topiramate

topiramate /to·pi·ra·mate/ (to-pi´rah-mat) a substituted monosaccharide used as an anticonvulsant in the treatment of partial seizures.

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topiramate

Topamax

Pharmacologic class: Sulfamate-substituted monosaccharide derivative

Therapeutic class: Anticonvulsant

Pregnancy risk category C

Action

Blocks sodium channels, enhancing the action of gamma-amino butyrate (a neurotransmitter); also inhibits amino acid excitatory receptors

Availability

Sprinkle capsules: 15 mg, 25 mg

Tablets: 25 mg, 50 mg, 100 mg, 200 mg

⊘Indications and dosages

➣ Adjunct in partial-onset seizures, primary generalized tonic-clonic seizures, and seizures associated with Lennox-Gastaut syndrome

Adults and children older than age 17: Initially, 25 to 50 mg P.O. daily. To achieve adequate response, may increase by 25 to 50 mg weekly, up to 200 mg b.i.d.

Children ages 2 to 16: Initially, less than 25 mg P.O. daily; increase at 1- or 2-week intervals in increments of 1 to 3 mg/kg/day given in two divided doses to achieve adequate response.

➣ Migraine prophylaxis

Adults: Dosage titrated to 100 mg P.O. daily as follows: 25 mg/day during week 1, 25 mg b.i.d. during week 2, 25 mg in morning and 50 mg in evening during week 3, and 50 mg b.i.d. during week 4

Dosage adjustment

• Renal impairment

Off-label uses

• Cluster headaches
• Infantile spasms
• Mood stabilization

Contraindications

• Hypersensitivity to drug or its components

Precautions

Use cautiously in:
• renal or hepatic impairment, dehydration, urolithiasis, glaucoma, myopia
• pregnant or breastfeeding patients.
• children younger than age 2 (safety and efficacy not established).

Administration

• Give without regard to meals.
• Don't break tablets, because of bitter taste.
• Administer capsules either whole or by opening capsule carefully and sprinkling entire contents into small amount of soft food. Instruct patient to swallow mixture immediately without chewing sprinkles.
☞ Don't stop therapy suddenly. Dosage must be tapered.

Route	Onset	Peak	Duration
P.O.	Unknown	2 hr	12 hr

Adverse reactions

CNS: dizziness, drowsiness, fatigue, malaise, poor memory and concentration, nervousness, psychomotor slowing, speech and language problems, aggressive reaction, agitation, anxiety, confusion, depression, irritability, ataxia, paresthesia, hyperesthesia, tremor, suicide attempt, increased seizures

EENT: abnormal vision, diplopia, nystagmus, acute myopia, secondary angle-closure glaucoma, decreased hearing, rhinitis, sinusitis, epistaxis, pharyngitis

GI: nausea, constipation, abdominal pain, dry mouth, gastroenteritis, increased salivation (in children), anorexia

GU: renal calculi, urinary incontinence, leukorrhea

Hematologic: purpura, leukopenia, thrombocytopenia

Metabolic: hypocalcemia, hyperchloremia, hypernatremia, hyponatremia, hypophosphatemia, hypoglycemia

Musculoskeletal: myalgia, back pain, leg pain

Respiratory: pneumonia

Skin: rash, skin disorder, alopecia, dermatitis, hypertrichosis, eczema, seborrhea, skin discoloration

Other: altered taste, weight loss, thirst, fever, flulike symptoms, hot flashes, infection, edema, allergic reaction

Interactions

Drug-drug. Carbamazepine: decreased topiramate blood level and effects

Carbonic anhydrase inhibitors (such as acetazolamide): increased risk of renal calculi

CNS depressants: increased risk of CNS depression and other adverse cognitive or neuropsychiatric reactions

Hormonal contraceptives: decreased contraceptive efficacy

Phenytoin: increased phenytoin blood level and effects, decreased topiramate blood level and effects

Valproic acid: decreased effects of both drugs

Drug-diagnostic tests. ALT, AST: increased levels

Calcium, cholesterol, glucose, phosphate: decreased levels

Sodium: increased or decreased level

Drug-behaviors. Alcohol use: increased CNS depression

Patient monitoring

☞ Monitor seizure type and pattern. Report new seizure types or worsening seizure pattern.
• Assess neurologic status closely. Report significant adverse reactions.
☞ Watch for and immediately report signs and symptoms of depression or suicidal ideation.
• Monitor fluid intake and output. Report indications of urinary tract infection, urinary incontinence, or renal calculi.
☞ Monitor vision. If patient becomes acutely nearsighted with symptoms of angle-closure glaucoma (cloudy vision, eye pain), stop drug and contact prescriber right away.

Patient teaching

• Tell patient he may take with or without food.
• Caution patient not to crush or break tablets.
• If patient takes capsules, tell him he may open them, sprinkle contents onto small amount of soft food, and consume immediately. Tell him not to store this mixture.
☞ Caution patient not to stop drug suddenly. Dosage must be tapered.
• Instruct patient to drink plenty of fluids to reduce risk of kidney stones.
☞ Tell patient drug may cause new seizure types or worsen seizure pattern. Instruct him to report these developments immediately.
☞ Instruct patient (and significant other as appropriate) to immediately report signs or symptoms of depression or suicidal thoughts.
☞ Advise patient to immediately report vision changes, especially nearsightedness, cloudy vision, or eye pain.
• Caution patient not to drive or perform other hazardous activities.
• Tell patient not to drink alcohol during drug therapy.
• Advise female patient to notify prescriber of suspected pregnancy.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, and behaviors mentioned above.