Clofazimine
Clofazimine Uses, Dosage, Side Effects, Food Interaction and all others data.
Clofazimine is a highly lipophilic antimicrobial riminophenazine dye used in combination with other agents, such as dapsone, for the treatment of leprosy. It was originally described in 1957 and was the prototypical riminophenazine dye - a bright-red dye that, in its clinical use, results in long-lasting discoloration of the skin and bodily fluids. Although it carries in vitro activity against other mycobacterium, such as Mycobacterium tuberculosis, it is generally considered an ineffective treatment in comparison to classic tuberculosis treatments such as rifampicin and isoniazid.
Clofazimine exerts a slow bactericidal effect on Mycobacterium leprae (Hansen's bacillus) due primarily to its action on the bacterial outer membrane, though there is some evidence that activity on the bacterial respiratory chain and ion transporters may play a role. It also exerts anti-inflammatory properties due to the suppression of T-lymphocyte activity. Clofazimine has a relatively long duration of action owing to its long residence time in the body, but is still administered daily.
Approximately 75-100% of patients receiving clofazimine will experience an orange-pink to brownish-black discoloration of the skin, conjunctivae, and bodily fluids. Skin discoloration may take several months or years to reverse following the cessation of therapy. Clofazimine has also been implicated in abdominal obstruction, in some cases fatal, due to the deposition of drug and formation of crystals in the intestinal mucosa - complaints of abdominal pain and nausea/vomiting should be investigated promptly, and the doses of clofazimine should be lowered or discontinued if it is found to be the culprit.
| Trade Name | Clofazimine |
| Availability | Discontinued |
| Generic | Clofazimine |
| Clofazimine Other Names | Clofazimin, Clofazimina, Clofazimine, Clofaziminum, Riminophenazine |
| Related Drugs | rifampin, dapsone, thalidomide, Rifadin, Thalomid, Rimactane |
| Type | Oral |
| Formula | C27H22Cl2N4 |
| Weight | Average: 473.396 Monoisotopic: 472.122152138 |
| Protein binding | Clofazimine is bound primarily to beta-lipoproteins (and, to a lesser extent, alpha-lipoproteins) in the serum. This binding was saturable at concentrations of ~10 µg/mL. Binding to gamma-globulin and albumin is negligible. |
| Groups | Approved, Investigational |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | United States |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Clofazimine is a riminophenazine antimycobacterial used to treat leprosy.
Clofazimine is indicated for the treatment of lepromatous leprosy, including dapsone-resistant lepromatous leprosy and lepromatous leprosy complicated by erythema nodosum leprosum. To prevent the development of drug resistance, it should be used only in combination with other antimycobacterial leprosy treatments.
Clofazimine is also used to associated treatment for these conditions: Leprosy, Lepromatous
How Clofazimine works
Although the precise mechanism(s) of action of clofazimine have not been elucidated, its antimicrobial activity appears to be membrane-directed. It was previously thought that, due to its lipophilicity, clofazimine participated in the generation of intracellular reactive oxygen species (ROS) via redox cycling, specifically H2O2 and superoxide, which then exerted an antimicrobial effect. A more recent and compelling theory involves clofazimine interacting with bacterial membrane phospholipids to generate antimicrobial lysophospholipids - bactericidal efficacy may, then, arise from the combined membrane-destabilizing effects of both clofazimine and lysophospholipids, which interfere with K+ uptake and, ultimately, ATP production.
The anti-inflammatory activity of clofazimine is the result of its inhibition of T-lymphocyte activation and proliferation. Several mechanisms have been proposed, including direct antagonism of T-cell Kv 1.3 potassium channels and indirect action by promoting the release of E-series prostaglandins and reactive oxygen species from bystander neutrophils and monocytes.
Toxicity
The reported oral LD50 of clofazimine in rats and mice is 8400 mg/kg and >5000 mg/kg, respectively.
No specific data are available regarding the treatment of clofazimine overdosage. In cases of overdose consider gastrointestinal decontamination via gastric lavage or induced vomiting. Employ symptomatic and supportive measures as clinically indicated.
Food Interaction
- Take with food. Prescribing information for clofazimine recommends its administration with a meal.
Clofazimine Drug Interaction
Minor: sulfamethoxazole / trimethoprim, sulfamethoxazole / trimethoprimUnknown: epinephrine, epinephrine, amikacin liposome, amikacin liposome, diphenhydramine, diphenhydramine, apixaban, apixaban, clonazepam, clonazepam, acetylcysteine, acetylcysteine, esomeprazole, esomeprazole, sildenafil, sildenafil, cholecalciferol, cholecalciferol
Clofazimine Disease Interaction
Volume of Distribution
Clofazimine is highly lipophilic and therefore deposits primarily in fatty tissues and cells of the reticuloendothelial system, where it is taken up by macrophages and further distributed throughout the body. Crystalized deposits have been found in the mesenteric lymph nodes, adrenals, subcutaneous fat, liver, bile, gall bladder, spleen, small intestine, muscles, bones, and skin.
Elimination Route
Absorption varies from 45 to 62% following oral administration in leprosy patients. Co-administration of a 200mg dose of clofazimine with food resulted in a Cmax of 0.41 mg/L with a Tmax of 8 h; administered in a fasting state, the corresponding Cmax was 30% lower while the time to Cmax was 12 h.
Half Life
The mean elimination half-life is approximately 25 days.
Elimination Route
Part of an ingested dose of clofazimine is found in the feces, which may represent excretion in the bile, and a small amount is also eliminated in the sputum, sebum, and sweat. Excretion of unchanged drug and metabolites in a 24-hour urine collection was negligible.
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