topiramate

topiramate

(toe pie' rah mate)

Topamax

Pregnancy Category C

Drug class

Antiepileptic

Therapeutic actions

Mechanism of action not understood; antiepileptic effects may be due to the actions of blocking sodium channels in neurons with sustained depolarization; increasing GABA activity at receptors, thus potentiating the effects of this inhibitory neurotransmitter; and blocking excitatory neurotransmitters at neuron receptor sites.

Indications

·        Monotherapy for the treatment of patients > 10 yr with partial onset or primary generalized tonic-clonic seizures.

·        Adjunctive therapy for partial-onset seizure treatment in adults and children 2–16 yr

·        Adjunctive therapy for seizures associated with Lennox-Gastaut syndrome in adults and children > 2 yr

·        Adjunctive therapy for primary generalized tonic-clonic seizures in adults and children 2–16 yr

·        Prophylaxis of migraine headaches in adults

·        Unlabeled uses: Cluster headaches, infantile spasms, alcohol dependence, bulimia nervosa, weight loss

Contraindications and cautions

·        Contraindicated with hypersensitivity to any component of the drug.

·        Use cautiously with pregnancy (use only if benefits outweigh potential risks to fetus), lactation, renal or hepatic impairment, renal stones.

Available forms

Tablets—25, 50, 100, 200 mg; sprinkle capsules—15, 25 mg

Dosages

ADULTS > 17 YR

·        Migraine prophylaxis: Initially 25 mg PO in the evening for one wk; week two—25 mg PO bid, morning and evening; week three—25 mg PO in the morning and 50 mg PO in the evening; week four—50 mg PO morning and evening.

·        Seizure disorder: 200–400 mg PO daily in two divided doses. Therapy should be initiated at a dose of 25–50 mg/day titrated up in increments of 25–50 mg/wk.

PATIENTS > 10 YR

·        Monotherapy: 25 mg PO bid, titrating to maintenance dose of 200 mg PO bid over 6 wk. Week 1—25 mg bid; week 2—50 mg bid; week 3—75 mg bid; week 4—100 mg bid; week 5—150 mg bid; week 6—200 mg bid.

PEDIATRIC PATIENTS 2–16 YR

5–9 mg/kg/day PO in two divided doses. Therapy should be initiated at a nightly dose of 25 mg (or less, based on 1–3 mg/kg/day) for the first week. The dose may be titrated up by increments of 1–3 mg/kg/day (administered in two divided doses) at 1–2 wk intervals.

PATIENTS WITH RENAL OR HEPATIC IMPAIRMENT

For creatinine clearance < 70 mL/min, use one-half the usual dose; allow increased time to reach desired level. For patients with hepatic impairment, adjust slowly; monitor patient carefully.

Pharmacokinetics

Route	Onset	Peak
Oral	Rapid	2 hr

Metabolism: Hepatic; T_1/2: 21 hr

Distribution: Crosses placenta; enters breast milk

Excretion: Urine

Removed by hemodialysis: Supplemental dose may be needed.

Adverse effects

·        CNS: Ataxia, somnolence, dizziness, nystagmus, nervousness, anxiety, tremor, speech impairment, paresthesias, confusion, depression

·        GI: Nausea, dyspepsia, anorexia, vomiting

·        GU: Dysmenorrhea

·        Hematologic: Leukopenia

·        Respiratory: URI, pharyngitis, sinusitis

·        Other: Fatigue, rash, acute myopia and secondary angle-closure glaucoma (pain, visual disturbances, pupil dilation, redness, increased IOP), weight loss

Interactions

Drug-drug

·        Increased CNS depression if taken with alcohol or CNS depressants; use extreme caution

·        Increased risk of renal stone development with carbonic anhydrase inhibitors

·        Decreased effects of hormonal contraceptives with topiramate; suggest use of barrier contraceptives instead

·        Decreased serum levels if combined with phenytoin, carbamazepine

Nursing considerations

CLINICAL ALERT!

Name confusion has occurred between Topamax and Toprol-XL (metoprolol); use caution.

Assessment

·        History: Hypersensitivity to any component of the drug; pregnancy, lactation; renal or hepatic impairment; renal stones

·        Physical: Skin color, lesions; orientation, affect, reflexes, vision examination; R, adventitious sounds; LFTs, renal function tests

Interventions

·        WARNING: Reduce dosage; discontinue or substitute other antiepileptic gradually; abrupt discontinuation may precipitate status epilepticus.

·        WARNING: Stop the drug immediately and arrange for appropriate consultations at first sign of blurred vision, periorbital edema, or redness.

·        Administer with food if GI upset occurs.

·        Caution patient not to chew or break tablets because of bitter taste.

·        Have patient swallow sprinkle capsules whole or by carefully opening capsule and sprinkling onto a soft food. Swallow this immediately; do not allow it to be chewed.

·        Encourage patients with a history of renal stone development to maintain adequate fluid intake while using this drug.

·        Suggest using barrier contraceptives to patients taking this drug.

·        Arrange for consultation with appropriate epilepsy support groups as needed.

Teaching points

·        Take this drug exactly as prescribed. Do not break or chew tablets; they have a very bitter taste. Sprinkle capsule may also be swallowed whole. If using sprinkle capsules, open carefully and sprinkle onto soft food and swallow immediately; do not chew.

·        Do not discontinue this drug abruptly or change dosage except on the advice of your health care provider.

·        Arrange for frequent check-ups to monitor your response to this drug. It is very important that you keep all appointments for check-ups.

·        Wear a medical alert bracelet at all times so that any emergency medical personnel will know that you have epilepsy and are taking antiepileptic medication.

·        Avoid using alcohol while you are taking this drug; serious sedation could occur.

·        You may experience these side effects: Drowsiness, dizziness, sleepiness (avoid driving or performing other tasks that require alertness; symptoms may occur initially but usually disappear with continued therapy); vision changes (avoid performing tasks that require visual acuity); GI upset (take drug with food; eat frequent small meals).

·        Report fatigue, vision changes, speech problems, personality changes.

Adverse effects in Italic are most common; those in Bold are life-threatening.