- Capsules, sprinkle 15 mg
- Capsules, sprinkle 25 mg
- Tablets 25 mg
- Tablets 50 mg
- Tablets 100 mg
- Tablets 200 mg
- Tablets 25 mg
- Tablets 50 mg
- Tablets 100 mg
- Tablets 200 mg
CO Topiramate (Canada)
Sandoz Topiramate (Canada)
Precise mechanism is unknown, but topiramate may block repetitively elicited action potentials, affect ability of chloride ion to move into neurons, and antagonize an excitatory amino acid receptor.
Topiramate absorption is rapid. T max is 2 h. Bioavailability is about 80% and is not affected by food. Steady state is reached in about 4 days.
Topiramate is 15% to 41% bound to plasma proteins.
Topiramate is not extensively metabolized.
Topiramate is primarily eliminated unchanged in urine (about 70% of a dose). Plasma Cl is about 20 to 30 mL/min following oral administration. Topiramate half-life is 21 h.
Special PopulationsRenal Function Impairment
Cl is reduced 42% in moderately impaired and 54% in severely impaired patients.Hepatic Function Impairment
Cl may be decreased.Children
Pediatric patients have a 50% higher Cl and shorter half-life than adults. Consequently, plasma concentrations for the same mg/kg dose may be lower in children than adults.
Indications and Usage
Initial monotherapy for partial onset or primary generalized tonic-clonic seizures; adjunctive therapy for partial onset seizures, primary generalized tonic-clonic seizures, seizures associated with Lennox-Gastaut syndrome, prophylaxis of migraine headache.
Adjunctive therapy for bipolar disorder, alcohol and cocaine dependence, binge eating disorder, bulimia nervosa, cluster headaches, infantile spasms, weight loss or obesity, and smoking.
Dosage and AdministrationEpilepsy, adjunctive therapy
Adults 17 yr of age and older
PO 200 to 400 mg daily in 2 divided doses in adults with partial seizures and 400 mg daily in 2 divided doses in adults with primary generalized tonic–clonic seizures. Initiate therapy at 25 to 50 mg daily and titrate to an effective dose in increments of 25 to 50 mg weekly. Doses over 400 mg do not improve response. Daily doses above 1,600 mg have not been studied.Children 2 to 16 yr of age
PO 5 to 9 mg/kg/day in 2 divided doses. Initiate therapy at 25 mg or less (based on range of 1 to 3 mg/kg/day) nightly for first wk and titrate to an effective dose at 1- to 2-wk intervals by increments of 1 to 3 mg/kg/day in 2 divided doses.Epilepsy, monotherapy
Adults and Children 10 yr of age and older
PO 400 mg daily in 2 divided doses. Initiate therapy at 50 mg daily and titrate to an effective dose in increments of 25 to 50 mg weekly.Migraine
PO 50 mg in the morning and evening. Clinical outcome guides dose and titration rate; however, the recommended titration rate is:
- Week 1: 25 mg in the evening.
- Week 2: 25 mg in the morning and evening.
- Week 3: 25 mg in the morning and 50 mg in the evening.
- Week 4: 50 mg in the morning and evening.
Dosage adjustment of 50% of the usual adult dose is recommended.
- Sprinkle capsules may be swallowed whole or administered by carefully opening the capsule and sprinkling the entire contents on a small amount (teaspoon) of soft food. The mixture should be swallowed immediately and not chewed. Do not store for future use.
Store tablets at controlled room temperature (59° to 86°F). Store capsules at temperatures below 77°F. Keep tightly capped and protect from moisture.
