clofazimine
Sources réglementaires consultées
Indications approuvées
- Lèpre lépromateuse, y compris résistante à la dapsone ou compliquée d’érythème noueux lépreux, dans un traitement combiné.
Contre-indications
Absolues
- Hypersensibilité à la clofazimine ou aux excipients.
Mises en garde cliniques
- Elle peut se déposer dans la muqueuse intestinale et provoquer obstruction, saignement, infarctus splénique et décès ; explorer la douleur abdominale et réduire, espacer ou arrêter. — DailyMed, set_id 2e07448f-f888-4747-80ab-570c1b621250
- Elle peut prolonger le QT et provoquer des torsades ; surveiller l’ECG, surtout avec la bédaquiline, et arrêter si QTcF ≥500 ms ou si une arythmie ventriculaire significative apparaît. — DailyMed, set_id 2e07448f-f888-4747-80ab-570c1b621250
- Mise en garde majeure · La coloration de la peau et des fluides est fréquente et peut provoquer dépression ou idées suicidaires ; informer et surveiller les effets psychologiques. — DailyMed, set_id 2e07448f-f888-4747-80ab-570c1b621250
Interactions médicamenteuses
- SévèreBédaquiline ou autres médicaments allongeant le QT
Mécanisme: L’allongement du QT peut être additif.
Recommandation: Éviter si possible ou intensifier la surveillance ECG et électrolytique.
DailyMed, set_id 2e07448f-f888-4747-80ab-570c1b621250
- ModéréeSubstrats du CYP3A4/5
Mécanisme: La clofazimine peut augmenter leurs concentrations.
Recommandation: Surveiller la toxicité du substrat et adapter si nécessaire.
DailyMed, set_id 2e07448f-f888-4747-80ab-570c1b621250
Effets indésirables
Communs (≥1%)
Pigmentation cutanée, sécheresse, ichtyose, douleur abdominale, diarrhée, nausées et vomissements
Rares mais graves
Obstruction ou hémorragie intestinale, torsades de pointes, dépression et suicide
Grossesse et allaitement
Elle peut pigmenter la peau du nouveau-né et présenter un risque fœtal ; utiliser seulement si le bénéfice l’emporte sur le risque. Elle est excrétée dans le lait et peut pigmenter le nourrisson ; envisager une alternative ou une décision sur l’allaitement.
Bibliographie récente (PubMed)
For decades, poor treatment options and low-quality evidence plagued care for patients with rifampin-resistant tuberculosis. The advent of new drugs to treat tuberculosis and enhanced funding now permit randomized, controlled trials of shortened-duration, all-oral treatments for rifampin-resistant tuberculosis. We conducted a phase 3, multinational, open-label, randomized, controlled noninferiority trial to compare standard therapy for treatment of fluoroquinolone-susceptible, rifampin-resistant tuberculosis with five 9-month oral regimens that included various combinations of bedaquiline (B), delamanid (D), linezolid (L), levofloxacin (Lfx) or moxifloxacin (M), clofazimine (C), and pyrazinamide (Z). Participants were randomly assigned (with the use of Bayesian response-adaptive randomization) to receive one of five combinations or standard therapy. The primary end point was a favorable outcome at week 73, defined by two negative sputum culture results or favorable bacteriologic, clinical, and radiologic evolution. The noninferiority margin was -12 percentage points. Among the 754 participants who underwent randomization, 699 were included in the modified intention-to-treat analysis, and 562 in the per-protocol analysis. In the modified intention-to-treat analysis, 80.7% of the patients in the standard-therapy group had favorable outcomes. The risk difference between standard therapy and each of the four new regimens that were found to be noninferior in the modified intention-to-treat population was as follows: BCLLfxZ, 9.8 percentage points (95% confidence interval [CI], 0.9 to 18.7); BLMZ, 8.3 percentage points (95% CI, -0.8 to 17.4); BDLLfxZ, 4.6 percentage points (95% CI, -4.9 to 14.1); and DCMZ, 2.5 percentage points (95% CI, -7.5 to 12.5). Differences were similar in the per-protocol population, with the exception of DCMZ, which was not noninferior in that population. The proportion of participants with grade 3 or higher adverse events was similar across the r
