Topamax

Initial monotherapy for the treatment of partial-onset or primary generalized tonic-clonic seizures in patients ≥2 yr. Adjunctive therapy for the treatment of partial-onset seizures, primary generalized tonic-clonic seizures, & seizures associated w/ Lennox-Gastaut syndrome in patients ≥2 yr. Preventive treatment of migraine in adults.

Epilepsy (monotherapy) Adult & ped patient ≥10 yr 400 mg/day in 2 divided doses achieved by titration. Wk 1: 25 mg morning dose + 25 mg evening dose. Wk 2: 50 mg morning dose + 50 mg evening dose. Wk 3: 75 mg morning dose + 75 mg evening dose. Wk 4: 100 mg morning dose + 100 mg evening dose. Wk 5: 150 mg morning dose + 150 mg evening dose. Wk 6: 200 mg morning dose + 200 mg evening dose. Ped patient 2-9 yr Initially 25 mg/day nightly for the 1st wk, increased to 50 mg/day (25 mg bd) in the 2nd wk based upon tolerability. Increase dose by 25-50 mg/day each subsequent wk as tolerated. Attempt titration to min maintenance dose over 5-7 wk of total titration period. Attempt additional titration to higher dose (up to max maintenance dose) at 25-50 mg/day wkly increments based upon tolerability & clinical response. Total daily maintenance dose (min-max): Patient weighing >38 kg 250-400 mg/day in 2 equally divided doses, 32-38 kg 250-350 mg/day in 2 equally divided doses, 23-31 kg 200-350 mg/day in 2 equally divided doses, 12-22 kg 200-300 mg/day in 2 equally divided doses, ≤11 kg 150-250 mg/day in 2 equally divided doses. Epilepsy (adjunctive therapy) Adult ≥17 yr Initiate at 25-50 mg/day, followed by titration to effective dose in increments of 25-50 mg/day every wk. Total daily dose: 200-400 mg/day in 2 divided doses (partial-onset seizures or seizures associated w/ Lennox-Gastaut syndrome); 400 mg/day in 2 divided doses (primary generalized tonic-clonic seizures). Ped patient 2-16 yr Begin titration at ≤25 mg/day nightly for the 1st wk, then increase dose at 1- or 2-wk intervals by increments of 1-3 mg/kg/day in 2 divided doses to achieve optimal clinical response. Total daily dose: 5-9 mg/kg/day in 2 divided doses. Max total daily dose: 400 mg/day. Migraine Adult 100 mg/day in 2 divided doses achieved by titration. Wk 1: 25 mg evening dose. Wk 2: 25 mg morning dose + 25 mg evening dose. Wk 3: 25 mg morning dose + 50 mg evening dose. Wk 4: 50 mg morning dose + 50 mg evening dose.

May be taken with or without food: Do not break.

Risk of acute myopia & secondary angle closure glaucoma syndrome; visual field defects; oligohidrosis & hyperthermia; hyperchloremic, non-anion gap, metabolic acidosis; suicidal behavior & ideation; cognitive/neuropsychiatric adverse reactions; decreased bone mineral density; -ve effects on growth (height & wt); serious skin reactions (SJS & TEN); hyperammonemia w/ or w/o encephalopathy; kidney stones. Consider discontinuation if visual problems occur at any time during treatment. Closely monitor for evidence of decreased sweating & increased body temp. Measure baseline & periodic serum bicarbonate during treatment. Monitor for emergence or worsening of depression, suicidal thoughts or behavior, &/or any unusual changes in mood or behavior. Rapid titration rate & higher initial dose were associated w/ higher incidences of cognitive-related dysfunction. Gradually w/draw treatment to minimize potential for seizures or increased seizure frequency in patients w/ or w/o history of seizures or epilepsy. Carefully monitor growth (height & wt) of childn receiving prolonged therapy. Discontinue treatment at the 1st sign of rash (unless rash is clearly not drug-related), & do not resume use if signs or symptoms suggest SJS/TEN. Hydration is recommended to reduce new stone formation. Caution when given w/ other drugs that predispose patients to heat-related disorders (eg, other carbonic anhydrase inhibitors & drugs w/ anticholinergic activity). Topiramate treatment or interaction of concomitant topiramate & valproic acid treatment may exacerbate existing defects or unmask deficiencies in patients w/ inborn errors of metabolism or reduced hepatic mitochondrial activity. Reports of hypothermia in association w/ concomitant use of topiramate & valproic acid both in conjunction w/ hyperammonemia & in the absence of hyperammonemia. Avoid concomitant use w/ any other drug producing metabolic acidosis. Avoid use in patients on ketogenic diet. ½ of usual adult dose is recommended in patients w/ renal impairment (CrCl <70 mL/min/1.73 m²). Supplemental dose may be required to avoid rapid drops in plasma conc during hemodialysis. Can cause fetal harm when administered to a pregnant woman. Infants exposed in utero have an increased risk of major congenital malformations (eg, oral clefts) & of being small for gestational age. Development of topiramate-induced metabolic acidosis in the mother &/or in the fetus might affect the fetus' ability to tolerate labor. Possible occurrence of transient metabolic acidosis following birth. Associated w/ pre-term labor & premature delivery. Use during pregnancy only if potential benefit outweighs potential risk. Women of childbearing potential should use effective contraception. Consider developmental & health benefits of breastfeeding along w/ mother's clinical need for treatment & any potential adverse effects on breastfed infant. Not approved for treatment of epilepsy in ped patients <2 yr.

Epilepsy (monotherapy): Adult ≥16 yr: Paresthesia, wt loss, anorexia. Ped patient 6-15 yr: Fever, wt loss. Epilepsy (adjunctive therapy): Adult ≥16 yr: Dizziness, speech disorders/related speech problems, somnolence, nervousness, psychomotor slowing, abnormal vision. Ped patient 2-15 yr: Fatigue, somnolence. Migraine: Paresthesia, anorexia, wt loss, taste perversion, diarrhea, difficulty w/ memory, hypoesthesia, nausea.

Decreased plasma conc w/ phenytoin or carbamazepine. Concomitant administration w/ valproic acid has been associated w/ hypothermia & hyperammonemia w/ & w/o encephalopathy. Increased severity of metabolic acidosis & increased risk of kidney stone formation w/ other carbonic anhydrase inhibitors (eg, zonisamide or acetazolamide). Extreme caution if used in combination w/ alcohol & other CNS depressants. Possibility of decreased contraceptive efficacy & increased breakthrough bleeding in combination w/ contraceptives. Increased C_max & AUC w/ hydrochlorothiazide. Decreased exposure of pioglitazone & its active metabolites. Increased systemic exposure of lithium. Increased conc of amitriptyline.

Anticonvulsants / Antimigraine Preparations

N03AX11 - topiramate ; Belongs to the class of other antiepileptics.

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