Veterinary Medicine - January 2008 - (Page 46)

Systemic antifungals PEER-REVIEWED conazole is available as 50- and 200-mg tablets. The typical cost of voriconazole for a 44-lb dog (5 mg/kg orally twice a day) is about $40/day. Potential indications Voriconazole is the drug of choice for invasive Aspergillus species infections in people because of its fungicidal activity and its safety as compared with amphotericin B.16 Voriconazole also has activity against many organisms such as Aspergillus, Candida, Cryptococcus, and mg/kg, a fourfold increase, resulted in a disproportionate increase in area under the curve—a ninefold increase. Therefore, dose adjustments must be made cautiously.31 There are no reports of the pharmacokinetics of voriconazole in cats. POSACONAZOLE Posaconazole is an itraconazole derivative recently approved by the FDA for use in people and is available as a 40mg/ml suspension. The typical cost of posaconazole for a 44-lb dog (5 mg/kg orally once a day) is about $11/day. Adverse effects The liver was the primary organ affected in toxicology studies, but the kidneys and adrenal glands may also be affected, and anemia may occur.32 Evidence of hepatotoxicosis occurred in acute (30 days at Potential indications Posaconazole has similar activity as the other azoles except that it has increased activity against resistant strains of Aspergillus and Candida species.33 Complete blood counts and serum chemistry pro les should be evaluated routinely during long-term therapy. Fusarium species that develop resistance to other azoles.16 Pharmacokinetics Similar to itraconazole, the oral absorption of posaconazole is increased when it is administered with food and decreased when it is administered with gastric acid suppression therapy. In dogs that received 10 mg/kg, the half-life was seven hours, the oral bioavailability was 27% in fed dogs, the CMAX was 3.5 µg/ml, and the TMAX was three hours.34,35 Posaconazole is primarily metabolized and inactivated by glucuronide conjugate formation in most species. No pharmacokinetic or metabolism studies are available in cats. Pharmacokinetics Voriconazole’s plasma protein binding is intermediate (about 51%).31 Complete absorption occurs in dogs receiving oral voriconazole with a CMAX of 6.5 g/ml at three hours after a single 6 mg/kg dose.20 Voriconazole penetrates the CNS and is effective against CNS fungal infections.16 Voriconazole primarily undergoes hepatic metabolism with the metabolites excreted in the urine and feces.31 About 5% of the total dose is eliminated in the urine of dogs as unchanged drug with an approximate 4.5-hour half-life after a single dose. The plasma concentration of voriconazole remained above the minimum fungicidal concentration against Aspergillus species for 24 hours after a single 6-mg/kg oral dose in dogs.31 However, multiple doses resulted in increased metabolism of voriconazole and subsequently reduced drug exposure as measured by the area under the curve with 16 days of treatment. Increasing the dose of voriconazole from 3 mg/kg to 12 24 mg/kg) and chronic (six to 12 months at 12 mg/kg) toxicology studies in dogs, including cell necrosis and increased alanine transaminase and alkaline phosphatase activities. Increased liver weight, centrilobular hypertrophy, proliferation of smooth endoplasmic reticulum, and induction of CYP occurred in a dosedependent manner.32 Administration of intravenous voriconazole (10 mg/kg) in dogs resulted in unspeci ed acute toxicosis.32 In rats, high intravenous doses (50 mg/kg) resulted in CNS signs such as mydriasis, titubation (loss of balance during movement), depression, prostration, extensor rigidity, ptosis, and dyspnea.32 In people, voriconazole produced unspeci ed changes in the retina at therapeutic drug concentrations, which resulted in blurred vision; the visual effects were reversible, and no histopathologic changes were observed.32 Voriconazole can exhibit drug-drug interactions similar to uconazole’s. Additionally, concurrent administration of phenobarbital may increase the metabolism of voriconazole with subsequent decreased ef cacy.16 Drug interactions and adverse effects Posaconazole should be used cautiously in cats; dose extrapolation may not be appropriate because of decreased formation of glucuronide conjugates in cats. However, a single case report of posaconazole (5 mg/kg orally once a day for 16 weeks) administered to a cat with an itraconazole-resistant Aspergillus species infection demonstrated ef cacy with minimal adverse effects, which included erythema and pruritus of the pinna and super cial excoriations of the temporal region.36 Posaconazole’s adverse effect pro le and drug-drug interactions are expected to be similar to those of itraconazole.34 Gastrointestinal adverse effects such as nausea, vomiting, and diarrhea are commonly reported in people. Complete blood counts and serum chemistry pro les should be evaluated routinely 46 January 2008 VETERINARY MEDICINE

Table of Contents Feed for the Digital Edition of Veterinary Medicine - January 2008

Veterinary Medicine - January 2008 Contents Digital Extra Letters Toxicology Brief Idea Exchange A Challenging Case: Phimosis in a Young Adult Dog The Indications and Technique for Continuous Ambulatory Electrocardiographic Recording in Dogs A Review of Selected Systemic Antifungal Drugs for Use in Dogs and Cats CE Form Advertiser Index Marketplace/Classifieds Mind Over Miller

Veterinary Medicine - January 2008

For optimal viewing of this digital publication, please enable JavaScript and then refresh the page. If you would like to try to load the digital publication without using Flash Player detection, please click here.