Clofazimine

Pharmaceuticals -> Listed in ZINC15

Pharmaceuticals -> Antibiotics

1.51e-03 g/L

0.3 [ug/mL] (The mean of the results at pH 7.4)

Breast Feeding; Lactation; Milk, Human; Anti-Infective Agents; Leprostatic Agents

FDA approved drugs -> Active ingredient

FDA approved drugs -> Active ingredient

Antileprosy medicines

210-212 °C

210 - 212 °C

216.35 Ų [M+H]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

216.8 Ų [M+H]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

Warning

H315 (50%): Causes skin irritation [Warning Skin corrosion/irritation]

P261, P264, P264+P265, P271, P273, P280, P302+P352, P304+P340, P305+P351+P338, P319, P321, P332+P317, P337+P317, P362+P364, P403+P233, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 2 reports by companies from 2 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

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.

J - Antiinfectives for systemic use

QJ - Antiinfectives for systemic use

J04BA01

Clofazimine exerts a slow bactericidal effect on <i>Mycobacterium leprae</i> (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. Its use should be avoided in patients with hepatic dysfunction.

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.