Use in Adults
Antiepileptics
THIS GUIDE PROVIDES A PARTIAL LISTING OF PRESCRIBING INFORMATION FOR THIS MEDICATION. FOR A FULL LISTING OF PRESCRIBING INFORMATION PLEASE REFER TO THE PACKAGE INSERT. CLICK ON THE BRAND NAME® TO VIEW THE LINK TO THE PACKAGE INSERT.
Topiramate (Topamax®, Trokendi XR®, Qudexy XR®) FDA APPROVED FOR MIGRAINE PREVENTION Click Here to expand
Brands:
Common Side Effects:
Headache Specialist Suggestions:
Precautions and Risk:
Contraindications:
Pregnancy & Breast Feeding:
Click Topamax® and navigate to #8 Use in Specific Populations (8.1 & 8.2)
Drug Interactions:
- Topamax®, (topiramate) For Complete Prescribing Information Click Here for the Package Insert
- Trokendi XR®, (topiramate) For Complete Prescribing Information Click Here for the Package Insert
- Qudexy XR®, (topiramate) For Complete Prescribing Information Click Here for the Package Insert
- Immediate Release
- 25, 50, 100 and 200 mg tabs
- 15 mg sprinkle capsules
- Extended Release
- Trokendi XR
- 25, 50, 100 and 200 mg capsules
- Qudexy XR
- 50, 100, 200 mg capsules
- 25, 50, 100, 150, and 200 mg sprinkle caps
- Trokendi XR
- 25 mgs once daily at night is the most common initial dosage
- Might start a 12.5 mg sprinkle capsule once daily if the patient has medication intolerances
- 50-200 mg daily
- The clinical studies administered topiramate BID
- Many headache specialists however will administer immediate release topiramate once daily to improve compliance and reduce medication side effects.
- The clinical studies administered topiramate BID
- Immediate Release
- Office visit #1:
- Start with 25 mgs once at night for the first 2 weeks and then can increase to 25 mgs by mouth twice per day
- Stay on that dosage until the next office visit
- Office visit #2 (2 months later)
- If satisfactory response (e.g., defined as a 50% decrease in the frequency of migraine days per month)
- Continue current dosage, if no unacceptable side effects
- If unsatisfactory response and no intolerable side effects
- Increase the dosage to 25 mgs in the morning and 50 mgs in the evening
- Then two weeks later, increase the dosage to 50 mg twice per day
- If the patient has side effects with BID dosing, then consider switching to qhs dosing and/or changing to an extended release topiramate
- If satisfactory response (e.g., defined as a 50% decrease in the frequency of migraine days per month)
- Office visit #1:
- Extended Release
- Office visit #1:
- Start with 50 mgs by mouth each evening
- Stay on that dosage until the next office visit
- Office visit #2 (2 months later)
- If satisfactory response (e.g., defined as a 50% decrease in the frequency of migraine days per month)
- Continue current dosage if no unacceptable side effects
- If unsatisfactory response and no intolerable side effects
- Increase the dosage to 100 mgs by mouth each evening
- If satisfactory response (e.g., defined as a 50% decrease in the frequency of migraine days per month)
- Office visit #1:
Common Side Effects:
- Paresthesias
- It is thought that consumption of potassium containing foods such as orange juice and bananas can be used to reduce or eliminate paresthesias
- Blunted appetite leading to weight loss (typically a 5-8 pound weight loss)
- Difficulties with word retrieval
- Kidney stones (1%)
- Inform them that carbonated beverages may taste “flat” because of the carbonic hydrase component in the topiramate
Headache Specialist Suggestions:
- Headache specialists consider topiramate as an important and effective preventive medication.
- Topiramate is one of the few migraine preventives that has weight loss as a side effect.
