Terbinafine in Veterinary Dermatology: The New Antifungal on the Block

As far as antifungals for skin disease, terbinafine is the new kid on the block and its hangin’ tough.  Terbinafine has gained popularity in veterinary dermatology given that it is now relatively inexpensive with the availability of affordable generics.  Terbinafine is an allylamine antifungal that reversibly inhibits squalene epoxidase, decreasing sterol (mainly ergosterol) synthesis and results in an accumulation of squalene in the fungal cell membrane (Moriello et al. 2017, Plumb’s Veterinary Drug Handbook 2014). It is fungicidal towards dermatophytes and typically fungistatic towards yeast (Plumb’s Veterinary Drug Handbook 2014).  Unlike the azole antifungals, terbinafine’s actions are not mediated via the cytochrome P-450 enzyme system, limiting the concerns for potential drug interactions (Moriello et al. 2017, Plumb’s Veterinary Drug Handbook 2014).  The most commonly recommended dose range is 30-40 mg/kg once daily (Berger et al. 2012, Gimmler et al. 2015, Guillot et al 2003, Moriello et al 2017, Plumb’s Veterinary Drug Handbook 2014,  Rosales et al 2005).

Given the limited use in veterinary patients, side effects of terbinafine are not as well established compared to other oral antifungal drugs, but it does appear to be well tolerated in dogs and cats.  The most commonly reported side effects include vomiting, diarrhea, decreased appetite; less commonly reported side effects include elevated liver enzymes, excessive panting (dogs), and facial pruritus (cats)  (Berger et al. 2012, Gimmler et al. 2015, Guillot et al 2003, Moriello et al 2017, Plumb’s Veterinary Drug Handbook 2014,  Rosales et al 2005).

Terbinafine for Dermatophytosis:
Terbinafine has become one of the preferred treatments for feline dermatophytosis due to its efficacy and safety (Moriello et al 2017).  Compared to other antifungals (itraconazole, fluconazole, ketoconazole and griseofulvin), terbinafine has the lowest MIC for veterinary isolates of Microsporum canis and Trichophyton spp  (Hofbauer et al 2002, Tan and Seyyal 2008). In a shelter cat study using 250 mg terbinafine tablets (all doses once daily for 21 days), cats <2.8 kg received 1/4 of a tablet (62.5 mg) per dose, cats 2.85.5 kg received 1/2 of a tablet (125 mg) per dose, and cats >5.5 kg received 1 tablet (250 mg) per dose (Moriello et al. 2013). Cats also received lime sulfur rinses twice weekly.  Clinical and mycological cures were comparable to treatment trials using itraconazole (Moriello et al. 2013).

Several studies have shown that terbinafine concentrates very highly in cat hairs (Foust et al 2007, Moriello et al. 2017).  In a publication in cats, after 14 days of oral treatment, the half-life of terbinafine in the hair was found to be 1.8 weeks (Foust et al 2007).   The levels of terbinafine in the hair were above the MIC90 for Microsporum canis for five weeks (Foust et al 2007)   Given the concentration in feline keratin/hairs, pulse dosing with terbinafine is likely to be efficacious for feline dermatophytosis; however, there are only limited studies on the efficacy of pulse dosing terbinafine for feline dermatophytosis. In one publication evaluating pulse therapy, cats given 20 mg/kg orally once daily for 7 days and then 21 days off had clinical and mycological cures and terbinafine concentrations in hair were maintained above therapeutic levels (Balda et al 2009). Cats given higher doses (40 mg/kg) in a similar pulse dosing schedule or continuous administration accumulated higher concentrations, but some developed vomiting in the first-week therapy, and higher hepatic enzyme serum activities (Balda et al. 2009). There were no alterations in the values of ALT in the pulse therapy group (Balda et al. 2009).

