RECENT MAJOR CHANGES

• Warnings and Precautions (5.3) [04/2009]
• Warnings and Precautions (5.8) [12/2009]

INDICATIONS AND USAGE

Topiramate is an antiepileptic (AED) agent indicated for:

• Monotherapy epilepsy: Initial monotherapy in patients ≥10 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).

DOSAGE AND ADMINISTRATION

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

DOSAGE FORMS AND STRENGTHS

• Tablets: 25 mg, 50 mg, 100 mg, and 200 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 topiramate as rapidly as possible (5.1).
• Oligohidrosis and hyperthermia: Monitor decreased sweating and increased body temperature, especially in pediatric patients (5.2).
• Suicidal behavior and ideation: Antiepileptic drugs increase the risk of suicidal behavior or ideation (5.3).
• Metabolic acidosis: Baseline and periodic measurement of serum bicarbonate is recommended. Consider dose reduction or discontinuation of topiramate if clinically appropriate (5.4).
• Cognitive/neuropsychiatric: Topiramate may cause cognitive dysfunction. Patients should use caution when operating machinery including automobiles. Depression and mood problems may occur in epilepsy and other populations (5.5).
• Withdrawal of AEDs: Withdrawal of topiramate should be done gradually (5.6).
• 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 hyperammonemia. Measure ammonia if encephalopathic symptoms occur (5.8).
• Kidney stones: Use with other carbonic anhydrase inhibitors, other drugs causing metabolic acidosis, or in patients on a ketogenic diet should be avoided (5.9).

ADVERSE REACTIONS

The most common (>5% more frequent than placebo or low dose topiramate 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, and confusion.

TO REPORT SUSPECTED ADVERSE REACTIONS, CONTACT TORRENT PHARMA INC. AT 1-269-544-2299 OR FDA AT 1-800-FDA-1088 OR WWW.FDA.GOV/MEDWATCH.

DRUG INTERACTIONS

Summary of antiepileptic drug (AED) interactions with topiramate (7.1).

• Concomitant administration of valproic acid and topiramate has been associated with hyperammonemia with and without encephalopathy (5.7).
• 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, a possible effect of topiramate (7.4)
• Lithium levels should be monitored when co-administered with high-dose topiramate (7.5)
• Other Carbonic Anhydrase Inhibitors: monitor the patient for the appearance or worsening of metabolic acidosis (7.6)