Posaconazole and Voriconazole – Treating Invasive Fungal Infections in Small Animals

Background

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.

Formulations

Drug Formulation Dose Innovator v Generic
Posaconazole
(Noxafil®)		 Solution 40 mg/ml No Generic available
Tablet 100 mg extended release Generic available
Voriconazole
(Vfend®)		 Solution 40 mg/ml Generic available
Tablet 50, 200 mg Generic available

 

Clinical Uses

Use Organisms Notes
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.


Adverse-Effects

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 [1Quimby 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.]. 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 [2Vishkautsan 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.].

Drug-to-Drug Interactions

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.

Recommended Dosages

Drug Species Formulation Dose Route
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).

REFERENCES:

  1. 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.
  2. 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.