Tuberculosis (TB) remains a leading cause of infectious death worldwide, and poverty is a major driver. Clinically, TB presents as "latent" TB and active TB disease, and the treatment for each is different. TB drugs can display "early bactericidal activity (EBA)" and / or "sterilizing activity" (clearing persisters). Isoniazid is excellent at the former, and rifampin is excellent at the latter. Pyrazinamide and ethambutol complete the first-line regimen for drug-susceptible TB, each playing a specific role. Drug-resistant TB is an increasing concern, being met, in part, with repurposed drugs (including moxifloxacin, levofloxacin, linezolid, clofazimine, and beta-lactams) and new drugs (including bedaquiline, pretomanid, and delamanid). One challenge is to select drugs without overlapping adverse drug reaction profiles. QTc interval prolongation is one such concern, but to date, it has been manageable. Drug penetration into organism sanctuaries, such as the central nervous system, bone, and pulmonary TB cavities remain important challenges. The pharmacodynamics of most TB drugs can be described by the area under the curve (AUC) divided by the minimal inhibitory concentration (MIC). The hollow fiber infection model (HFIM) and various animal models (especially mouse and macaque) allow for sophisticated pharmacokinetic/pharmacodynamic experiments. These experiments may hasten the selection of the most potent, shortest possible regimens to treat even extremely drug resistant TB. These findings can be translated to humans by optimizing drug exposure in each patient, using therapeutic drug monitoring and dose individualization.
Recurrent aphthous stomatitis (RAS) is a common chronic disease in the oral mucosa that affects about 20% of the population. It is characterized by solitary or multiple, recurrent, small ulcers with erythematous haloes and yellow/gray floors. RAS can be managed through a wide variety of preventative measures and therapies, intending to reduce ulcer pain, stimulate ulcer healing, and/or prevent ulcer recurrence. First-line treatment options include topical medications in the form of corticosteroids (triamcinolone acetonide), anti-inflammatory drugs (amlexanox), antibiotics (doxycycline), and antiseptics (lidocaine). In more severe cases of RAS where local treatment is insufficient, systemic drugs in the form of corticosteroids (prednisone), immunomodulatory drugs (thalidomide), and antibiotics/antimicrobials (clofazimine) can prove effective. This review will summarize current treatment options for RAS with discussion of prevention, topical measures, natural treatments, systemic therapies, and new potential therapies. Furthermore, this review will provide recommendations on therapeutic options for RAS based on disease severity and patient circumstances.
Non-Tuberculous mycobacteria (NTM) are opportunistic environmental bacteria. Globally, NTM incidence is increasing and modeling suggests that, without new interventions, numbers will continue to rise. Effective treatments for NTM infections remain suboptimal. Standard therapy for Mycobacterium avium complex, the most commonly isolated NTM, requires a 3-drug regime taken for approximately 18 months, with rates of culture conversion reported between 45 and 70%, and high rates of relapse or reinfection at up to 60%. New therapeutic options for NTM treatment are urgently required. A survey of ongoing clinical trials for new NTM therapy listed on ClinicalTrials.Gov using the terms 'Mycobacterium avium', 'Mycobacterium abscessus', 'Mycobacterium intracellulare', 'Non tuberculous Mycobacteria' and 'Nontuberculous Mycobacteria' and a selection criterion of interventional studies using antibiotics demonstrates that most trials involve dose and combination therapy of the guideline based therapy or including one or more of; Amikacin, Clofazimine, Azithromycin and the anti-TB drugs Bedaquiline and Linezolid. The propensity of NTMs to form biofilms, their unique cell wall and expression of both acquired and intrinsic resistance, are all hampering the development of new anti-NTM therapy. Increased investment in developing targeted treatments, specifically for NTM infections is urgently required. Limited information indicates that clofazimine appears in milk in relatively large amounts. Human milk enhances the solubilization and possibly the absorption of clofazimine in infants.[1,2] Milk can be colored pink to red by the drug and breastfed infant's skin can be discolored the typical red color that is common in persons taking the drug.[3-5] No serious or permanent toxicity has been reported in breastfed infants; however, an alternate drug might be considered.