- Might consider its use in the following patients:
- Those with a BMI ≥ 30 as topiramate has been shown to cause weight loss/appetite blunting
- Those with comorbid seizure disorder and migraine
- Those with chronic migraine as it has been shown to be effective in this patient population
- Those with medication overuse headaches
- Those with migraine and intracranial hypertension as the carbonic anhydrase inhibition of topiramate may lower intracranial pressures
- Might avoid its use in the following patients:
- Those with kidney stones if known to be calcium phosphate stones
- Those who are anorexic and cannot tolerate further weight loss
- Those with mild cognitive impairment or dementia
- One of the most common side effects is cognitive impairment.
- Use of extended release topiramate may help minimize any word finding difficulty if that emerges as a side effect with immediate release topiramate.
- Advantages are:
- High efficacy, modest cost and long track record of safety for migraine prevention.
- Weight loss/appetite blunting is a desired side effect for many patients.
- Disadvantages are:
- Contraindication of use during pregnancy.
- Extended release topiramate may require a prior authorization by insurers.
Precautions and Risk:
- Acute myopia and secondary angle closure glaucoma: Untreated elevated intraocular pressure can lead to permanent visual loss. Discontinue topiramate if it occurs.
- Visual field defects: These have been reported independent of elevated intraocular pressure. Consider discontinuation of topiramate.
- Oligohydrosis and hyperthermia: Monitor decreased sweating and increased body temperature, especially in pediatric patients.
- Metabolic acidosis: Measure baseline and periodic measurement of serum bicarbonate, if there is a history to suggest these would be helpful.
- Suicidal behavior and ideation: Antiepileptic drugs may increase the risk of suicidal behavior or ideation. Monitor during the initiation or escalation of dosage phase.
- Cognitive/neuropsychiatric: Topiramate may cause cognitive dysfunction, typically notices as difficulty with word retrieval or short term recall. These are completely reversable side effects. Often dosage may resolve cognitive side effects.
- Fetal toxicity: Topiramate use during pregnancy can cause cleft lip and/or palate and may increase the risk of being small for gestational age. So, avoid during pregnancy and have women of childbearing potential use appropriate birth control while using this medication.
- Withdrawal of AEDs: Withdrawal of topiramate should be done gradually.
- Kidney stones: Avoid use with other carbonic anhydrase inhibitors, other drugs causing metabolic acidosis, or in patients on a ketogenic diet. May want to avoid in patients with known history of renal stones, unless metabolic analysis indicates a history of calcium phosphate stones in past.
- Osteoporosis: Can be associated with osteoporosis. Alternative treatments should be given in those with osteoporosis/osteopenia
Contraindications:
- Recent alcohol use within 6 hours prior to or 6 hours after topiramate use, if using a long- acting form.
- Metabolic acidosis with concomitant metformin use.
- Pregnancy as it has been associated with birth defects such as cleft lip and palate.
Pregnancy & Breast Feeding:
Click Topamax® and navigate to #8 Use in Specific Populations (8.1 & 8.2)
Drug Interactions:
- Oral contraceptives: Decreased contraceptive efficacy and increased breakthrough bleeding, especially at doses greater than 200 mg per day. At daily dosages above 200mg, the estradiol component of combined oral contraceptives is reduced by approximately 18%.
- Phenytoin or carbamazepine: Concomitant administration with topiramate may decrease plasma concentrations of topiramate.
- Lithium: Monitor lithium levels when co-administered with high dose topiramate.
- Consider starting a preventive therapy in those with 4 or more migraine days per month.
- Have the patients keep a headache diary to assess the frequency of migraine days per month. This will also help in assessing the response of the preventive medication.
- Counsel patients that it may take 1-4 months after the start of an oral preventive to see an adequate response.
- Set realistic goals with your patients. Explain that a preventive medication is not a cure for migraines. A good response would be a 50% or more reduction in the frequency of migraine days per month. For some patients, a significant reduction in migraine severity may be a good response.
- Counsel patients on potential side effects, so they are not frightened or concerned if they experience them.
- Consider checking a basic metabolic profile 2 months after its initiation and periodically thereafter to rule out metabolic acidosis.
