Clofazimine

Clofazimine is available in the following forms:

• Oral Capsule

Leprosy

Treatment of lepromatous leprosy, including dapsone-resistant lepromatous leprosy and leprosy complicated by erythema nodosum leprosum (ENL) reactions.1 2 37 86 113 114 115 136 145 146 147 148 149 193 194 195 196 197 198 199 200 201 218 Used in conjunction with other anti-infectives active against Mycobacterium leprae.1 2 37 86 113 114 115 136 145 146 147 148 149 193 194 195 196 197 198 199 200 201 218

Treatment of multibacillary leprosy (>5 lesions or skin smear positive for acid-fast bacteria) in rifampin-based multiple-drug regimens.1 2 37 86 113 114 115 136 145 146 147 148 149 193 194 195 196 197 198 199 200 201 218 WHO recommends a 12-month multiple-drug regimen that includes rifampin, clofazimine, and dapsone.193 198 199 200 201 218

Treatment of paucibacillary leprosy (1–5 lesions) when dapsone cannot be used.1 2 37 86 113 114 115 136 145 146 147 148 149 193 194 195 196 197 198 199 200 201 WHO recommends a 6-month multiple-drug regimen of rifampin and dapsone;193 200 218 if dapsone must be discontinued because of severe adverse effects, WHO recommends that clofazimine be substituted.200

Rifampin-based multiple-drug regimens are recommended for the treatment of all forms of leprosy;193 194 195 196 197 198 199 200 201 multiple-drug regimens may reduce infectiousness of the patient more rapidly and delay or prevent emergence of rifampin-resistant M. leprae.193 200

Alternative for treatment and prevention of erythema nodosum leprosum (ENL) reactions (lepra type 2 reactions) in leprosy patients.1 2 37 40 41 69 71 81 82 84 86 93 147 148 149 154 155 156 157 158 164 193 195 196 198 Not as effective or as rapidly acting as other agents used in the treatment of ENL (e.g., corticosteroids, thalidomide);2 37 93 193 203 210 213 do not use alone for treatment of severe ENL.193 203

Has been used for treatment of reversal (type 1) reactions† in patients with borderline or tuberculoid leprosy.2 37 71 81 93 Efficacy not fully evaluated;37 81 196 may aggravate the reactional state in some patients.81

Not effective in the treatment of other leprosy-associated inflammatory reactions1 (e.g., Lucio’s phenomenon, downgrading reactions).37 129 130

Not commercially available in the US, but may be obtained for treatment of leprosy from the National Hansen’s Disease Program (NHDP) of the US Department of Health and Human Services, Health Resources and Services Administration (HRSA).214 215 216 In rare circumstances, also may be made available from NHDP for other uses.214 215 (See Restricted Distribution under Dosage and Administration.)

Treatment of leprosy and management of leprosy reactional states is complicated and should be undertaken in consultation with a specialist familiar with the disease.215 216 219 For information, consult NHDP by phone at 225-578-9861 or 800-642-2477, by fax at 225-578-9856, or on the Internet at .215 216 219

Mycobacterium Avium Complex (MAC) Infections

Has been used in multiple-drug regimens for treatment of pulmonary and localized extrapulmonary Mycobacterium avium complex (MAC) infections†, but safety and efficacy not established.28 43 44 45 46 48 49 50 92 95 152 167 ATS and IDSA state the role of clofazimine in the treatment of MAC lung disease is not established.183

Should not be used for treatment of disseminated MAC infections†, including infections that have failed to respond to or are resistant to other drugs.183 186 There is some evidence clofazimine is ineffective in these infections and may even be associated with reduced survival.179 183 186

Use of clofazimine for the treatment of any disease other than leprosy is discouraged by WHO and the manufacturer since indiscriminate use may promote emergence of resistant strains of M. leprae.214 (See Restricted Distribution under Dosage and Administration.)

Treatment of MAC infections is complicated and should be directed by clinicians familiar with mycobacterial diseases; consultation with a specialist is particularly important when the patient cannot tolerate first-line drugs or when the infection has not responded to prior therapy or is caused by macrolide-resistant MAC.183

Multidrug-resistant Tuberculosis (MDRTB)

Has been used in multiple-drug regimens for the treatment of MDRTB†, but safety and efficacy not established.217 Not included in current CDC, ATS, and IDSA recommendations for treatment of tuberculosis.47

Use of clofazimine for the treatment of any disease other than leprosy is discouraged by WHO and the manufacturer since indiscriminate use may promote emergence of resistant strains of M. leprae.214 (See Restricted Distribution under Dosage and Administration.)

Inflammatory or Pustular Dermatoses

Has been used in a variety of inflammatory or pustular dermatoses†, but safety and efficacy not established.53 56 59 62 63 65 100 104 107 110 132 133

Use of clofazimine for the treatment of any disease other than leprosy is discouraged by WHO and the manufacturer since indiscriminate use may promote emergence of resistant strains of M. leprae.214 (See Restricted Distribution under Dosage and Administration.)

Clofazimine is taken to treat leprosy (Hansen's disease). It is sometimes given with other medicines for leprosy. When clofazimine is used to treat ``flare-ups'' of leprosy, it may be given with a cortisone-like medicine. Clofazimine may also be used for other problems as determined by your doctor.

clofazimine is available only with your doctor's prescription.

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For clofazimine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to clofazimine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Studies on clofazimine have been done only in adult patients, and there is no specific information comparing use of clofazimine in children with use in other age groups.

Geriatric

Many medicines have not been studied specifically in older people. Therefore, it may not be known whether they work exactly the same way they do in younger adults or if they cause different side effects or problems in older people. There is no specific information comparing use of clofazimine in the elderly with use in other age groups.

