Zonisamide (Zonegran)



Excerpt from Cafer's Mood Stabilizers and Antiepileptics


Zonisamide (ZONEGRAN)
 Pronunciation: zoe NIS a mide / ZAHN uh gran
“Zone is mighty, Zone is grand”
Zonisamide (Zonegran) mascot by Jason Cafer MD cafermed
❖ Antiepileptic 
❖ Voltage-gated sodium channel blocker 
❖ Glutamate ⇩
FDA approved for:
❖ Focal seizures
Used off label for: 
❖ Other types of seizures 

❖ PTSD nightmares 
❖ Sleep-related eating disorder 
❖ Obesity 
❖ Binge eating disorder 
❖ Alcohol use disorder 
❖ Migraine prophylaxis 
❖ Parkinsonian symptoms associated with Lewy body dementia


Zonisamide (Zonegran) is a broad-spectrum antiepileptic drug (AED) that blocks sodium and calcium channels and increases dopaminergic and serotonergic transmission. It is unrelated to other antiseizure medications. 

Zonegran can cause weight loss:
Zonegran can cause weight loss by Jason Cafer MD (cafermed)
Zonisamide decreases appetite and has been shown to decrease binge-eating. Cognitive impairment including “brain fog”, confusion, difficulty concentrating, and word-finding difficulty are relatively common. It is not used as a mood stabilizer because it may cause irritability. There have been rare cases of zonisamide-induced psychosis.


Due to carbonic anhydrase inhibitor activity (although weak) there is a chance of kidney stones (4%) and metabolic acidosis. Aplastic anemia and agranulocytosis have been reported. Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported. Oligohidrosis (decreased ability to sweat) has occurred with children. 


Half-life is over 60 hours. About 30% is excreted unchanged in the urine.

Zonisamide has a sulfonamide structure. It is contraindicated in patients allergic to sulfa drugs. Other sulfonamides include the antibiotic sulfamethoxazole (Bactrim, Septra) and the  disease-modifying antirheumatic drug (DMARD) sulfasalazine.

Dosing: Start 100 mg daily. May increase by 100 mg q 2 weeks for a maximum of 600 mg. However, doses above 400 mg are rarely more effective. As with any antiepileptic medication, taper dose gradually to discontinue. 

Dynamic interactions: 
❖ Sedative (mild) 
❖ Hypokalemia 
❖ Metabolic acidosis 
❖ Decreased renal perfusion
Kinetic interactions:
❖ Kinetic interactions: 
❖ Urine alkalization (minor) 
❖ 3A4 substrate (minor)
Zonisamide (Zonegran) is a CYP3A4 substrate by Jason Cafer MD
Zonisamide (Zonegran) decreases lithium levels visual by jason cafer md

Zonegran pill picture cafermed


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