zoe-NISS-a-mide

Therapeutic Classification: anticonvulsants

Pharmacologic Classification: sulfonamides

• Partial seizures.

• Raises the threshold for seizures and reduces duration of seizures probably by action on sodium and calcium channels.

• Decreased frequency of partial seizures.

Absorption: Well absorbed following oral administration.

Distribution: Well distributed to extravascular tissues. Binds extensively to red blood cells.

Metabolism/Excretion: Mostly metabolized by the liver via the CYP3A4 isoenzyme; 35% excreted unchanged in urine.

Half-life: 63 hr (plasma).

(plasma concentrations†)

†Requires 2 wk of dosing to achieve steady-state plasma concentrations.

Contraindicated in:

• Hypersensitivity to zonisamide or sulfonamides
• Renal impairment (CCr <50 mL/min)
• OB: Pregnancy
• Lactation: Lactation.

Use Cautiously in:

• All patients (may ↑ risk of suicidal thoughts/behaviors)
• Hepatic or renal impairment (may require slower titration/more frequent monitoring; ↑ risk of metabolic acidosis with renal impairment)
• Respiratory disorders, diarrhea, or undergoing surgery (↑ risk of metabolic acidosis)
• Women of reproductive potential
• Pedi: Children 16 yr (↑ risk of oligohydrosis, hyperthermia, and/or metabolic acidosis).

Derm: DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS), oligohydrosis (↑ in children), rash, STEVENS-JOHNSON SYNDROME, TOXIC EPIDERMAL NECROLYSIS.

EENT: amblyopia, angle closure glaucoma, ↑ intraocular pressure, myopia, pharyngitis, tinnitus.

F and E: metabolic acidosis.

GI: anorexia, nausea, vomiting.

GU: kidney stones.

Metab: hyperammonemia, hyperthermia (↑ in children).

Neuro: drowsiness, fatigue, abnormal gait, agitation/irritability, depression, dizziness, encephalopathy, hyperesthesia, incoordination, psychomotor slowing, psychosis, SUICIDAL THOUGHTS, tremor, weakness.

Resp: cough.

Drug-Drug:

• Levels and effects may be ↓ by phenytoin, carbamazepine, phenobarbital, or valproate.
• May enhance the adverse/toxic effect of carbonic anhydrase inhibitors; avoid concurrent use.
• Valproate and topiramate may ↑ risk of hyperammonemia.

• PO (Adults and Children >16 yr): 100 mg once daily initially for 2 wk; may ↑ by 100 mg/day every 2 wk, based on clinical response and tolerability, to 400 mg once daily. Can be given as a single daily dose or in 2 divided doses.
• PO (Infants and Children): Initial: 1–2 mg/kg/day given in two divided doses/day; ↑ dose in increments of 0.5–1 mg/kg/day every 2 wk (maximum dose: 12 mg/kg/day).

(Generic available)

• Capsules: 25 mg; 50 mg; 100 mg;
• Oral suspension (strawberry flavor): 100 mg/5 mL;

• Monitor closely for notable changes in behavior that could indicate the emergence or worsening of suicidal thoughts or behavior or depression.
• Monitor frequency, duration, and characteristics of seizures.
• Monitor for signs/symptoms of encephalopathy (mental status changes, vomiting, lethargy).
• Monitor patient frequently for development of skin rash. Unexplained rash may require discontinuation of therapy.
• Monitor for signs and symptoms of DRESS (fever, rash, lymphadenopathy, and/or facial swelling) or associated with involvement of other organ systems (hepatitis, nephritis, hematologic abnormalities, myocarditis, myositis) during therapy. May resemble an acute viral infection. Eosinophilia is often present. Discontinue therapy if signs occur.
• Assess patient for allergy to sulfa drugs.

• Monitor renal function periodically during therapy. May cause ↑ creatinine and BUN.
  • Measure serum bicarbonate before starting and periodically during therapy. Metabolic acidosis may be more frequent and severe in younger patients.
  • May cause ↑ in serum alkaline phosphatase.
  • Monitor serum ammonia levels if signs/symptoms of encephalopathy occur.

• PO: May be administered with or without meals. Capsules should be swallowed whole.
  • Shake oral suspension before administering. Store suspension at room temperature and protect from light. After opening the bottle, discard any unused suspension after 30 days.

• Instruct patient to take zonisamide as directed, even if feeling well. Consult health care professional if a dose is missed. Do not discontinue abruptly without consulting health care professional; may cause seizures. Instruct patient to read the Medication Guide before starting and with each Rx refill, changes may occur.
• Instruct patient to measure dose from suspension using measuring device supplied by pharmacy or with product, not household devices.
• Instruct patient to contact health care professional immediately if skin rash or visual disturbances occur or seizures worsen. Patient should also contact health care professional if a child taking zonisamide is not sweating as usual, with or without a fever, or if they develop fever, sore throat, oral ulcers, easy bruising, depression, unusual thoughts, or speech or language problems.
• May cause drowsiness. Caution patient to avoid driving or other activities requiring alertness until cleared by health care professional and effects of medication are known.
• Advise patient to increase fluid intake to at least 6–8 glasses of water/day to minimize risk of kidney stones. Instruct patient to contact health care professional if symptoms of kidney stones (sudden back pain, abdominal pain, blood in urine) occur.
• Advise patient and family to notify health care professional if thoughts about suicide or dying, attempts to commit suicide, new or worse depression, new or worse anxiety, feeling very agitated or restless, panic attacks, trouble sleeping, new or worse irritability, acting aggressive, being angry or violent, acting on dangerous impulses, an extreme increase in activity and talking, or other unusual changes in behavior or mood occur.
• Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
• May cause fetal harm. Advise females of reproductive potential to use effective contraception throughout therapy. Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected and to avoid breastfeeding.

• Decrease in frequency and duration of partial seizures.

Zonegran, Zonisade