugs that are used in combination with clofazimine. These abnormalities often resolve even with continuation of clofazimine therapy. Appearance of frank jaundice and hepatitis during multidrug therapy of leprosy should lead to temporary discontinuation of all three medications, but then with careful restarting of clofazimine once the liver injury has resolved.

Drug Class: Antiinfective Agents, Leprosy Agents

Other Drugs in the Subclass, Leprosy Agents: Dapsone , Rifampin



Clofazimine – Lamprene®


Antiinfective Agents


Product labeling at DailyMed, National Library of Medicine, NIH


Clofazimine 2030-63-9 C27-H22-Cl2-N4
Clofazimine chemical structure


References updated: 13 October 2017

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    (Among 176 patients treated with multidrug therapy for leprosy in India, 79 [45%] had 84 drug related adverse effects, including 73 from dapsone, 8 rifampin and 16 clofazimine manifested by skin discoloration in 2, gastrointestinal upset in 13 and hematemesis in 3).
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    (History of the development of therapies for leprosy starting with sulfonamides, and then sulfones such as dapsone, followed by clofazimine and then rifampin, maturing with multidrug therapy using all three for a defined period [1 or 2 years] with monthly rifampin).
  • Szeto W, Garcia-Buitrago MT, Abbo L, Rosenblatt JD, Moshiree B, Morris MI. Clofazimine enteropathy: a rare and underrecognized complication of mycobacterial therapy. Open Forum Infect Dis 2016; 3: ofw004. [PMC free article: PMC5084711] [PubMed: 27800519]
    (68 year old woman with lymphoma and hematopoietic cell transplant developed abdominal pain and diarrhea one month after starting clofazimine for Mycobacterium abscessus infection, which was nevertheless continued for 6 months, the pain, diarrhea and weight loss resolving with stopping; no mention of ALT elevations or hepatotoxicity).
  • Smith CS, Aerts A, Saunderson P, Kawuma J, Kita E, Virmond M. Multidrug therapy for leprosy: a game changer on the path to elimination. Lancet InfectDis 2017; 17: e293-e7. [PubMed: 28693853]
    (Leprosy is still present in 100 low income countries with more than 200,000 cases diagnosed yearly despite multidrug therapy that is highly effective and has been used on 16 million patients supported by long term efforts by WHO, financial support by the Nippon Foundation and donation of the 3 drug combination by Novartis).
  • Martiniano SL, Wagner BD, Levin A, Nick JA, Sagel SD, Daley CL. Safety and effectiveness of clofazimine for primary and refractory nontuberculous mycobacterial infection. Chest 2017; 152: 800-9. [PubMed: 28483608]
    (Among 117 patients with non-tuberculosis mycobacterial infections who were treated with clofazimine in combination with other agents for a median of 1 year, adverse events included skin rash or discoloration [66%], gastrointestinal complaints [55%] and ALT elevations of greater than 3 times ULN [3%], but no instances of clinically apparent liver injury).
  • https://www​.hrsa.gov​/hansens-disease/index.html .
    (Website for the National Hansen's Disease [Leprosy] Program with information on diagnosis and treatment, including means of obtaining triple therapy).


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