- What Is Drug Used For?
- Pharmacology / Actions
- Before you take Drug
- Contraindications / Precautions / Warnings
- Adverse Effects
- Reproductive / Nursing Safety
- Overdosage / Acute Toxicity
- Drug Interactions
- Laboratory Considerations
- How to use Drug
- Client Information
- Chemistry / Synonyms
- Storage / Stability
- Dosage Forms / Regulatory Status
- Human-Labeled Products:
Highlights of Prescribing Information
- Antiseizure medication that may be useful as an “add-on” drug for refractory epilepsy
- Half-life of 15 hours makes twice daily dosing possible
- Adverse effect profile not fully elucidated for dogs; sedation, ataxia, & inappetence have been reported
- Known teratogen in dogs
- Contraindicated in patients hypersensitive to sulfonamides
- Expense may be an issue
What Is Drug Used For?
Zonisamide may be useful as an “add-on” drug for refractory epilepsy in dogs.
Pharmacology / Actions
The exact mechanism of action for zonisamide is not known. It may produce its antiseizure activity by blocking sodium channels and reducing transient inward currents, thereby stabilizing neuronal membranes and suppressing neuronal hypersynchronization. It does not appear to potentiate GABA. Zonisamide has weak carbonic anhydrase inhibitory activity.
In dogs, zonisamide is well absorbed after oral administration and has low protein binding. The elimination half-life in dogs is about 15 hours. Most of the drug is excreted via the kidneys into the urine, but about 20% is metabolized, primarily in the liver.
Before you take Drug
Contraindications / Precautions / Warnings
Zonisamide is contraindicated in patients hypersensitive to it or to any of the sulfonamide drugs.
Because there has been limited use of this drug in veterinary patients the adverse effect profile is not fully known. Adverse effects that have been reported in dogs include sedation, ataxia, and inappetence.
In humans, the most common adverse effects associated with zonisamide include anorexia, nausea, dizziness, somnolence, agitation and headache. Rarely, serious dermatologic reactions (Stevens-Johnson syndrome, TEN), blood dyscrasias, oligohidrosis, and hyperthermia have been reported in humans.
Reproductive / Nursing Safety
When zonisamide was administered to pregnant dogs at 10 or 30 mg/kg/day (approximate therapeutic dosages in dogs), ventricular septal defects, cardiomegaly and various valvular and arterial anomalies were seen at the higher dose. A plasma level of 25 meg/ mL was the threshold level for malformation. If this drug is to be used in pregnant dogs, the owner must accept the significant risks associated with its use.
It is not known if zonisamide enters maternal milk; use with caution in nursing animals.
Overdosage / Acute Toxicity
The LD50 of zonisamide in dogs is reportedly 1 g/kg. In human overdoses, effects reported include coma, bradycardia, hypotension, and respiratory depression. Treatment recommendations include GI evacuation, if ingestion was recent, and supportive therapy. Because of the drug’s long half-life, support may be required for several days.
The following drug interactions have either been reported or are theoretical in humans or animals receiving zonisamide and may be of significance in veterinary patients:
■ PHENOBARBITAL: While there is concern that drugs that induce liver enzymes (e.g., phenobarbital) can increase the metabolism and clearance of zonisamide, it is not known if this significantly alters the pharmacokinetics of zonisamide in dogs. Since most dogs subsequently receiving zonisamide have been on phenobarbital chronically and only about 20% of a dose of drug is biotransformed, it may not be significant.
■ No specific laboratory interactions or considerations were noted
■ While plasma concentrations of zonisamide are not routinely monitored in human patients, in dogs, the therapeutic range has been suggested to be from 10-40 mcg/mL
How to use Drug
Drug dosage for dogs:
a) For refractory epilepsy: 10 mg/kg q12h PO twice daily ()
b) As a secondary anticonvulsant for refractory epilepsy: 8-12 mg/kg PO q8h ()
c) 8-12 mg/kg PO q8-12h()
d) Initial dose: 5-10 mg/kg PO q12h; gradual adaptation in dosing is recommended. Reduce phenobarbital doses by 25% at the time of starting zonisamide. ()
■ Adverse effects
■ Clients must understand that the clinical use of this agent is relatively “investigational” in veterinary patients, that it must be dosed often in dogs and, also, the potential costs
■ Caution clients not to stop therapy abruptly or “rebound” seizures may occur
■ Have clients maintain a seizure diary to help determine efficacy
Chemistry / Synonyms
A sulfonamide unrelated to other antiseizure drugs, zonisamide occurs as a white powder with a pKa of 10.2. It is moderately soluble in water (0.8 mg/mL).
Zonisamide may also be known as: AD-810, CI-912, PD-110843, Excegran, or Zonegran.
Storage / Stability
Zonisamide capsules should be stored at 25°C (76°F); excursions permitted to 15-30°C (59-86°F). Store in a dry place and protected from light.
Dosage Forms / Regulatory Status
Veterinary-Labeled Products: None
Zonisamide Capsules: 25 mg, 50 mg & 100 mg; Zonegran* (Eisai); generic; (Rx)
Selections from the book: “Plumb’s Veterinary Drug Handbook. Sixth Edition”. 2008