image141Terbinafine for Malassezia Dermatitis
Terbinafine has been evaluated in several studies for the treatment of Malassezia dermatitis in dogs.  It is generally considered to be less effective for Malassezia compared to azole antifungals such as ketoconazole or fluconazole; in vitro studies generally, yield higher MIC levels for terbinafine compared to azole antifungals (Gupta et al 2000).  One publication comparing the efficacy of ketoconazole (10 mg/kg once daily) and terbinafine (30 mg/kg once daily) for 21 days found no significant difference in outcome (Guillot et al. 2003).  A pilot study comparing the efficacy of terbinafine given at 30 mg/kg once daily for 21 days vs. pulse dosing (30 mg/kg given once daily for 2 consecutive days per week) found no difference in outcome for the treatment of Malassezia dermatitis in dogs (Berger et al. 2012).   In a pharmacokinetic study of terbinafine in dogs given 30 mg/kg once daily for 21 days, concentrations of terbinafine did not achieve high levels in the stratum corneum and sebum compared to the serum, and levels barely exceeded MIC90 for Malassezia (Gimmler et al 2015).  The authors suggested that doses higher than 30 mg/kg may be needed to treat Malassezia dermatitis in dogs (Gimmler et al. 2015)

Terbinafine for Otitis Externa

Terbinafine is the active antifungal in two recently approved treatments for otitis in dogs.  Osurnia® (florfenicol/terbinafine/betamethasone) is approved for the treatment of ear infections in dogs associated with susceptible strains of Staphylococcus pseudintermedius and Malassezia pachydermatis, given as two doses one week apart (Osurnia® Product Insert). Claro® (florfenicol/terbinafine/mometasone) is approved for the treatment of otitis externa in dogs associated with susceptible strains of Malassezia pachydermatis and Staphylocccus pseudintermedius with a single-dose treatment (Claro® Product Insert).

Submitted by

Brian Palmeiro, VMD, Diplomate ACVD

References:

  1. Balda A, Larsson C. 2009. Evaluation of Terbinafine Hair Concentration in Persian Cats with Dermatophytosis and Healthy carriers of Microsporum canis treated with Pulse or Continuous Therapy.   WSAVA World Congress Proceedings. Accessed via Veterinary Information Network; vin.com
  2. Berger DJ, Lewis TP, Schick AE, et al. 2012. Comparison of once-daily versus twice-weekly terbinafine administration for the treatment of canine Malassezia dermatitis – a pilot study. Vet Dermatol Vol 23 (5) pp. 418-e79.
  3. Foust A L, Marsella R, Akucewich L H, et al: Evaluation of persistence of terbinafine in the hair of normal cats after 14 days of daily therapy. Vet Dermatol 2007 Vol 18 (4) pp. 246-51.
  4. Gimmler JR, White AG, Kennis RA, et al. 2015. Determining canine skin concentrations of terbinafine to guide the treatment of Malassezia dermatitis. Vet Dermatol Vol 26 (6) pp. 411-e96.
  5. Guillot J, Bensignor E, Jankowski F, et al. 2003. Comparative efficacies of oral ketoconazole and terbinafine for reducing Malasseziapopulation sizes on the skin of basset hounds. Vet Dermatol Vol 14 (3) pp. 153-157.
  6. Gupta A, Kohli, Li et al. 2000. In vitro susceptibility of the seven Malassezia species to ketoconazole, voriconazole, itraconazole, and terbinafine. Br J Dermatol; 142 (4): 758-65.
  7. Hofbauer B, Leitner I, Ryder N. 2002. In vitro susceptibility of Microsporum canis and other dermatophyte isolates from veterinary infections during therapy with terbinafine or griseofulvin. Med Mycol; 40: 179-183.
  8. Moriello K, Coyner K, Trimmer A, et al. 2013. Treatment of shelter cats with oral terbinafine and concurrent lime sulphur rinses. Vet Dermatol Vol 24 (6) pp. 618-e150.
  9. Moriello K A, Coyner K, Paterson S, et al. 2017.  Diagnosis and treatment of dermatophytosis in dogs and cats: Clinical Consensus Guidelines of the World Association for Veterinary Dermatology. Vet Dermatol Vol 28 (3) pp. 266-e68.
  10. Rosales MS, Marsella R, Kunkle G, et al. 2005. Comparison of the clinical efficacy of oral terbinafine and ketoconazole combined with cephalexin in the treatment of Malasseziadermatitis in dogs – A pilot study. Vet Dermatol Vol 16 (3) pp. 171-176.
  11. Tan D, Seyyal A. 2008. Antifungal susceptibility testing to different antifungal agents to isolates of M canis from dogs. J An Vet Advan; 7: 226-230.
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