topiramate
Topamax

Available forms
Available by prescription only
Capsules: 15 mg, 25 mg
Tablets: 25 mg, 100 mg, 200 mg

Indications and dosages
 Adjunctive therapy for partial seizures, primary generalized tonic-clonic seizures, or Lennox-Gastaut syndrome. Adults: Initially, 25 to 50 mg daily followed by adjustments of 25 to 50 mg weekly.
≡ Dosage adjustment. Adjust up to maximum daily dose of 400 mg in two divided doses. Adjustment schedule is as follows.

Week A.M. dose P.M. dose 1 None 50 mg 2 50 mg 50 mg 3 50 mg 100 mg 4 100 mg 100 mg 5 100 mg 150 mg 6 150 mg 150 mg 7 150 mg 200 mg 8 200 mg 200 mg

Children ages 2 to 16: 5 to 9 mg/kg P.O. daily in two divided doses. Dosage adjustment should begin at 1 to 3 mg/kg daily for 1 week. Then increase at 1- to 2-week intervals by 1 to 3 mg/kg daily to achieve optimal clinical response. Dosage adjustment should be guided by clinical outcome.
≡ Dosage adjustment. For patients with moderate to severe renal impairment, reduce dose by 50%. A supplemental dose may be required during hemodialysis.

Pharmacodynamics
Anticonvulsant action: Mechanism of action is unknown. Thought to block action potential, suggestive of a sodium channel-blocking action. Drug may potentiate activity of gamma-aminobutyric acid (GABA) and antagonize the ability of kainate to activate the kainate/AMPA subtype of excitatory amino acid (glutamate) receptor. Topiramate also has weak carbonic anhydrase inhibitor activity, which is unrelated to its anticonvulsant properties.

Pharmacokinetics
Absorption: Rapidly absorbed. Relative bioavailability of drug is about 80% compared with a solution and isn’t affected by food.
Distribution: Plasma levels increase proportionately with dose; mean elimination half-life is 21 hours. Steady state is reached in 4 days in patients with normal renal function. Drug is 13% to 17% bound to plasma proteins.
Metabolism: Not extensively metabolized.
Excretion: About 70% of an administered dose is eliminated unchanged in urine. Mean plasma half-life is 21 hours.

Contraindications and precautions
Contraindicated in patients hypersensitive to drug or its components.

Interactions
Drug-drug. Carbamazepine, phenytoin: Decreases topiramate levels. Monitor patient closely.
Carbonic anhydrase inhibitors, such as acetazolamide and dichlorphenamide: May increase risk of renal stone formation. Avoid use together.
CNS depressants: Causes risk of topiramate-induced CNS depression and other adverse cognitive and neuropsychiatric events. Use together cautiously.
Hormonal contraceptives: Decreases contraceptive effect. Advise patient to use another method of contraception.
Phenobarbital, primidone, valproic acid: Increases phenytoin levels. Monitor patient closely.
Drug-lifestyle. Alcohol use: Causes CNS depression and other adverse cognitive and neuropsychiatric events. Discourage alcohol use.

Adverse reactions
CNS: fatigue; malaise; fever; abnormal coordination; agitation; apathy; asthenia; ataxia; confusion; depression; difficulty with concentration, attention, language, and memory; dizziness; emotional lability; euphoria; generalized tonic-clonic seizures; hallucination; hyperkinesia; hypertonia; hypoanesthesia; hypokinesia; insomnia; mood problems; nervousness; paresthesia; personality disorder; psychomotor slowing; psychosis; somnolence; speech disorders; stupor; suicide attempts;tremor; vertigo.
CV: edema, chest pain, palpitations.
EENT: abnormal vision, conjunctivitis, taste perversion, diplopia, eye pain, epistaxis, hearing or vestibular problems, pharyngitis, sinusitis, tinnitus, nystagmus.
GI: abdominal pain, anorexia, constipation, diarrhea, dry mouth, dyspepsia, flatulence, gastroenteritis, gingivitis, nausea, vomiting.
GU: amenorrhea, dysuria, dysmenorrhea, leukorrhea, hematuria, impotence, intermenstrual bleeding, menstrual disorder, menorrhagia, micturition frequency, renal calculus, urinary incontinence, urinary tract infection, vaginitis.
Hematologic: anemia, leukopenia.
Metabolic: weight changes.
Musculoskeletal: back pain, leg pain, myalgia, gait abnormality.
Respiratory: bronchitis, cough, dyspnea, upper respiratory tract infection.
Skin: acne, alopecia, aggressive reaction, increased sweating, pruritus, rash.
Other: body odor, flulike symptoms, hot flashes.

Effects on lab test results
• May increase AST and ALT levels.
• May decrease hemoglobin and WBC count.

Overdose and treatment
In acute overdose after recent ingestion, institute gastric lavage or emesis. Activated charcoal isn’t recommended. Institute supportive treatment. Hemodialysis is an effective means of removing drug.

Special considerations
• Because of their bitter taste, tablets shouldn’t be broken.
• Capsules can be opened and contents sprinkled on soft food.
 ALERT Don’t confuse Topamax (topiramate) with Toprol XL (metoprolol).
• If necessary, stop anticonvulsants gradually to minimize the increased risk of seizures.
• Discontinue drug if an ocular adverse event occurs, characterized by acute myopia and secondary angle-closure glaucoma.
• Monitor patient for seizures.
Breast-feeding patients
• It isn’t known whether drug appears in breast milk. Use cautiously in breast-feeding women.
Pediatric patients
• Safety and efficacy in children younger than age 2 haven’t been established.
Geriatric patients
• No age-related problems have been seen in elderly patients; however, age-related renal abnormalities should be considered.

Patient education
• Carefully review dosing schedule with patient to avoid under- or overmedication.
• Tell patient to maintain adequate fluid intake during therapy because of potential to form renal stones.
• Advise patient to avoid hazardous activities until effects of drug are known. • Tell patient to report changes in vision immediately.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use