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Special Alerts
Topiramate (Topamax®): Increased Risk of Oral Clefts in Newborns Associated with Topiramate Use During Pregnancy
March 2011
The U.S. Food and Drug Administration (FDA) is notifying healthcare providers and patients of new data indicating an increased risk of oral clefts (cleft lip and/or palate) in infants exposed to topiramate (Topamax®) during pregnancy. The data, from the North American Antiepileptic Drug (NAAED) Pregnancy Registry, reported that the prevalence of oral clefts was 1.4% for infants exposed to topiramate during the first trimester of pregnancy, versus 0.38%-0.55% for infants exposed to other antiepileptic drugs and 0.07% with no exposure. Similar data was reported in the UK Epilepsy and Pregnancy Registry supporting the new warning.
As a result of this new human data, the pregnancy category of topiramate was changed from a C to D . Pregnancy category D means studies in pregnant women have demonstrated a risk to the fetus, but the potential benefits of the drug in pregnant women may outweigh the risks in certain situations. Women of childbearing age should discuss appropriate birth control options if taking or planning to take topiramate. Pregnant women or women who become pregnant while taking topiramate should not discontinue the medication abruptly, but should notify their healthcare provider to discuss alternative treatment options.
Patients exposed to topiramate during pregnancy are encouraged to enroll themselves into the AED Pregnancy Registry by calling 1-888-233-2334. Additional information is available at http://www.aedpregnancyregistry.org/
For additional information, please refer to: http://www.fda.gov/Drugs/DrugSafety/ucm245085.htm
Pronunciation
(toe PYRE a mate)
Generic Available (U.S.)
Yes
Medication Guide
An FDA-approved patient medication guide, which is available with the product information and at http://www.fda.gov/downloads/Drugs/DrugSafety/UCM152837.pdf, must be dispensed with this medication.
REMS Components
Medication Guide
U.S. Brand Names
Canadian Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Monotherapy or adjunctive therapy for partial onset seizures and primary generalized tonic-clonic seizures; adjunctive treatment of seizures associated with Lennox-Gastaut syndrome; prophylaxis of migraine headache
Use: Unlabeled/Investigational
Diabetic neuropathy, infantile spasms, neuropathic pain; prophylaxis of cluster headache
Pregnancy Risk Factor
D
Pregnancy Considerations
Topiramate was found to be teratogenic in animal studies. Based on limited data, topiramate was found to cross the placenta. An increase risk of oral clefts (cleft lip and/or palate) has been observed following first trimester exposure. Data, from the North American Antiepileptic Drug (NAAED) Pregnancy Registry, reported that the prevalence of oral clefts was 1.4% for infants exposed to topiramate during the first trimester of pregnancy, versus 0.38% to 0.55% for infants exposed to other antiepileptic drugs and 0.07% with no exposure. Hypospadias and other congenital anomalies have also been reported. Although not evaluated during pregnancy, metabolic acidosis may be induced by topiramate. In general, metabolic acidosis during pregnancy may result in adverse effects and fetal death. Maternal serum concentrations may decrease during the second and third trimesters of pregnancy therefore therapeutic drug monitoring should be considered in pregnant women who require therapy.Patients exposed to topiramate during pregnancy are encouraged to enroll themselves into the AED Pregnancy Registry by calling 1-888-233-2334. Additional information is available at www.aedpregnancyregistry.org.
Lactation
Enters breast milk/use caution
Breast-Feeding Considerations
Based on limited data, topiramate was found in breast milk. Infant plasma concentrations of topiramate have been reported as 10% to 20% of the maternal plasma concentration.
Contraindications
There are no contraindications listed in the manufacturers' labeling.
Canadian labeling (not in U.S. labeling): Hypersensitivity to topiramate or any component of the formulation or container; pregnancy and women in childbearing years not using effective contraception (migraine prophylaxis only)
Warnings/Precautions
Concerns related to adverse effects:
• CNS effects: Cognitive dysfunction, psychiatric disturbances (mood disorders), and sedation (somnolence or fatigue) may occur with use; incidence may be related to rapid titration and higher doses; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving). May also cause paresthesia, dizziness, and ataxia.
• Glaucoma: Has been associated with acute myopia and secondary angle-closure glaucoma in adults and children, typically within 1 month of initiation; discontinue in patients with acute onset of decreased visual acuity or ocular pain.