Divalproex Sodium, Valproic Acid (Depakote®) FDA APPROVED FOR MIGRAINE PREVENTION CLICK HERE TO EXPAND
Brands:
Suggested Titration Schedule:
Contraindications:
Important Drug Interactions:
Counseling Tips:
- Depakote DR® (divalproex sodium) For Complete Prescribing Information Click Here for the Package Insert
- Depakote ER® (divalproex sodium) For Complete Prescribing Information Click Here for the Package Insert
- Depakote Sprinkles® (divalproex sodium) For Complete Prescribing Information Click Here for the Package Insert
- Valproic Acid Capsule For Complete Prescribing Information Click Here for Package Insert
- Divalproex DR (delayed release)
- 125, 250 and 500 mg tablets
- Most commonly administered 2X per day, but can be give 3X per day
- Divalproex ER (extended release)
- 250 and 500 mg tablets
- Most commonly administered 1X per day, but can be given 2X per day
- Divalproex sprinkles
- 125 mg capsules
- Most commonly administered 2X per day
- 250 mg once daily
- Might use 125 mg as starting dosage in those with medication intolerances
Suggested Titration Schedule:
- Divalproex ER
- Office visit #1
- Check liver function tests (LFTs) and platelets before starting medication; would not use if LFTs elevated or abnormally low platelets
- Start at 250 mgs once daily in the evening
- If tolerated after two weeks, then increase to 500 mg once daily at night
- Office visit #2 (2 months later)
- If satisfactory response (e.g., defined as a 50% decrease in the frequency of migraine days per month) or with significant reduction in severity of migraine attacks
- Continue current dosage if no unacceptable side effects
- If satisfactory response (e.g., defined as a 50% decrease in the frequency of migraine days per month) or with significant reduction in severity of migraine attacks
- Office visit #1
- If unsatisfactory response and no intolerable side effects
- Increase the dosage to 1000 mgs by mouth each evening
- Check LFTs, CBC and divalproex levels
- discontinue medication if LFTs abnormal
- if divalproex levels high then reduce dosage
- if any cognitive change, check ammonia levels
- discontinue if platelets fall below 120K or have noticeably dropped from baseline
- Divalproex DR
- Office visit #1
- Check liver function tests (LFTs) and platelets before starting medication; would not use if LFTs elevated or if platelet count is abnormal
- Start at 250 mgs once daily in the evening
- If tolerated increase to 250 mg twice daily 2 weeks later
- Office visit #2 (2 months later)
- If satisfactory response (e.g., defined as a 50% decrease in the frequency of migraine days per month) or marked reduction in migraine severity is achieved
- Continue current dosage if no unacceptable side effects
- If satisfactory response (e.g., defined as a 50% decrease in the frequency of migraine days per month) or marked reduction in migraine severity is achieved
- Office visit #1
- If unsatisfactory response and no intolerable side effects
- Increase the dosage to 500 mg twice daily
- Check LFTs, CBC and divalproex levels
- discontinue medication if LFTs abnormal
- if divalproex levels high then reduce dosage
- if cognitive change, check ammonia level
- discontinue if platelets are reduced
- Divalproex DR: 250-750 mg by mouth two times daily
- Divalproex ER: 500-1500 mg by mouth daily
- Divalproex Immediate Release: 250-500 mgs po tid
- Divalproex is an FDA approved preventive medication that is effective as a migraine preventive medication.
- It should not be used during pregnancy or in women of childbearing age on inadequate contraception, it should be considered in specific patients.
- Caution patients regarding their diet as weight gain is often a side effect.
- Might also consider use in the following groups of patients:
- Those that have failed one of the first line preventives
- Beta blockers, tricyclic antidepressants and topiramate are also considered “first line” preventives.
- Those with chronic migraine
- Those with epilepsy or bipolar disease
- Those that use appropriate contraceptive measure if female and are of child-bearing age
- Avoid use in the following groups of patients:
- Women of childbearing age that do not use adequate birth control
- Those with hepatic disease
- Those with mitochondrial disease
- Those with thrombocytopenia
- Those with BMIs greater than 30 as divalproex may cause weight gain
- Those with urea cycle abnormalities
- Children under age 2.
- Advantages are:
- Good efficacy, modest cost and its long track record of use.
