Page 797 - Clinical Small Animal Internal Medicine

70 Seizures and Movement Disorders 765

Administration and Monitoring Potassium bromide can 25% at the time of starting zonisamide due to the
VetBooks.ir be administered at a starting dose of 40 mg/kg/day when enhanced hepatic enzyme induction and clearance of
zonisamide.
used as sole therapy or 30 mg/kg/day when used as an
add‐on drug to phenobarbital. Potassium bromide serum
concentration should be measured at one month and at Adverse Effects The major adverse effects include
the first steady‐state concentration (approximately 8–12 sedation, dry eye, ataxia, inappetence, and vomiting,
weeks). The recommended goal is to achieve steady‐state often related to metabolic and renal tubular acidosis.
trough serum concentrations of 25 μg/mL for phenobar- Cats are more likely to develop adverse effects of ano-
bital and 2000 mg/L for potassium bromide. The range is rexia, vomiting, diarrhea, and ataxia at doses over 10
highly individualized according to the seizure pattern of mg/kg/day. A decrease in circulating total serum T4
each dog. Further reductions in phenobarbital can be levels can occur and acute idiosyncratic hepatic necro-
attempted if a seizure‐free period is maintained for six sis has been reported in the dog. Patients with a history
months. The dosage is adjusted according to the formu- of sulfa drug hypersensitivity should not be prescribed
lae given below. zonisamide.
Potassium bromide monotherapy is recommended for
dogs with underlying liver disease, less frequent seizure Dosage and Monitoring Zonisamide is available as a
activity (<3 per year) and for some dogs with idiopathic generic medication in dosages of 25 mg, 50 mg, and 100
epilepsy. The use of potassium bromide monotherapy is mg. The starting dose in dogs is 10 mg/kg every 12 hours
not recommended for high initial frequency seizure and 5 mg/kg once daily in cats. Trough serum drug levels
activity, if secondary epilepsy is present, or if unwar- should be obtained at 14 and 45 days, then every six
ranted adverse effects persist (e.g., weakness, extreme months if no seizures are observed or in 10 days after a
polydipsia). drug adjustment.
Adjustment of bromide dose can be calculated with
the following formula: Levetiracetam
This is the S‐enantiomer of the ethyl analogue of
Target Css Actual Css Clearance/Bioavailability piracetam and has a unique mechanism of action medi-
2000 mg/L Actual Css 002 ated by binding to the presynaptic vesicular protein,
.
g

//
Newmgkgday addedtoexistingdose e SV2A, which decreases glutamate neurotransmitter. The

drug has shown to be an effective add‐on AED in the cat
but not as conclusive in the dog.
where Css = steady‐state concentration.
Second‐Generation AEDs Pharmacology In dogs, the drug is well absorbed, is rap-
Zonisamide idly metabolized with an estimated elimination half‐life
This is a substituted 1,2‐benzisoxazole derivative that of 4–8 hours, and is predominantly renal excreted
works by both blocking the propagation of epileptic (>80%). However, wide fluctuations of drug metabolism
discharges and suppressing focal epileptogenic activ- occur in the dog. The oral dose should be increased
ity. Broad‐spectrum antiepileptic activity has been when dogs are receiving phenobarbital concurrently as
reported against a variety of seizure types, with lower serum levels can potentially be related to the
particular improvement in the treatment of adult induction of serum hydrolases. A new extended‐release
myoclonus epilepsy. Zonisamide can be an efficacious formulation of levetiracetam has been shown to have a
and well‐tolerated drug in dogs with recurrent half‐life in excess of seven hours in dogs following
generalized seizures refractory to phenobarbital or oral administration, giving rise to the potential for
potassium bromide therapy. Over 70% of dogs twice‐daily administration
with refractory idiopathic epilepsy responded well to
zonisamide add‐on therapy in one study, with 58% Adverse Effects Levetiracetam is the best tolerated of all
responding favorably in another. the current AEDs used in veterinary medicine. Sedation
is the most common initial adverse effect that typically
Pharmacology Zonisamide is well absorbed, has a rela- dissipates over time.
tively long half‐life (18–28 hours) and high protein‐bind-
ing affinity (70%) in dogs. In cats, zonisamide is more Dosage and Monitoring The initial dose of 10–20 mg/
slowly metabolized, with a half‐life of 33 hours. kg orally q12h is gradually incremented to ≥20 mg/kg
Zonisamide is hepatic metabolized and thus influenced orally q8h. The therapeutic range is not well defined
by concurrent administration of other similarly metabo- and drug monitoring is recommended only to establish
lized drugs. Phenobarbital dosages should be reduced by the pharmacokinetic pattern of the individual patient.