Prevalence and clinical characteristics of phenobarbitone-associated adverse effects in epileptic cats

Abstract

Objectives The study objective was to investigate the prevalence and clinical characteristics of phenobarbitone-associated adverse effects in epileptic cats. Methods The medical records of two veterinary referral clinics from 2007 to 2017 were searched for cats fulfilling the inclusion criteria of a diagnosis of epilepsy, treatment with phenobarbitone and available follow-up information on the occurrence of adverse effects. Follow-up information was obtained from the medical records of the primary veterinarian and referral institutions and a questionnaire completed by the cats’ owners. Results Seventy-seven cats met the inclusion criteria. Fifty-eight were affected by idiopathic epilepsy and 19 by structural epilepsy. One or more of the following adverse effects were reported in 47% of the cats: sedation (89%); ataxia (53%); polyphagia (22%); polydipsia (6%); polyuria (6%); and anorexia (6%). Logistic regression analyses revealed significant associations between adverse effect occurrence and both phenobarbitone starting dosage and administration of a second antiepileptic drug (AED). For each 1 mg/kg q12h increment of phenobarbitone, the likelihood of adverse effects increased 3.1 times. When a second AED was used, the likelihood of adverse effects increased 3.2 times. No association was identified between epilepsy aetiology and adverse effect occurrence. An idiosyncratic adverse effect, characterised by severe neutropenia and granulocytic hypoplasia, was diagnosed in one cat. This resolved following phenobarbitone discontinuation. Conclusions and relevance The prevalence of phenobarbitone-associated adverse effects was 47%. Sedation and ataxia were most common. These are type A adverse effects and are predictable from phenobarbitone’s known pharmacological properties. In the majority of cases, adverse effects occurred within the first month of treatment and were transient. Idiosyncratic (type B) adverse effects, which were not anticipated given the known properties of the drug, occurred in one cat. Increased phenobarbitone starting dosage and the addition of a second AED were significantly associated with the occurrence of adverse effects.

A retrospective evaluation of phenobarbital‐induced hematologic changes in 69 cats

“…The most reported dose-dependent adverse effects in catstreated with PB-were sedation, pelvic limb ataxia, polyuria, polydipsia/polyphagia, weight loss, increased alanine transaminase/ alkaline phosphatase activities, and behavioral changes. 7,8 Idiosyncratic drug reactions are not only unpredictable but mostly unavoidable and occur in only a small proportion of patients at therapeutic doses. The most common are cytopenia, lymphadenopathy, pseudolymphoma, skin eruptions, pyrexia, and coagulopathy.…”

“…The most common are cytopenia, lymphadenopathy, pseudolymphoma, skin eruptions, pyrexia, and coagulopathy. 7,8 Furthermore, the effect of PB on the liver is well known, leading to hepatic enzyme induction; however, these changes have not been observed in cats. 9 Compared with a study in PB-treated dogs by Pakozdy et al…”

“…Idiosyncratic drug reactions are not only unpredictable but mostly unavoidable and occur in only a small proportion of patients at therapeutic doses. The most common are cytopenia, lymphadenopathy, pseudolymphoma, skin eruptions, pyrexia, and coagulopathy 7,8 . Furthermore, the effect of PB on the liver is well known, leading to hepatic enzyme induction; however, these changes have not been observed in cats 9 …”

“…8,14 However, a study by Marsh et al showed that despite relatively low PB serum levels in three cats who had received both LEV and PB, the cats had unexpected side effects. 7 In our study, we did not observe an overdosing with LEV administration. Nevertheless, the effect of PB on hematocrit in these patients is questionable since most cats recovered after a few months without the need to discontinue treatment.…”

“…Compared with other studies, the onset of cytopenias is approximately 2-12 weeks in cats and 1-107 months in dogs after the start of the PB treatment. 4,5,7,8,14 In most studies, the time of resolution of cytopenias after discontinuing PB therapy was about 4-10 weeks in cats and 2-3 weeks in dogs. However, the resolution of anemia was longer than that of neutropenia in dogs.…”