ZONISAMIDE

brands

Class

• Anticonvulsant, voltage-sensitive sodium channel modulator; T-type calcium channel modulator; structurally a sulfonamide

ZONISAMIDE commonly prescribed for

(Bold for FDA approved)

How ZONISAMIDE works

• Unknown

• Modulates voltage-sensitive sodium channels by an unknown mechanism

• Also modulates T-type calcium channels

• Facilitates dopamine and serotonin release

• Inhibits carbonic anhydrase

How long until ZONISAMIDE works

• Should reduce seizures by 2 weeks

• Onset of action as well as convincing therapeutic efficacy have not been demonstrated for uses other than adjunctive treatment of partial seizures

Notable Side Effects

• Sedation, depression, difficulty concentrating, agitation, irritability, psychomotor slowing, dizziness, ataxia

• Headache

• Nausea, anorexia, abdominal pain, vomiting

• Kidney stones

• Elevated serum creatinine and blood urea nitrogen

Life Threatening Side Effects

• Rare serious rash (Stevens–Johnson syndrome, toxic epidermal necrolysis) (sulfonamide)

• Rare oligohidrosis and hyperthermia (pediatric patients)

• Rare blood dyscrasias (aplastic anemia; agranulocytosis)

• Sudden hepatic necrosis

• Sudden unexplained deaths have occurred (unknown if related to zonisamide use)

• Rare activation of suicidal ideation and behavior (suicidality)

weight gain

unusual

sedation

common

What to do about ZONISAMIDE side effects

• Wait

• Wait

• Wait

• Take more of the dose at night to reduce daytime sedation

• Lower the dose

• Switch to another agent

usual dosage range

• 100–600 mg/day in 1–2 doses

Dosage Forms

• Capsule 25 mg, 50 mg, 100 mg

long term use

• Safe

• Consider periodic monitoring of blood urea nitrogen and creatinine

habit forming

• No

Renal Impairment

• Zonisamide is primarily renally excreted

• Use with caution

• May require slower titration

Hepatic Impairment

• Use with caution

• May require slower titration

Cardiac Impairment

• No specific recommendations

Elderly

• Some patients may tolerate lower doses better

• Elderly patients may be more susceptible to adverse effects

Children and Adolescents

• Cases of oligohidrosis and hyperthermia have been reported

• Not approved for use in children under age 16

• Use in children for the expert only, with close monitoring, after other options have failed

Pregnancy

• Effective June 30, 2015, the FDA requires changes to the content and format of pregnancy and lactation information in prescription drug labels, including the elimination of the pregnancy letter categories; the Pregnancy and Lactation Labeling Rule (PLLR or final rule) applies only to prescription drugs and will be phased in gradually for drugs approved on or after June 30, 2001

• Controlled studies have not been conducted in pregnant women

• Use in women of childbearing potential requires weighing potential benefits to the mother against the risks to the fetus

• Antiepileptic Drug Pregnancy Registry: 1-888-233-2334, www.aedpregnancyregistry.org

• Taper drug if discontinuing

• Seizures, even mild seizures, may cause harm to the embryo/fetus

• Lack of convincing efficacy for treatment of conditions other than epilepsy suggests risk/benefit ratio is in favor of discontinuing zonisamide during pregnancy for these indications

Breast Feeding

• Unknown if zonisamide is secreted in human breast milk, but all psychotropics are assumed to be secreted in breast milk

• Recommended either to discontinue drug or bottle feed

• If drug is continued while breast feeding, infant should be monitored for possible adverse effects

• If child becomes irritable or sedated, breast feeding or drug may need to be discontinued