Indicated for:

Monotherapy Epilepsy:

• As initial monotherapy for the treatment of partial-onset or primary generalized tonic-clonic seizures in patients 6 years of age and older.

Adjunctive Therapy Epilepsy:

• As adjunctive therapy for the treatment of partial-onset seizures, primary generalized tonic-clonic seizures, and seizures associated with Lennox-Gastaut syndrome in patients 6 years of age and older.

Migraine:

• The preventive treatment of migraine in patients 12 years of age and older.

TROKENDI XR is contraindicated in patients with recent alcohol use (i.e.,within 6 hours prior to and 6 hours after TROKENDI XR use).

In patients with renal impairment (creatinine clearance less than 70 mL/min/1.73 m²), one-half of the usual adult dose of TROKENDI XR is recommended.

To avoid rapid drops in topiramate plasma concentration during hemodialysis, a supplemental dose of TROKENDI XR may be required. The actual adjustment should take into account 1) the duration of dialysis period, 2) the clearance rate of the dialysis system being used, and 3) the effective renal clearance of topiramate in the patient being dialyzed.

A syndrome consisting of acute myopia associated with secondary angle closure glaucoma has been reported in patients receiving topiramate. Elevated intraocular pressure of any etiology, if left untreated, can lead to serious sequelae including permanent vision loss.

Visual field defects (independent of elevated intraocular pressure) have been reported in clinical trials and in postmarketing experience in patients receiving topiramate.

Oligohydrosis (decreased sweating), resulting in hospitalization in some cases, has been reported in association with topiramate use. Caution should be used when TROKENDI XR is given with other drugs that predispose patients to heat-related disorders; these drugs include, but are not limited to, other carbonic anhydrase inhibitors and drugs with anticholinergic activity.

TROKENDI XR can cause hyperchloremic, non-anion gap, metabolic acidosis (i.e., decreased serum bicarbonate below the normal reference range in the absence of chronic respiratory alkalosis). Conditions or therapies that predispose patients to acidosis (such as renal disease, severe  respiratory disorders, status epilepticus, diarrhea, ketogenic diet or specific drugs) may be additive to the bicarbonate lowering effects of TROKENDI XR.

Chronic metabolic acidosis in pediatric patients may also reduce growth rates, which may decrease the maximal height achieved.

Antiepileptic drugs (AEDs) increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Patients treated with any AED, including TROKENDI XR for any indication should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior.

Immediate-release topiramate can cause, and therefore expected to be caused by TROKENDI XR, cognitive/neuropsychiatric adverse reactions. The most frequent of these can be classified into three general categories: 1) Cognitive-related dysfunction (e.g., confusion, psychomotor slowing, difficulty with concentration/attention, difficulty with memory, speech or language problems, particularly word-finding difficulties); 2) Psychiatric/behavioral disturbances (e.g.,depression or mood problems); and 3) Somnolence or fatigue.

Topiramate treatment can cause hyperammonemia with or without encephalopathy.

Topiramate increases the risk of kidney stones.

Topiramate is associated with an increased risk for bleeding.

Hypothermia, defined as a drop in body core temperature to < 35ºC (95ºF), has been reported in association with topiramate use with concomitant valproic acid (VPA) both in conjunction with and in the absence of hyperammonemia.

In patients with or without a history of seizures or epilepsy, antiepileptic drugs, including TROKENDI XR, should be gradually withdrawn to minimize the potential for seizures or increased seizure frequency.

Serious skin reactions (Stevens-Johnson Syndrome [SJS] and Toxic Epidermal Necrolysis [TEN]) have been reported in patients receiving topiramate.TROKENDI XR should be discontinued at the first sign of a rash, unless the rash is clearly not drug-related.

Concomitant administration of phenytoin or carbamazepine with topiramate resulted in a clinically significant decrease in plasma concentrations of topiramate when compared to topiramate given alone.

Concomitant administration of valproic acid and topiramate has been associated with hypothermia and hyperammonemia with and without encephalopathy.

Concomitant use of topiramate, a carbonic anhydrase inhibitor, with any other carbonic anhydrase inhibitor (e.g., zonisamide or acetazolamide) may increase the severity of metabolic acidosis and may also increase the risk of kidney stone formation.

Because of the potential of topiramate to cause CNS depression, as well as other cognitive and/or neuropsychiatric adverse reactions, TROKENDI XR should be used with extreme caution if used in  combination with alcohol and other CNS depressants.

The possibility of decreased contraceptive efficacy and increased breakthrough bleeding may occur in patients taking combination oral contraceptive products with TROKENDI XR. Patients taking estrogen containing contraceptives should be asked to report any change in their bleeding patterns. Contraceptive efficacy can be decreased even in the absence of breakthrough bleeding.

A decrease in the exposure of pioglitazone and its active metabolites were noted with the concurrent use of pioglitazone and immediate-release topiramate in a clinical trial.

An increase in systemic exposure of lithium following topiramate doses of up to 600 mg/day can occur. Lithium levels should be monitored when co-administered with high-dose TROKENDI XR.

Some patients may experience a large increase in amitriptyline concentration in the presence of TROKENDI XR and any adjustments in amitriptyline dose should be made according to the patients’ clinical response and not on the basis of plasma levels.

TROKENDI XR can cause fetal harm when administered to a pregnant woman. Data from pregnancy registries indicate that infants exposed to topiramate in utero have an increased risk for cleft lip and/or cleft palate (oral clefts) and for being small for gestational age.

Based on limited information, topiramate has also been associated with pre-term labor and premature delivery.

Topiramate is excreted in human milk.

GoToSource

• Use in patients under 6 years of age. GoToSource

• Obesity, bipolar disorder, eating disorders including bulimia nervosa, alcohol dependence, adjunctive treatment for schizophrenia, post-traumatic stress disorder and unipolar depression. GoToSource

• Tourette syndrome. GoToSource

• Cocaine dependence. GoToSource

• West syndrome. GoToSource

• Adjunctive treatment for obsessive-compulsive disorder. GoToSource

• Smoking cessation. GoToSource

• Idiopathic intracranial hypertension. GoToSource

• Weight loss. GoToSource

• Neuropathic pain. GoToSource

• Resistant major depressive disorder. GoToSource

Increased risk for atherosclerosis (hardening and narrowing of the arteries). GoToSource

Hypohidrosis (decreased sweating) and hyperthermia (elevated body temperature). GoToSource

Ocular syndrome with acute myopia, sudden vision loss and secondary angle closure glaucoma. GoToSource

Hyperchloremic (too much chloride in the blood) and metabolic acidosis (build up of acid in the body). GoToSource

Fetal harm including increased risk for cleft lip and/or cleft palate (oral clefts). GoToSource

Kidney stones. GoToSource

Bone disease (osteopenia, osteoporosis, osteomalacia) and hypothyroidism (underactive thyroid). GoToSource

Increased risk of suicidal thoughts and behavior. GoToSource

Depression. GoToSource

Severe intractable epistaxis (nosebleed). GoToSource

Mania. GoToSource

Lawsuits filed for birth defects.