Clofazimine
Clofazimine is a highly lipophilic, phenazine dye antimycobacterial antibiotic. It is primarily utilized in veterinary medicine as part of a multi-drug regimen for treating leprosy-like syndromes (e.g., feline leprosy, canine leproid granuloma) and *Mycobacterium avium* complex (MAC) infections. **Clinical Pearls:** * **Combination Therapy:** Because mycobacteria are notoriously difficult to eradicate and prone to developing resistance, clofazimine is almost never used as a monotherapy. * **Lipophilicity:** Its extreme lipophilicity causes it to accumulate heavily in fat and the reticuloendothelial system (macrophages). * **Staining:** The drug's nature as a dye leads to its hallmark side effect: profound, long-lasting discoloration of the skin, eyes, and bodily fluids. * **Availability:** It can be very difficult for veterinarians to obtain and accurately dose for small animals, often requiring the assistance of a compounding pharmacist.
Mecanismo: Clofazimine exerts a slowly bactericidal effect against susceptible mycobacteria (*M. leprae*, *M. tuberculosis*, *M. avium* complex, *M. bovis*, *M. chelonei*). * **DNA Binding:** It binds directly to mycobacterial DNA (preferentially at guanine base sequences) → blocks template function → **inhibits DNA replication and cell growth**. * **Intracellular Accumulation:** It is heavily taken up by macrophages, concentrating the drug exactly where intracellular mycobacteria reside. * **Immunomodulation:** Exhibits anti-inflammatory and immunosuppressive properties, likely by inhibiting T-lymphocyte activation and proliferation, though the exact mechanism remains poorly understood.
Dosificación por especie
- Avian mycobacteriosis · 6 mg/kg PO once daily · PO · q24h · Protocol 1: with rifampin 45 mg/kg and ethambutol 30 mg/kg.
- Avian mycobacteriosis (recommended regime for raptors) · 1.5 mg/kg PO q24h · PO · q24h · Protocol 2: with ethambutol 20 mg/kg, cycloserine 5 mg/kg, enrofloxacin 15 mg/kg q12h.
- Mycobacterium avium complex (MAC) as part of a multi-drug regimen · 4 mg/kg PO once daily · PO · q24h · Other drugs that may be used in combination include doxycycline, clarithromycin, and/or enrofloxacin.
- M. avium intracellularae complex infections, leprosy, or opportunistic mycobacteriosis · 4-8 mg/kg PO once a day · PO · q24h · 4 weeks · Usually as part of a multi-drug protocol.
- Mycobacterial infections · 4-8 mg/kg · PO · q24h · 2-6 months · Generally used in combination therapy with other antimicrobials including fluoroquinolones and clarithromycin.
- Treatment of feline leprosy · 25-50 mg once per day or 50 mg every other day · PO · q24h or q48h · Using a regimen of either two or three drugs (with clarithromycin and/or rifampin).
- Treatment of localized atypical mycobacterial infections · 8 mg/kg PO once daily · PO · q24h · At least 4 weeks beyond complete clinical resolution · Perform wide surgical excision of lesion if possible. Base antibiotic selection on culture and susceptibility results.
Vías de administración
Contraindicaciones
- Use with caution in patients with pre-existing gastrointestinal conditions (diarrhea, abdominal pain)
- Known hypersensitivity to clofazimine
Efectos adversos
- Skin, eye, and body fluid discoloration (pink to brownish-black)
- Gastrointestinal pain, nausea, vomiting, diarrhea (dose-limiting)
- Hepatotoxicity (reported in a dog receiving concurrent rifampin)
- Photosensitization (reported in a cat)
- Nausea
- Diarrhoea
- Discoloration of skin, eyes, and body fluids (red-brown/orange)
- Renal impairment
- Hepatic impairment
- Photosensitization
Interacciones farmacológicas
- Isoniazid · May reduce clofazimine levels in the skin and increase amounts in plasma and urine; clinical significance is unclear.
- Dapsone · May reduce the anti-inflammatory effects of clofazimine; clinical significance is unclear.
Monitorización
- Efficacy against mycobacterial disease
- Adverse effects (primarily gastrointestinal)
- Hepatic function (especially in dogs)
- Hepatic function (ALT, AST, ALP, Bilirubin)
- Renal function (BUN, Creatinine, SDMA)
- Clinical signs of photosensitization
- Gastrointestinal tolerance
Sobredosis
Very limited data is available. The LD50 for rabbits is 3.3 g/kg and is greater than 5 g/kg in mice, rats, and guinea pigs. Treatment, if required, would include gut emptying and supportive care. Contact an animal poison control center for additional guidance.
La referencia de fármacos de VetSheet está destinada a veterinarios colegiados como apoyo a la decisión clínica, no sustituye el juicio profesional ni la ficha técnica vigente del fabricante.