TOPAMAX- topiramate tablet, coated
TOPAMAX- topiramate capsule, coated pellets
Janssen Pharmaceuticals, Inc.
1 INDICATIONS AND USAGE
1.1 Monotherapy Epilepsy
TOPAMAX® (topiramate) Tablets and TOPAMAX® (topiramate capsules) Sprinkle Capsules are indicated as initial monotherapy in patients 2 years of age and older with partial onset or primary generalized tonic-clonic seizures. Safety and effectiveness in patients who were converted to monotherapy from a previous regimen of other anticonvulsant drugs have not been established in controlled trials [see Clinical Studies (14.1)].
1.2 Adjunctive Therapy Epilepsy
TOPAMAX® Tablets and TOPAMAX® Sprinkle Capsules are indicated as adjunctive therapy for adults and pediatric patients ages 2 to 16 years with partial onset seizures or primary generalized tonic-clonic seizures, and in patients 2 years of age and older with seizures associated with Lennox-Gastaut syndrome [see Clinical Studies (14.2)].
TOPAMAX® Tablets and TOPAMAX® Sprinkle Capsules are indicated for adults and adolescents 12 years of age and older for the prophylaxis of migraine headache [see Clinical Studies (14.3)]. The usefulness of TOPAMAX® in the acute treatment of migraine headache has not been studied.
2 DOSAGE AND ADMINISTRATION
On occasion, the addition of TOPAMAX® to phenytoin may require an adjustment of the dose of phenytoin to achieve optimal clinical outcome. Addition or withdrawal of phenytoin and/or carbamazepine during adjunctive therapy with TOPAMAX® may require adjustment of the dose of TOPAMAX®.
Because of the bitter taste, tablets should not be broken.
TOPAMAX® can be taken without regard to meals.
Adults and Pediatric Patients 10 Years and Older
Overdoses of TOPAMAX® have been reported. Signs and symptoms included convulsions, drowsiness, speech disturbance, blurred vision, diplopia, mentation impaired, lethargy, abnormal coordination, stupor, hypotension, abdominal pain, agitation, dizziness and depression. The clinical consequences were not severe in most cases, but deaths have been reported after poly-drug overdoses involving TOPAMAX®.
Topiramate overdose has resulted in severe metabolic acidosis [see Warnings and Precautions (5.4)].
A patient who ingested a dose between 96 and 110 g topiramate was admitted to a hospital with a coma lasting 20 to 24 hours followed by full recovery after 3 to 4 days.
In acute TOPAMAX® overdose, if the ingestion is recent, the stomach should be emptied immediately by lavage or by induction of emesis. Activated charcoal has been shown to adsorb topiramate in vitro. Treatment should be appropriately supportive. Hemodialysis is an effective means of removing topiramate from the body.
Topiramate is a sulfamate-substituted monosaccharide. TOPAMAX® (topiramate) Tablets are available as 25 mg, 50 mg, 100 mg, and 200 mg round tablets for oral administration. TOPAMAX® (topiramate capsules) Sprinkle Capsules are available as 15 mg and 25 mg sprinkle capsules for oral administration as whole capsules or opened and sprinkled onto soft food.
Topiramate is a white crystalline powder with a bitter taste. Topiramate is most soluble in alkaline solutions containing sodium hydroxide or sodium phosphate and having a pH of 9 to 10. It is freely soluble in acetone, chloroform, dimethylsulfoxide, and ethanol. The solubility in water is 9.8 mg/mL. Its saturated solution has a pH of 6.3. Topiramate has the molecular formula C12 H21 NO8 S and a molecular weight of 339.36. Topiramate is designated chemically as 2,3:4,5-Di-O -isopropylidene-?-D-fructopyranose sulfamate
TOPAMAX® Tablets contain the following inactive ingredients: carnauba wax, hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, polyethylene glycol, polysorbate 80, pregelatinized starch, purified water, sodium starch glycolate, synthetic iron oxide, and titanium dioxide.
TOPAMAX® Sprinkle Capsules contain topiramate-coated beads in a hard gelatin capsule. The inactive ingredients are black pharmaceutical ink, cellulose acetate, gelatin, povidone, sodium lauryl sulfate, sorbitan monolaurate, sugar spheres (sucrose and starch) and titanium dioxide.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
The precise mechanisms by which topiramate exerts its anticonvulsant and migraine prophylaxis effects are unknown; however, preclinical studies have revealed four properties that may contribute to topiramate’s efficacy for epilepsy and migraine prophylaxis. Electrophysiological and biochemical evidence suggests that topiramate, at pharmacologically relevant concentrations, blocks voltage-dependent sodium channels, augments the activity of the neurotransmitter gamma-aminobutyrate at some subtypes of the GABA-A receptor, antagonizes the AMPA/kainate subtype of the glutamate receptor, and inhibits the carbonic anhydrase enzyme, particularly isozymes II and IV.
