Rationale for Alternative Anticonvulsants

• Seizures refractory when blood levels of phenobarbital (Pb) and bromide (Br; KBr or NaBr) are at the recommended maximum levels. (Refractory seizures are especially common in larger breeds of dogs.)
  
• Pet owner unable to tolerate side-effects (e.g. sedation).
  
• Pb induced hepatotoxicosis or bone marrow problems.
  
• Preferred Pb concentration not higher than ~30 ug/mL.

Use of Alternative Anticonvulsants

• Used most often in dogs that are refractory to Pb and Br. Can use one of the medications described below alone, or in conjunction with Pb or Br, or with both Br and Pb.
  
• All alternative anticonvulsants are expensive (monthly cost ~ $200 or more for a 20 kg dog).
  
• Although alternative anticonvulsants can be used alone, cost usually dictates they be used for refractory cases in conjunction with Pb and/or Br.
  
• Goals of additional therapies are:
  1. Reduce seizure frequency to once per month or less.
  2. No cluster seizures or fewer clusters.

Felbamate (Felbatol®)

• One of the oldest alterative anticonvulsants.
  
• Dosing
  1. Starting dose is 15 mg/kg q 8h.
  2. Can increase in 15-30 mg increments every 2-3 weeks.
  3. Therapeutic ranges listed as 20-100 ug/mL, but therapeutic monitoring is not usually done.
  
  
• Side effects
  1. Medication generally well-tolerated; clinically apparent toxicities usually not seen until dosages approach 300 mg/kg/day.
  2. Side effects in people (liver disease and bone marrow suppression) have not been significant problems in dogs.
  3. Occasional tremors.
  4. Anecdotal reports of keratoconjunctivitis sicca (KCS).
  
  
• Pharmacokinetics
  As ~1/3 undergoes hepatic metabolism, it may not be good choice for dogs with Pb-induced hepatotoxicosis.

Gabapentin (Neurontin®)

• Dosing
  1. Dogs—starting dose is 10-15 mg/kg q 8h.
  2. Can increase to 30-60 mg/kg, if needed for therapeutic effect.
  3. Some prefer to give q 6 h, which is not feasible for most owners.
  4. Therapeutic level is listed at 4-16 mg/L; drug level monitoring is available but not usually done.
  5. Cats—5-10 mg/kg q 12 h.
  6. Also used for phantom pain, nerve pain, tail chasing, feline hyperesthesia syndrome.
  
  
• Side effects
  1. Considered to be very safe.
  2. Can occasionally cause sedation.
  
  
• Pharmacokinetics
  Undergoes both renal excretion and hepatic metabolism.

Zonisamide (Zonegran®)

• Dosing
  1. 5-10 mg/kg q 12 h; advantageous vs q 8 h drugs.
  2. Start at low end of dosage range and increase.
  3. 7-10 days to reach therapeutic blood levels.
  4. Measure peak levels at 2 h post-pill.
  5. Aim for 10-40 ug/mL.
  
  
• Side effects
  1. Considered fairly safe.
  2. Occasional sedation and ataxia.
  3. Occasional vomiting.
  4. A sulfa-derivative with potential to cause hypothyroidism, liver disease, KCS, immune-mediated disease, and blood dyscrasias. Not recommended for dogs with sulfonamide hypersensitivity (e.g. Doberman pinschers, rottweilers, miniature schnauzers, white- or dilute-coat colored breeds).
  
  
• Pharmacokinetics
  Long half life (~15 h). Mostly hepatic metabolism; may need higher dose due to induction of drug-metabolizing enzymes, if Pb is also used. Use cautiously in dogs with Pb-induced hepatotoxicosis.