Topiramate (Lexi-Drugs)

Pronunciation

(toe PYRE a mate)

Brand Names: US

Qudexy XR; Topamax; Topamax Sprinkle; Trokendi XR

Brand Names: Canada

Abbott-Topiramate [DSC]; ACCEL-Topiramate [DSC]; AG-Topiramate; APO-Topiramate; Auro-Topiramate; DOM-Topiramate; GD-Topiramate [DSC]; GLN-Topiramate; JAMP-Topiramate; Mar-Topiramate; MINT-Topiramate; MYLAN-Topiramate; PHL-Topiramate [DSC]; PMS-Topiramate; PRO-Topiramate; Q-Topiramate [DSC]; RAN-Topiramate; SANDOZ Topiramate; TEVA-Topiramate; Topamax; Topamax Sprinkle

Pharmacologic Category

Anticonvulsant, Miscellaneous

Dosing: Adult

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 (In clinical trials, adult doses were withdrawn by decreasing in weekly intervals of 50 to 100 mg daily gradually over 2 to 8 weeks for seizure treatment, and by decreasing in weekly intervals by 25 to 50 mg daily for migraine prophylaxis.) Bioequivalence has not been demonstrated between Trokendi XR and Qudexy XR.

Epilepsy, monotherapy: Partial-onset seizure and primary generalized tonic-clonic seizure: Oral:

Immediate release: Initial: 25 mg twice daily; may increase weekly by 50 mg daily up to 100 mg twice daily (week 4 dose); thereafter, may further increase weekly by 100 mg daily up to the recommended dose of 200 mg twice daily.

Extended release: Initial: 50 mg daily for 1 week; may increase weekly by 50 mg daily up to 200 mg once daily (week 4 dose); thereafter, may further increase weekly by 100 mg daily up to the recommended dose of 400 mg once daily.

Epilepsy, adjunctive therapy: Partial-onset seizure, primary generalized tonic-clonic seizure, or Lennox-Gastaut syndrome: Oral: Note: Doses >1600 mg have not been studied.

Immediate release: Initial: 25 mg once or twice daily for 1 week; may increase weekly by 25 to 50 mg daily until response; usual maintenance dose: 100 to 200 mg twice daily (partial-onset seizures or Lennox-Gastaut syndrome) or 200 mg twice daily (primary generalized tonic-clonic seizures). Doses >400 mg have not shown additional benefit for treatment of partial-onset seizures.

Extended release: Initial: 25 to 50 mg once daily for 1 week; may increase weekly by 25 to 50 mg daily until response; usual maintenance dose: 200 to 400 mg once daily (partial-onset seizures, Lennox-Gastaut syndrome) or 400 mg once daily (primary generalized tonic-clonic seizures). Doses >400 mg daily have not shown additional benefit for treatment of partial-onset seizures.

Migraine prophylaxis: Oral:

Immediate release: Initial: 25 mg once daily (in evening); may increase weekly by 25 mg daily up to the recommended dose of 100 mg daily given in 2 divided doses. Increased intervals between dose adjustments may be considered. Doses >100 mg daily have shown no additional benefit.

Extended release: Initial: 25 mg once daily; increase based on response and tolerability in weekly increments of 25 mg to the recommended dose of 100 mg once daily. Increased intervals between dose adjustments may be considered.

Alcohol use disorder (off-label use): Oral: Immediate release: Initial: 25 mg once daily; increase dose weekly to a maximum of 300 mg/day in 2 divided doses by weeks 5 to 14 (Johnson 2007) or weeks 8 to 12 (Johnson 2003; Johnson 2004).

Antipsychotic-induced weight gain (off-label use): Oral: Initial: 25 mg twice daily for one week; continue to increase in increments of 25 to 50 mg each week based on response and tolerability up to 300 mg/day. Target doses in clinical trials ranged from 100 to 300 mg/day (Ko 2005; Mahmood 2013; Narula 2010; Nickel 2005b).

Binge eating disorder (off-label use): Oral: Initial: 25 mg once daily; titrate to a target dose of 400 mg/day (McElroy 2007). Dosage increases were made weekly in progressively larger increments ranging from 25 to 100 mg/day; doses were divided twice daily. Higher doses were not well tolerated (McElroy 2003).

Borderline personality disorder (off-label use): Oral: Initial: 25 to 50 mg/day; increase in increments of 25 to 50 mg each week based on response and tolerability up to a target dose of 200 to 250 mg/day (Loew 2006; Nickel 2004; Nickel 2005a). Additional data may be necessary to further define the role of topiramate in this condition.

Bulimia nervosa (off-label use): Oral: Initial: 25 mg once daily for week 1; titrate at weekly intervals in 25 to 50 mg increments to the minimal effective dose or a maximum of 400 mg/day (Hedges 2003; Hoopes 2003).

Cluster headache prophylaxis (off-label use): Oral: Initial: 25 mg daily, titrated at weekly intervals in 25 mg increments, up to 200 mg daily (Pascual 2007)

Essential tremor (off-label use): Oral: Initial: 25 mg once daily; increase dose at weekly intervals based on response and tolerability in 25 mg increments up to 100 mg/day and then in 50 mg increments up to 400 mg/day (Ondo 2006). Alternatively, once 200 mg/day is achieved, doses may be increased weekly in 100 mg increments up to 400 mg/day (Connor 2008). For dosages ≥50 mg/day administer in 2 divided doses (Ondo 2006). Average doses in clinical trials were 292 mg/day (median: 375 mg/day) (Ondo 2006) and 215 mg/day (range: 25 to 400 mg/day) (Connor 2008)

Dosing: Geriatric

Most older adults have creatinine clearances <70 mL/minute/1.73 m2; obtain a serum creatinine and calculate creatinine clearance prior to initiation of therapy. An initial dose of 25 mg/day may be recommended, followed by incremental increases of 25 mg at weekly intervals until an effective dose is reached; refer to adult dosing for titration schedule.

Dosing: Renal Impairment: Adult

CrCl ≥70 mL/minute/1.73 m2: There are no dosage adjustments provided in the manufacturer’s labeling.

CrCl <70 mL/minute/1.73 m2: Reduce dose to 50% of normal dose and titrate more slowly.

Hemodialysis: 50 to 100 mg twice daily; administer a supplemental dose (50 to 100 mg) post-dialysis (Israni 2006). Topiramate is cleared by hemodialysis.

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer’s labeling. However, topiramate clearance in hepatic impairment may be reduced. Use with caution.

Dosing: Pediatric

Note: Do not abruptly discontinue therapy; taper dosage gradually to prevent rebound effects.

Infantile spasms: Oral: Limited data available; dosing regimens variable. Consider twice-daily therapy once dose titration begins:

Newly diagnosed infantile spasm: Weight-directed dosing: Infants and Children 3 to 24 months: Immediate release: Initial: 1 to 3 mg/kg/day administered as 1 or 2 daily doses; titrate every 3 to 7 days in 1 to 3 mg/kg/day increments as tolerated until seizures controlled; reported mean dose range: 9.1 to 14 mg/kg/day; reported range: 4 to 27 mg/kg/day. Dosing based on two small studies; first was an open-label trial of 15 pediatric patients (mean age: 8 months; age range: 4 to 14 months) with newly diagnosed infantile spasms which used an initial dose of 3 mg/kg/day in 2 divided doses; doses were increased by 3 mg/kg/day every 3 days until seizures were controlled or toxicity developed; mean dose required: 14 mg/kg/day (9 to 27 mg/kg/day); median rate of spasm reduction was 41% within the first 2 months of therapy with 20% of patients becoming spasm free (three of 15 patients) and 33% achieving a 50% reduction in spasm frequency (five of 15 patients) (Hosain, 2006). In another trial of 20 pediatric patients (median age: 6.5 months; range: 3 to 24 months) with newly diagnosed infantile spasms, an initial dose of 1 mg/kg/day was used; dose was increased by 1 mg/kg/day at weekly intervals until seizures were controlled up to a maximum daily dose: 12 mg/kg/day; reported mean stabilizing dose: 9.1 mg/kg/day (4 to 12 mg/kg/day); results showed 30% of patients became spasm free (six of 20 patients) and 70% achieved at least a 50% reduction in spasm frequency (Kwon, 2006)

Refractory: Fixed dosing: Infants ≥3 months to Children ≤4 years; weight ≥7 kg: Immediate release: Initial: 25 mg/day once daily; titrate in 25 mg/day increments every 2 to 3 days as tolerated until seizures controlled up to a maximum daily dose: 24 mg/kg/day; dosing is from an open-label trial of 11 pediatric patients (mean age: 24 months) which reported a mean stabilizing dose of 15 mg/kg/day (8.3 to 23.7 mg/kg/day); results showed statistically significant decrease in spasm frequency with 45% of patients becoming spasm free (Glauser, 1998). In an extension phase of this study in eight of the initial subjects, the mean dose was 29 mg/kg/day (maximum daily dose: 50 mg/kg/day); 50% of the remaining patients (four of eight) were seizure free and all patients except one maintained a ≥50% reduction in spasm frequency (Glauser, 2000)

Anticonvulsant, adjunctive therapy: Oral:

Children and Adolescents 2 to 16 years:

Partial onset seizures or Lennox-Gastaut syndrome:

Immediate release: Children and Adolescents 2 to 16 years: Initial: 1 to 3 mg/kg/day (maximum dose: 25 mg/dose) administered nightly for 1 week; increase at 1- to 2-week intervals in increments of 1 to 3 mg/kg/day in 2 divided doses; titrate dose to response; usual maintenance: 5 to 9 mg/kg/day in 2 divided doses

Extended release:

Qudexy XR: Children and Adolescents 2 to 16 years: Initial: 25 mg once daily (approximately 1 to 3 mg/kg/day) administered nightly for 1 week; increase at 1- to 2-week intervals in increments of 1 to 3 mg/kg/day rounded to the nearest appropriate capsule size administered once daily; titrate dose to response; usual maintenance: 5 to 9 mg/kg/dose once daily; range: 5 to 9 mg/kg/dose once daily

