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Trokendi XR: 7 things you should know

Medically reviewed by Carmen Fookes, BPharm. Last updated on Dec 3, 2020.

1. How it works

  • Trokendi XR is a brand (trade) name for topiramate extended-release capsules that may be used to reduce the frequency and duration of seizures. Trokendi XR also prevents the development of migraine headaches.
  • Experts aren't sure exactly how topiramate works in either epilepsy or to prevent migraines but research suggests it dampens down excessive nerve firing, enhances the actions of GABA, and blocks the effects of other chemical messengers.
  • Trokendi XR belongs to the class of medicines known as carbonic anhydrase inhibitors or carbonic anhydrase inhibitor anticonvulsants. It may also be called an anticonvulsant.

2. Upsides

  • May be used as sole therapy or in addition to other medications for the treatment of partial-onset or primary generalized tonic-clonic seizures in adults and children over the age of six.
  • May be used in addition to other medications for the treatment of Lennox-Gastaut syndrome in adults and children over the age of six years.
  • May be used to prevent the development of migraine headaches in adults and children aged 12 years and older.
  • Does not require monitoring of blood concentrations of topiramate.
  • Available as a generic under the name topiramate extended-release.

3. Downsides

If you are between the ages of 18 and 60, take no other medication or have no other medical conditions, side effects you are more likely to experience include:

  • Paresthesias (abnormal sensations of the skin such as tingling, pricking, chilling, burning, or numbness) and drowsiness are the most common side effects reported. Other side effects include a reduced ability to sweat and increased body temperature. This is more likely to occur in children, especially in hot weather or when used in conjunction with other drugs that also raise body temperature (such as acetazolamide or hyoscine). Hypothermia (low body temperature) has also been reported when topiramate is taken in conjunction with valproate.
  • Confusion, difficulty with concentration/attention, forgetfulness, speech or language difficulties, depression or mood problems, flushing, fever, tiredness, fatigue, or weight loss are common side effects. May cause hypothermia or hyperammonemia with or without encephalopathy; the risk is greater with concomitant valproate use.
  • Sudden eye pain and decreased vision associated with or without glaucoma have been reported; symptoms may occur in both children and adults and typically start within 1 month of starting therapy. Seek urgent medical attention; drug discontinuation may be necessary to avoid permanent vision loss.
  • The risk of kidney stones in people taking topiramate is two to four times higher than in the general population.
  • May cause disturbances in bicarbonate levels leading to metabolic acidosis; caution when used with metformin. Monitor baseline and perform periodic serum bicarbonate levels during treatment.
  • Alcohol should be avoided 6 hours before taking Trokendi XR and for 6 hours afterward. Laboratory studies have shown that alcohol significantly changes the pattern of topiramate release from Trokendi XR capsules. This could cause levels of topiramate to be markedly higher soon after dosing and subtherapeutic later in the day.
  • Rarely, has been associated with sudden unexplained death.
  • Requires dosage slow titration. The usual starting dosage is 50mg once daily which is increased each week by 50mg to 100mg, up to a recommended dosage of 400mg/day in adults and children aged 10 years of age and older. Dosing in children aged 6 to less than 10 years is based on weight and should be increased over 5 to 7 weeks to 250mg to 400mg.
  • When used in addition to other treatments the recommended total daily dose of Trokendi XR as adjunctive therapy in adults with partial-onset seizures or Lennox-Gastaut Syndrome is 200mg to 400mg orally once daily and with primary generalized tonic-clonic seizures is 400mg orally once daily. In those aged 6 to 16 years, the recommended total daily dose is 5 mg/kg to 9 mg/kg orally once daily.
  • When used to treat migraine the recommended total daily dose of Trokendi XR in adults and adolescents 12 years of age and older is 100 mg once daily. The initial starting dose is 25mg once daily which is increased over 4 weeks by 25mg/day/week, to 100mg once daily.
  • Should not be stopped suddenly when used to treat epilepsy. Rather, the dosage should slowly be reduced.
  • Trokendi XR will not treat an acute migraine, it will only help prevent one from developing.
  • As with other antiepileptics, Trokendi XR may increase the risk of suicidal thoughts or behavior; monitor for worsening depression or mood changes.
  • Dosage may need reducing in people with kidney disease to one-half of normal. Supplemental doses may be required in people undergoing hemodialysis.
  • May interact with several other drugs including seizure medications (such as phenytoin, carbamazepine), oral contraceptives, lithium, and pioglitazone. A dosage adjustment may be required.
  • Reliable contraception should be used if Trokendi XR is taken by women of childbearing age as the use of topiramate has been associated with oral clefts or being small for gestational age.

