Important Safety Information

EPRONTIA^™ (topiramate) oral solution, 25 mg/mL

Indications:

• Initial monotherapy for the treatment of partial-onset or primary generalized tonic- clonic seizures in patients 2 years of age and older.
• Adjunctive therapy for the treatment of partial-onset seizures, primary generalized tonic-clonic seizures, or seizures associated with Lennox-Gastaut syndrome in patients 2 years of age and older.
• Preventive treatment of migraine in patients 12 years of age and older.

Inform patients that a calibrated measuring device is recommended to measure and deliver the prescribed dose accurately. A household teaspoon or tablespoon is not an adequate measuring device.

Additional Important Safety Information

Warnings and Precautions:

Acute Myopia and Secondary Angle Closure Glaucoma: A syndrome consisting of acute myopia associated with secondary angle closure glaucoma has been reported in patients receiving EPRONTIA (topiramate). Symptoms typically occur within 1 month of initiation of EPRONTIA therapy. Symptoms include acute onset of decreased visual acuity and/or ocular pain. Ophthalmologic findings include myopia, anterior chamber shallowing, ocular hyperemia (redness), and increased intraocular pressure. Primary treatment to reverse symptoms is discontinuation of EPRONTIA.

Visual Field Defects: Visual field defects have been reported in clinical trials and post-marketing experience in patients receiving topiramate. In clinical trials, most of these events were found to be reversible after topiramate discontinuation. If visual problems occur, consideration should be given to discontinuing the drug.

Oligohydrosis (decreased sweating) and Hyperthermia: Oligohydrosis, infrequently resulting in hospitalization, has been reported in association with EPRONTIA use. The majority of these reports have been in pediatric patients. Patients, especially pediatric patients, should be monitored for evidence of decreased sweating and increase in body temperature, especially in hot weather. Caution should be used when EPRONTIA is prescribed with other drugs that predispose patients to heat-related disorders. These drugs include, but are not limited to, other carbonic anhydrase inhibitors and other drugs with anticholinergic activity.

Metabolic Acidosis: Metabolic acidosis was commonly observed in adults and pediatric patients in clinical trials and is caused by renal bicarbonate loss due to carbonic anhydrase inhibition by topiramate. 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. EPRONTIA treatment that causes metabolic acidosis during pregnancy can possibly produce adverse effects on the fetus and might also cause metabolic acidosis in the neonate from possible transfer of topiramate to the fetus. Baseline and periodic serum bicarbonate measurements are recommended during EPRONTIA treatment. If metabolic acidosis develops, consideration should be given to either dose reduction or discontinuation of therapy using dose tapering.

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

Cognitive/Neuropsychiatric Adverse Reactions: EPRONTIA can cause cognitive/neuropsychiatric adverse reactions. The most frequent adverse reactions can be classified into 3 categories: 1) cognitive-related dysfunction (confusion, difficulty with concentration, difficulty with memory, speech or language problems); 2) psychiatric/behavior disorders; 3) somnolence or fatigue.

Fetal Toxicity: EPRONTIA can cause fetal harm when administered to pregnant women. The benefits and risks should be considered when administering this drug in women of childbearing potential.

Withdrawal of Antiepileptic Drugs: EPRONTIA should be gradually withdrawn to minimize the potential for seizures or increased seizure frequency. If rapid withdrawal is required, appropriate monitoring is recommended.

Serious Skin Reactions: Serious skin reactions (Stevens-Johnson Syndrome [SJS] and Toxic Epidermal Necrolysis [TEN]) have been reported. EPRONTIA should be discontinued at the first sign of a rash unless the rash is clearly unrelated to the drug. If signs or symptoms suggest SJS/TEN, use of this drug should not be resumed and alternative therapy should be considered. Inform patients about the signs of serious skin reactions.

Hyperammonemia and Encephalopathy (Without and With Concomitant Valproic Acid Use): Topiramate treatment can cause hyperammonemia with or without encephalopathy, the risk of which appears to be dose related, and which has been reported more frequently with concomitant use of valproic acid. In patients who develop unexplained lethargy, vomiting or changes in mental status associated with topiramate, hyperammonemic encephalopathy should be considered and an ammonia level should be measured.

Kidney Stones: EPRONTIA can cause an increased risk of kidney stones. The concomitant use of topiramate with any other drug producing metabolic acidosis, or potentially in patients on a ketogenic diet, may increase the risk of kidney stone formation. Instruct patients to stay well hydrated while taking EPRONTIA.

Hypothermia with Concomitant Valproic Acid Use: Hypothermia has been reported in association with topiramate use with concomitant valproic acid both in conjunction with hyperammonemia and in the absence of hyperammonemia. Consider discontinuation of topiramate or valproate in patients who develop hypothermia. Blood ammonia levels should be assessed during clinical management.

Adverse Reactions:

The most common side effects for EPRONTIA include:

• Tingling of the arms and legs
• Not feeling hungry
• Nausea
• A change in the way foods taste
• Diarrhea
• Weight loss
• Nervousness
• Upper respiratory tract infections
• Speech problems
• Tiredness

• Dizziness
• Sleepiness/drowsiness
• Slow reactions
• Difficulty with memory
• Pain in the abdomen
• Fever
• Abnormal vision
• Decreased feeling or sensitivity, especially in the skin

Use in Specific Populations:

Women of Reproductive Potential

Women of childbearing potential who are not planning a pregnancy should use effective contraception because of the risks of oral clefts and small for gestational age (SGA).

Renal Impairment

The clearance of EPRONTIA is reduced in patients with moderate (creatinine clearance 30 to 69 mL/min/1.73 m²) and severe (creatinine clearance <30 mL/min/1.73 m²) renal impairment. A dosage adjustment is recommended in patients with moderate or severe renal impairment.

Patients Undergoing Hemodialysis

EPRONTIA is cleared by hemodialysis at a rate that is 4 to 6 times greater than in a normal individual. A dosage adjustment may be required.

The Important Safety Information does not include all the information needed to use EPRONTIA safely and effectively. Visit EPRONTIA.com for full prescribing information.

To report SUSPECTED ADVERSE REACTIONS, contact Azurity Pharmaceuticals, Inc. at 1-855-379-0383, or FDA at 1-800-FDA-1088 or www.fda.gov/MedWatch.

HCP-EPR-1.6