- Disadvantages are:
- Weight gain as a side effect
- The potential teratogenicity
- Rare side effects (e.g., hepatotoxicity, cytopenias and hemorrhagic pancreatitis, suicidal ideation).
- General
- Appetite stimulation, can lead to weight gain
- Alopecia
- Neurological
- Dizziness, drowsiness, tremor (reversible), nervousness and insomnia
- Can cause memory impairment, but less common than topiramate
- Suicidal thoughts in 1-2%
- Gastrointestinal
- Nausea, abdominal pain and diarrhea
- Do not use in children under two years of age.
- Pregnancy- this drug should not be used during pregnancy
- Hepatotoxicity: Monitor liver function tests.
- Pancreatitis: Depakote should ordinarily be discontinued.
- Stevens Johnson syndrome- rare cases of Stevens Johnson syndrome have been reported with use of divalproex
- Suicidal behavior or ideation: Antiepileptic drugs, including Depakote, increase the risk of suicidal thoughts or behavior.
- Thrombocytopenia: Monitor platelet counts and coagulation tests.
- Hyperammonemia and hyperammonemic encephalopathy: Measure ammonia level if unexplained lethargy and vomiting or changes in mental status, and with concomitant topiramate use; discontinue valproate.
- Hypothermia: Hypothermia has been reported during valproate therapy with or without associated hyperammonemia. This adverse reaction can also occur in patients using concomitant topiramate.
- Multi-organ hypersensitivity reaction: Discontinue
- Somnolence in the elderly: Depakote dosage should be increased slowly and with regular monitoring for fluid and nutritional intake.
- Risk of severe hepatic failure
- Risk of fetal malformations including neural tube defects
- Use appropriate birth control in women during their child-bearing ages
- Stop immediately if pregnant
- Rare reports of hemorrhagic pancreatitis
- Avoid in those with certain types of mitochondrial disease
- May put them at higher risk for hepatic failure
Contraindications:
- Persons with a known allergy to divalproex, valproic acid or its derivatives
- Pregnancy
- Its use has been associated with neural tube defects in infants exposed to divalproex during pregnancy.
- Avoid use for migraine prevention in women of child-bearing potential who are not using effective contraception.
- Use in patients with mitochondrial disorders caused by mutations in mitochondrial DNA polymerase gamma (POLG, e.g., Alpers-Huttenlocher syndrome) and in children younger than 2 years with suspected POLG-related disorder because of increased risk of life-threatening liver failure.
- Urea cycle disorders.
- Significant hepatic disease
- Click Depakote ER® and navigate to #8 Use in Specific Populations (8.1 & 8.2)
Important Drug Interactions:
- Hepatic enzyme-inducing drugs: (e.g., phenytoin, carbamazepine, primidone, phenobarbital, rifampin) can increase valproate clearance, while enzyme inhibitors (e.g., felbamate) can decrease valproate clearance. Therefore, increased monitoring of valproate and concomitant drug concentrations and dose adjustment is indicated whenever enzyme-inducing or inhibiting drugs are introduced or withdrawn.
- Aspirin, carbapenem antibiotics: Monitoring of valproate concentrations is recommended.
- Topiramate: Hyperammonemia and encephalopathy.
- Valproate: Co-administration of valproate and divalproex can affect the pharmacokinetics of other drugs (e.g., diazepam, ethosuximide, lamotrigine, phenytoin) by inhibiting their metabolism or protein binding displacement.
Counseling Tips:
- Consider starting a preventive therapy in those with 4 or more migraine days per month.
- Have the patients keep a headache diary to assess the frequency of migraine days per month. This will also help in assessing the response of the preventive medication.
- Counsel patients that it may take 1-4 months after the start of an oral preventive to see an adequate response.
- Set realistic goals with your patients. Explain that a preventive medication is not a cure for migraines. A good response would be a 50% or more reduction in the frequency of migraine days per month. For some with migraine, a significant reduction in severity may be a good response.
- Counsel patients on potential side effects.
- Divalproex ER may be preferred to divalproex DR because of its once daily dosage.