Primidone and it's active metabolites, phenylethamalonamide (PEMA) and phenobarbital have similar anticonvulsant actions.  While the exact mechanisms for this activity are unknown, these agents raise seizure thresholds or alter seizure patterns.

It is believed that the majority of Primidone's anti-seizure effect is derived from the conversion of Primidone to Phenobarbital.  Since studies have shown that Primidone carries a greater risk of liver disease, most veterinarians prescribe Phenobarbital instead of Primidone.  However, one study showed that a very small percentage of dogs with seizures unresponsive to Phenobarbital, had improved control with Primidone.

Primidone Facts:

Mean Elimination Half-Life:  Primidone 2 hours

                                                PEMA 7 hours

                                                Phenobarbital 41 hours

Time to Reach Steady State Concentrations: 

Target Serum Concentration:  15 to 40 ug/ml of Phenobarbital

Adverse Effects:  The adverse effects in dogs are similar for both Primidone and Phenobarbital.  Dogs may exhibit increased symptoms of anxiety and agitation when initiating therapy.  These effects may be transitory in nature and often will resolve with small dosage increases.  Occasionally, dogs will exhibit profound depression at lower dosage ranges.  Excessive hunger, excessive thirst, excessive urination, lethargy and ataxia (hind end weakness) are common.  

The risk of liver disease is greater with Primidone than with Phenobarbital.

Monitoring:  There are many monitoring protocols but in general, Primidone (or Phenobarbital)  levels should be checked approximately 14 days after initiating therapy to determine the blood serum levels.   

Once you have obtained seizure control, your vet will probably want to monitor blood serum concentrations every 6 months to be sure that the serum level has not drifted out of range. 

Liver enzymes and bile acid tests should be performed regularly. 

Cautions and Warnings:  Primidone should not be used in dogs with liver disease.  Use cautiously in patients who are hypovolemic, anemic, have borderline hypoadrenal function, or cardiac or respiratory disease.

Discontinuing Therapy:  Never discontinue therapy or alter the dose of this medication, without first consulting with your veterinarian.

Braund, KG, Clinical Syndromes in Veterinary Neurology
Tilley, LP, The 5 Minute Veterinary Consult, Lawrence Patrick Tilley
Plumb, DC, Veterinary Drug Handbook