|Systematic (IUPAC) name|
|Metabolism||Hepatic through CYP3A4|
|Biological half-life||63 hours in plasma|
|Excretion||Renal (62%); Faeces (3%)|
|ATC code||N03AX15 (WHO)|
|PDB ligand ID||ZON (PDBe, RCSB PDB)|
|Molar mass||212.227 g/mol|
|Melting point||162 °C (324 °F)|
Zonisamide is a sulfonamide anticonvulsant approved for use as an adjunctive therapy in adults with partial-onset seizures; infantile spasm, mixed seizure types of Lennox–Gastaut syndrome, myoclonic, and generalized tonic clonic seizure.
Zonisamide is approved in the United States, United Kingdom, and Australia for adjunctive treatment of partial seizures in adults and in Japan for both adjunctive and monotherapy for partial seizures (simple, complex, secondarily generalized), generalized (tonic, tonic-clonic (grand mal), and atypical absence) and combined seizures. For epilepsy, most studies have used oral zonisamide in daily doses ranging from 200 to 600 milligrams/day, divided in 2 daily doses, adjusted to maintain serum levels of 15 to 40 micrograms/milliliter
An open trial on zonisamide in seven Parkinson's disease patients had positive results, according to this 2001 report. Since then, it has been reported to treat the resting tremor that other therapies may leave behind. By early November 2005, Dainippon Sumitomo had filed a NDA for the use of zonisamide in Parkinson's disease; it is to be marketed as Tremode.
It has also been studied for obesity with significant positive effects on body weight and there are three ongoing clinical trials for this indication. It is to be sold, when combined with bupropion, under the brand name Empatic.
Very common (>10% incidence) adverse effects include:
Common (1-10% incidence) adverse effects include:
- Affect lability
- Psychotic disorder
- Disturbance in attention
- Speech disorder
- Abdominal pain
- Influenza-like illness
- Oedema peripheral
- Weight loss
Uncommon (0.1-1% incidence) adverse effects include:
Rare/Very rare (<0.1% incidence) adverse effects include:
- Aplastic anaemia
- Drug-induced hypersensitivity syndrome
- Drug rash with eosinophilia and systemic symptoms
- Metabolic acidosis
- Renal tubular acidosis
- Grand mal seizure
- Myasthenic syndrome
- Neuroleptic malignant syndrome
- Status epilepticus
- Pneumonia aspiration
- Respiratory disorder
- Hypersensitivity-type Pneumonitis
- Hepatocellular damage
- Erythema multiforme
- Stevens-Johnson syndrome
- Toxic epidermal necrolysis
- Renal failure
- Urine abnormality
- Heat stroke
- Blood creatine phosphokinase increased
- Blood creatinine increased
- Blood urea increased
- Liver function tests abnormal
Zonisamide and other carbonic anhydrase inhibitors such as topiramate, furosemide, and hydrochlorothiazide have been known to interfere with amobarbital, which has led to inadequate anesthetization during the Wada test. Zonisamide may also interact with other carbonic anhydrase inhibitors to increase the potential for metabolic acidosis.
Additionally, the metabolism of zonisamide is inhibited by ketoconazole, ciclosporin, miconazole, fluconazole and carbamazepine (in descending order of inhibition) due to their effects on the CYP3A4 enzyme.
Mechanism of action
Zonisamide is an antiseizure drug chemically classified as a sulfonamide and unrelated to other antiseizure agents. The precise mechanism by which zonisamide exerts its antiseizure effect is unknown, although it is believed that the drug blocks sodium and T-type calcium channels, which leads to the suppression of neuronal hypersynchronization (that is, seizure-form activity). It is also known to be a weak carbonic anhydrase inhibitor (similarly to the anticonvulsant, acetazolamide). It is also known to modulate GABAergic and glutamatergic neurotransmission.
Variable, yet relatively rapid rate of absorption with a time to peak concentration of 2.8-3.9 hours. Food has no effect on the bioavailability of zonisamide
Zonisamide was discovered by Uno and colleagues in 1972 and launched by Dainippon Sumitomo Pharma (formerly Dainippon Pharmaceutical) in 1989 as Excegran in Japan. It was marketed by Élan in the United States starting in 2000 as Zonegran, before Élan transferred their interests in zonisamide to Eisai Co., Ltd. in 2004. Eisai also markets Zonegran in Asia (China, Taiwan, and fourteen others) and Europe (starting in Germany and the United Kingdom).
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- Official Dainippon Sumitomo Pharma Website (English version)