Trokendi XR: Children and Adolescents 6 to 16 years, able to swallow capsule whole: Initial: 25 mg once daily (approximately 1 to 3 mg/kg/day) administered nightly for 1 week; increase at 1- to 2-week intervals in increments of 1 to 3 mg/kg/day rounded to the nearest appropriate capsule size administered once daily; titrate dose to response; usual maintenance: 5 to 9 mg/kg/dose once daily

Primary generalized tonic-clonic seizures:

Immediate release: Children and Adolescents 2 to 16 years: Initial: 1 to 3 mg/kg/day (maximum dose: 25 mg/dose) administered nightly for 1 week; increase over 8 weeks in increments of 1 to 3 mg/kg/day in 2 divided doses to a target dose of 6 mg/kg/day in 2 divided doses

Extended release:

Qudexy XR: Children and Adolescents 2 to 16 years: Initial: 25 mg once daily (approximately 1 to 3 mg/kg/day) administered nightly for 1 week; increase over 8 weeks in increments of 1 to 3 mg/kg/day rounded to the nearest appropriate capsule size to a target dose of 6 mg/kg/day once daily; range: 5 to 9 mg/kg/dose once daily

Trokendi XR: Children and Adolescents 6 to 16 years, able to swallow capsule whole: Initial: 25 mg once daily (approximately 1 to 3 mg/kg/day) administered nightly for 1 week; increase over 8 weeks in increments of 1 to 3 mg/kg/day rounded to the nearest appropriate capsule size to a target dose of 6 mg/kg/day once daily

Adolescents ≥17 years:

Partial onset seizures or Lennox-Gastaut syndrome:

Immediate release: Initial: 25 to 50 mg/day administered daily for 1 week; increase at weekly intervals by 25 to 50 mg/day; administer in 2 divided doses; titrate dose to response; usual maintenance dose: 100 to 200 mg twice daily; maximum daily dose: 1600 mg/dayNote: Doses above 400 mg/day have not been shown to increase efficacy in dose-response studies in adults.

Extended release: Quedexy XR, Trokendi XR: Initial: 25 to 50 mg once daily for 1 week; increase at weekly intervals by 25 to 50 mg/day once daily; titrate dose to response; longer intervals between dosage adjustment may be used; usual maintenance dose: 200 to 400 mg once daily; maximum daily dose: 1600 mg/day; higher doses have not been studied

Primary generalized tonic-clonic seizures:

Immediate release: Initial: 25 to 50 mg/day once daily for 1 week; increase over 8 weeks in increments of 25 to 50 mg/day in 2 divided doses; titrate dose to response; usual maintenance dose: 200 mg twice daily; use slower initial titration rate (>2 week intervals); maximum daily dose: 1600 mg/dayNote: Doses above 400 mg/day have not been shown to increase efficacy in dose-response studies in adults.

Extended release: Qudexy XR, Trokendi XR: Initial: 25 mg to 50 mg once daily for 1 week; increase at weekly intervals by 25 to 50 mg/day increments once daily; titrate dose to response; usual maintenance dose: 400 mg once daily; maximum daily dose: 1600 mg/day; higher doses have not been studied

Anticonvulsant, monotherapy: Partial onset seizures or primary generalized tonic-clonic seizures: Oral:

Immediate release:

Children 2 to <10 years: Initial: 25 mg once daily (in evening); may increase if tolerated to 25 mg twice daily in week 2; thereafter, may increase by 25 to 50 mg/day at weekly intervals over 5 to 7 weeks up to the lower end of the target daily maintenance dosing range (ie, to the minimum recommended maintenance dose); if additional seizure control is needed and therapy is tolerated, may further increase by 25 to 50 mg/day at weekly intervals up to the upper end of the target daily maintenance dosing range (ie, to the maximum recommended maintenance dose):

Target daily maintenance dosing range:

≤11 kg: 150 to 250 mg/day in 2 divided doses

12 to 22 kg: 200 to 300 mg/day in 2 divided doses

23 to 31 kg: 200 to 350 mg/day in 2 divided doses

32 to 38 kg: 250 to 350 mg/day in 2 divided doses

>38 kg: 250 to 400 mg/day in 2 divided doses

Children ≥10 years and Adolescents: Initial: 25 mg twice daily; increase at weekly intervals by 50 mg/day increments up to a dose of 100 mg twice daily (week 4 dose); thereafter, may further increase at weekly intervals by 100 mg/day increments up to the recommended maximum dose of 200 mg twice daily

Extended release: Qudexy XR, Trokendi XR: Children ≥10 years and Adolescents: Initial: 50 mg once daily for 1 week; increase at weekly intervals by 50 mg/day increments up to a dose of 200 mg once daily (week 4 dose); thereafter, may increase at weekly intervals by 100 mg/day increments up to the recommended dose of 400 mg once daily

Migraine prophylaxis: Oral:

Children 6 to <12 years; weight: ≥20 kg: Limited data available: Immediate release: Initial: 15 mg once daily for 1 week; then increase to 15 mg twice daily for 1 week; then increase to 25 mg twice daily for 7 days; continue to gradually titrate to effect up to target dose of 2 to 3 mg/kg/day divided twice daily; maximum daily dose: 200 mg/day; dosing based on a double-randomized, placebo-controlled trial of 90 pediatric patients <12 years (treatment arm: n=59; mean age: 11.3 years as part of a larger trial with a total of 108 pediatric patients receiving topiramate compared to 49 receiving placebo) which showed a mean reduction in migraine days/month with topiramate and significantly more topiramate patients experienced ≥75% reduction in mean monthly migraine days compared to placebo (32% vs 14%) for overall study population; mean maintenance dose: 2 mg/kg/day; treatment duration of maintenance dose: 12 weeks (Winner, 2005)

Children ≥12 years and Adolescents: Initial: 25 mg/day once daily at night for 1 week; increase at weekly intervals in 25 mg/day increments as tolerated and indicated to recommended dose of 50 mg twice daily; in a double-blind, placebo-controlled, dose-finding trial of 103 pediatric patients ≥12 years (mean age: 14.2 years), the daily dose of 100 mg/day was shown to significantly decrease frequency of migraine attacks compared to a lower dose of 50 mg/day (Lewis, 2009)

Dosing: Renal Impairment: Pediatric

Oral:

Infants, Children, and Adolescents: There are no dosage adjustments provided in the manufacturer’s labeling; however, the following guidelines have been used by some clinicians (Aronoff 2007):

GFR >50 mL/minute/1.73 m2: No dosage adjustment necessary

GFR 10 to 50 mL/minute/1.73 m2: Administer 50% of dose

GFR <10 mL/minute/1.73 m2: Administer 25% of dose

Hemodialysis/peritoneal dialysis (PD): Administer 25% of dose; supplemental dose after hemodialysis needed

Continuous renal replacement therapy (CRRT): Administer 50% of dose

Dosing: Hepatic Impairment: Pediatric

Children and Adolescents: There are no dosage adjustments provided in the manufacturer’s labeling; however, clearance may be reduced. Carefully adjust dose as plasma concentrations may be increased if normal dosing is used.

Use: Labeled Indications

Epilepsy:

Monotherapy: As initial monotherapy in patients ≥2 years (immediate release and Qudexy XR) or ≥6 years (Trokendi XR) with partial-onset or primary generalized tonic-clonic seizures

Adjunctive therapy: As adjunctive therapy in patients ≥2 years (immediate release and Qudexy XR) or ≥6 years (Trokendi XR only) with partial-onset seizures, primary generalized tonic-clonic seizures, or seizures associated with Lennox-Gastaut syndrome

Migraine: Prophylaxis of migraine headache in patients ≥12 years.

Use: Off-Label: Adult

  Alcohol use disorderLevel of Evidence [B, G]

Data from meta-analyses and controlled trials indicate that topiramate has moderate efficacy in the management of alcohol use disorder by decreasing consumption and cravings and improving quality of life and feelings of well-being (Blodgett 2014; Johnson 2003; Johnson 2004; Johnson 2007; Jonas 2014). Additional trials may be necessary to further define the role of topiramate in this condition.

Based on the American Psychiatric Association guidelines for the pharmacological treatment of patients with alcohol use disorder, topiramate is suggested for patients with alcohol use disorder (moderate to severe) who want to decrease or abstain from use of alcohol and either prefer topiramate or are unable to tolerate or are unresponsive to naltrexone and acamprosate (APA [Reus 2018]). Access Full Off-Label Monograph

  Antipsychotic-induced weight gainLevel of Evidence [B, G]

Data from multiple meta-analyses with varying degrees of heterogeneity support the use of topiramate in promoting modest weight loss and preventing weight gain associated with second-generation antipsychotics in patients with schizophrenia (evidence is more limited in patients with bipolar disorder). Additional data are necessary to further define the role of topiramate in this condition.

Based on the Canadian Network for Mood and Anxiety Treatments (CANMAT) recommendations for the management of patients with mood disorders and comorbid metabolic disorders, topiramate is recommended as a second-line option after nonpharmacologic strategies for managing weight gain in patients with bipolar and major depressive disorders, and is recognized as often being used as a secondary prevention strategy for antipsychotic-related weight gain. Access Full Off-Label Monograph

  Binge eating disorderLevel of Evidence [B, G]

Data from large controlled trials and clinical practice guidelines support the use of topiramate for the treatment of binge eating disorder, based on reductions in binge eating episodes and body weight; however, topiramate may be poorly tolerated. Access Full Off-Label Monograph

  Borderline personality disorderLevel of Evidence [C, G]

Data from two meta-analyses evaluating several small randomized, controlled trials suggest that topiramate may be beneficial for the treatment of interpersonal problems, impulsivity, anxiety, anger and general psychiatric pathology associated with borderline personality disorder Ref. Additional data may be necessary to further define the role of topiramate in this condition.

Based on the World Federation of Societies of Biological Psychiatry guidelines for the treatment of personality disorders, mood stabilizers like topiramate may be indicated for the treatment of impulsive and aggressive behavior in patients with borderline personality disorder Ref.

