Peer-reviewed veterinary case report
Fluconazole caused sedation and high phenobarbital in two dogs
By Jaramillo, Maria et al.·Published in Journal of veterinary internal medicine·2025·Department of Clinical Sciences, United States·View original on PubMed →
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Original publication title: Adverse Drug-Drug Interaction Between Phenobarbital and Fluconazole in Two Dogs.
- Species:
- dog
Plain-English summary
Two dogs with epilepsy were given fluconazole, an antifungal medication, while they were already on phenobarbital, a common antiseizure drug. After starting fluconazole, both dogs became very sleepy and uncoordinated, and their blood levels of phenobarbital increased significantly. Once the fluconazole was stopped, their symptoms improved and the phenobarbital levels returned to normal. This case highlights that fluconazole can interfere with how phenobarbital is processed in the body, leading to potential toxicity, so it's important for vets to monitor phenobarbital levels if these medications are used together.
People also search for: dog seizure medication interaction · fluconazole side effects in dogs · phenobarbital toxicity symptoms in dogs
Abstract
Phenobarbital (PB) is an antiseizure medication widely used in dogs that is metabolized by hepatic cytochrome P450 (CYP) enzymes. Fluconazole, a commonly prescribed antifungal medication, inhibits several CYP isoenzymes and can impair PB metabolism. Genetic polymorphisms such as the CYP2C41 gene deletion can alter CYP activity and influence drug interactions, although not well characterized in dogs. We describe two epileptic dogs on chronic PB treatment that developed marked sedation and ataxia, and increased serum PB concentrations after receiving fluconazole. Both dogs were homozygous for the CYP2C41 deletion. Discontinuation of fluconazole resulted in decreased PB concentrations and resolution of clinical signs. These findings suggest fluconazole can inhibit PB metabolism, leading to clinically relevant toxicity, and this interaction does not require CYP2C41 enzyme expression. Monitoring PB concentrations during fluconazole co-administration is advised. Further characterization of the role of CYP enzymes in PB metabolism in dogs is needed to better predict drug interactions.
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Search related cases →Original publication on PubMed: https://pubmed.ncbi.nlm.nih.gov/40682369/