TOPIRAMATE

brands

Class

• Anticonvulsant, voltage-sensitive sodium channel modulator

TOPIRAMATE commonly prescribed for

(Bold for FDA approved)

How TOPIRAMATE works

• Blocks voltage-sensitive sodium channels by an unknown mechanism

• Inhibits release of glutamate

• Potentiates activity of GABA

• Carbonic anhydrase inhibitor

How long until TOPIRAMATE works

• Should reduce seizures by 2 weeks

• Not clear that it has mood-stabilizing properties, but some bipolar patients may respond and, if so, it may take several weeks to months to optimize an effect on mood stabilization

Notable Side Effects

• Sedation, asthenia, dose-dependent dizziness, ataxia, dose-dependent parasthesia, nystagmus, nervousness, tremor

• Dose-dependent nausea, appetite loss, weight loss

• Visual field defects

• Problems concentrating, confusion, memory problems, psychomotor retardation, language problems, speech problems

• Mood problems, dose-dependent fatigue, taste perversion

Life Threatening Side Effects

• Metabolic acidosis

• Kidney stones

• Hyperammonemia with or without encephalopathy has been reported (may be dose-related; may be more likely with concomitant valproate use)

• Secondary angle-closure glaucoma

• Rare severe dermatologic reactions (purpura, Stevens–Johnson syndrome)

• Oligohidrosis and hyperthermia (more common in children)

• Sudden unexplained deaths have occurred in epilepsy (unknown if related to topiramate use)

• Rare activation of suicidal ideation and behavior (suicidality)

weight gain

unusual

sedation

common

What to do about TOPIRAMATE side effects

• Wait

• Wait

• Wait

• Take at night to reduce daytime sedation

• Increase fluid intake to reduce the risk of kidney stones

• Switch to another agent

usual dosage range

• Adults, immediate-release: 200–400 mg/ day in 2 divided doses for epilepsy; 50–300 mg/day for adjunctive treatment of bipolar disorder

• Adults, extended-release: 200–400 mg/ day as adjunct for partial-onset seizures; 400 mg/day as adjunct for primary generalized tonic–clonic seizures; 400 mg/ day as monotherapy for seizures

• Migraine: initial 25 mg/night for the first week; increase weekly in 25 mg increments; approved dose 100 mg/day in 2 divided doses

Dosage Forms

• Tablet 25 mg, 50 mg, 100 mg, 200 mg

• Sprinkle capsule 15 mg, 25 mg

• Extended-release capsule 25 mg, 50 mg, 100 mg, 150 mg, 200 mg

• Oral solution 25 mg/mL

long term use

• Probably safe

• Periodic monitoring of serum bicarbonate levels may be required

habit forming

• No

Renal Impairment

• Topiramate is renally excreted, so the dose should be lowered by half

• Can be removed by hemodialysis; patients receiving hemodialysis may require supplemental doses of topiramate

Hepatic Impairment

• Reduce dose and increase intervals between dosing

Cardiac Impairment

• Drug should be used with caution

Elderly

• Elderly patients may be more susceptible to adverse effects

Children and Adolescents

• Approved for use in adolescents ages 12 and older for migraine prophylaxis

• Approved for use in children age 2 and older for treatment of partial-onset seizures (adjunct and monotherapy), primary generalized tonic–clonic seizures (adjunct and monotherapy), and seizures associated with Lennox–Gastaut syndrome (adjunct only)

• Clearance is increased in pediatric patients

• Seizures (immediate-release, ages 2–16): initial 1–3 mg/kg per day at night; after 1 week increase by 1–3 mg/kg per day every 1–2 weeks with total daily dose administered in 2 divided doses; recommended dose generally 5–9 mg/kg per day in 2 divided doses

• Seizures (extended release, monotherapy, ages 2 through 9): initial 25 mg once at night for the first week; titrate over 5 to 7 weeks; recommended dose is based on weight

• Seizures (extended-release, adjunct): initial 25 mg once nightly (1–3 mg/kg/night) for first week; increase at 1- or 2-week intervals by increments of 1–3 mg/kg/night; recommended dose 5–9 mg/kg/night

• Effectiveness was not demonstrated in infants/toddlers 1 to 24 months of age with refractory partial-onset seizures; some adverse effects/toxicities not observed in older patients did occur

Pregnancy

• Increased risk of cleft lip/palate

• Increased risk of being small for gestational age

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

• Hypospadias has occurred in some male infants whose mothers took topiramate during pregnancy

• Lack of convincing efficacy for treatment of bipolar disorder suggests risk/benefit ratio is in favor of discontinuing topiramate in bipolar patients during pregnancy

• For bipolar patients, topiramate should generally be discontinued before anticipated pregnancies

• Antiepileptic Drug Pregnancy Registry: (888) 233–2334 or http://www .aedpregnancyregistry.org

• Taper drug if discontinuing

• For bipolar patients, given the risk of relapse in the postpartum period, mood stabilizer treatment, especially with agents with better evidence of efficacy than topiramate, should generally be restarted immediately after delivery if patient is unmedicated during pregnancy

• Atypical antipsychotics may be preferable to topiramate if treatment of bipolar disorder is required during pregnancy

• Bipolar symptoms may recur or worsen during pregnancy and some form of treatment may be necessary

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

Breast Feeding

• Some drug is found in mother’s breast milk

• Recommended either to discontinue drug or formula feed

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

• If infant shows signs of irritability or sedation, drug may need to be discontinued

• Bipolar disorder may recur during the postpartum period, particularly if there is a history of prior postpartum episodes of either depression or psychosis

• Relapse rates may be lower in women who receive prophylactic treatment for postpartum episodes of bipolar disorder

• Atypical antipsychotics and anticonvulsants such as valproate may be safer and more effective than topiramate during the postpartum period when treating nursing mother with bipolar disorder