• Hyperammonemia/encephalopathy: Hyperammonemia with or without encephalopathy may occur with monotherapy or in combination with valproic acid and has been documented in patients who have tolerated each drug alone. Risk may be increased in patients with inborn errors of metabolism or decreased hepatic mitochondrial activity. Monitor for lethargy, vomiting, or unexplained changes in mental status.
• Hyperthermia: May be associated (rarely) with severe oligohydrosis and hyperthermia, most frequently in children; use caution and monitor closely during strenuous exercise, during exposure to high environmental temperature, or in patients receiving other carbonic anhydrase inhibitors and drugs with anticholinergic activity.
• Metabolic acidosis (hyperchloremic, nonanion gap): May decrease serum bicarbonate concentrations, due to inhibition of carbonic anhydrase and increased renal bicarbonate loss. Decreases in serum bicarbonate are relatively common (7% to 67%) but usually mild-to-moderate (average decrease of 4 mEq/L at dose of 400 mg/day in adults and 6 mg/kg/day in children). Treatment-emergent metabolic acidosis is less common; however, risk may be increased in patients with a predisposing condition (renal, respiratory and/or hepatic impairment), ketogenic diet, or concurrent treatment with other drugs which may cause acidosis. Metabolic acidosis may occur at dosages as low as 50 mg/day. Serum bicarbonate should be monitored, as well as potential complications of chronic acidosis (nephrolithiasis, osteomalacia, and reduced growth rates in children). Dose reduction or discontinuation (by tapering dose) should be considered in patients with persistent or severe metabolic acidosis. If treatment is continued, alkali supplementation should be considered.
• Renal calculus: Topiramate exhibits weak carbonic anhydrase inhibitory properties and may increase the risk of kidney stones about 2-4 times that of the untreated population. Kidney stones have been reported in children and adults (incidence higher in males). The risk of stones may be reduced by increasing fluid intake.
• Suicidal ideation: Pooled analysis of trials involving various antiepileptics (regardless of indication) showed an increased risk of suicidal thoughts/behavior (incidence rate: 0.43% treated patients compared to 0.24% of patients receiving placebo); risk observed as early as 1 week after initiation and continued through duration of trials (most trials ≤24 weeks). Monitor all patients for notable changes in behavior that might indicate suicidal thoughts or depression; notify healthcare provider immediately if symptoms occur.
Disease-related concerns:
• Hepatic impairment: Use with caution in patients with hepatic impairment; clearance may be reduced. Dosage adjustment may be required.
• Renal impairment: Use with caution in patients with renal impairment; dosage adjustment may be required.
Concurrent drug therapy issues:
• Hydrochlorothiazide: Concurrent use of topiramate and hydrochlorothiazide may increase the risk for hypokalemia; monitor potassium closely.
• Sedatives: Effects with other sedative drugs or ethanol may be potentiated.
• Valproic acid: Concurrent use of topiramate and valproic acid may increase the risk of hyperammonemia and associated encephalopathy; valproic acid dose-dependency was observed in limited pediatric studies.
Special populations:
• Pediatrics: Safety and efficacy have not been established in children <2 years of age for adjunctive treatment of seizures and <10 years of age for monotherapy treatment of seizures. Safety and efficacy have not been established in children for migraine prophylaxis. Weight loss may occur most often early in therapy; in clinical trials of at least 1 year, the majority of patients with weight loss had a resumption of weight gain within the study period.
Other warnings/precautions:
• Withdrawal: Anticonvulsants should not be discontinued abruptly because of the possibility of increasing seizure frequency; therapy should be withdrawn gradually to minimize the potential of increased seizure frequency, unless safety concerns require a more rapid withdrawal. Doses were also gradually withdrawn in migraine prophylaxis studies (decreased in weekly intervals by 25-50 mg/day).
Adverse Reactions
Adverse events are reported for placebo-controlled trials of adjunctive therapy in adult and pediatric patients. Unless otherwise noted, the percentages refer to incidence in epilepsy trials. Note: A wide range of dosages were studied; incidence of adverse events was frequently lower in the pediatric population studied.
