Zonisamide
Pronouncation: (zoe-NIS-ah-MIDE)Class: Anticonvulsant, Sulfonamide
Trade Names:
Zonegran
- Capsules 25 mg
- Capsules 50 mg
- Capsules 100 mg
Pharmacology
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Unknown; however, may produce anticonvulsant effects through action at sodium and calcium channels.
Pharmacokinetics
Absorption
The C max is 2 to 5 mcg/mL and T max is 2 to 6 h. In the presence of food, T max is delayed to 4 to 6 h, but has no effect on bioavailability.
Distribution
Vd is about 1.45 L/kg. It is about 40% bound to plasma proteins and extensively binds to erythrocytes, resulting in an 8-fold higher concentration in RBCs than plasma.
Metabolism
It undergoes acetylation to form N-acetyl zonisamide and reduction to form the open ring metabolite, 2-sulfamoylacetyl phenol (SMAP).
Elimination
Renal Cl is about 3.5 mL/min. Elimination t ½ is about 63 h. It is excreted primarily in urine as parent drug and as glucuronide metabolite. About 62% is recovered in urine and about 3% in feces by day 10. Plasma Cl is about 0.3 to 0.35 mL/min/kg in patients not receiving enzyme-inducing antiepilepsy drugs.
Special Populations
Renal Function ImpairmentRenal Cl decreases with decreased renal function. Marked renal function impairment was associated with an increase in zonisamide AUC of 35%.
Indications and Usage
Adjunctive therapy in the treatment of partial seizures in adult epileptic patients.
Contraindications
Hypersensitivity to sulfonamides or zonisamide.
Dosage and Administration
Adults (over 16 yr)PO 100 mg/day initially, then the dose may be increased by 100 mg/day at intervals of at least 2 wk (max, 600 mg/day).
Storage/Stability
Store capsules at controlled room temperature (59° to 86°F). Protect from moisture and light.
Drug Interactions
Drugs that induce liver enzymes (eg, carbamazepine, phenobarbital, phenytoin)May increase the metabolism and Cl and decrease the t ½ of zonisamide.
Laboratory Test Interactions
None well documented.
Adverse Reactions
Because zonisamide is used as adjunctive therapy, figures obtained when zonisamide is added to concomitant antiepileptic drug therapy cannot be used to predict the frequency of adverse reactions in the course of usual medical practice. Except for potentially serious adverse reactions (eg, blood dyscrasias, CV events), which have been reported to occur in less than 1% of the patients, the following adverse reactions have been reported in at least 1% of zonisamide-treated patients:
Cardiovascular
Vascular insufficiency; atrial fibrillation; heart failure; ventricular extrasystoles.
CNS
Somnolence; dizziness; headache; agitation; irritability; fatigue; tiredness; difficulty concentrating; memory difficulty; mental slowing; ataxia; paresthesia; confusion; depression; insomnia; anxiety; nervousness; schizophrenic/schizophreniform behavior; speech abnormalities; difficult verbal expression; tremor; convulsion; abnormal gait; hyperesthesia; incoordination.
Dermatologic
Rash; pruritus.
EENT
Nystagmus; diplopia; taste perversion; amblyopia; tinnitus.
GI
Nausea; anorexia; vomiting; abdominal pain; diarrhea; dyspepsia; constipation; dry mouth.
Hematologic
Ecchymosis; leukopenia; anemia; lymphadenopathy; thrombocytopenia; microcytic anemia.
Hepatic
Increased ALT and AST.
Metabolic
Weight loss.
Respiratory
Rhinitis; pulmonary embolus; pharyngitis; increased cough.
Miscellaneous
Flu-like syndrome; asthenia; accidental injury.
Precautions
Pregnancy
Category C .
Lactation
Undetermined.
Children
Safety and efficacy in children younger than 16 yr not established.
Elderly
Select dose with caution, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and comorbidity.
Hypersensitivity
May present as fatal or severe reactions such as Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias.
Renal Function
Do not use if glomerular filtration rate is less than 50 mL/min.
Cognitive adverse reactions
Frequent CNS adverse reactions, including depression, psychosis, psychomotor slowing, somnolence, fatigue, and difficulty with concentration, speech, or language problems have occurred.
Kidney stones
May occur.
Oligohydrosis and hyperthermia in pediatric patients
Oligohydrosis, sometimes resulting in heat stroke and hospitalization, has been reported in pediatric patients.
Serious skin reactions
Consider discontinuing drug.
Sudden death
Sudden unexplained death has occurred.
Withdrawal seizures
Abrupt withdrawal may precipitate increased seizure frequency or status epilepticus; gradually discontinue or decrease dose.
Overdosage
Symptoms
CNS symptoms, bradycardia, hypotension, respiratory depression, coma.
Patient Information
- Advise patient to read the patient information leaflet before starting therapy and with each refill.
- Instruct patient to take exactly as prescribed and not to change the dose or discontinue unless advised by health care provider.
- Advise patient that dose is gradually increased no more often than every 2 wk until max benefit has been obtained.
- Advise patient to swallow capsule whole. Do not chew, crush, or break capsule.
- Advise patient that each dose may be taken without regard to meals but to take with food if stomach upset occurs.
- Warn patient that if a dose is missed not to double up on the next dose.
- Advise patient to increase fluid intake (6 to 8 glasses of water/day) while taking this medication to reduce the risk of kidney stones from forming.
- Advise patient that if medication needs to be discontinued it will be slowly withdrawn over a period of weeks unless safety concerns (eg, rash) require a more rapid withdrawal.
- Caution patient that drug may cause drowsiness and to use caution while driving or performing other tasks requiring mental alertness until tolerance is determined.
- Advise women of childbearing potential to use effective contraception during treatment with zonisamide.
- Advise women to notify health care provider if pregnant, planning to become pregnant, or breast-feeding.
- Instruct patient to contact health care provider immediately if developing a skin rash, sudden back pain, abdominal pain, blood in urine, fever, sore throat, oral ulcers, easy bruising, depression, unusual thoughts, speech or language problems, decreased sweating, or rise in body temperature.
- Instruct parent or caregiver to contact health care provider immediately if a child taking zonisamide is not sweating as usual with or without a fever.
- Instruct patient to inform health care provider if seizures become worse or if new types of seizures occur.
- Advise patient to inform health care provider if experiencing symptoms of depression.
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More Zonisamide resources:
Zonisamide - Includes detailed dosage instructions.
Seizures, Benign Essential Tremor, Parkinsonian Tremor
