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Clinical data | |
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Trade names | Zonegran, Zonisade |
AHFS/Drugs.com | Monograph |
MedlinePlus | a603008 |
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Routes of administration | By mouth |
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Pharmacokinetic data | |
Bioavailability | ~100%[3] |
Protein binding | 40%[3] |
Metabolism | Liver through CYP3A4[3] |
Elimination half-life | 63 hours in plasma[3] |
Excretion | Kidney (62%); Faeces (3%)[3] |
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ECHA InfoCard | 100.118.526 |
Chemical and physical data | |
Formula | C8H8N2O3S |
Molar mass | 212.22 g·mol−1 |
3D model (JSmol) | |
Melting point | 162 °C (324 °F) |
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Zonisamide, sold under the brand name Zonegran among others, is a medication used to treat the symptoms of epilepsy and Parkinson's disease.[4][5] Chemically it is a sulfonamide. It serves as an anticonvulsant used primarily as an adjunctive therapy in adults with Parkinson's disease, partial-onset seizures; infantile spasm, mixed seizure types of Lennox–Gastaut syndrome, myoclonic and generalized tonic clonic seizure.[6] Despite this it is also sometimes used as a monotherapy for partial-onset seizures.[5][7]
In 2020, it was the 276th most commonly prescribed medication in the United States, with more than 1 million prescriptions.[8][9]
Zonisamide is approved in the United States,[1][10] and United Kingdom[11] for adjunctive treatment of partial seizures in adults and 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.[12] In Australia it is marketed as both an adjunctive therapy and monotherapy for partial seizures only.[7]
It has been approved for the treatment of the motor symptoms of Parkinson's disease (PD), as an adjunct to levodopa, in a few countries such as Japan.[4][5] In Japan, zonisamide has been used as an adjunct to levodopa treatment since 2009.[13] In addition, there is clinical evidence that zonisamide in combination with levodopa control of motor symptoms of PD but evidence for the treatment of the non motor symptoms of PD lacking.[14][15]
Adverse effects by incidence:[3][16][17]
Very common (>10% incidence) adverse effects include:
Common (1-10% incidence) adverse effects include:
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.[18] Zonisamide may also interact with other carbonic anhydrase inhibitors to increase the potential for metabolic acidosis.[3]
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.[19]
Zonisamide is not known to inhibit cytochrome P450 enzymes when present at therapeutic concentrations.[20]
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).[7] It is also known to be a weak carbonic anhydrase inhibitor (similarly to the anticonvulsant topiramate). It is also known to modulate GABAergic and glutamatergic neurotransmission.[7][21][22][23][24]
Variable, yet relatively rapid rate of absorption with a time to peak concentration of 2.8-3.9 hours. Bioavailability is close to 100% and food has no effect on the bioavailability of zonisamide but may affect the rate of absorption.[25][20]
Zonisamide is metabolized mostly by the CYP3A4 isoenzyme, but also CYP3A7 and CYP3A5,[26] to 2-(sulphamoylacetyl)-phenol via reductive cleavage of the 1,2-benzisoxazole ring.[27]
Zonisamide was discovered by Uno and colleagues in 1972[28] and launched by Dainippon Sumitomo Pharma (formerly Dainippon Pharmaceutical) in 1989 as Excegran in Japan.[29] 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.[30] Eisai also markets Zonegran in Asia (China, Taiwan, and fourteen others)[31] and Europe (starting in Germany and the United Kingdom).[32]
In an open-label trial zonisamide attenuated the symptoms of tardive dyskinesia.[33]
It has also been studied for obesity[34] with significant positive effects on body weight loss and there are three ongoing clinical trials for this indication.[35][36][37] It was to be sold, when combined with bupropion, under the brand name Empatic, until its development was discontinued.[38]
Zonisamide has been studied for and used as a migraine preventative medication, when topiramate is either ineffective or cannot be continued due to side effects.[5]
It has also been used off-label by psychiatrists as a mood stabilizer to treat bipolar depression.[39][40]