Topiramate - Warnings and Precautions

5 WARNINGS AND PRECAUTIONS Acute myopia and secondary angle closure glaucoma: can lead to permanent visual loss; discontinue topiramate extended-release capsules as soon as possible Visual field defects: consider discontinuation of topiramate extended-release capsules Oligohydrosis and hyperthermia: monitor decreased sweating and increased body temperature, especially in pediatric patients Metabolic acidosis: baseline and periodic measurement of serum bicarbonate is recommended; consider dose reduction or discontinuation of topiramate extended-release capsules if clinically appropriate Suicidal behavior and ideation: antiepileptic drugs increase the risk of suicidal behavior or ideation Cognitive/neuropsychiatric adverse reactions: use caution when operating machinery including cars; depression and mood problems may occur Fetal toxicity: use during pregnancy can cause major congenital malformations, including but not limited to cleft lip and/or palate, and being small for gestational age Withdrawal of AEDs: withdraw topiramate extended-release capsules gradually Decrease in Bone Mineral Density: has been shown to decrease bone mineral density and bone mineral content in pediatric patients Negative effects on growth (height and weight): may slow height increase and weight gain; carefully monitor children receiving prolonged therapy Serious skin reactions: If SJS or TEN is suspected, discontinue topiramate extended-release capsules Hyperammonemia/encephalopathy: measure ammonia if encephalopathic symptoms occur Kidney stones: avoid use with other carbonic anhydrase inhibitors, other drugs causing metabolic acidosis, or in patients on a ketogenic diet Hypothermia has been reported with and without hyperammonemia during topiramate treatment with concomitant valproic acid use 5.1 Acute Myopia and Secondary Angle Closure Glaucoma Syndrome A syndrome consisting of acute myopia associated with secondary angle closure glaucoma has been reported in patients receiving topiramate.

Symptoms include acute onset of decreased visual acuity and/or ocular pain.

Ophthalmologic findings can include some or all of the following: myopia, mydriasis, anterior chamber shallowing, ocular hyperemia (redness), choroidal detachments, retinal pigment epithelial detachments, macular striae, and increased intraocular pressure.

This syndrome may be associated with supraciliary effusion resulting in anterior displacement of the lens and iris, with secondary angle closure glaucoma.

Symptoms typically occur within 1 month of initiating topiramate therapy.

In contrast to primary narrow angle glaucoma, which is rare under 40 years of age, secondary angle closure glaucoma associated with topiramate has been reported in pediatric patients as well as adults.

The primary treatment to reverse symptoms is discontinuation of topiramate extended-release capsules as rapidly as possible, according to the judgment of the treating physician.

Other measures, in conjunction with discontinuation of topiramate extended-release capsules, may be helpful.

Elevated intraocular pressure of any etiology, if left untreated, can lead to serious sequelae including permanent vision loss.

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

In clinical trials, most of these events were reversible after topiramate discontinuation.

If visual problems occur at any time during treatment with topiramate extended-release capsules, consideration should be given to discontinuing the drug.

5.3 Oligohydrosis and Hyperthermia Oligohydrosis (decreased sweating), resulting in hospitalization in some cases, has been reported in association with topiramate use.

Decreased sweating and an elevation in body temperature above normal characterized these cases.

Some of the cases were reported after exposure to elevated environmental temperatures.

The majority of the reports have been in pediatric patients.

Patients, especially pediatric patients, treated with topiramate extended-release capsules should be monitored closely for evidence of decreased sweating and increased body temperature, especially in hot weather.

Caution should be used when topiramate extended-release capsules are 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.

5.4 Metabolic Acidosis Topiramate extended-release capsules 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).

This metabolic acidosis is caused by renal bicarbonate loss due carbonic anhydrase inhibition by topiramate extended-release capsules.

Topiramate extended-release capsule-induced metabolic acidosis can occur at any time during treatment.

Bicarbonate decrements are usually mild to moderate (average decrease of 4 mEq/L at daily doses of 400 mg in adults and at approximately 6 mg/kg/day in pediatric patients); rarely, patients can experience severe decrements to values below 10 mEq/L.

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 topiramate extended-release capsules.

Metabolic acidosis was commonly observed in adult and pediatric patients treated with immediate-release topiramate in clinical trials.

The incidence of decreased serum bicarbonate in pediatric trials for adjunctive treatment of Lennox-Gastaut syndrome or refractory partial-onset seizures was as high as 67% for immediate-release topiramate (at approximately 6 mg/kg/day), and 10% for placebo.