  Bulimia nervosaLevel of Evidence [B, G]

In small controlled trials, topiramate demonstrated efficacy in the treatment of bulimia nervosa; however, adverse reactions with topiramate are common. Additional trials may be necessary to further define the role of topiramate in this condition.

The American Psychiatric Association guidelines for the treatment of patients with eating disorders state that topiramate is effective but, because adverse effects are common, it should only be used when other medications are ineffective. Because topiramate is associated with weight loss, its use may be problematic in normal- or lower-weight patients. According to World Federation of Societies of Biological Psychiatry guidelines for the pharmacological treatment of eating disorders, topiramate has demonstrated efficacy in the management of bulimia nervosa but is associated with a moderate benefit-risk ratio. Access Full Off-Label Monograph

  Cluster headache (prophylaxis)Level of Evidence [C]

Data from a limited number of preliminary clinical trials suggest that topiramate may be beneficial in the prevention of cluster headache Ref. Additional data may be necessary to further define the role of topiramate in this condition.

  Essential tremorLevel of Evidence [B, G]

Data from a randomized, double blind, controlled study, and a pooled analysis of 3 double-blind, placebo controlled, crossover studies support the use of topiramate in the treatment of essential tremor; however, many patients experienced treatment-limiting adverse effects including paresthesia, nausea, concentration/attention difficulty, and somnolence (Connor 2008; Ondo 2006). Additional trials may be necessary to further define the role of topiramate in this condition. Access Full Off-Label Monograph

Based on the American Academy of Neurology practice parameter for the treatment of essential tremor, topiramate given for limb tremor associated with essential tremor is probably effective and use of topiramate may be considered in the management of this condition.

Level of Evidence Definitions
  Level of Evidence Scale
Use: Unsupported: Adult
Neuropathic pain

Data from a meta-analysis of 3 parallel-group, double-blind, placebo-controlled trials in diabetic neuropathy and a double-blind, randomized, cross-over study in lumbar radiculopathy demonstrated negative results indicating that topiramate is no more effective than placebo in the treatment of neuropathic pain. In addition, withdrawals due to adverse events were significantly higher in patients receiving topiramate than placebo (Wiffen 2013).

American Academy of Neurology evidence-based guidelines for the treatment of painful diabetic neuropathy (PDN) describe topiramate as an agent with insufficient evidence to support or refute use in the treatment of PDN (AAN [Bril 2011]). However, a consensus statement from the International Association for the Study of Pain suggests that topiramate may be considered in patients who have not responded to first or second-line medications (Dworkin 2007).

Clinical Practice Guidelines

Alcohol Use Disorder:

American Psychiatric Association (APA), “Practice Guideline for the Pharmacological Treatment of Patients With Alcohol Use Disorder,” January 2018

Bipolar Disorder:

Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD), “Collaborative Update of CANMAT Guidelines for the Management of Patients with Bipolar Disorder – Update 2013,” February 2013

Essential Tremor:

American Academy of Neurology, “Practice Parameter: Therapies for Essential Tremor,” June 2005

Metabolic Disorders:

Canadian Network for Mood and Anxiety Treatments (CANMAT), “Recommendations for the Management of Patients with Mood Disorders and Comorbid Metabolic Disorders,” February 2012

Migraine Prophylaxis:

Neurology, “Evidence-Based Guideline Update: Pharmacologic Treatment for Episodic Migraine Prevention in Adults,” April 2012

Personality Disorders:

World Federation of Societies of Biological Psychiatry (WFSBP), “WFSBP guidelines for biological treatment of personality disorders,” 2007.

Seizure Disorders:

American Academy of Neurology and American Epilepsy Society, “Practice guideline update summary: Efficacy and tolerability of the new antiepileptic drugs I: Treatment of new-onset epilepsy,” 2018

American Academy of Neurology and American Epilepsy Society, “Practice guideline update summary: Efficacy and tolerability of the new antiepileptic drugs II: Treatment-resistant epilepsy, “ 2018

Administration: Oral

Administer without regard to meals. Administer the immediate release formulation in divided doses. It is not recommended to crush, break, or chew immediate release tablets due to bitter taste. Swallow extended release (ER) and sprinkle capsules whole. Sprinkle capsules and Qudexy XR capsules may also be opened to sprinkle the entire contents on a small amount (~1 teaspoon) of soft food; swallow immediately and do not chew. Do not store drug/food mixture for future use. Do not sprinkle Trokendi XR capsules on food, chew, or crush. Avoid alcohol use with Trokendi XR within 6 hours prior to and 6 hours after administration.

Administration: Pediatric

Oral: May be administered without regard to food.

Immediate release:

Tablets: Broken tablets have a bitter taste; tablets may be crushed, mixed with water, and administered immediately.

Sprinkle capsules: Swallow sprinkle capsules whole or open and sprinkle contents on small amount of soft food (eg, 1 teaspoonful of applesauce, oatmeal, ice cream, pudding, custard, or yogurt); swallow sprinkle/food mixture immediately; do not chew; do not store for later use; drink fluids after dose to make sure mixture is completely swallowed.

Extended release:

Qudexy XR: May be swallowed whole or may be opened and sprinkled on a small amount (~1 teaspoon) of soft food; swallow immediately and do not chew.

Trokendi XR: Swallow capsules whole; do not sprinkle capsules on food, chew, or crush. Avoid alcohol use with within 6 hours prior to and 6 hours after administration.

Hazardous Drugs Handling Considerations

Hazardous agent (NIOSH 2016 [group 3]).

Use appropriate precautions for receiving, handling, administration, and disposal. Gloves (single) should be worn during receiving, unpacking, and placing in storage.

NIOSH recommends single gloving for administration of intact tablets or capsules. If manipulating tablets/capsules (eg, to prepare an oral suspension), NIOSH recommends double gloving, a protective gown, and preparation in a controlled device; if not prepared in a controlled device, respiratory and eye/face protection as well as ventilated engineering controls are recommended. NIOSH recommends double gloving, a protective gown, and (if there is a potential for vomit or spit up) eye/face protection for administration of an oral liquid/feeding tube administration (NIOSH 2016). Assess risk to determine appropriate containment strategy (USP-NF 2017).

Storage/Stability

Extended release capsules: Store at 15°C to 30°C (59°F to 86°F). Protect from moisture. Protect from light.

Sprinkle capsules: Store at or below 25°C (77°F). Protect from moisture.

Tablets: Store at 15°C to 30°C (59°F to 86°F). Protect from moisture.

Extemporaneously Prepared

20 mg/mL Oral Suspension (ASHP Standard Concentration) (ASHP 2017)

A 20 mg/mL oral suspension may be made with topiramate tablets or powder, Ora-Plus and Ora-Sweet. Measure out 2,000 mg of topiramate (equivalent tablets or powder). If using tablets, crush in a mortar and reduce to a fine powder. Add 10 mL of Ora-Plus and mix to a uniform paste; mix while adding an additional 40 mL of Ora-Plus in incremental proportions. Add a small amount of Ora-Sweet and mix. Transfer to a calibrated, amber bottle; rinse mortar with Ora-Sweet and add sufficient quantity to make 100 mL. Label “shake well.” Stable for 90 days refrigerated or at room temperature (Allen 2017).

Allen LV Jr. Contemporary compounding: topiramate 20 mg/mL oral suspension. U.S. Pharmacist. 2017;42(5):46-47.

Medication Patient Education with HCAHPS Considerations

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience nausea, change in taste, lack of appetite, diarrhea, anxiety, fatigue, loss of strength and energy, headache, dry mouth, flushing, or hair loss. Have patient report immediately to prescriber signs of infection, signs of acidosis (confusion, fast breathing, tachycardia, abnormal heartbeat, severe abdominal pain, nausea, vomiting, fatigue, shortness of breath, or loss of strength and energy), signs of depression (suicidal ideation, anxiety, emotional instability, or confusion), signs of liver problems (dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or jaundice), signs of bleeding (vomiting blood or vomit that looks like coffee grounds; coughing up blood; hematuria; black, red, or tarry stools; bleeding from the gums; abnormal vaginal bleeding; bruises without a reason or that get bigger; or any severe or persistent bleeding), signs of a kidney stone (back pain, abdominal pain, or hematuria), abnormal heartbeat, abnormal breathing, pale skin, bradycardia, sweating a lot, vomiting, twitching, confusion, difficulty focusing, change in balance, severe dizziness, passing out, inability to eat, difficult urination, seizures, burning or numbness feeling, excessive weight loss, bone pain, angina, memory impairment, muscle pain, muscle weakness, tinnitus, difficulty speaking, tremors, abnormal gait, involuntary eye movements, agitation, irritability, panic attacks, mood changes, blurred vision, eye redness, vision changes, eye pain, or eye irritation (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

Medication Safety Issues
  Sound-alike/look-alike issues:
  Administration issues
Medication Guide and/or Vaccine Information Statement (VIS)

An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:

Qudexy XR: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/205122s003s005lbl.pdf#page=69

Topamax: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020505s057_020844s048lbl.pdf#page=50

Trokendi XR: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/201635s011s017lbl.pdf#page=58

Contraindications

Extended release: Recent alcohol use (ie, within 6 hours prior to and 6 hours after administration) (Trokendi XR only); patients with metabolic acidosis who are taking concomitant metformin (Qudexy XR only).

Immediate release: There are no contraindications listed in the manufacturer’s labeling.

Canadian 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 (confusion, psychomotor slowing, difficulty with concentration/attention, difficulty with memory, speech or language problems), psychiatric disturbances (depression or 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.

• 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; incidence may be dose-related. Risk may be increased in patients with inborn errors of metabolism or decreased hepatic mitochondrial activity. May be asymptomatic; monitor for lethargy, vomiting, or unexplained changes in mental status.

• Metabolic acidosis: May be associated with hyperchloremic nonanion gap metabolic acidosis due to inhibition of carbonic anhydrase and increased renal bicarbonate loss. Decreases in serum bicarbonate are relatively common (up to 67% of epilepsy patients and 77% of migraine patients) 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). However, risk may be increased in patients with a predisposing condition (renal, respiratory and/or hepatic impairment), diarrhea, ketogenic diet, status epilepticus, 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, nephrocalcinosis, osteomalacia/osteoporosis, and reduced growth rates and/or reduced weight 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.

