Posaconazole and Voriconazole – Treating Invasive Fungal Infections in Small Animals
Posaconazole and voriconazole are next generation azoles most closely related to itraconazole and fluconazole, respectively. As compared with the prior generation azoles, posaconazole and voriconazole are more active against molds (Asper) and yeasts (Crypto) with good activity against enzootic dimorphic fungi (Blasto, Histo, Cocci). They are approved by the FDA for the prevention (posa-) or treatment (vori-) of invasive aspergillosis in humans. Posaconazole is also labeled for the prevention of invasive candidiasis. Voriconazole is also labeled for the treatment of invasive candidiasis and invasive mold infections caused by Scedosporium or Fusarium.
U.S. patent protections have expired for both drugs and FDA approved generic formulations are now available. This has greatly decreased the price, making them financially feasible treatment options for some animals.
|Drug||Formulation||Dose||Innovator v Generic|
|Solution||40 mg/ml||No Generic available|
|Tablet||100 mg extended release||Generic available|
|Solution||40 mg/ml||Generic available|
|Tablet||50, 200 mg||Generic available|
|Invasive Mold Infection||Asper, Mucor, Fusarium, other molds||Consider combination therapy with terbinafine (30-40 mg/kg/day)|
|Salvage Therapy||Blasto, Histo, Cocci, Crypto, Candida||When first line therapy has failed after 2-3 months of treatment.|
As with any azole, hepatoxicity and gastrointestinal upset are possible. Liver enzyme activity should be monitored 3-4 weeks after starting the drug then every 1-6 months during treatment, pending duration of treatment and clinical findings. Voriconazole can cause neurotoxicity in cats . This was described in early studies when high doses were used. A more recent pharmacokinetic study showed that much lower doses might be effective and greatly decrease the chance of neurotoxicity .
Azoles work by inhibition of a fungal CYP 450 enzyme affecting ergosterol synthesis important for integrity of the cell wall. Azoles are effective because they are relatively specific to fungal CYP 450 enzymes. Lesser mammalian CYP 450 enzyme inhibition still occurs. Since these are metabolic enzymes, inhibition can lead to increased blood levels of drugs administered concurrently. Very few of these have been studied directly in dogs or cats. Increased blood levels of the following drugs are possible – amitriptyline, amlodipine, benzodiazepines, cisapride, corticosteroids, cyclosporine, ivermectin, and macrolide antibiotics.
|Posaconazole||Dog||Tablet ER||5 mg/kg EOD||PO|
|Solution||5 mg/kg BID|
|Cat||Solution||15 mg/kg once then 7.5 mg/kg/day|
|Voriconazole||Dog||Tablet or Solution||5 mg/kg BID||PO|
|Cat||Solution||12.5 mg (total dose) q 72 h|
Therapeutic drug monitoring should be considered for both drugs.
Estimated Monthly Costs
|Drug||Species (weight)||Formulation||Cost (USD)|
|Posaconazole||K9 (20 kg)||100 mg Tablet ER||257|
|Feline (5 kg)||40 mg/ml Solution||457|
|Voriconazole||K9 (20 kg)||200 mg Tablet||103|
|Feline (5 kg)||40 mg/ml Solution||37|
Prices vary. Cost for generic drugs based on lowest GoodRx price (May 2021). Cost for posaconazole solution is based on CVS price (May 2021).
- Quimby JM, Hoffman SB, Duke J, et al. Adverse neurologic events associated with voriconazole use in 3 cats. J Vet Intern Med 2010;24:647-649.
- Vishkautsan P, Papich MG, Thompson GR, 3rd, et al. Pharmacokinetics of voriconazole after intravenous and oral administration to healthy cats. Am J Vet Res 2016;77:931-939.