Zonisamide (Zonegran, Zonisade, and others)

How Medicare covers it

Part D (forms used at home). Part A during a covered inpatient stay. No Part B clinician-administered form in the CMS Part B spending file.

What it treats

Partial seizures in adults with epilepsy, as an add-on (adjunctive) treatment — meaning it is used together with other seizure medicines, not alone. This entry is based on the Zonegran capsule label.

What it is for, in depth

Zonisamide is prescribed for adults with epilepsy who still have partial (focal) seizures on their current seizure medicine — it is added on, not used as the only drug. Its safety and effectiveness below age 16 are not established in this label. It comes as 25 mg, 50 mg, and 100 mg capsules in the package, plus a 20 mg/mL oral suspension; many effects are dose-related, so dosing is built up and reviewed against tolerability.

How it works

The precise way zonisamide stops seizures is not known. Lab studies suggest it blocks sodium channels and certain calcium currents, which stabilizes nerve cell membranes and calms the over-synchronized firing that causes seizures. It is chemically a sulfonamide and also inhibits carbonic anhydrase.

How it is taken

Taken by mouth once or twice a day, with or without food, swallowing the capsules whole. This label's capsules are 25 mg and 100 mg; the package also includes a 20 mg/mL oral suspension (Zonisade) and 50 mg capsules, which follow their own product directions.

Common side effects

The most common effects, at least 4% more often than with placebo, were sleepiness, loss of appetite, dizziness, unsteady walking (ataxia), agitation or irritability, and trouble with memory or concentration. About 12% of patients in trials stopped because of a side effect, most often sleepiness, fatigue, unsteady walking, and loss of appetite.

Serious warnings

The label warns about metabolic acidosis (too much acid in the blood) and high ammonia with encephalopathy, especially with other carbonic anhydrase inhibitors, plus kidney stone risk. Its sulfonamide chemistry also means severe sulfonamide-type reactions are a concern, and its CNS effects — sleepiness, slowed thinking, memory problems — led many trial patients to stop.

Who should be careful

It must not be used by anyone who has shown hypersensitivity to sulfonamides or to zonisamide. People taking another carbonic anhydrase inhibitor, and people who drink alcohol or take other CNS depressants, need monitoring for acidosis and CNS effects.

Major interactions

It has not been formally studied with alcohol or other CNS depressant drugs, but because it can cause CNS depression and thinking problems, use with alcohol or other depressants needs caution. Using it with another carbonic anhydrase inhibitor (such as topiramate or acetazolamide) can worsen metabolic acidosis and raise the risk of kidney stones and high ammonia.

Cost and saving notes

Zonisamide is sold as a generic capsule and is covered under Medicare Part D. If your plan's tier makes it hard to afford, you can ask your plan for a tier exception. If you qualify for Extra Help, the Part D low-income help, your drug costs will be much lower.

Why it is in its tier

Zonisamide (Zonegran, Zonisade, and others) sits on Tier 2 in 87.95% of the plans that list it (4833 of 5495 listing plans). Tier 2 is the generic tier — low copays. The data-visible drivers: It is sold both as a brand product and in generic form, and the CMS dashboard puts its average Part D spending at about $186 per beneficiary for 2024 — a relatively low-cost drug, which matches where plans place it. It is listed by 100.0% of Part D plans. The tier shown is the most common one; individual plans vary.

Sources

• ZONEGRAN (ZONISAMIDE) CAPSULE [ADVANZ PHARMA (US) CORP.] — DailyMed
• MedlinePlus — National Library of Medicine
• MedlinePlus — Zonisamide

What official patient guides say

Zonisamide comes as a capsule to take by mouth (the capsule form in this package). MedlinePlus says it is usually taken once or twice a day, with or without food, at around the same time(s) every day. Take it exactly as directed — do not take more or less of it or take it more often than your doctor prescribed. Swallow the capsules whole; do not split, chew, or crush them. Your doctor will probably start you on a low dose and raise it slowly, no more often than once every 2 weeks. Zonisamide may help control your condition but will not cure it, and it may take 2 weeks or longer before you feel its full benefit. Keep taking it even if you feel well, and do not stop taking it without talking to your doctor, even if you have side effects such as odd changes in behavior or mood — stopping suddenly can make seizures worse, so your doctor will probably lower your dose slowly. Your doctor or pharmacist will give you the manufacturer's patient information sheet (Medication Guide) when you start and each time you refill; read it carefully. If you miss a dose, MedlinePlus says to talk to your doctor about what to do. Do not take a double dose to make up for a missed one. Keep the capsules in the container they came in, tightly closed and out of reach of children. Store them at room temperature, away from light, extra heat and moisture, and not in the bathroom. Do not flush leftover medicine. Ask your pharmacist about a medicine take-back program.

Source: MedlinePlus — Zonisamide

Part D formulary coverage

Source: CMS Prescription Drug Plan Formulary, Pharmacy Network, and Pricing Information Files — Monthly file 2026-10-15 (plan year 2027), file 2027_20261008.zip (data.cms.gov dataset ed1496ea-23e7-41f1-9292-172fa842ccfb): basic drugs formulary file + plan information file, both dated 20261031 inside the zip; downloaded and aggregated 2026-10-30. Medication RxCUI sets resolved through the NLM RxNav (RxNorm) API.

What you pay

Without insurance, the cash benchmark is 2.74972 per unit (ZONISADE 100 MG/5 ML ORAL SUSP) — about nan for 30 units. NADAC benchmark — the average price pharmacies pay (CMS, as of 2026-11-04). Pharmacy shelf prices vary.

A tier is not a price; what you pay depends on your plan, pharmacy, and benefit stage; Extra Help or Medicaid can lower it further.

Sources: CMS Plan Benefit Package + formulary data; CMS NADAC · Checked 2026-11-08

Coverage by plan and tier

Of the 5,495 Medicare drug plans we track for 2027, 5,495 list Zonisamide (Zonegran, Zonisade, and others) — 100% of plans. Most of those plans put it on Tier 2: 4,833 plans, 88.0% of the plans that list it. Other plans place it on Tier 1 (489 plans), Tier 3 (135 plans) or Tier 4 (38 plans). For example: Aetna Medicare Dual Extra (HMO D-SNP) puts it on Tier 2; Aetna Medicare Dual Extra Care (PPO D-SNP) puts it on Tier 2; Aetna Medicare Value Plus (PPO) puts it on Tier 2. You can compare these plans side by side on our Medicare Advantage hub. A tier is not a price. What you pay also depends on whether you have met your plan';s deductible, whether the drug costs a flat copay or a share of the price, and whether you get Extra Help or Medicaid.

Read next

• Part D in 2027: The $700 Deductible, the $2,400 Cap, and the $35 Insulin Rule
• Extra Help in 2027: Lower Drug Copays and Who Qualifies
• Checking Medicare Savings Programs and Extra Help

Part D spending averages (2024)

Source: CMS Medicare Part D Spending by Drug (Drug Spending Dashboard), release RY26 P04 V10, data through 2024 (DSD_PTD_RY26_P04_V10_DY24_BGM.csv), downloaded 2026-10-30

Companies covering this drug

Part D and Medicare Advantage plan sponsors that list this drug on a formulary, 50 at a time.