Drug InteractionsAlcohol, CNS depressants
CNS depression and adverse reactions may be increased.Amitriptyline
Plasma concentrations may be increased by topiramate.Carbamazepine
Effects of topiramate may be decreased.Carbonic anhydrase inhibitors (eg, acetazolamide)
Increased risk of renal stone formation.Contraceptives, oral
Efficacy of oral contraceptives may be decreased; there is a possibility of increased breakthrough bleeding.Digoxin, lithium
Plasma concentrations may be decreased by topiramate.Hydrochlorothiazide, lamotrigine
Topiramate plasma concentrations may be increased.Metformin
Plasma concentrations may be increased by topiramate, while topiramate oral Cl may be reduced.Phenytoin
Effects of phenytoin may be increased, while those of topiramate may decrease.Pioglitazone
Plasma concentrations of the active metabolites of pioglitazone may be decreased.Risperidone
Exposure to risperidone may be decreased.Valproic acid
Effects of valproic acid and topiramate may be decreased. The risk of hyperammonemia may be increased.
Laboratory Test Interactions
None well documented.
Hypertension (2%); bradycardia (1%).
Paresthesia (51%); dizziness (32%); fatigue (30%); somnolence (29%); psychomotor slowing (21%); nervousness (19%); ataxia (16%); confusion, difficulty with concentration, difficulty with memory (14%); depression, speech disorders (13%); behavior problems, mood problems, nystagmus (11%); language problems (10%); aggressive reaction, insomnia, tremor (9%); abnormal gait, hypoaesthesia (8%); cognitive problems (7%); anxiety (6%); hyperkinesia (5%); abnormal coordination, involuntary muscle contraction (4%); agitation, apathy, decreased libido, emotional liability, hypertonia (3%); aggravated depression, depersonalization, hyporeflexia, stupor, vertigo (2%); aggravated migraine, convulsions, headache, sensory disturbance, syncope (1% or more).
Alopecia (5%); pruritus, rash (4%); acne, skin disorder (3%); dermatitis, erythematous rash, hypertrichosis (2%); eczema, increased sweating, seborrhea, skin discoloration (1%); bullous skin reactions (including erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis), pemphigus (postmarketing).
Taste perversion (15%); abnormal vision (13%); diplopia (10%); pharyngitis (6%); blurred vision (4%); conjunctivitis, decreased hearing, eye abnormality, otitis media, tinnitus (2%); abnormal accommodation, abnormal lacrimation, eye pain, myopia (1% or more).
Anorexia (24%); nausea (14%); diarrhea (11%); abdominal pain, dyspepsia (7%); increased saliva (6%); constipation, dry mouth (5%); gastritis, gastroenteritis, vomiting (3%); gastroesophageal reflux, taste loss (2%); dysphagia, fecal incontinence, flatulence, GI disorder, gingivitis, glossitis, gum hyperplasia, tooth disorder (1% or more); pancreatitis (postmarketing).
Breast pain, urinary incontinence, UTI (4%); cystitis, menstrual disorder, premature ejaculation, renal calculus, vaginal hemorrhage (3%); amenorrhea, dysuria, hematuria, leukorrhea, menorrhagia, micturition frequency, prostatic disorder (2%); abnormal urine, genital moniliasis, intermenstrual bleeding, nocturia (1% or more); renal tubular acidosis (postmarketing).
Purpura (8%); epistaxis (4%); anemia, leukopenia (2%); hematoma, increased PT, thrombocytopenia (1%).
Gamma-GT increased (3%); hepatic failure (including fatalities), hepatitis (postmarketing).
Weight decrease (21%); thirst (2%); hypoglycemia, increased appetite, weight increase (1%).
Arthralgia (7%); leg cramps, myalgia (2%).
Upper respiratory tract infection (18%); sinusitis (10%); bronchitis, rhinitis (7%); pneumonia (5%); coughing (4%); dyspnea (3%); asthma, respiratory disorder (1% or more).
Injury (14%); fever, viral infection (9%); infection (7%); asthenia (6%); back pain (5%); chest pain, flu-like symptoms, leg pain (4%); allergy (3%); allergic reaction, edema, hot flushes, neoplasm (2%); body odor, moniliasis, neurosis, pallor, pain, rigors, skeletal pain (1% or more).
Measurement of baseline and periodic serum bicarbonate is recommended.
Category C .