• Oligohidrosis/hyperthermia: May be associated with oligohidrosis 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.

• Ophthalmic effects: 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 and/or ocular pain.

• Renal calculus: Topiramate exhibits weak carbonic anhydrase inhibitory properties and may increase the risk of kidney stones about 2 to 4 times that of the untreated population. Kidney stones have been reported in children and adults (incidence higher in males). Consider avoiding use in patients on a ketogenic diet. The risk of kidney 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.

• Visual field defects: Has been reported independent of increased intraocular pressure; generally reversible upon discontinuation. Consider discontinuation if visual problems occur at any time during treatment.

Disease-related concerns:

• Depression: Use with caution in patients with depression or suicidal tendencies.

• Eating disorders: The exacerbation and development of eating disorders, including anorexia nervosa and bulimia, has been reported in case reports of adolescents receiving topiramate for migraines or chronic headaches and an adult receiving topiramate for epilepsy. Prior to initiation of topiramate screen for a history of eating disorder symptoms, eating disorder risk factors (eg, history of dieting behavior), cognitive symptoms of eating disorders (eg, weight or shape concerns, fear of gaining weight, drive for thinness), and any recent changes in social functioning including increased withdrawal or isolation. Inquire whether the patient has unrealistic or unhealthy weight goals. Evaluate exercise habits (eg, look for over-exercising or compulsive exercising above that of similarly athletic peers) and dietary intake; assess rigid patterns or avoidance of specific categories of foods and preoccupation with maintaining a “healthy diet” or experimentation with fad diets. In adolescents assess developmental weight history with growth curves. Monitor eating behaviors and weight closely in patients receiving topiramate who have eating disorder symptoms or risk factors (Lebow 2015; Rosenow 2002).

• Hepatic impairment: Use caution with hepatic impairment; clearance may be reduced. Dosage adjustment may be required.

• Renal impairment: Use caution with renal impairment; clearance may be reduced. Dosage adjustment may be required.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Elderly: Use with caution; dosage adjustment may be necessary. Weight loss, cognitive impairment, sedation, and gait/balance disturbances may be more pronounced in the older adult cohort (Sommer 2010).

Other warnings/precautions:

• Withdrawal: Do not discontinue 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).

Geriatric Considerations

Despite evidence of benefit as monotherapy in the older adult population, this drug may not be a drug of choice in the elderly until all other therapies for seizures have been exhausted. This is due to a cadre of adverse effects which can be pronounced in the older adult patient. Weight loss, gait/balance impairments, tremor, sedation, and cognitive impairment can be especially troublesome in the older adult (Blaszczyk 2015; Groselj 2005; Sommer 2010). Because of the cognitive impairment issues which can manifest with topiramate (eg, word recall, short-term memory impairment), this medication should be identified as potentially at issue when a patient is being worked up for dementia.

Since most elderly will have a CrCl <70 mL/minute, it is important to either measure or estimate by calculation the CrCl prior to initiating therapy.

Warnings: Additional Pediatric Considerations

 In pediatric clinical trials for adjunctive treatment of seizures, persistent decreases in serum bicarbonate occurred in 67% of patients receiving topiramate (versus 10% of those receiving placebo). Markedly low serum bicarbonate values were reported in 11% of pediatric patients receiving topiramate (versus 0% of those receiving placebo). In pediatric monotherapy trials, persistent decreases in serum bicarbonate occurred in 9% of patients receiving 50 mg/day and 25% of patients receiving 400 mg/day. Markedly low serum bicarbonate values were reported in 1% to 6% of pediatric patients receiving topiramate monotherapy. The risk of topiramate-induced metabolic acidosis may be increased in patients with predisposing conditions (eg, diarrhea, status epilepticus, hepatic impairment, renal dysfunction, severe respiratory disorders, ketogenic diet, surgery) or concurrent treatment with other drugs that may cause acidosis. Metabolic acidosis may be more common and more severe in infants and children <2 years of age with up to 45% of patients receiving 25 mg/kg/day developing metabolic acidosis in clinical trials. Monitor for potential complications of chronic acidosis including nephrolithiasis, nephrocalcinosis, osteomalacia/osteoporosis, and reduction in growth rates (including weight). Reductions in Z scores (from baseline) for length, weight, and head circumference were observed in infants and toddlers who received long-term topiramate (for up to 1 year) for intractable partial epilepsy; reductions in Z scores for length and weight correlated to the severity of metabolic acidosis. Serum bicarbonate should be monitored at baseline and periodically during topiramate therapy. The most common adverse effects of topiramate observed in children include the following: Anorexia, cognitive problems, dizziness, fatigue, fever, flushing, headache, mood problems, parethesia, somnolence, and weight loss; neuropsychiatric and cognitive adverse effects were reported with a lower incidence in children than adults. Pediatric patients <24 months of age may be at increased risk for topiramate-associated hyperammonemia, especially when used concurrently with valproic acid; monitor closely for lethargy, vomiting, or unexplained changes in mental status.

Risk of nephrolithiasis (kidney stones) is higher in children; reported incidence in adults: 1.5%; in pediatric patients <24 months with long-term use (up to 1 year): 7% (kidney or bladder stones); one retrospective study evaluating long-term use (1 year) in children with epilepsy (n=96; mean age: 6.9 ± 3.8 years) reported an incidence of 5.2% (Mahmoud, 2011); risk may be increased with ketogenic diet or concomitant drugs that produce metabolic acidosis; avoid use while on topiramate therapy; maintain adequate hydration during therapy; monitor for signs or symptoms of kidney or bladder or kidney stone development.

Extended release dosage forms (Qudexy XR and Trokendi XR) are not bioequivalent and should not be interchanged. Qudexy XR capsules may be opened and contents sprinkled on a small amount (~1 teaspoon) of soft food. Do not open and sprinkle Trokendi XR capsules on food, nor chew or crush; doing so may disrupt the triphasic release properties.

Pregnancy Considerations

Based on limited data (n=5), topiramate was found to cross the placenta and could be detected in neonatal serum (Ohman 2002).

Topiramate may cause fetal harm if administered to a pregnant woman. An increased risk of oral clefts (cleft lip and/or palate) and for being small for gestational age (SGA) has been observed following in utero exposure. Data from the North American Antiepileptic Drug (NAAED) Pregnancy Registry reported that the prevalence of oral clefts was 1.1% for infants exposed to topiramate during the first trimester of pregnancy, versus 0.36% for infants exposed to a reference antiepileptic drug, and 0.12% for infants with no exposure born to mothers without epilepsy; the relative risk of oral clefts in infants exposed to topiramate was calculated to be 9.6 (95% CI: 4 to 23). Data from the NAAED Pregnancy Registry reported that the prevalence of small for gestational age newborns was 19.7% for newborns exposed to topiramate in utero, versus 7.9% for newborns exposed to a reference antiepileptic drug, and 5.4% for newborns with no exposure born to mothers without epilepsy. Although not evaluated during pregnancy, metabolic acidosis may be induced by topiramate. Metabolic acidosis during pregnancy may result in adverse effects and fetal death. Pregnant women and their newborns should be monitored for metabolic acidosis. In general, maternal polytherapy with antiepileptic drugs may increase the risk of congenital malformations; monotherapy with the lowest effective dose is recommended. Newborns of women taking antiepileptic medications may be at an increased risk of a 1 minute Apgar score <7 (Harden 2009).

Maternal serum concentrations may decrease during the second and third trimesters of pregnancy; therefore, therapeutic drug monitoring should be considered during pregnancy and postpartum in patients who require therapy (Ohman 2009; Westin 2009).

Effective contraception should be used in females of reproductive potential who are not planning a pregnancy; consider use of alternative medications in women who wish to become pregnant.

Data collection to monitor pregnancy and infant outcomes following exposure to topiramate is ongoing. Patients may enroll themselves into the NAAED Pregnancy Registry by calling 1-888-233-2334. Additional information is available at www.aedpregnancyregistry.org.

Breast-Feeding Considerations

Topiramate is present in breast milk.

The relative infant dose (RID) of topiramate is ~3% to 23% when calculated using a range of breast milk concentrations obtained from three lactating women and compared to a weight-adjusted maternal dose of 150 to 200 mg/day (Ohman 2002).

In general, breastfeeding is considered acceptable when the RID of a medication is <10%; when the RID is >25% breastfeeding should generally be avoided (Anderson 2016; Ito 2000).

The RID of topiramate was calculated using a range of milk concentrations of 1.6 to 14.6 micromolar, providing an estimated daily infant dose via breast milk of ~0.1 to 0.7 mg/kg/day. These milk concentrations were obtained following maternal administration of oral topiramate 150 to 200 mg/day in three women 2 weeks’ to 3 months’ postpartum; concomitant medications included carbamazepine or valproic acid, both of which may have had an impact on maternal serum concentrations. Topiramate was detected in the plasma of the breastfed infants at ~10% to 20% of the maternal plasma concentration (Ohman 2002).

Diarrhea and somnolence have been reported in breastfed infants. In 1 infant, resolution of diarrhea occurred 2 days after breastfeeding was stopped (Westergren 2014).

According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother.

Briggs’ Drugs in Pregnancy & Lactation
Adverse Reactions

Adverse events are reported for adult and pediatric patients for various indications and regimens. Note: A wide range of dosages were studied. Incidence of adverse events was frequently lower in the pediatric population studied.