PATIENT COUNSELING INFORMATION
See FDA-approved Medication Guide. Inform patients and their caregivers of the availability of a Medication Guide, and instruct them to read this prior to taking TOPAMAX®. Instruct patients to take TOPAMAX® only as prescribed.
Instruct patients taking TOPAMAX® to seek immediate medical attention if they experience blurred vision, visual disturbances, or periorbital pain [see Warnings and Precautions (5.1), (5.2)].
Oligohidrosis and Hyperthermia
Closely monitor TOPAMAX® -treated patients, especially pediatric patients, for evidence of decreased sweating and increased body temperature, especially in hot weather. Counsel patients to contact their healthcare professionals immediately if they develop a high or persistent fever, or decreased sweating [see Warnings and Precautions (5.3)].
Warn patients about the potential significant risk for metabolic acidosis that may be asymptomatic and may be associated with adverse effects on kidneys (e.g., kidney stones, nephrocalcinosis), bones (e.g., osteoporosis, osteomalacia, and/or rickets in children), and growth (e.g., growth delay/retardation) in pediatric patients, and on the fetus [see Warnings and Precautions (5.4) and Use in Specific Populations (8.1)].
Suicidal Behavior and Ideation
Counsel patients, their caregivers, and families that AEDs, including TOPAMAX® , may increase the risk of suicidal thoughts and behavior, and advise of the need to be alert for the emergence or worsening of the signs and symptoms of depression, any unusual changes in mood or behavior or the emergence of suicidal thoughts, or behavior or thoughts about self-harm. Instruct patients to immediately report behaviors of concern to their healthcare providers [see Warnings and Precautions (5.5)].
Interference with Cognitive and Motor Performance
Warn patients about the potential for somnolence, dizziness, confusion, difficulty concentrating, or visual effects, and advise patients not to drive or operate machinery until they have gained sufficient experience on TOPAMAX® to gauge whether it adversely affects their mental performance, motor performance, and/or vision [see Warnings and Precautions (5.6)].
Even when taking TOPAMAX® or other anticonvulsants, some patients with epilepsy will continue to have unpredictable seizures. Therefore, advise all patients taking TOPAMAX® for epilepsy to exercise appropriate caution when engaging in any activities where loss of consciousness could result in serious danger to themselves or those around them (including swimming, driving a car, climbing in high places, etc.). Some patients with refractory epilepsy will need to avoid such activities altogether. Discuss the appropriate level of caution with patients, before patients with epilepsy engage in such activities.
Inform pregnant women and women of childbearing potential that use of TOPAMAX® during pregnancy can cause fetal harm, including an increased risk for cleft lip and/or cleft palate (oral clefts), which occur early in pregnancy before many women know they are pregnant. There may also be risks to the fetus from chronic metabolic acidosis with use of TOPAMAX® during pregnancy [see Warnings and Precautions (5.7) and Use in Specific Populations (8.1), (8.9)]. When appropriate, counsel pregnant women and women of childbearing potential about alternative therapeutic options. This is particularly important when TOPAMAX® use is considered for a condition not usually associated with permanent injury or death.
Advise women of childbearing potential who are not planning a pregnancy to use effective contraception while using TOPAMAX® , keeping in mind that there is a potential for decreased contraceptive efficacy when using estrogen-containing birth control with topiramate [see Drug Interactions (7.3)].
Encourage pregnant women using TOPAMAX® , to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry. The registry is collecting information about the safety of antiepileptic drugs during pregnancy. To enroll, patients can call the toll-free number, 1-888-233-2334. Information about the North American Drug Pregnancy Registry can be found at https://www.massgeneral.org/aed/ [see Use in Specific Populations (8.1)].
Hyperammonemia and Encephalopathy
Warn patients about the possible development of hyperammonemia with or without encephalopathy. Although hyperammonemia may be asymptomatic, clinical symptoms of hyperammonemic encephalopathy often include acute alterations in level of consciousness and/or cognitive function with lethargy or vomiting. This hyperammonemia and encephalopathy can develop with TOPAMAX® treatment alone or with TOPAMAX® treatment with concomitant valproic acid (VPA).
Instruct patients to contact their physician if they develop unexplained lethargy, vomiting, or changes in mental status [see Warnings and Precautions (5.10)].
Instruct patients, particularly those with predisposing factors, to maintain an adequate fluid intake in order to minimize the risk of kidney stone formation [see Warnings and Precautions (5.11)].
Instructions for a Missing Dose
Instruct patients that if they miss a single dose of TOPAMAX® , it should be taken as soon as possible. However, if a patient is within 6 hours of taking the next scheduled dose, tell the patient to wait until then to take the usual dose of TOPAMAX® , and to skip the missed dose. Tell patients that they should not take a double dose in the event of a missed dose. Advise patients to contact their healthcare provider if they have missed more than one dose.