RECENT MAJOR CHANGES

INDICATIONS AND USAGE

TOPAMAX® is an antiepileptic (AED) agent indicated for:

• Monotherapy epilepsy: Initial monotherapy in patients ≥ 2 years of age with partial onset or primary generalized tonic-clonic seizures (1.1)
• Adjunctive therapy epilepsy: Adjunctive therapy for adults and pediatric patients (2 to 16 years of age) with partial onset seizures or primary generalized tonic-clonic seizures, and in patients ≥2 years of age with seizures associated with Lennox-Gastaut syndrome (LGS) (1.2)
• Migraine: Treatment for adults for prophylaxis of migraine headache (1.3)

DOSAGE AND ADMINISTRATION

See DOSAGE AND ADMINISTRATION, Epilepsy: Monotherapy and Adjunctive Therapy Use for additional details (2.1)

DOSAGE FORMS AND STRENGTHS

• Tablets: 25 mg, 50 mg, 100 mg, and 200 mg (3)
• Sprinkle Capsules: 15 mg and 25 mg (3)

CONTRAINDICATIONS

None.

WARNINGS AND PRECAUTIONS

• Acute myopia and secondary angle closure glaucoma: Untreated elevated intraocular pressure can lead to permanent visual loss. The primary treatment to reverse symptoms is discontinuation of TOPAMAX® as rapidly as possible (5.1)
• Oligohidrosis and hyperthermia: Monitor decreased sweating and increased body temperature, especially in pediatric patients (5.2)
• Metabolic acidosis: Baseline and periodic measurement of serum bicarbonate is recommended. Consider dose reduction or discontinuation of TOPAMAX® if clinically appropriate (5.3)
• Suicidal behavior and ideation: Antiepileptic drugs increase the risk of suicidal behavior or ideation (5.4)
• Cognitive/neuropsychiatric: TOPAMAX® may cause cognitive dysfunction. Patients should use caution when operating machinery including automobiles. Depression and mood problems may occur in epilepsy and migraine populations (5.5)
• Fetal Toxicity: TOPAMAX® use during pregnancy can cause cleft lip and/or palate (5.6)
• Withdrawal of AEDs: Withdrawal of TOPAMAX® should be done gradually (5.7)
• Hyperammonemia and encephalopathy associated with or without concomitant valproic acid use: Patients with inborn errors of metabolism or reduced mitochondrial activity may have an increased risk of hyper-ammonemia. Measure ammonia if encephalopathic symptoms occur (5.9)
• Kidney stones: Use with other carbonic anhydrase inhibitors, other drugs causing metabolic acidosis, or in patients on a ketogenic diet should be avoided (5.10)
• Hypothermia has been reported with and without hyperammonemia during topiramate treatment with concomitant valproic acid use (5.11)

ADVERSE REACTIONS

The most common (≥5% more frequent than placebo or low-dose TOPAMAX® in monotherapy) adverse reactions in controlled, epilepsy clinical trials were paresthesia, anorexia, weight decrease, fatigue, dizziness, somnolence, nervousness, psychomotor slowing, difficulty with memory, difficulty with concentration/attention, cognitive problems, confusion, mood problems, fever, infection, and flushing. The most common (≥5% more frequent than placebo) adverse reactions in controlled, migraine clinical trials were paresthesia and taste perversion (6) .

To report SUSPECTED ADVERSE REACTIONS, contact Janssen Pharmaceuticals, Inc. at 1-800-JANSSEN (1-800-526-7736) or FDA at 1-800-FDA-1088 or WWW.FDA.GOV/MEDWATCH.

DRUG INTERACTIONS

Summary of antiepileptic drug (AED) interactions with TOPAMAX® (7.1)

• Oral contraceptives: Decreased contraceptive efficacy and increased breakthrough bleeding should be considered, especially at doses greater than 200 mg/day (7.3)
• Metformin is contraindicated with metabolic acidosis, an effect of TOPAMAX® (7.4)
• Lithium levels should be monitored when co-administered with high-dose TOPAMAX® (7.5)
• Other carbonic anhydrase inhibitors: Monitor the patient for the appearance or worsening of metabolic acidosis (7.6)

USE IN SPECIFIC POPULATIONS

• Renal impairment: In renally impaired patients (creatinine clearance less than 70 mL/min/1.73 m2), one-half of the adult dose is recommended (2.4)
• Patients undergoing hemodialysis: Topiramate is cleared by hemodialysis. Dosage adjustment is necessary to avoid rapid drops in topiramate plasma concentration during hemodialysis (2.6)
• Pregnancy: Increased risk of cleft lip and/or palate. Pregnancy registry available (8.1)
• Nursing mothers: Caution should be exercised when administered to a nursing mother (8.3)
• Geriatric use: Dosage adjustment may be necessary for elderly with impaired renal function (8.5)