Note: In general, seniors or children, people with certain medical conditions (such as liver or kidney problems, heart disease, diabetes, seizures) or people who take other medications are more at risk of developing a wider range of side effects. View complete list of side effects

4. Bottom Line

Trokendi XR is an extended-release form of topiramate that may be used to reduce the frequency and duration of seizures or to prevent the development of migraine headaches. Paresthesias and drowsiness are the most common side effects reported and it has been associated with some severe side effects such as vision loss and an increased risk of kidney stones.

5. Tips

  • Can be taken with or without food.
  • Swallow the capsules whole and do not attempt to break open. Do not sprinkle on food, chew, or crush.
  • Trokendi XR is usually started at a low dosage and then titrated up slowly until an effective dose is reached (experts suggest increasing by 50 to 100 mg/day every week). Your doctor will explain this to you.
  • Trokendi XR should be discontinued slowly to minimize the potential for seizures unless a rapid withdrawal is justified. Your doctor will tell you how to slowly discontinue Trokendi XR.
  • Seek urgent medical attention if you develop eye pain, blurred vision, or visual disturbances while taking Trokendi XR.
  • Also, report any changes in mood or the development of depression or suicidal thoughts to your doctor.
  • Keep up your fluid intake and avoid dehydration as Trokendi XR can increase the risk of kidney stones developing. Trokendi XR may also make you sweat less or give you a fever. Contact your doctor if your fever does not go away, you develop abdominal pain with or without vomiting, or you are unable to sweat.
  • Do not drive or operate machinery or perform other hazardous tasks if Trokendi XR makes you dizzy or drowsy.
  • Do not drink alcohol 6 hours before taking Trokendi XR and for 6 hours afterward. Laboratory studies have shown that alcohol significantly changes the pattern of topiramate release from Trokendi XR capsules. This could cause levels of topiramate to be markedly higher soon after dosing and subtherapeutic later in the day. Alcohol can also potentiate side effects such as drowsiness and dizziness and should be avoided.
  • Trokendi XR should not be taken during pregnancy or while breastfeeding. Ensure you use adequate contraception while taking Trokendi XR and see your doctor immediately if you inadvertently become pregnant.

6. Response and Effectiveness

  • The approval of Trokendi XR was based on the effectiveness of topiramate and the demonstration of the pharmacokinetic equivalence of Trokendi XR to immediate-release topiramate through the analysis of specific concentrations and other pharmacokinetic parameters at multiple time points
  • Peak concentrations of topiramate are reached approximately 24 hours following a single 200 mg oral dose of Trokendi XR. At steady-state, blood levels of topiramate from Trokendi XR administered once-daily are equivalent to topiramate immediate-release administered twice-daily.
  • Some improvement may be noticed within a few weeks of taking Trokendi XR; however, it may take over a year before the full effects are seen with regards to reducing seizure frequency. With regards to migraine headaches, the full effects may not be seen for 16 to 26 weeks.
  • For migraines, the change in the mean 4-week migraine headache period frequency from baseline to the double-blind phase was -1.4, -2.1, and -2.4 in the immediate-release topiramate 50, 100, and 200 mg per day groups, respectively, versus -1.1 in the placebo group. This was assessed in studies of 26 weeks duration.

7. Interactions

Medicines that interact with Trokendi XR may either decrease its effect, affect how long it works for, increase side effects, or have less of an effect when taken with Trokendi XR. An interaction between two medications does not always mean that you must stop taking one of the medications; however, sometimes it does. Speak to your doctor about how drug interactions should be managed.

Common medications that may interact with Trokendi XR include:

  • amitriptyline
  • antidepressants, such as monoamine oxidase inhibitors (eg, isocarboxazid, selegiline, or tranylcypromine)
  • antiepileptics, such as carbamazepine, phenytoin, and valproate (a dosage adjustment may be required). Hypothermia (an unintentional drop in body core temperature to less than 35ºC [95ºF]) has been reported when valproate and topiramate have been used together.
  • diuretics, such as HCTZ
  • ginkgo
  • lithium
  • metformin (contraindicated in metabolic acidosis)
  • oral contraceptives (may cause decreased contraceptive efficacy)
  • other carbonic anhydrase inhibitors, such as acetazolamide or dichlorphenamide (may increase the severity of metabolic acidosis or risk of kidney stone formation)
  • pioglitazone
  • tramadol.

Alcohol may affect the release of topiramate from Trokendi XR and enhance its sedative effects.

Any medication that causes sedation, depresses the CNS, or increases the risk of bleeding, may potentially interact with Trokendi XR.

Note that this list is not all-inclusive and includes only common medications that may interact with Trokendi XR. You should refer to the prescribing information for Trokendi XR for a complete list of interactions.

References

Trokendi XR (topiramate) [Package insert]. Updated 03/2020. Supernus Pharmaceuticals, Inc. https://www.drugs.com/pro/trokendi-xr.html

Further information

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use Trokendi XR only for the indication prescribed.

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