Pregnancy

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking clofazimine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using clofazimine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Bedaquiline

Using clofazimine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Aluminum Hydroxide
• Fosphenytoin
• Magnesium Hydroxide
• Phenytoin

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using clofazimine with any of the following may cause an increased risk of certain side effects but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use clofazimine, or give you special instructions about the use of food, alcohol, or tobacco.

• Orange Juice

Other Medical Problems

The presence of other medical problems may affect the use of clofazimine. Make sure you tell your doctor if you have any other medical problems, especially:

• Liver disease—Clofazimine may on rare occasion cause hepatitis and liver disease

• Stomach or intestinal problems, history of—Clofazimine often causes some stomach upset, but on rare occasion may cause severe, sharp abdominal pain and burning, which may be a sign of a serious side effect

Clofazimine should be taken with meals or milk.

To help clear up your leprosy completely, it is very important that you keep taking clofazimine for the full time of treatment , even if you begin to feel better after a few months. You may have to take it every day for as long as 2 years to life. If you stop taking clofazimine too soon, your symptoms may return.

clofazimine works best when there is a constant amount in the blood. To help keep the amount constant, do not miss any doses. Also, it is best to take each dose at the same time every day. If you need help in planning the best time to take your medicine, check with your health care professional.

Dosing

The dose of clofazimine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of clofazimine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For the treatment of leprosy (Hansen's disease) :
  • Adults and teenagers: 50 to 100 milligrams once a day. clofazimine must be taken with other medicines for the treatment of Hansen's disease.
  • Children: Dose must be determined by the doctor.

Missed Dose

If you miss a dose of clofazimine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• Some drugs may have another patient information leaflet. Check with your pharmacist. If you have any questions about clofazimine, please talk with your doctor, nurse, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about clofazimine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using clofazimine.

Review Date: October 4, 2017

Applies to clofazimine: oral capsule

Gastrointestinal

Gastrointestinal (GI) side effects have included clofazimine enteropathy. Abdominal and epigastric pain, diarrhea, nausea, vomiting, and GI intolerance have been reported in 40% to 50% of patients. Rare reports of GI bleeding, bowel obstruction, anorexia, constipation, weight loss, and eosinophilic enteritis have been reported in less than 1% of patients.[Ref]

Clofazimine enteropathy may manifest as colicky abdominal pain, nausea, vomiting, diarrhea, and weight loss. In some cases these side effects have prompted unnecessary discontinuation or exploratory laparotomy. Exploratory laparotomy findings in some patients with clofazimine-associated severe abdominal pain have often shown diffuse visceral hyperpigmentation, lymphadenopathy, eosinophilic mucosal and submucosal infiltration. Clofazimine crystalline infiltration in the intestinal and gall bladder mucosa, and in the bile, liver, and spleen have been documented.[Ref]

Dermatologic

The reddish-brown rash may become generalized, but typically involves only lepromatous lesions in patients with leprosy. The discoloration is reversible upon drug discontinuation, may be seen for up to 5 years, and may also involve the tears, saliva, feces, and sputum.[Ref]

Dermatologic side effects have been commonly reported. These have included pigmentation from pink to brownish-black in 75% to 100% of the patients within a few weeks of treatment. Ichthyosis and dryness have been reported in 8% to 28% of patients. Rash and pruritus have been reported in 1% to 5% of patients. Erythroderma, acneiform eruptions, monilial cheilosis have been reported in less than 1% of patients. Phototoxicity and erythroderma have been reported rarely. Melanosis has also been observed, which resolved at a slower rate after the drug was discontinued.[Ref]

Ocular

Ocular side effects have included corneal and conjunctival pigmentation and decreased visual acuity. Diminished vision and ocular dryness, burning, itching, and irritation have been reported in greater than 1% of patients. Macular pigmentary abnormalities have also been reported.[Ref]

Rare cases of "bull's eye" retinopathy due to annular macular pigmentary abnormalities have been reported, but may have been associated with CMV retinitis in some of the patients since they also had AIDS and, in some cases, evidence of CMV infection.[Ref]

Metabolic

Metabolic side effects have been unusually reported. These have included significant increases in the fasting serum glucose and hypokalemia.[Ref]

Hypersensitivity

Hypersensitivity side effects have rarely included exfoliative dermatitis.[Ref]

Rare cases of exfoliative dermatitis have been believed to be due to hypersensitivity since rechallenge with even small doses reproduced the signs and symptoms.[Ref]

Cardiovascular

Cardiovascular side effects including thromboembolism have been reported.

Genitourinary

Genitourinary side effects including cystitis have been reported in less than 1% of patients.

Musculoskeletal

Musculoskeletal side effects including bone pain have been reported in less than 1% of patients.

Nervous system

Nervous system side effects including dizziness, drowsiness, fatigue, headache, giddiness, neuralgia, taste disorder, and vascular pain have been reported in less than 1% of patients.[Ref]

Psychiatric

Psychiatric side effects including depression secondary to skin discoloration have been reported. At least two cases of suicides have also been reported.

Hematologic

Hematologic side effects including elevated erythrocyte sedimentation rate (ESR) have been reported in greater than 1% of patients. Eosinophilia, splenic infarction, anemia, and lymphadenopathy have been reported in less than 1% of patients.[Ref]

Hepatic

Hepatic side effects including hepatitis, jaundice, enlarged liver, elevated AST (SGOT), and elevated total bilirubin have been reported in less than 1% of patients.[Ref]

Other

Other side effects including elevated albumin, fever, and edema have been reported in less than 1% of patients.

Some side effects of clofazimine may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

Clofazimine is excreted into human milk. Skin pigmentation is reported in at least one nursing infant. Clofazimine should not be used during breast-feeding unless necessary.

Substance Name

Clofazimine

CAS Registry Number

2030-63-9

Drug Class

Leprostatic Agents