>10%:
Central nervous system: Somnolence (15% to 29%), dizziness (4% to 25%; dose dependent), fatigue (9% to 16%; dose-dependent), nervousness (9% to 18%), ataxia (6% to 16%), psychomotor slowing (3% to 13%; dose dependent), speech problems (2% to 13%), memory difficulties (2% to 12%), behavior problems (children 11%), confusion (4% to 11%)
Endocrine & metabolic: Serum bicarbonate decreased (dose related: 7% to 67%; marked reductions [to <17 mEq/L] 1% to 11%)
Gastrointestinal: Anorexia (4% to 24%; dose dependent), nausea (6% to 10%; migraine trial: 9% to 14%)
Neuromuscular & skeletal: Paresthesia (1% to 11%; migraine trial: 35% to 51%)
Ocular: Abnormal vision (2% to 13%)
Respiratory: Upper respiratory infection (migraine trial: 12% to 14%)
Miscellaneous: Injury (14%)
1% to 10%:
Cardiovascular: Chest pain (2% to 4%), edema (2%), hypertension (1% to 2%), bradycardia (1%), pallor (1%), syncope (1%)
Central nervous system: Difficulty concentrating (5% to 10%), aggressive reactions (2% to 9%), depression (5% to 9%; dose dependent, insomnia (4% to 8%), mood problems (≤6%), abnormal coordination (4%), agitation (3%), cognitive problems (3%), emotional lability (3%), anxiety (2% to 3%; dose dependent), hypoesthesia (2%; migraine trial: 6% to 8%), stupor (2%), vertigo (2%), fever (migraine trial: 1% to 2%), apathy (1%), hallucination (1%), neurosis (1%), psychosis (1%), seizure (1%), suicide attempt (1%)
Dermatologic: Pruritus (migraine trial: 2% to 4%), skin disorder (2% to 3%), alopecia (2%), dermatitis (2%), hypertrichosis (2%), rash erythematous (1% to 2%), eczema (1%), seborrhea (1%), skin discoloration (1%)
Endocrine & metabolic: Breast pain (4%), hot flashes (1% to 2%), libido decreased (<1% to 2%), menstrual irregularities (1% to 2%), hypoglycemia (1%), metabolic acidosis (hyperchloremia, nonanion gap)
Gastrointestinal: Weight loss (4% to 9%), dyspepsia (2% to 7%), abdominal pain (5% to 6%), salivation increased (6%), constipation (4% to 5%), gastroenteritis (2% to 3%), vomiting (migraine trial: 1% to 3%), diarrhea (2%; migraine trial: 9% to 11%), dysgeusia (2%; migraine trial: 8% to 15%), xerostomia (2%), loss of taste (migraine trial: ≤2%), appetite increased (1%), dysphagia (1%), fecal incontinence (1%), flatulence (1%), GERD (1%), gingivitis (1%), glossitis (1%), gum hyperplasia (1%), weight gain (1%)
Genitourinary: Incontinence (2% to 4%), UTI (2%), premature ejaculation (migraine trial: ≤3%), cystitis (2%), leukorrhea (2%), impotence (1%), nocturia (1%)
Hematologic: Purpura (8%), leukopenia (2%), anemia (1%), hematoma (1%), prothrombin time increased (1%), thrombocytopenia (1%)
Neuromuscular & skeletal: Tremor (3% to 9%), gait abnormal (3% to 8%), arthralgia (migraine trial: 1% to 7%), weakness (6%), hyperkinesia (5%), back pain (1% to 5%), involuntary muscle contractions (2%; migraine trial: 2% to 4%), leg cramps (2%), leg pain (2%), myalgia (2%), hyporeflexia (2%), rigors (1%), skeletal pain (1%)
Ocular: Diplopia (1% to 10%), nystagmus (10%), conjunctivitis (1%), lacrimation abnormal (1%), myopia (1%)
Otic: Hearing decreased (2%), tinnitus (2%), otitis media (migraine trial: 1% to 2%)
Renal: Hematuria (2%), renal calculus (migraine trial ≤2%)
Respiratory: Rhinitis (4% to 7%), pharyngitis (6%), sinusitis (5%; migraine trial: 6% to 10%), pneumonia (5%), epistaxis (2% to 4%), cough (migraine trial: 2% to 4%), bronchitis (migraine trial: 3%), dyspnea (migraine trial: 1% to 3%)
Miscellaneous: Viral infection (2% to 7%: migraine trial: 3% to 4%), flu-like syndrome (3%), allergy (2%), infection (2%), thirst (2%), body odor (1%), diaphoresis (1%), moniliasis (1%)
<1% (Limited to important or life-threatening): Angina, apraxia, AV block, bone marrow depression, deep vein thrombosis, dehydration, delirium, diabetes mellitus, dyskinesia, electrolyte imbalance, eosinophilia, euphoria, granulocytopenia, hyperammonemia/encephalopathy (with or without valproate therapy), hyperesthesia, hypotension, liver enzymes increased, lymphadenopathy, lymphopenia, manic reaction, neuropathy, pancytopenia, paranoid reaction, photosensitivity, pulmonary embolism, tongue edema