>10%:

Central nervous system: Paresthesia (adolescents & adults: 19% to 51%; children & adolescents: 3% to 12%), fatigue (8% to 15%), drowsiness (adolescents & adults: 6% to 15%), dizziness (adolescents & adults: 6% to 14%), memory impairment (1% to 11%)

Endocrine & metabolic: Decreased serum bicarbonate (adolescents & adults: 14% to 77%; children & adolescents: 9% to 25%; >5 mEq/L to <17 mEq/L: 1% to 11%), hyperammonemia (adolescents: 14% to 26%; ≥50% above ULN [adolescents]: 9%), weight loss (4% to 17%)

Gastrointestinal: Abdominal pain (adolescents & adults: 6% to 15%), anorexia (adolescents & adults: 4% to 15%), dysgeusia (adolescents & adults: 3% to 15%), nausea (adolescents & adults: 8% to 13%), diarrhea (2% to 11%)

Respiratory: Upper respiratory tract infection (13% to 26%)

Miscellaneous: Fever (1% to 12%)

1% to 10%:

Cardiovascular: Flushing (children & adolescents: ≤5%), chest pain (adults: 1% to 2%)

Central nervous system: Disturbance in attention (≤10%), lack of concentration (≤10%), depression (adults: 7% to 9%; children & adolescents: ≤3%), insomnia (adolescents & adults: 6% to 9%), mood disorder (1% to 8%), hypoesthesia (adolescents & adults 4% to 7%), anxiety (adolescents & adults: 4% to 6%), cognitive dysfunction (1% to 6%), psychomotor retardation (adolescents & adults: 2% to 5%), headache (children and adolescents: 4%), nervousness (adolescents & adults: 4%), ataxia (adolescents & adults: 1% to 4%), behavioral problems (children & adolescents: ≤3%), confusion (≤3%), hypertonia (adults: ≤3%), vertigo (children and adolescents: ≤3%), agitation (adolescents & adults: 2%), exacerbation of depression (adolescents & adults: 2%), speech disturbance (adolescents & adults: 1%)

Dermatologic: Alopecia (1% to 4%), pruritus (adolescents & adults: 1% to 4%), skin rash (1% to 4%), acne vulgaris (adults: 2% to 3%)

Endocrine & metabolic: Menstrual disease (adolescents & adults: 3%), intermenstrual bleeding (children and adolescents: ≤3%), increased gamma-glutamyl transferase (adults: 1% to 3%), increased thirst (adolescents & adults: 2%)

Gastrointestinal: Dyspepsia (adolescents & adults: 4% to 5%), constipation (adolescents & adults: 1% to 4%), gastroenteritis (adolescents & adults: 3%), gastritis (adults: ≤3%), xerostomia (adolescents & adults: 1% to 3%), gastroesophageal reflux disease (adults: 1% to 2%), ageusia (adolescents & adults: 1%)

Genitourinary: Urinary tract infection (adolescents & adults: 1% to 4%), premature ejaculation (adolescents & adults: 3%), decreased libido (adults: ≤3%), urinary frequency (≤3%), vaginal hemorrhage (adults: ≤3%), cystitis (adults: 1% to 3%), urinary incontinence (children & adolescents: 1% to 3%), dysuria (adults: ≤2%)

Hematologic & oncologic: Hemorrhage (4% to 5%), anemia (children & adolescents: 1% to 3%), neoplasm (adolescents & adults: 2%)

Hypersensitivity: Hypersensitivity reaction (adolescents & adults: 2% to 4%)

Infection: Viral infection (3% to 8%), infection (2% to 8%)

Neuromuscular & skeletal: Arthralgia (adolescents & adults: 3% to 7%), asthenia (≤6%), muscle spasm (≤3%), lower extremity pain (adolescents & adults: 2% to 3%)

Ophthalmic: Conjunctivitis (adolescents & adults: 2% to 7%), blurred vision (adolescents & adults: 4%), visual disturbance (adolescents & adults: 1% to 2%)

Otic: Otitis media (adolescents & adults: 1% to 2%)

Renal: Nephrolithiasis (adolescents & adults: ≤3%)

Respiratory: Sinusitis (1% to 10%), cough (adolescents & adults: 2% to 7%), rhinitis (2% to 7%), pharyngitis (adolescents & adults: 5% to 6%), bronchitis (1% to 5%), epistaxis (children and adolescents: ≤4%), dyspnea (adolescents & adults: 1% to 3%)

Miscellaneous: Accidental injury (adolescents & adults: 9%), language problems (adolescents & adults: 6% to 7%)

Frequency not defined:

Cardiovascular: Hypotension, orthostatic hypotension, syncope

Central nervous system: Attempted suicide, suicidal ideation, suicidal tendencies

Endocrine & metabolic: Hyperchloremia (children & adolescents), increased serum total protein (children & adolescents), increased uric acid (children & adolescents)

Gastrointestinal: Gingival hemorrhage, hematuria

Hematologic & oncologic: Abnormal phosphorus levels (decreased; children & adolescents), decreased neutrophils (children & adolescents), decreased white blood cell count (children & adolescents), eosinophilia, quantitative disorders of platelets (increased; children & adolescents),

Hepatic: Increased serum alkaline phosphatase (children & adolescents)

Neuromuscular & skeletal: Myalgia

Ophthalmic: Myopia, scotoma, visual field defect

Renal: Increased blood urea nitrogen (children & adolescents), increased serum creatinine (children & adolescents)

<1%, postmarketing, and/or case reports: Acute myopia with secondary angle-closure glaucoma, bullous rash, erythema multiforme, hepatic failure, hepatitis, hyperammonemic encephalopathy, hyperchloremic metabolic acidosis (nonanion gap), hyperthermia, hypohidrosis, maculopathy, major hemorrhage (children), pancreatitis, pemphigus, Stevens-Johnson syndrome, toxic epidermal necrolysis

Allergy and Idiosyncratic Reactions
Metabolism/Transport Effects

None known.

Drug Interactions 

Alcohol (Ethyl): May enhance the CNS depressant effect of Topiramate. Alcohol (Ethyl) may increase the serum concentration of Topiramate. This applies specifically to use with the extended-release topiramate capsules (Trokendi XR). Also, topiramate concentrations may be subtherapeutic in the later portion of the dosage interval. Management: Concurrent use of alcohol within 6 hours of ingestion of extended-release topiramate (Trokendi XR) is contraindicated. Any use of alcohol with topiramate should be avoided when possible and should only be undertaken with extreme caution. Risk X: Avoid combination

Alizapride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Alpha-/Beta-Agonists (Indirect-Acting): Carbonic Anhydrase Inhibitors may increase the serum concentration of Alpha-/Beta-Agonists (Indirect-Acting). Risk C: Monitor therapy

Amantadine: Carbonic Anhydrase Inhibitors may increase the serum concentration of Amantadine. Risk C: Monitor therapy

Amitriptyline: Topiramate may enhance the CNS depressant effect of Amitriptyline. Topiramate may increase serum concentrations of the active metabolite(s) of Amitriptyline. Topiramate may increase the serum concentration of Amitriptyline. Risk C: Monitor therapy

Amphetamines: Carbonic Anhydrase Inhibitors may decrease the excretion of Amphetamines. Risk C: Monitor therapy

Anticholinergic Agents: May enhance the adverse/toxic effect of Topiramate. Risk C: Monitor therapy

Azelastine (Nasal): CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal). Risk X: Avoid combination

Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Risk D: Consider therapy modification

Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Bromopride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Bromperidol: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Buprenorphine: CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine patches (Butrans brand) at 5 mcg/hr in adults when used with other CNS depressants.Risk D: Consider therapy modification

Cannabidiol: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Cannabis: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

CarBAMazepine: May decrease the serum concentration of Topiramate. Risk D: Consider therapy modification

Carbonic Anhydrase Inhibitors: May enhance the adverse/toxic effect of other Carbonic Anhydrase Inhibitors. The development of acid-base disorders with concurrent use of ophthalmic and oral carbonic anhydrase inhibitors has been reported. Management: Avoid concurrent use of different carbonic anhydrase inhibitors if possible. Monitor patients closely for the occurrence of kidney stones and with regards to severity of metabolic acidosis. Risk X: Avoid combination

Chlormethiazole: May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Risk D: Consider therapy modification

Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Risk C: Monitor therapy

CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Risk C: Monitor therapy

Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Doxylamine: May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended. Risk C: Monitor therapy

Dronabinol: May enhance the CNS depressant effect of CNS Depressants. 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 (eg, opioids, barbiturates) with concomitant use. Exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Risk D: Consider therapy modification

Esketamine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Estrogen Derivatives (Contraceptive): Topiramate may decrease the serum concentration of Estrogen Derivatives (Contraceptive). 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

Flecainide: Carbonic Anhydrase Inhibitors may increase the serum concentration of Flecainide. Risk C: Monitor therapy

Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. 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

HYDROcodone: CNS Depressants may enhance the CNS depressant effect of HYDROcodone. Management: Avoid concomitant use of hydrocodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug.Risk D: Consider therapy modification

HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Kava Kava: May enhance the adverse/toxic effect of CNS Depressants. Risk C: Monitor therapy

Lacosamide: Antiepileptic Agents (Sodium Channel Blockers) may enhance the adverse/toxic effect of Lacosamide. Specifically the risk for bradycardia, ventricular tachyarrhythmias, or a prolonged PR interval may be increased. Risk C: Monitor therapy

Lithium: Topiramate may increase the serum concentration of Lithium. Risk C: Monitor therapy

Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Risk C: Monitor therapy

Loop Diuretics: May enhance the hypokalemic effect of Topiramate. Risk C: Monitor therapy

Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. 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

Memantine: Carbonic Anhydrase Inhibitors may increase the serum concentration of Memantine. Risk C: Monitor therapy

MetFORMIN: Topiramate may enhance the adverse/toxic effect of MetFORMIN. Risk C: Monitor therapy

Methenamine: Carbonic Anhydrase Inhibitors may diminish the therapeutic effect of Methenamine. Management: Consider avoiding this combination. Monitor for decreased therapeutic effects of methenamine if used concomitant with a carbonic anhydrase inhibitor. 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

MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Risk C: Monitor therapy

Mianserin: May diminish the therapeutic effect of Anticonvulsants. Risk C: Monitor therapy

Minocycline: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Mirtazapine: CNS Depressants may enhance the CNS depressant effect of Mirtazapine. Risk C: Monitor therapy

Nabilone: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Opioid Agonists: CNS Depressants may enhance the CNS depressant effect of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug.Risk D: Consider therapy modification

Orlistat: May decrease the serum concentration of Anticonvulsants. Risk C: Monitor therapy

Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Risk X: Avoid combination

Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification

Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Risk X: Avoid combination

Perampanel: May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination. Risk D: Consider therapy modification

Phenytoin: Topiramate may increase the serum concentration of Phenytoin. Phenytoin may decrease the serum concentration of Topiramate. Risk C: Monitor therapy

Pioglitazone: Topiramate may decrease the serum concentration of Pioglitazone. Risk C: Monitor therapy

Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Risk C: Monitor therapy

Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Risk C: Monitor therapy

Primidone: Carbonic Anhydrase Inhibitors may enhance the adverse/toxic effect of Primidone. Specifically, osteomalacia and rickets. Carbonic Anhydrase Inhibitors may decrease the serum concentration of Primidone. Risk C: Monitor therapy

Progestins (Contraceptive): Topiramate may decrease the serum concentration of Progestins (Contraceptive). 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

QuiNIDine: Carbonic Anhydrase Inhibitors may decrease the excretion of QuiNIDine. Risk C: Monitor therapy

ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Risk C: Monitor therapy

Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Risk C: Monitor therapy

Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Risk C: Monitor therapy

Salicylates: May enhance the adverse/toxic effect of Carbonic Anhydrase Inhibitors. Salicylate toxicity might be enhanced by this same combination. Management: Avoid these combinations when possible.Dichlorphenamide use with high-dose aspirin as contraindicated. If another combination is used, monitor patients closely for adverse effects. Tachypnea, anorexia, lethargy, and coma have been reported. Risk D: Consider therapy modification

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

Sodium Oxybate: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to combined use. When combined use is needed, consider minimizing doses of one or more drugs. Use of sodium oxybate with alcohol or sedative hypnotics is contraindicated. Risk D: Consider therapy modification

Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification

Tapentadol: May enhance the CNS depressant effect of CNS Depressants. Management: Avoid concomitant use of tapentadol and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification

Tetrahydrocannabinol: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Tetrahydrocannabinol and Cannabidiol: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Risk X: Avoid combination

Thiazide and Thiazide-Like Diuretics: May enhance the hypokalemic effect of Topiramate. Thiazide and Thiazide-Like 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

Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Ulipristal: Topiramate may decrease the serum concentration of Ulipristal. Risk X: Avoid combination

Valproate Products: Topiramate may enhance the adverse/toxic effect of Valproate Products. Risk C: Monitor therapy

Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Risk D: Consider therapy modification

Food Interactions

Ketogenic diet may increase the possibility of acidosis and/or kidney stones. Management: Monitor for symptoms of acidosis or kidney stones.

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, nephrocalcinosis, osteomalacia/osteoporosis, and reduced growth rates and/or weight 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); weight and eating behaviors in patients with eating disorder symptoms or risk factors; sedation

Advanced Practitioners Physical Assessment/Monitoring

Obtain electrolytes (including sodium bicarbonate at baseline and periodically), serum creatinine, and ammonia levels (if altered mental status occurs). Dosage adjustment may be needed in renal impairment. Monitor therapeutic effectiveness (seizure activity, type, duration) at beginning of therapy and throughout. Monitor weight periodically. Monitor for visual changes/disturbances. Assess for signs and symptoms of acidosis. Assess eating and weight behaviors in patients with eating disorder symptoms or risk factors. Teach patient seizure safety precautions.

Nursing Physical Assessment/Monitoring

Check ordered labs and report abnormalities. Monitor therapeutic response (seizure activity, force, type, duration) at beginning of therapy and throughout. Use and teach seizure/safety precautions. Monitor weight periodically. Monitor for visual changes/disturbances. Educate patient to monitor for weight loss or changes in appetite and to report.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule ER 24 Hour Sprinkle, Oral:

Qudexy XR: 25 mg, 50 mg, 100 mg, 150 mg, 200 mg

Generic: 25 mg, 50 mg, 100 mg, 150 mg, 200 mg

Capsule Extended Release 24 Hour, Oral:

Trokendi XR: 25 mg [contains brilliant blue fcf (fd&c blue #1), sodium benzoate]

Trokendi XR: 50 mg, 100 mg, 200 mg [contains brilliant blue fcf (fd&c blue #1), fd&c yellow #6 (sunset yellow), sodium benzoate]

Capsule Sprinkle, Oral:

Topamax Sprinkle: 15 mg, 25 mg

Generic: 15 mg, 25 mg

Tablet, Oral:

Topamax: 25 mg, 50 mg, 100 mg, 200 mg

Generic: 25 mg, 50 mg, 100 mg, 200 mg

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule Sprinkle, Oral:

Topamax Sprinkle: 15 mg, 25 mg

Tablet, Oral:

Topamax: 25 mg, 100 mg, 200 mg [contains POLYSORBATE 80]

Generic: 25 mg, 50 mg, 100 mg, 200 mg

Anatomic Therapeutic Chemical (ATC) Classification
  • N03AX11
Generic Available (US)

May be product dependent

Pricing: US

Capsule ER 24 Hour Sprinkle (Qudexy XR Oral)

25 mg (per each): $9.57

50 mg (per each): $12.47

100 mg (per each): $24.71

150 mg (per each): $30.39

200 mg (per each): $33.80

Capsule ER 24 Hour Sprinkle (Topiramate ER Oral)

25 mg (per each): $8.84

50 mg (per each): $11.52

100 mg (per each): $22.81

150 mg (per each): $28.06

200 mg (per each): $31.21

Capsule ER 24 Hour Therapy Pack (Trokendi XR Oral)

25 mg (per each): $11.47

50 mg (per each): $14.94

100 mg (per each): $29.61

200 mg (per each): $40.50

Capsule, sprinkles (Topamax Sprinkle Oral)

15 mg (per each): $6.87

25 mg (per each): $8.31

Capsule, sprinkles (Topiramate Oral)

15 mg (per each): $2.42

25 mg (per each): $2.92

Tablets (Topamax Oral)

25 mg (per each): $7.27

50 mg (per each): $14.50

100 mg (per each): $19.80

200 mg (per each): $23.18

Tablets (Topiramate Oral)

25 mg (per each): $2.22 – $2.55

50 mg (per each): $4.42 – $5.10

100 mg (per each): $6.04 – $6.96

200 mg (per each): $7.07 – $8.15

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer’s AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

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

Note: Immediate release preparations are bioequivalent (sprinkle capsule and tablet); extended release capsules (Trokendi XR) administered once daily is bioequivalent to twice daily administration of immediate release formulations.

Absorption: Good, rapid; immediate release formulation is unaffected by food. A single Trokendi XR dose with a high-fat meal increased the Cmax by 37% and shortened the Tmax to approximately 8 hours; this effect is significantly reduced following repeat administrations. A single Qudexy XR dose with a high-fat meal delayed the Tmax by 4 hours.

Distribution: Vd: 0.6 to 0.8 L/kg

Protein binding: 15% to 41% (inversely related to plasma concentrations)

Metabolism: Not extensively metabolized. Minor amounts metabolized in liver via hydroxylation, hydrolysis, and glucuronidation; there is evidence of renal tubular reabsorption; percentage of dose metabolized in liver and clearance are increased in patients receiving enzyme inducers (eg, carbamazepine, phenytoin)

Bioavailability: ~80% (immediate release)

Half-life elimination:

Immediate release:

Not receiving concomitant enzyme inducers or valproic acid:

Neonates (full-term) with hypothermia: ~43 hours (Filippi 2009)

Infants and Children 9 months to <4 years: 10.4 hours (range: 8.5 to 15.3 hours) (Mikaeloff 2004)

Children 4 to 7 years: Mean range: 7.7 to 8 hours (Rosenfeld 1999)

Children 8 to 11 years: Mean range: 11.3 to 11.7 hours (Rosenfeld 1999)

Children and Adolescents 12 to 17 years: Mean range: 12.3 to 12.8 hours (Rosenfeld 1999)

Receiving concomitant enzyme inducers (eg, carbamazepine, phenytoin, phenobarbital):

Neonates (full-term) with hypothermia: 26.5 hours (Filippi 2009)

Infants and Children 9 months to <4 years: 6.5 hours (range: 3.75 to 10.2 hours) (Mikaeloff 2004)

Children and Adolescents 4 to 17 years: 7.5 hours (Rosenfeld 1999)

Receiving valproic acid: Infants and Children 9 months to 4 years: 9.2 hours (range: 7.23 to 12 hours) (Mikaeloff 2004)

Adults: 19 to 23 hours (mean: 21 hours)

Adults with renal impairment: 59 ± 11 hours

Extended release: Qudexy XR: ~56 hours; Trokendi XR: ~31 hours

Time to peak, serum:

Immediate release:

Neonates (full-term) with hypothermia: 3.8 hours (Filippi 2009)

Infants and Children 9 months to <4 years: 3.7 hours (range: 1.5 to 10.2 hours) (Mikaeloff 2004)

Children 4 to 17 years: Mean range: 1 to 2.8 hours (Rosenfeld 1999)

Adults: 2 hours; range: 1.4 to 4.3 hours

Extended release: Qudexy XR: ~20 hours; Trokendi XR: ~24 hours

Excretion: Urine (~70% as unchanged drug); may undergo renal tubular reabsorption

Clearance:

Not receiving concomitant enzyme inducers or valproic acid:

Neonates (full-term) with hypothermia: 13.4 mL/kg/hour (Filippi 2009)

Infants and Children 9 months to <4 years: 46.5 mL/kg/hour (range: 30.5 to 70.9 mL/kg/hour) (Mikaeloff 2004)

Children 4 to 17 years: 27.6 mL/kg/hour (Rosenfeld 1999)

Receiving concomitant enzyme inducers:

Neonates (full-term) with hypothermia: 17.9 mL/kg/hour (Filippi 2009)

Infants and Children 9 months to <4 years: 85.4 mL/kg/hour (range: 46.2 to 135 mL/kg/hour) (Mikaeloff 2004)

Children and Adolescents 4 to 17 years: 60.6 mL/kg/hour (Rosenfeld 1999)

Receiving valproic acid: Infants and Children 9 months to <4 years: 49.6 mL/kg/hour (range: 26.6 to 60.2 mL/kg/h) (Mikaeloff 2004)

Adults: 20 to 30 mL/minute

Pharmacodynamics/Kinetics: Additional Considerations

Renal function impairment: Clearance is reduced 42% in moderately impaired (creatinine clearance [CrCl] 30 to 69 mL/minute/1.73 m2) and 54% in severely impaired (CrCl <30 mL/minute/1.73 m2) patients. Significantly hemodialyzed; dialysis clearance is 120 mL/minute (4-6 times higher than in adults with normal renal function).