ChildrenTreatment of epilepsy
Safety and efficacy not established in children younger than 2 yr of age for adjunctive treatment and younger than 10 yr of age for monotherapy.Treatment of migraine
Safety and efficacy not established.
Consider age-related changes in renal function.
Reduce dose 50% if CrCl less than 70 mL/min.
Administer with caution.
Acute myopia secondary to angle-closure glaucoma has been reported.
Supplemental dose may be necessary before prolonged dialysis.
Risk of developing kidney stones may be increased.
Hyperchloremic, non-anion gap, metabolic acidosis has been associated with topiramate treatment.
Oligohidrosis and hyperthermia
Have been reported, mostly in children.
Sudden unexplained death in epilepsy has been reported at an incidence of 0.0035 per patient year.
Gradually withdraw therapy to minimize potential of increased seizure frequency.
Abdominal pain, abnormal coordination, agitation, blurred vision, convulsions, death, depression, diplopia, dizziness, drowsiness, hypotension, lethargy, mentation impaired, severe metabolic acidosis, speech disturbance, stupor.
- Advise patient, family, or caregiver to read the patient information leaflet before starting therapy and with each refill.
- Instruct patient, family, or caregiver to continue other medications for seizures unless advised to do otherwise by health care provider.
- Advise patient, family, or caregiver that medication will be started at a low dose and then gradually increased as tolerated until max benefit has been obtained.
- Instruct patient, family, or caregiver to take (give) exactly as prescribed and not to change the dose or discontinue therapy unless advised by health care provider.
- Advise patient using topiramate for migraine prophylaxis that medication must be taken daily as prescribed to prevent migraine headaches. Inform patient that topiramate does not work when taken as needed to try to treat a migraine headache.
- Advise patient to swallow tablet whole. Chewing the tablet may leave a bitter taste.
- Advise patient, family, or caregiver that sprinkle capsules may be swallowed whole or opened and the entire contents sprinkled onto a small amount (eg, teaspoon) of soft food (eg, applesauce) and then consumed immediately without chewing. Advise patient, family, or caregiver to give fluid (eg, water) to help wash the sprinkle/food mixture down. Caution patient, family, or caregiver not to prepare ahead of time and store for future use.
- Advise patient, family, or caregiver that each dose may be taken without regard to meals but to take with food if stomach upset occurs.
- Instruct patient, family, or caregiver that if a dose is missed to skip that dose and not double the next dose.
- Advise patient, family, or caregiver to maintain adequate fluid intake to reduce chance of developing kidney stones.
- Instruct patient, family, or caregiver to discontinue therapy and immediately contact health care provider of any of the following: sudden change in vision; blurred vision, eye pain, or pain around the eye; decreased sweating and elevated body temperature; unexplained rapid breathing or shortness of breath; pounding in the chest or abnormal heart rhythm; stupor.
- Advise patient, family, or caregiver that if medication needs to be discontinued, it will be slowly withdrawn over a period of 2 wk or more unless safety concerns (eg, rash) require a more rapid withdrawal.
- Advise patient to avoid alcoholic beverages and other depressants while taking this medication.
- Caution patient that drug may cause dizziness, drowsiness, confusion, or difficulty concentrating and to use caution while driving or performing other tasks requiring mental alertness or coordination until tolerance is determined.
- Advise patient that topiramate may cause weight loss and to consider additional food intake if weight loss occurs.
- Advise women using oral contraceptives that topiramate may reduce their effectiveness and to consider using an alternate method of contraception.
- Advise patient that medication may cause photosensitivity (sensitivity to sunlight) and to avoid unnecessary exposure to UV light (sunlight, tanning booths), use sunscreen, and wear protective clothing when exposed to UV light until tolerance is determined.
- Instruct patient, family, or caregiver to contact health care provider if seizures get worse or if new types of seizures occur.
- Advise patient, family, or caregiver to contact health care provider if bothersome adverse reactions occur.
- Advise patient to carry identification (eg, card, bracelet) indicating medication usage and epilepsy.
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