Postmarketing and/or case reports: Accommodation abnormality, delusion, erythema multiforme, eye pain, flushing, headache, hepatic failure, hepatitis, hyperthermia (severe), hypokalemia, maculopathy, migraine aggravated, oligohydrosis, pancreatitis, pemphigus, rash, renal tubular acidosis, Stevens-Johnson syndrome, suicide, suicidal ideation, syndrome of acute myopia/secondary angle-closure glaucoma, toxic epidermal necrolysis, vision blurred
Metabolism/Transport Effects
Inhibits CYP2C19 (weak); Induces CYP3A4 (weak)
Drug Interactions
Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy
CarBAMazepine: May decrease the serum concentration of Topiramate. Risk D: Consider therapy modification
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Exceptions: Levocabastine (Nasal). Risk C: Monitor therapy
Contraceptives (Estrogens): Topiramate may decrease the serum concentration of Contraceptives (Estrogens). Contraceptive failure is possible. Management: Risk appears greatest for higher topiramate doses (200 mg/day or greater). Some have recommended using at least 50 mcg/day of ethinyl estradiol, but the effectiveness of this is unclear. Consider a nonhormonal form of contraception. Risk D: Consider therapy modification
Contraceptives (Progestins): Topiramate may decrease the serum concentration of Contraceptives (Progestins). Management: Caution patients that this combination may be associated with reduced contraceptive effectiveness. Consider adding an additional (non-hormonal) contraceptive method. Risk D: Consider therapy modification
Divalproex: Topiramate may enhance the hepatotoxic effect of Divalproex. Risk C: Monitor therapy
Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (e.g., opioids, barbiturates) with concomitant use. Risk D: Consider therapy modification
Fosphenytoin: May decrease the serum concentration of Topiramate. Topiramate may increase the serum concentration of Fosphenytoin. Risk C: Monitor therapy
HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Management: For patients being treated with hydroxyzine, a reduction in the dose of any other CNS depressants that are to be used in combination is recommended. With concurrent use, monitor patients closely for excessive response to the combination. Risk D: Consider therapy modification
Ketorolac: May diminish the therapeutic effect of Anticonvulsants. Risk C: Monitor therapy
Ketorolac (Nasal): May diminish the therapeutic effect of Anticonvulsants. Risk C: Monitor therapy
Ketorolac (Systemic): May diminish the therapeutic effect of Anticonvulsants. Risk C: Monitor therapy
Lithium: Topiramate may increase the serum concentration of Lithium. Risk C: Monitor therapy
Mefloquine: May diminish the therapeutic effect of Anticonvulsants. Mefloquine may decrease the serum concentration of Anticonvulsants. Management: Mefloquine is contraindicated for malaria prophylaxis in persons with a history of convulsions. Monitor anticonvulsant concentrations and treatment response closely with concurrent use. Risk D: Consider therapy modification
Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. Risk D: Consider therapy modification
Phenytoin: May decrease the serum concentration of Topiramate. Topiramate may increase the serum concentration of Phenytoin. Risk C: Monitor therapy
Saxagliptin: CYP3A4 Inducers may decrease the serum concentration of Saxagliptin. Risk C: Monitor therapy
Selective Serotonin Reuptake Inhibitors: CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Risk C: Monitor therapy
Thiazide Diuretics: May enhance the hypokalemic effect of Topiramate. Thiazide Diuretics may increase the serum concentration of Topiramate. Management: Monitor for increased topiramate levels/adverse effects (e.g., hypokalemia) with initiation/dose increase of a thiazide diuretic. Closely monitor serum potassium concentrations with concomitant therapy. Topiramate dose reductions may be necessary. Risk D: Consider therapy modification
Valproic Acid: Topiramate may enhance the hepatotoxic effect of Valproic Acid. Risk C: Monitor therapy
Ethanol/Nutrition/Herb Interactions
Ethanol: May increase CNS depression; monitor for increased effects with coadministration. Caution patients about effects.
Food: Ketogenic diet may increase the possibility of acidosis and/or kidney stones.
