Phenobarbital has been widely used for seizure management since the 1900s and is effective for seizure control in both dogs and cats.2,4 The anticonvulsant effect of phenobarbital is likely due to increased intracellular chloride secondary to prolonged opening of the γ-aminobutyric acid receptors on the postsynaptic membrane. Increased intracellular chloride causes increased negative membrane potential, which reduces nerve firing.5
Adverse effects are rare in cats but common in dogs6 and can include sedation, ataxia, weakness, polydipsia, polyphagia, and polyuria. Hepatopathy and hepatotoxicity have been well-documented in dogs receiving phenobarbital. Hepatopathy/toxicity has not been reported in cats receiving phenobarbital long-term; therefore, elevated ALP or ALT in cats receiving phenobarbital should prompt investigation into other hepatopathies.4 Clinical adverse effects and risk for hepatopathy are serum phenobarbital-dependent; therefore, maintaining serum phenobarbital concentrations <35 μg/mL can be targeted to reduce these adverse effects. Conversely, blood dyscrasias are idiosyncratic and not dependent on serum concentration. Blood dyscrasias have been reported in 4.2% of dogs receiving phenobarbital. If anemia, thrombocytopenia, leukopenia, or pancytopenia are noted, phenobarbital should be safely and swiftly removed from administration and replaced by another anticonvulsant.7 CBC monitoring is recommended 14 days after starting phenobarbital and every 6 months thereafter.
A typical starting dosage for dogs and cats is 2-5 mg/kg PO every 12 hours (reported range, 1.8-10 mg/kg/day).2,4,6,8-10 Steady state is expected 10 to 14 days after initiation of treatment in both species.11,12 The reference interval for monitoring serum concentrations at steady state levels for dogs is 15 to 40 µg/mL; however, the author agrees that optimal therapeutic success is frequently obtained with serum phenobarbital concentrations of 25 to 30 µg/mL, which can help limit toxicity.4,9-11
A therapeutic reference interval for cats is not available, but seizure control was achieved in a study in 93% of cats with serum phenobarbital concentrations of 15 to 45 µg/mL, regardless of the underlying cause.4 Transdermal phenobarbital has been investigated for use in cats.13,14 In these studies, serum phenobarbital concentrations in healthy cats were within the therapeutic reference range for dogs13,14; however, a prospective clinical trial in epileptic cats showed the serum concentrations did not correlate with the dose administered.15 Additional routes of administration in cats are being explored. Clinicians are encouraged to monitor forthcoming literature for additional options beyond per os administration of phenobarbital.