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 Clcr <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.

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