Herb/Nutraceutical: Avoid evening primrose (seizure threshold decreased).
Storage
Store at room temperature of 15°C to 30°C (59°F to 86°F). Protect from moisture.
Mechanism of Action
Anticonvulsant activity may be due to a combination of potential mechanisms: Blocks neuronal voltage-dependent sodium channels, enhances GABA(A) activity, antagonizes AMPA/kainate glutamate receptors, and weakly inhibits carbonic anhydrase.
Pharmacodynamics/Kinetics
Absorption: Good, rapid; unaffected by food
Protein binding: 15% to 41% (inversely related to plasma concentrations)
Metabolism: Hepatic via P450 enzymes
Bioavailability: ~80%
Half-life elimination: Mean: Adults: Normal renal function: 21 hours; shorter in pediatric patients; clearance is 50% higher in pediatric patients; Elderly: ~24 hours
Time to peak, serum: ~1-4 hours
Excretion: Urine (~70% to 80% as unchanged drug)
Dialyzable: Significantly hemodialyzed; dialysis clearance: 120 mL/minute (4-6 times higher than in adults with normal renal function); supplemental doses may be required
Dosage
Oral: Note: Do not abruptly discontinue therapy; taper dosage gradually to prevent rebound effects. (In clinical trials, adult doses were withdrawn by decreasing in weekly intervals of 50-100 mg/day gradually over 2-8 weeks for seizure treatment, and by decreasing in weekly intervals by 25-50 mg/day for migraine prophylaxis.)
Epilepsy, monotherapy: Children ≥10 years and Adults: Partial onset seizure and primary generalized tonic-clonic seizure: Initial: 25 mg twice daily; may increase weekly by 50 mg/day up to 100 mg twice daily (week 4 dose); thereafter, may further increase weekly by 100 mg/day up to the recommended maximum of 200 mg twice daily.
Canadian labeling: Children ≥6 years and Adults: Initial: 25 mg once daily (in evening); may increase to 25 mg twice daily in weeks 2 or 3, and up to 50 mg twice daily by weeks 3 or 4; may further increase weekly in increments of 50 mg/day up to recommended maximum of 200 mg twice daily.
Epilepsy, adjunctive therapy:
Children 2-16 years:
Partial onset seizure or seizure associated with Lennox-Gastaut syndrome: Initial: 25 mg (1-3 mg/kg/day) once daily (in evening); may increase every 1-2 weeks in increments of 1-3 mg/kg/day up to the recommended maximum of 5-9 mg/kg/day in 2 divided doses
Primary generalized tonic-clonic seizure: Use initial dose listed above for partial onset seizures, but use slower initial titration rate; titrate to the recommended maintenance dose of 6 mg/kg/day by the end of 8 weeks
Canadian labeling: Initial: 25 mg (1-3 mg/kg/day) once daily (in evening); may increase every 1-2 weeks in increments of 1-3 mg/kg/day up to the recommended maximum of 5-9 mg/kg/day in two divided doses
Adolescents ≥17 years and Adults:
Partial onset seizures: Initial: 25 mg once or twice daily for 1 week; may increase weekly by 25-50 mg/day until response; usual maintenance dose: 100-200 mg twice daily. Doses >1600 mg/day have not been studied.
Primary generalized tonic-clonic seizures: Use initial dose as listed above for partial onset seizures, but use slower initial titration rate; titrate upwards to recommended dose by the end of 8 weeks; usual maintenance dose: 200 mg twice daily. Doses >1600 mg/day have not been studied.
Canadian labeling: Initial: 25 mg once or twice daily; may increase weekly by 50 mg/day up to the recommended dose of 100-200 mg twice daily (maximum recommended dose: 800 mg/day; doses >400 mg/day have shown no additional benefit)
Migraine prophylaxis: Adults: Initial: 25 mg once daily (in evening); may increase weekly by 25 mg/day, up to the recommended dose of 100 mg/day given in 2 divided doses. Doses >100 mg/day have shown no additional benefit.