Hepatic function impairment: Clearance is reduced by a mean of 26% in patients with moderate to severe hepatic impairment.

Geriatric: Half-life elimination is longer. Plasma and renal clearance were reduced 21% and 19%, respectively. Reduced clearance resulted in slightly higher Cmax (23% for immediate release; 30% for Trokendi XR) and AUC (25% for immediate release; 44% for Trokendi XR). Topiramate clearance is decreased only to the extent that renal function is reduced. Tmax for Trokendi XR is shorter (16 hours).

Local Anesthetic/Vasoconstrictor Precautions

No information available to require special precautions

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).

Effects on Bleeding

No information available to require special precautions

FDA Approval Date
December 24, 1996
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Brand Names: International

Acomicil (ES); Conviban (EG); Epilramate (TW); Epimate (BH, EG, LK, PH, ZW); Epiramat (UA); Epitomax (FI, FR); Epitop (PH); Etopira (BD); Fagodol (ES); Gabatopa (KR); Ipramax (BH, LB); Moramax (TH); Piramed (BD); Pradox (TH); Rondigal (CR, DO, GT, HN, NI, PA, SV); Seziril (LK); Tamate (AU); Tiramate (NZ); Topagan (LB); Topamac (AR, CO, EC, IN, PE, PY, UY); Topamax (AE, AT, AU, BB, BE, BG, BH, BR, CH, CL, CN, CY, CZ, DE, EE, EG, ES, FI, GB, HK, HR, IE, IL, IQ, IR, IT, JM, JO, KR, KW, LB, LK, LT, LU, LV, LY, MT, MX, MY, NL, NZ, OM, PH, PK, PL, PT, QA, RO, RU, SA, SG, SI, SK, SY, TH, TR, TW, VE, VN, YE, ZA); Topamax Sprinkle (AE, BB, CY, HK, KR, KW, NZ, SA); Topictal (CR, DO, EC, GT, HN, NI, PA, PY, SV); Topilepsin (UA); Topimax (CR, DK, DO, GT, HN, IS, NI, NO, PA, SE, SV); Topina (JP); Topinmate (TW); Topirol (PH); Topiromax (UA); Topiron (KR); Topirva (BD); Topitrim (IL); Topmate (BD, KR); Topnotch (EG); Topomac (GR); Topvex (PH); Toramat (LB); Toramate (TW)

Topiramate (Patient Education – Adult Medication)
You must carefully read the “Consumer Information Use and Disclaimer” below in order to understand and correctly use this information
Pronunciation

(toe PYRE a mate)

Brand Names: US

Qudexy XR; Topamax; Topamax Sprinkle; Trokendi XR

Brand Names: Canada

Topamax

What is this drug used for?
  • It is used to treat seizures.
  • It is used to prevent migraine headaches.
  • It may be given to you for other reasons. Talk with the doctor.
What do I need to tell my doctor BEFORE I take this drug?
  • If you have an allergy to topiramate or any other part of this drug.
  • If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
  • This drug may interact with other drugs or health problems.
  • Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this drug with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.
What are some things I need to know or do while I take this drug?
  • Avoid driving and doing other tasks or actions that call for you to be alert until you see how this drug affects you.
  • Sweating less and high body temperatures have happened with this drug. Sometimes, this has led to the need for treatment in a hospital. Be careful in hot weather and while being active. Call your doctor right away if you have a fever or you do not sweat during activities or in warm temperatures.
  • Patients who take this drug may be at a greater risk of having thoughts or actions of suicide. The risk may be greater in people who have had these thoughts or actions in the past. Call the doctor right away if signs like low mood (depression), nervousness, restlessness, grouchiness, panic attacks, or changes in mood or actions are new or worse. Call the doctor right away if any thoughts or actions of suicide occur.
  • Very bad and sometimes deadly liver problems have happened with this drug. Call your doctor right away if you have signs of liver problems like dark urine, feeling tired, not hungry, upset stomach or stomach pain, light-colored stools, throwing up, or yellow skin or eyes.
  • This drug may cause an acid blood problem (metabolic acidosis). The chance may be higher in children and in people with kidney problems, breathing problems, or diarrhea. The chance may also be higher if you take certain other drugs, if you have surgery, or if you are on a ketogenic diet. Over time, metabolic acidosis can cause kidney stones, bone problems, or growth problems in children.
  • This drug may raise the chance of bleeding. Sometimes, bleeding can be life-threatening. Talk with the doctor.
  • This drug may cause very bad eye problems. If left untreated, this can lead to lasting eyesight loss. Call your doctor right away if you have new eye signs like blurred eyesight or other changes in eyesight, eye pain, or eye redness.
  • Taking this drug with valproic acid can cause low body temperature. This can also cause tiredness, confusion, or coma. Talk with the doctor.
  • Use with care in children. Talk with the doctor.
  • This drug may affect growth in children and teens in some cases. They may need regular growth checks. Talk with the doctor.
  • Birth control pills and other hormone-based birth control may not work as well to prevent pregnancy. Use some other kind of birth control also like a condom when taking this drug.
  • If you are taking hormone-based birth control and you have any change in your bleeding pattern, talk with your doctor.
  • Use birth control that you can trust to prevent pregnancy while taking this drug.
  • This drug may cause harm to the unborn baby if you take it while you are pregnant. If you are pregnant or you get pregnant while taking this drug, call your doctor right away.
  • Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.
What are some side effects that I need to call my doctor about right away?
  • WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:
  • Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
  • Signs of too much acid in the blood (acidosis) like confusion; fast breathing; fast heartbeat; a heartbeat that does not feel normal; very bad stomach pain, upset stomach, or throwing up; feeling very sleepy; shortness of breath; or feeling very tired or weak.
  • Signs of infection like fever, chills, very bad sore throat, ear or sinus pain, cough, more sputum or change in color of sputum, pain with passing urine, mouth sores, or wound that will not heal.
  • Signs of high ammonia levels like a heartbeat that does not feel normal, breathing that is not normal, feeling confused, pale skin, slow heartbeat, seizures, sweating, throwing up, or twitching.
  • Any unexplained bruising or bleeding.
  • Black, tarry, or bloody stools.
  • Throwing up blood or throw up that looks like coffee grounds.
  • Feeling confused.
  • Not able to focus.
  • Not able to sleep.
  • Change in balance.
  • Very bad dizziness or passing out.
  • Not able to eat.
  • Back pain, belly pain, or blood in the urine. May be signs of a kidney stone.
  • Trouble passing urine.
  • A burning, numbness, or tingling feeling that is not normal.
  • A big weight loss.
  • If seizures are worse or not the same after starting this drug.
  • Bone pain.
  • Chest pain or pressure.
  • Memory problems or loss.
  • Muscle pain or weakness.
  • Trouble speaking.
  • Shakiness.
  • Trouble walking.
  • Not able to control eye movements.
What are some other side effects of this drug?
  • All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:
  • Upset stomach.
  • Change in taste.
  • Weight loss.
  • Not hungry.
  • Diarrhea.
  • Feeling nervous and excitable.
  • Dizziness.
  • Feeling sleepy.
  • Feeling tired or weak.
  • Headache.
  • Hair loss.
  • Flushing.
  • These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.
  • You may report side effects to your national health agency.
How is this drug best taken?
  • Use this drug as ordered by your doctor. Read all information given to you. Follow all instructions closely.
  • All products:
  • Take with or without food.
  • To gain the most benefit, do not miss doses.
  • Keep taking this drug as you have been told by your doctor or other health care provider, even if you feel well.
  • Do not stop taking this drug all of a sudden without calling your doctor. You may have a greater risk of seizures. If you need to stop this drug, you will want to slowly stop it as ordered by your doctor.
  • Drink lots of noncaffeine liquids unless told to drink less liquid by your doctor.
  • Tell all of your health care providers that you take this drug. This includes your doctors, nurses, pharmacists, and dentists.
  • Have blood work checked as you have been told by the doctor. Talk with the doctor.
  • Talk with your doctor before you use other drugs and natural products that slow your actions.
  • This drug may affect how much of some other drugs are in your body. If you are taking other drugs, talk with your doctor. You may need to have your blood work checked more closely while taking this drug with your other drugs.
  • Tablets:
  • Swallow whole. Do not chew, break, or crush.
  • Avoid drinking alcohol while taking this drug.
  • Sprinkle capsule and long-acting sprinkle capsule:
  • You may swallow whole or sprinkle the contents on a spoonful of soft food like applesauce. Do not crush or chew before you swallow.
  • If mixed, swallow the mixed drug right away. Do not store for use at a later time.
  • Drink fluids right after eating the food and drug mixture to make sure the drug is swallowed.
  • Avoid drinking alcohol while taking this drug.
  • Long-acting capsules:
  • Swallow whole. Do not chew, open, or crush.
  • Do not sprinkle this drug on food.
  • Avoid drinking alcohol while taking this drug. This is most important within 6 hours before or 6 hours after taking this drug.
What do I do if I miss a dose?
  • Long-acting capsules:
  • Call your doctor to find out what to do.
  • Long-acting sprinkle capsules:
  • Take a missed dose as soon as you think about it.
  • If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
  • Do not take 2 doses at the same time or extra doses.
  • If you miss 2 doses, call your doctor.
  • All other products:
  • Take a missed dose as soon as you think about it.
  • If it is less than 6 hours until the next dose, skip the missed dose and go back to the normal time.
  • Do not take 2 doses at the same time or extra doses.
  • If you miss 2 doses, call your doctor.
How do I store and/or throw out this drug?
  • Store at room temperature.
  • Keep lid tightly closed.
  • Protect from light.
  • Store in a dry place. Do not store in a bathroom.
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Throw away unused or expired drugs. Do not flush down a toilet or pour down a drain unless you are told to do so. Check with your pharmacist if you have questions about the best way to throw out drugs. There may be drug take-back programs in your area.
General drug facts
  • If your symptoms or health problems do not get better or if they become worse, call your doctor.
  • Do not share your drugs with others and do not take anyone else’s drugs.
  • Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
  • Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
  • Some drugs may have another patient information leaflet. If you have any questions about this drug, please talk with your doctor, nurse, pharmacist, or other health care provider.
  • If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.
Topiramate (Patient Education – Pediatric Medication)
You must carefully read the “Consumer Information Use and Disclaimer” below in order to understand and correctly use this information
Pronunciation

