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Oral Diseases
Published in Ayşe Serap Karadağ, Lawrence Charles Parish, Jordan V. Wang, Roxburgh's Common Skin Diseases, 2022
Marcia Ramos-e-Silva, José Wilson Accioly Filho, Sueli Carneiro, Nurimar Conceição Fernandes
Management: There is no satisfactory treatment. Any intervention should be to the prevention of lip deformities and facial paralysis. Local measures, such as cold compresses, may reduce the edema, and Vaseline® or other lip moisturizers to prevent lip fissures. Sometimes, intralesional injections of corticosteroids, alone or in combination with cheiloplasty, a surgical procedure, may show more favorable results, especially in severe cases. Clofazimine has been used successfully in some cases, in a regimen of 100 mg per day with reduction after 10 days to 200–400 mg weekly for 3–6 months. Skin color change, nausea, and vomiting are frequent adverse reactions, and the patient should be informed.
Leprosy: Therapy-related emergencies
Published in Biju Vasudevan, Rajesh Verma, Dermatological Emergencies, 2019
Clofazimine is a lipophilic iminophenazine dye, having both antimicrobial and anti-inflammatory activities. Being lipophilic, it concentrates well in the lipid-rich tissues, particularly the reticuloendothelial system and intestine, breast, and liver. The skin, gastrointestinal tract, and eyes are the most common sites affected by clofazimine. It has a long half-life of approximately 70 days. Clofazimine in the usual recommended dosage (50 mg OD or 100 mg alternate day) as a component of MDT is well tolerated. However, the higher dosage commonly used in lepra reactions can cause enteritis [6,8,9]. In a review of 14 cases of clofazimine enteropathy, 10 patients (71.4%) had to undergo exploratory laparotomy [38].
Lichen planus pigmentosus
Published in Dimitris Rigopoulos, Alexander C. Katoulis, Hyperpigmentation, 2017
Efstratios Vakirlis, Dimitrios Ioannides
A prospective clinical and immunohistochemical study by Baranda et al. evaluated the effect of clofazimine therapy on the expression of adhesion and lymphocyte activation molecules in EDP in six patients. Four out of six patients experienced marked improvement after 3 months of therapy with 100 mg/day clofazimine. The authors detected clearance of these molecules after the 3-month therapy with clofazimine.58
Treatment of cryptosporidiosis: nitazoxanide yes, but we can do better
Published in Expert Review of Anti-infective Therapy, 2023
Maria A. Caravedo, A. Clinton White
High through-put phenotypic screening for activity again Cryptosporidium identified clofazimine as a highly active agent. Clofazimine is one of the main antimicrobials used for Leprosy and is increasingly used for resistant Mycobacteria. Since there was extensive data on safety and dosing from prior studies, the initial study in human cryptosporidiosis was a phase 2 trial in AIDS patients. In a carefully designed placebo-controlled trial, Iroh et al. found no evidence of clinical efficacy and, using quantitative parasitology, no evidence of antiparasitic effects [44]. Zhang et al. performed a pharmacokinetic/pharmacodynamic model to investigate the drug levels of clofazimine. The serum levels were significantly lower than levels required to kill the parasites in vitro. The authors suggested that clofazimine preparations with better absorption might be more effective [45]. However, Cryptosporidium is localized to the intestinal epithelium and there is no evidence that serum levels are an important measure. In fact, some animal models suggest poorer efficacy when drugs are better absorbed.
Nontuberculous mycobacterial lung disease caused by Mycobacterium avium complex - disease burden, unmet needs, and advances in treatment developments
Published in Expert Review of Respiratory Medicine, 2021
Jakko van Ingen, Marko Obradovic, Mariam Hassan, Beth Lesher, Erin Hart, Anjan Chatterjee, Charles L. Daley
A phase 2 study investigating the use of clofazimine monotherapy in patients with MAC-LD is ongoing in the US as of December 2020 [68], and an RCT comparing clofazimine-ethambutol-azithromycin versus rifampicin-ethambutol-azithromycin was recently completed in the Netherlands. In addition to ongoing clinical trials, clofazimine and other investigational agents (e.g. bedaquiline, moxifloxacin, and linezolid) have been evaluated in retrospective cohort studies and case series. Clofazimine, which in vitro is active against MAC and is synergistic with macrolides and amikacin [116,117], was effective for the treatment of MAC-LD in several cohort studies; however, side effects (e.g. dermatologic, gastrointestinal) have limited its use to select groups of patients [63,84,86,118]. Clofazimine is also important as a replacement drug in case of rifampicin or ethambutol intolerance [119]. Results from a study conducted in NTM-infected mice demonstrated that inhaled clofazimine improved bacterial elimination from the lungs of mice compared with negative controls and oral clofazimine (P < 0.05); however, these results are not confirmed in human studies [120].
Emerging opportunities of exploiting mycobacterial electron transport chain pathway for drug-resistant tuberculosis drug discovery
Published in Expert Opinion on Drug Discovery, 2020
Kuldeep K. Roy, Mushtaq Ahmad Wani
NADH dehydrogenase 2 (NDH-2) represents an established choke point in the electron transport chain of the mycobacterium species [21,59,60]. Moderate-to-high resolution structures of bacterial NDH-2, both in inhibitor-free and inhibitor-bound states, are available in the PDB (e.g. PDB-ID: 5WED, 4G73, 6BDO, etc.). Thioridazine is active in both the drug-sensitive and drug-resistant strains of mycobacterium and reported to be effective against dormant TB [21]. Against the same target, trifluoperazine is known to be another effective inhibitor, effectively inhibited the growth of Mtb resided intracellularly in macrophages [61]. Clofazimine, an antileprosy drug, is repurposed for the treatment of TB [17,18]. Clofazimine, a phenazine class of prodrug, is proposed to compete with menaquinone for its reduction by NDH-2 [17,18,21]. It should be noted here that none of the current ‘specific’ NDH-2 inhibitors are specific. They simply work as redox cycling agents. There is no binding to the target NDH-2 that we are aware of. Clofazimine is shown to act synergistically with BDQ (ATP synthase inhibitor) and Q203 (Cytochrome bcc-aa3 inhibitor) in the persistent killing of Mtb [17,62]. Meanwhile, Clofazimine is shown to shorten the duration of treatment of first-line treatment regimens [63].