Terbinafine
Terbinafine is a synthetic **allylamine antifungal** agent available in both oral and topical formulations. **Key Clinical Features:** * **Primary Use:** Highly effective against dermatophytic infections (e.g., *Microsporum*, *Trichophyton*) in dogs and cats. It is also utilized for systemic mycotic infections like *Aspergillus*, particularly in avian species. * **Favorable Interaction Profile:** Unlike azole antifungals (e.g., ketoconazole, itraconazole), terbinafine does not rely on the cytochrome P-450 enzyme system for its primary mechanism, resulting in significantly fewer drug interactions and no suppression of mammalian testosterone or cortisol synthesis. * **Pharmacologic Pearl:** Terbinafine is highly lipophilic and **keratinophilic**. It distributes extensively into the skin, sebum, and hair follicles, persisting in these tissues at therapeutic concentrations for weeks even after therapy is discontinued (allowing for pulse-therapy protocols). * **Tolerability:** Generally very well tolerated in veterinary patients, with mild gastrointestinal upset (vomiting) being the most commonly reported adverse effect.
Mecanismo: Terbinafine exerts its antifungal activity by interfering with fungal sterol biosynthesis at an early stage. * It selectively and reversibly inhibits the fungal enzyme **squalene monooxygenase** (also known as squalene 2,3-epoxidase). * This blockade prevents the conversion of squalene to lanosterol → leading to a profound deficiency of **ergosterol** (a critical component of the fungal cell membrane). * Simultaneously, the inhibition causes an intracellular **accumulation of squalene**, which is directly toxic to the fungal cell, leading to rapid cell death. This dual mechanism makes terbinafine primarily **fungicidal** against dermatophytes, though it may only be **fungistatic** against certain yeasts like *Candida spp.*
Dosificación por especie
- Dermatophytic infections (Pulse therapy) · 20 mg/kg · PO · q24h · 7 days on, then 21 days off · Maintained terbinafine concentrations in hair above therapeutic levels. Higher doses (40 mg/kg) or continuous administration caused emesis and elevated hepatic enzymes.
- Dermatophytic infections · 10-20 mg/kg · PO · q24h · Appears to be better tolerated than either ketoconazole or itraconazole.
- Dermatophytic infections (when other drugs are not tolerated) · 25 mg/kg · PO · q24h
- Dermatophyte (M. canis) mycetomas · 26-31 mg/kg · PO · q24h · 12-14 weeks · Achieved clinical and mycological cure in a case report of two cats.
- Cryptococcal infections (azole-resistant) · 10 mg/kg · PO · q24h · Life-long · Can rectify clinical signs, though cats with CNS cryptococcus usually require treatment for life.
- Antifungal (Systemic/Dermatophytosis) · 20-40 mg/kg · PO · q24h · Not specified
- Localized Malassezia infections · Apply a thin layer · topical · Not specified · Not specified · Use 1% cream.
- Avian mycotic infections (Aspergillus) · 10-15 mg/kg · PO · q12-24h · Appears to be well tolerated by a number of avian species.
- Avian mycotic infections (Aspergillus) · 1 mg/mL aqueous solution · Nebulization · Not specified
Vías de administración
Contraindicaciones
- Known hypersensitivity to terbinafine
- Active or chronic liver disease
- Significantly impaired renal function
- Perforated eardrum (for ear gel administration)
- Generalized demodicosis (topical or systemic use)
- Pregnant animals
- Breeding animals
Efectos adversos
- Vomiting
- Inappetence
- Diarrhea
- Lethargy (reported in cats)
- Hepatotoxicity / Liver failure (very rare, reported in humans)
- Neutropenia (very rare, reported in humans)
- Serious skin reactions like Toxic Epidermal Necrolysis or Stevens-Johnson syndrome (very rare, reported in humans)
- Diarrhoea
- Increased liver enzymes
- Pruritus (cats)
- Topical irritation (due to alcohol content in topical solutions)
- Transient deafness or impaired hearing (in elderly dogs after administration of ear gel)
Interacciones farmacológicas
- Cyclosporine · Terbinafine may increase the elimination and decrease the efficacy of cyclosporine.
- Rifampin · May increase terbinafine clearance, potentially requiring higher terbinafine doses. · moderate
- Beta-blockers · Terbinafine shares the CYP2D6 metabolic pathway and could theoretically alter the metabolism of beta-blockers.
- MAO Inhibitors (e.g., amitraz, selegiline) · Terbinafine shares the CYP2D6 metabolic pathway and could theoretically alter the metabolism of MAOIs.
- SSRIs (e.g., fluoxetine) · Terbinafine shares the CYP2D6 metabolic pathway and could theoretically alter the metabolism of SSRIs.
- Tricyclic Antidepressants · Terbinafine shares the CYP2D6 metabolic pathway and could theoretically alter the metabolism of TCAs.
- Cimetidine · May decrease the clearance of terbinafine, potentially increasing plasma concentrations (Clinical Pearl) · moderate
Monitoreo
- Clinical efficacy (resolution of fungal lesions)
- Baseline liver enzymes prior to therapy
- Periodic liver enzyme monitoring as needed, especially during long-term treatment
- CBC (baseline and periodic)
- Liver function tests (ALT, AST, Bilirubin)
- Renal function tests
- Clinical response (skin scrapings, fungal cultures)
Sobredosis
There is limited information regarding acute toxicity in veterinary species. In humans, acute ingestions of up to 5 grams have been reported without serious adverse effects. Treatment of massive overdose should be supportive and symptomatic.
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