(toe PYRE a mate)

Brand Names: US

Qudexy XR; Topamax; Topamax Sprinkle; Trokendi XR

Brand Names: Canada

Topamax

What is this drug used for?
  • It is used to treat seizures.
  • It is used to prevent migraine headaches.
  • It may be given to your child for other reasons. Talk with the doctor.
What do I need to tell the doctor BEFORE my child takes this drug?
  • If your child has an allergy to this drug or any part of this drug.
  • If your child is allergic to any drugs like this one or any other drugs, foods, or other substances. Tell the doctor about the allergy and what signs your child had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
  • This drug may interact with other drugs or health problems.
  • Tell the doctor and pharmacist about all of your child’s drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for your child to take this drug with all of his/her drugs and health problems. Do not start, stop, or change the dose of any drug your child takes without checking with the doctor.
What are some things I need to know or do while my child takes this drug?
  • All products:
  • Tell all of your child’s health care providers that your child is taking this drug. This includes your child’s doctors, nurses, pharmacists, and dentists.
  • Have your child avoid tasks or actions that call for alertness until you see how this drug affects your child. These are things like riding a bike, playing sports, or using items such as scissors, lawnmowers, electric scooters, toy cars, or motorized vehicles.
  • Do not stop giving this drug to your child all of a sudden without calling the doctor. Your child may have a greater risk of seizures. If your child needs to stop this drug, you will want to slowly stop it as told by the doctor.
  • Have blood work checked as you have been told by the doctor. Talk with the doctor.
  • Talk with the doctor before giving your child other drugs and natural products that may slow your child’s actions.
  • Sweating less and high body temperatures have happened with this drug. Sometimes, this has led to the need for treatment in a hospital. Have your child be careful in hot weather and while being active. Call your child’s doctor right away if your child has a fever or does not sweat during activities or in warm temperatures.
  • This drug may cause an acid blood problem (metabolic acidosis). The chance may be higher in children and in people with kidney problems, breathing problems, or diarrhea. The chance may also be higher if your child takes certain other drugs, has surgery, or is on a diet high in fat called a ketogenic diet. Over time, metabolic acidosis can cause kidney stones, bone problems, or growth problems in children.
  • This drug may raise the chance of bleeding. Sometimes, bleeding can be life-threatening. Talk with the doctor.
  • Taking this drug with valproic acid can cause low body temperature. This can also cause tiredness, confusion, or coma. Talk with your child’s doctor.
  • This drug may affect how much of some other drugs are in the body. If your child is taking other drugs, talk with the doctor. Your child may need to have blood work checked more closely while taking this drug with other drugs.
  • Use with care in children. Talk with the doctor.
  • This drug may affect growth in children and teens in some cases. They may need regular growth checks. Talk with the doctor.
  • If your child is or may be sexually active:
  • Have your child use birth control to prevent pregnancy while taking this drug.
  • Birth control pills and other hormone-based birth control may not work as well to prevent pregnancy. Be sure your child uses some other kind of birth control also, like a condom, when taking this drug.
  • If your child is taking hormone-based birth control and has any change in her bleeding pattern, talk with your child’s doctor.
  • If your child is pregnant or breast-feeding a baby:
  • This drug may cause harm to the unborn baby if your child takes it during pregnancy. If your child is pregnant or gets pregnant while taking this drug, call the doctor right away.
  • Tell the doctor if your child is breast-feeding a baby. You will need to talk about any risks to the baby.
  • Long-acting capsules:
  • Alcohol may interact with this drug. Be sure your child does not drink alcohol. This is most important within 6 hours before or 6 hours after taking this drug.
  • All other products:
  • Alcohol may interact with this drug. Be sure your child does not drink alcohol.
What are some side effects that I need to call my child’s doctor about right away?
  • WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your child’s doctor or get medical help right away if your child has any of the following signs or symptoms that may be related to a very bad side effect:
  • Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
  • Signs of infection like fever, chills, very bad sore throat, ear or sinus pain, cough, more sputum or change in color of sputum, pain with passing urine, mouth sores, or wound that will not heal.
  • Signs of too much acid in the blood (acidosis) like confusion; fast breathing; fast heartbeat; a heartbeat that does not feel normal; very bad stomach pain, upset stomach, or throwing up; feeling very sleepy; shortness of breath; or feeling very tired or weak.
  • Signs of high ammonia levels like a heartbeat that does not feel normal, breathing that is not normal, feeling confused, pale skin, slow heartbeat, seizures, sweating, throwing up, or twitching.
  • Any unexplained bruising or bleeding.
  • Black, tarry, or bloody stools.
  • Throwing up blood or throw up that looks like coffee grounds.
  • Feeling confused.
  • Not able to focus.
  • Not able to sleep.
  • Change in balance.
  • Very bad dizziness or passing out.
  • Not able to eat.
  • Back pain, belly pain, or blood in the urine. May be signs of a kidney stone.
  • Trouble passing urine.
  • A burning, numbness, or tingling feeling that is not normal.
  • A big weight loss.
  • If seizures are worse or not the same after starting this drug.
  • Bone pain.
  • Chest pain or pressure.
  • Memory problems or loss.
  • Muscle pain or weakness.
  • Trouble speaking.
  • Shakiness.
  • Trouble walking.
  • Not able to control eye movements.
  • Patients who take this drug may be at a greater risk of having thoughts or actions of suicide. The risk may be greater in people who have had these thoughts or actions in the past. Call the doctor right away if signs like low mood (depression), nervousness, restlessness, grouchiness, panic attacks, or changes in mood or actions are new or worse. Call the doctor right away if any thoughts or actions of suicide occur.
  • This drug may cause very bad eye problems. If left untreated, this can lead to lasting eyesight loss. Call the doctor right away if your child has eye problems like blurred eyesight or other changes in eyesight, eye pain, or eye redness.
  • Very bad and sometimes deadly liver problems have happened with this drug. Call your child’s doctor right away if your child has signs of liver problems like dark urine, feeling tired, not hungry, upset stomach or stomach pain, light-colored stools, throwing up, or yellow skin or eyes.
What are some other side effects of this drug?
  • All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your child’s doctor or get medical help if your child has any side effects that bother your child or do not go away.
  • Upset stomach.
  • Change in taste.
  • Weight loss.
  • Not hungry.
  • Diarrhea.
  • Feeling nervous and excitable.
  • Dizziness.
  • Feeling sleepy.
  • Feeling tired or weak.
  • Headache.
  • Hair loss.
  • Flushing.
  • These are not all of the side effects that may occur. If you have questions about side effects, call your child’s doctor. Call your child’s doctor for medical advice about side effects.
  • You may report side effects to your national health agency.
How is this drug best given?
  • Give this drug as ordered by your child’s doctor. Read all information given to you. Follow all instructions closely.
  • All products:
  • Give this drug with or without food.
  • To gain the most benefit, do not miss giving your child doses.
  • Keep giving this drug to your child as you have been told by your child’s doctor or other health care provider, even if your child feels well.
  • Have your child drink lots of noncaffeine liquids every day unless told to drink less liquid by your child’s doctor.
  • Tablets:
  • Have your child swallow whole. Do not let your child chew, break, or crush.
  • Sprinkle capsule and long-acting sprinkle capsule:
  • This drug may be swallowed whole or sprinkled on a spoonful of soft food like applesauce. Do not let your child crush or chew before swallowing.
  • If mixed, have your child swallow the mixed drug right away. Do not store for use at a later time.
  • Have your child drink fluids right after eating the food and drug mixture to make sure the drug is swallowed.
  • Long-acting capsules:
  • Have your child swallow whole. Do not let your child chew, open, or crush.
  • Do not sprinkle this drug on food.
What do I do if my child misses a dose?
  • Long-acting capsules:
  • Call your child’s doctor to find out what to do.
  • Long-acting sprinkle capsules:
  • Give a missed dose as soon as you think about it.
  • If it is close to the time for your child’s next dose, skip the missed dose and go back to your child’s normal time.
  • Do not give 2 doses at the same time or extra doses.
  • If you miss giving your child 2 doses, call the doctor.
  • All other products:
  • Give a missed dose as soon as you think about it.
  • If it is less than 6 hours until the next dose, skip the missed dose and go back to the normal time.
  • Do not give 2 doses at the same time or extra doses.
  • If you miss giving your child 2 doses, call the doctor.
How do I store and/or throw out this drug?
  • Store at room temperature.
  • Keep lid tightly closed.
  • Protect from light.
  • Store in a dry place. Do not store in a bathroom.
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Throw away unused or expired drugs. Do not flush down a toilet or pour down a drain unless you are told to do so. Check with your pharmacist if you have questions about the best way to throw out drugs. There may be drug take-back programs in your area.
General drug facts
  • If your child’s symptoms or health problems do not get better or if they become worse, call your child’s doctor.
  • Do not share your child’s drug with others and do not give anyone else’s drug to your child.
  • Keep a list of all your child’s drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your child’s doctor.
  • Talk with your child’s doctor before giving your child any new drug, including prescription or OTC, natural products, or vitamins.
  • Some drugs may have another patient information leaflet. If you have any questions about this drug, please talk with your child’s doctor, nurse, pharmacist, or other health care provider.
  • If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.