Cluster headache prophylaxis (unlabeled use): Adults: Initial: 25 mg/day, titrated at weekly intervals in 25 mg increments, up to 200 mg/day (Pascual, 2007)
Diabetic neuropathy (unlabeled use): Adults: Initial: 25 mg/day, titrated at weekly intervals in 25-50 mg increments to target dose of 400 mg daily in 2 divided doses (Raskin, 2004; Thienel, 2004)
Dosing adjustment in renal impairment: Clcr <70 mL/minute/1.73 m2: Administer 50% dose and titrate more slowly
Hemodialysis: Supplemental dose may be needed during hemodialysis
Dosing adjustment in hepatic impairment: Clearance may be reduced; however the manufacturer's labeling provides no specific dosing recommendations
Administration: Oral
May be administered without regard to meals
Capsule sprinkles: May be swallowed whole or opened to sprinkle the contents on a small amount (~1 teaspoon) of soft food (drug/food mixture should not be chewed; swallow immediately).
Tablet: Because of bitter taste, tablets should not be broken or chewed.
Monitoring Parameters
Seizure frequency, hydration status; electrolytes (recommended monitoring includes serum bicarbonate at baseline and periodically during treatment), serum creatinine; monitor for symptoms of acute acidosis and complications of long-term acidosis (nephrolithiasis, osteomalacia, and reduced growth rates in children); ammonia level in patients with unexplained lethargy, vomiting, or mental status changes; intraocular pressure, symptoms of secondary angle closure glaucoma; suicidality (eg, suicidal thoughts, depression, behavioral changes)
Patient Education
While using this medication, do not use alcohol. Maintain adequate hydration, unless instructed to restrict fluid intake, to prevent the development of kidney stones and dehydration. You may be at risk for decreased sweating and increased body temperature, especially in hot weather. You may experience drowsiness, dizziness, disturbed concentration, memory changes, blurred vision, mouth sores, nausea, vomiting, or loss of appetite. Wear identification of epileptic status and medications. Report behavioral or CNS changes, suicide ideation, depression, skin rash, muscle cramping, numbness in extremities, weakness, tremors, changes in gait, chest pain, irregular heartbeat, palpitations, hearing loss, cough, respiratory difficulty, or worsening of seizure activity or loss of seizure control. Seek immediate medical evaluation if you experience sudden vision changes, periorbital pain, flank pain, or blood in urine.
Geriatric Considerations
This drug may not be a drug of choice in the elderly until all other therapies for seizures have been exhausted. Follow the recommended titration schedule and adjust time intervals to meet patient's needs. Since most elderly will have a Clcr <70 mL/minute, it is important to either measure or estimate by calculation the Clcr prior to initiating therapy.
Additional Information
May be associated with weight loss in some patients
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Gingivitis, dysphagia, glossitis, gum hyperplasia, and xerostomia (normal salivary flow resumes upon discontinuation).
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Comment
Large double-blind studies have failed to differentiate this drug from placebo when used for bipolar disorder.
Nursing: Physical Assessment/Monitoring
Monitor therapeutic effectiveness (seizure activity, type, duration) at beginning of therapy and throughout. Taper dosage slowly when discontinuing. May cause weight loss; monitor weight periodically. Teach patient seizure safety precautions.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, sprinkle, oral: 15 mg, 25 mg
Topamax®: 15 mg, 25 mg
Tablet, oral: 25 mg, 50 mg, 100 mg, 200 mg
Topamax®: 25 mg, 50 mg, 100 mg, 200 mg
Pricing: U.S. (www.drugstore.com)
Capsule, sprinkles (Topiramate)
15 mg (60): $70.99
25 mg (60): $85.99
Tablets (Topamax)
25 mg (60): $201.99
50 mg (60): $382.01
100 mg (60): $536.97
200 mg (60): $626.00
Tablets (Topiramate)
25 mg (60): $29.99
50 mg (60): $39.99
100 mg (60): $49.99
200 mg (60): $49.99
Extemporaneously Prepared
A 6 mg/mL topiramate oral suspension may be made with tablets and one of two different vehicles (a 1:1 mixture of Ora-Sweet® and Ora-Plus®, or a mixture of Simple Syrup, NF and methylcellulose 1% with parabens). Crush six 100 mg tablets in a mortar and reduce to a fine powder. Add a small amount of methylcellulose gel and mix to a uniform paste (Note: Use a small amount of methylcellulose gel when using the 1:1 Ora-Sweet® and Ora-Plus® mixture as the vehicle; use 10 mL methylcellulose 1% with parabens when using Simple Syrup, NF as the vehicle); mix while adding the chosen vehicle in incremental proportions to almost 100 mL; transfer to a graduated cylinder; rinse mortar with vehicle, and add quantity of vehicle sufficient to make 100 mL. Store in plastic prescription bottles; label "shake well" and "refrigerate". Stable for 90 days refrigerated (preferred) or at room temperature.
