Topiramate
Topiramate (Topamax)
Topiramate
(toh-PYRE-ah-mayt)
Pregnancy Category: C Topamax (Rx)

Classification: Anticonvulsant, miscellaneous

See Also: See also Anticonvulsants.

Action/Kinetics: Precise mechanism not known. The following effects may contribute to the anticonvulsant activity. (1) Action potentials seen repetitively by sustained depolarization of neurons are blocked in a time-dependent manner, suggesting an effect to block sodium channels. (2) Increases the frequency at which GABA activates GABA_A receptors, thus enhancing the ability of GABA to cause a flux of chloride ions into neurons (i.e., enhanced effect of the inhibitory transmitter, GABA_A). (3) Antagonizes the ability of kainate to activate the kainate/AMPA subtype of excitatory amino acid aspartate, thus reducing the excitatory effect. Rapidly absorbed; peak plasma levels: About 2 hr. t1/2, elimination: 21 hr. Steady state is reached in about 4 days in those with normal renal function. Excreted mostly unchanged in the urine.

Uses: Add on treatment for partial onset seizures in adults and children, 2-16 years. Add on treatment for primary generalized tonic-clonic seizures in adults and children, 2-16 years old.

Contraindications: Lactation.

Special Concerns: Use with caution in impaired hepatic and renal function. Safety and efficacy have not been determined in children less than 2 years old.

Side Effects: Note: Side effects with an incidence of 0.1% or greater are listed. CNS: Psychomotor slowing, including difficulty with concentration and speech or language problems. Somnolence, fatigue, dizziness, ataxia, nystagmus, paresthesia, nervousness, difficulty with memory, tremor, confusion, depression, abnormal coordination, agitation, mood problems, aggressive reaction, hypoesthesia, apathy, emotional lability, depersonalization, hypokinesia, vertIgo, stupor, clonic/tonic seizures hyperkinesia, hypertonia, insomnia, personality disorder, impotence, hallucinations, euphoria, psychosis, decreased libido, suicide attempt hyporeflexia, neuropathy, migraine, apraxia, hyperesthesia, dyskinesia, hyperreflexia, dysphonia, scotoma, dystonia, coma, encephalopathy, upper motor neuron lesion, paranoid reaction, delusion, paranoia, delirium, abnormal dreaming, neuroses. GI: Nausea, dyspepsia, anorexia, abdominal pain, constipation, dry mouth, gingivitis, halitosis, diarrhea, vomiting, fecal incontinence, flatulence, gastroenteritis, gum hyperplasia, hemorrhoids, increased appetite, tooth caries, stomatitis, dysphagia, melena, gastritis, increased saliva, hiccough, gastroesophageal reflux, tongue edema, esophagitis, gall bladder disorder, gingival bleeding. CV: Palpitation, hypertension, hypotension, postural hypotension, AV block, bradycardia, bundle branch block, angina pectoris, vasodilation. Body as a whole: Asthenia, back pain, chest pain, flu-like symptoms, leg pain, hot flashes, body odor, edema, rigors, fever, malaise, syncope, enlarged abdomen. Respiratory: URI, pharyngitis, sinusitis, dyspnea, coughing, bronchitis, asthma, bronchospasm, pulmonary embolism. Dermatologic: Acne, alopecia, dermatitis, nail disorder, folliculitis, dry skin, urticaria, skin discoloration, eczema, photosensitivity reaction, erythematous rash, seborrhea, decreased sweating, abnormal hair texture, facial edema. GU: Breast pain, renal stone formation, dysmenorrhea, menstrual disorder, hematuria, intermenstrual bleeding, leukorrhea, menorrhagia, vaginitis, amenorrhea, UTI, micturition frequency, urinary incontinence, dysuria, renal calculus, ejaculation disorder, breast discharge, urinary retention, renal pain, nocturia, albuminuria, polyuria, oliguria. Musculoskeletal: Arthralgia, muscle weakness, arthrosis, osteoporosis, myalgia, leg cramps. Metabolic: Increased weight, decreased weight, dehydration, xeropthalmia. Hematologic: Anemia, leukopenia, lymphadenopathy, eosinophilia, lymphopenia, granulocytopenia, lymphocytosis, thrombocytothemia, purpura, thrombocytopenia. Dermatologic: Rash, pruritus, increased sweating, flushing. Ophthalmic: Diplopia, abnormal vision, eye pain, conjunctivitis, abnormal accommodation, photophobia, abnormal lacrimation, strabismus, color blindness, myopia, mydriasis, ptosis, visual field defect. Miscellaneous: Decreased hearing, epistaxis, taste perversion, tinnitus, taste loss, parosmia, goiter, basal cell carcinoma.

Laboratory Test Alterations: AST, ALT, alkaline phosphatase, creatinine. Hypokalemia, hypocalcemia, hyperlipemia, acidosis, hyperglycemia, hyperchloremia.

Overdose Management: Symptoms: See side effects. Treatment: Gastric lavage or induction of emesis if ingestion is recent. Supportive treatment. Hemodialysis.

Drug Interactions: Alcohol / CNS depression and cognitive and neuropsychiatric side effects Carbamazepine / Topiramate plasma levels Carbonic anhydrase inhibitors / Risk of renal stone formation CNS depressants / CNS depression and cognitive and neuropsychiatric side effects Oral contraceptives / Effect of oral contraceptives Phenytoin / Topiramate plasma levels and phenytoin plasma levels Valproic acid / Plasma levels of both topiramate and valproic acid

How Supplied: Sprinkle Capsule. Tablets: 25 mg, 100 mg, 200 mg.

Dosage
•Tablets Adjunctive therapy for treatment of partial onset seizures.
Adults, initial: 50 mg/day; then titrate to an effective dose of 400 mg/day in 2 divided doses. Titrate by adding 50 mg each week for eight weeks, until the dose is 400 mg/day. Doses greater than 400 mg/day have not been shown to improve the response. If C_CR < 70 mL/1.73 m², use one half of the usual adult dose. Children, 2-16 years: 5-9 mg/kg/day in two divided doses.