Isotretinoin
**Isotretinoin** is a first-generation synthetic retinoid primarily utilized in veterinary dermatology for the management of severe disorders of keratinization and sebaceous gland abnormalities. **Key Clinical Applications:** * **Canine lamellar ichthyosis** * **Cutaneous T-cell lymphoma** (epitheliotropic lymphoma) * **Intracutaneous cornifying epitheliomas** * **Multiple epidermal inclusion cysts** * **Comedo syndrome** in Miniature Schnauzers * **Sebaceous adenitis** (especially in Standard Poodles and Vizslas) * **Feline acne** > **Clinical Pearl:** Because of its profound effects on sebaceous glands, isotretinoin is often considered the retinoid of choice for sebaceous adenitis and Schnauzer comedo syndrome, whereas other retinoids (like acitretin) might be preferred for primary keratinization defects. Due to severe teratogenic risks in humans (FDA Category X), obtaining this medication for veterinary use can be highly restricted by manufacturers and distributors.
Mecanismo: Isotretinoin acts by regulating epithelial cell proliferation and differentiation. * **Receptor Binding:** Retinoids enter the cell and bind to intracellular **Retinoic Acid Receptors (RARs)** and **Retinoid X Receptors (RXRs)** → altering gene transcription. * **Sebosuppressive Effect:** It significantly reduces sebaceous gland size and activity → decreasing sebum production. * **Anti-keratinization & Anti-inflammatory:** Normalizes follicular desquamation (preventing comedone formation) and affects monocyte/lymphocyte function, altering cellular immune responses. * **Antimicrobial (Indirect):** By altering the microenvironment of the sebaceous pore (reducing sebum), it indirectly reduces bacterial populations.
Dosificación por especie
- Feline acne · 5 mg/kg PO once daily · PO · q24h
- Feline acne · 10 mg per cat once daily PO · PO · q24h
- Feline acne · 1-3 mg/kg q12-24h PO · PO · q12-24h
- Epitheliotrophic lymphoma, cutaneus lymphoma · 10 mg/cat once daily PO · PO · q24h
- Sebaceous adenitis when more conservative treatments have failed · 1 mg/kg PO q12h for one month; if improvement is noted reduce dose to 1 mg/kg PO once daily; long-term goal is to treat with either 1 mg/kg PO every other day or 0.5 mg/kg once daily · PO · q12h initially, then q24h or q48h · Long-term
- Sebaceous adenitis · 1-3 mg/kg PO once a day to twice daily · PO · q12-24h
- Schnauzer comedo syndrome · 1 mg/kg once daily or divided q12h PO · PO · q12-24h
- Sebaceous adenitis in poodles; granulomatous sebaceous adenitis in viszlas · 1-2 mg/kg once daily or divided q12h PO · PO · q12-24h
- Epitheliotrophic lymphoma, cutaneus lymphoma · 2 mg/kg once daily or divided q12h PO · PO · q12-24h
- Schnauzer comedo syndrome, sebaceous adenitis in poodles, ichthyosis, keratocanthoma, epitheliotropic lymphoma, and sebaceous gland hyperplasia and adenoma · 1-3 mg/kg q12-24h PO · PO · q12-24h
Vías de administración
Contraindicaciones
- Pregnancy (absolute contraindication - known teratogen)
- Nursing mothers
- Hypertriglyceridemia
- Severe renal disease
- Severe hepatic disease
- Known hypersensitivity to isotretinoin
Efectos adversos
- Dogs: Keratoconjunctivitis sicca (KCS) - most common
- Dogs: GI effects (anorexia, vomiting, diarrhea, abdominal distention)
- Dogs: CNS effects (lassitude, hyperactivity, behavioral changes, collapse)
- Dogs: Stiffness of limbs
- Dogs: Pruritus, exfoliative dermatitis, erythema of feet and mucocutaneous junctions/cheilitis
- Dogs: Polydipsia, swollen tongue
- Cats: Blepharospasm, periocular crusting, erythema
- Cats: Diarrhea
- Cats: Weight loss secondary to anorexia
Interacciones farmacológicas
- Vitamin A or other retinoids (etretinate, tretinoin) · May cause additive toxic effects.
- Cyclosporine · Isotretinoin may increase cyclosporine levels.
- Tetracyclines · Use with tetracyclines may increase the potential for the occurrence of pseudotumor cerebri (cerebral edema and increased CSF pressure).
Monitorización
- Clinical efficacy
- Liver function tests (baseline and if signs appear)
- Serum triglycerides and cholesterol
- Dogs: Schirmer Tear tests (monthly, especially in older dogs to monitor for KCS)
- Cats: Body weight (monitor for anorexia-induced weight loss)
Sobredosis
In a review of 147 exposures reported to the ASPCA APCC (140 dogs, 7 cats), only 5 dogs showed clinical signs, most commonly **hypersalivation**. Cats showed no clinical signs. Because of the drug's potential adverse effects, **gut emptying** should be considered with acute overdoses when warranted. Monitor for GI upset and CNS signs.
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