Nahata MC, Pai VB, and Hipple TF, Pediatric Drug Formulations, 5th ed, Cincinnati, OH: Harvey Whitney Books Co, 2004.
References
Bar-Oz B, Nulman I, Koren G, et al, “Anticonvulsants and Breast Feeding: A Critical Review,” Paediatr Drugs, 2000, 2(2):113-26.
Bril V, England J, Franklin GM, et al, "Evidence-Based Guideline: Treatment of Painful Diabetic Neuropathy: Report of the American Academy of Neurology, the American Association of Neuromuscular and Electrodiagnostic Medicine, and the American Academy of Physical Medicine and Rehabilitation," Neurology, 2011 [epub ahead of print]
Carroll DG, Kline KM, and Malnar KF, "Role of Topiramate for the Treatment of Painful Diabetic Peripheral Neuropathy," Pharmacotherapy, 2004, 24(9):1186-93.
Chong MS and Libretto SE, " The Rationale and Use of Topiramate for Treating Neuropathic Pain," Clin J Pain, 2003, 19(1):59-68.
Dib JG, "Focus on Topiramate in Neuropathic Pain," Curr Med Res Opin, 2004, 20(12):1857-61.
Doose DR, Walker SA, Gisclon LG, et al, “Single-Dose Pharmacokinetics and Effect of Food on the Bioavailability of Topiramate, a Novel Antiepileptic Drug,” J Clin Pharmacol, 1996, 36(10):884-91.
Glauser TA, Clark PO, and Strawsburg R, “A Pilot Study of Topiramate in the Treatment of Infantile Spasms,” Epilepsia, 1998, 39(12):1324-8.
Glauser TA, “Preliminary Observations on Topiramate in Pediatric Epilepsies,” Epilepsia, 1997, 38(Suppl 1):37-41.
Glauser TA, “Topiramate Use in Pediatric Patients,” Can J Neurol Sci, 1998, 25(3):S8-12.
Hershey AD, Powers SW, Vockell AL, et al, “Effectiveness of Topiramate in the Prevention of Childhood Headaches,” Headache, 2002, 42(8):810-18.
Krymchantowski AV, Bigal ME, and Moreira PR, “New and Emerging Prophylactic Agents for Migraine,” CNS Drugs, 2002, 16(9):611-34.
Mathew NT, Kailasam J, and Meadors L, “Prophylaxis of Migraine, Transformed Migraine, and Cluster Headache With Topiramate,” Headache, 2002, 42(8):796-803.
Ohman I, Vitols S, Luef G, et al, “Topiramate Kinetics During Delivery, Lactation, and in the Neonate: Preliminary Observations,” Epilepsia, 2002, 43(10):1157-60.
Pascual J, Lainez MJ, Dodick D, et al, “Antiepileptic Drugs for the Treatment of Chronic and Episodic Cluster Headache: A Review,” Headache, 2007, 47(1):81-9.
Raskin P, Donofrio PD, Rosenthal NR, et al, “Topiramate vs Placebo in Painful Diabetic Neuropathy: Analgesic and Metabolic Effects,” Neurology, 2004, 63(5):865-73.
Silberstein SD and Goadsby PJ, “Migraine: Preventative Treatment,” Cephalalgia, 2002, 22(7):491-512.
Sachdeo RC, “Topiramate. Clinical Profile in Epilepsy,” Clin Pharmacokinet, 1998, 34(5):335-46.
Story JR, Calder CS, Hart DE, et al, “Topiramate in Migraine Prevention: A Double-Blind, Placebo-Controlled Study,” Headache, 2001, 41(10):968-75.
Thienel U, Neto W, Schwabe SK, et al, “Topiramate in Painful Diabetic Polyneuropathy: Findings from Three Double-Blind Placebo-Controlled Trials,” Acta Neurol Scand, 2004, 110(4):221-31.
Westin AA, Nakken KO, Johannessen SI, et al, "Serum Concentration/dose Ratio of Topiramate During Pregnancy," Epilepsia, 2009, 50(3):480-5.
Young WB, Hopkins MM, Shechter AL, et al, “Topiramate: A Case Series Study in Migraine Prophylaxis,” Cephalalgia, 2002, 22(8):659-63.
International Brand Names
Lexi-Comp.com
Last full review/revision May 2011
Content last modified May 2011
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