TOPIRAMATE

TOPIRAMATe
(to-pir'a-mate)
Topamax
Classifications: gamma-aminobutyrate (gaba) enhancer; anticonvulsant;
Therapeutic: anticonvulsant
Pregnancy Category: C

Availability

25 mg, 100 mg, 200 mg tablets; 15 mg, 25 mg, 50 mg capsules

Action

Sulfamate-substituted monosaccharide with a broad spectrum of anticonvulsant activity. Exhibits sodium channel-blocking action, as well as enhancing the ability of GABA to induce a flux of chloride ions into the neurons, thus potentiating the activity of this inhibitory neurotransmitter (GABA).

Therapeutic Effect

Effectiveness indicated by a decrease in seizure activity. Effectively controls partial onset seizures in adults and children.

Uses

Adjunctive therapy for partial-onset seizures in adults and children age 2–16 y; generalized tonic-clonic seizures; migraine prophylaxis.

Unlabeled Uses

Cluster headache, bulimia nervosa, neuropathic pain, infantile spasms, weight loss.

Contraindications

Hypersensitivity to topiramate; metabolic acidosis; epilepsy, pregnancy (category C); children <2 y. Effect on labor and delivery is unknown.

Cautious Use

Moderate and severe renal impairment, hepatic impairment; COPD; severe pulmonary disease; lactation.

Route & Dosage

Partial-Onset Seizures
Adult: PO Initiate with 25 mg b.i.d., increase by 50 mg/wk to efficacy PO Maintenance Dose 200–400 mg/d divided b.i.d. (max: 1600 mg/d)
Child (2–16 y): PO Initiate with 1–3 mg/kg h.s. x 1 wk, then increase by 1–3 mg/kg/d in 2 divided doses q1–2wk to a target range of 5–9 mg/kg/d

Generalized Tonic-Clonic
Child: PO Initiate with 1–3 mg/kg h.s.; titrate to 6 mg/kg/d by the end of 8 wk

Migraine Prophylaxis
Adult: PO Initiate with 25 mg b.i.d., increase by 25 mg/wk to 200 mg/d or max tolerated dose

Renal Impairment
Cl_cr <70 mL/min: decrease dose by 50%

Administration

Oral

Make dosage increments of 50 mg at weekly intervals to the recommended dose, usually 400 mg/d.
Do not break tablets unless absolutely necessary because of bitter taste.
Store at 15°–30° C (59°–86° F) in a tightly closed container. Protect from light and moisture.

Adverse Effects (≥1%)

Body as a Whole: Fatigue, speech problems, weight loss; decreased sweating and hyperthermia in children; metabolic acidosis. CNS: Somnolence, dizziness, ataxia, psychomotor slowing, confusion, nystagmus, paresthesia, memory difficulty, difficulty concentrating, nervousness, depression, anxiety, tremor. GI: Anorexia. Special Senses: Angle closure glaucoma (rare).

Interactions

Drug: Increased CNS depression with alcohol and other cns depressants; may increase phenytoin concentrations; may decrease oral contraceptive, valproate concentrations; may increase risk of kidney stone formation with other carbonic anhydrase inhibitors. Carbamazepine, phenytoin, valproate may decrease topiramate concentrations. Herbal: Ginkgo may decrease anticonvulsant effectiveness.

Pharmacokinetics

Absorption: Rapidly absorbed from GI tract; 80% bioavailability. Peak: 2 h. Distribution: 13–17% protein bound. Metabolism: Minimally metabolized in the liver. Elimination: Primarily in urine. Half-Life: 21 h.

Nursing Implications

Assessment & Drug Effects

Monitor mental status and report significant cognitive impairment.
Lab tests: Periodically monitor CBC with Hgb and Hct.

Patient & Family Education

Do not stop drug abruptly; discontinue gradually to minimize seizures.
To minimize risk of kidney stones, drink at least 6–8 full glasses of water each day.
Exercise caution with potentially hazardous activities. Sedation is common, especially with concurrent use of alcohol or other CNS depressants.
Use or add barrier contraceptive if using hormonal contraceptives.
Be aware that psychomotor slowing and speech/language problems may develop while on topiramate therapy.
Report adverse effects that interfere with activities of daily living.

Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug

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