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drug adverse effects of anticonvulsants

Adverse effects: 1) suicide, 2-fold risk of suicidal behavior or ideation compared to patients receiving placebo [1,2,4] a) levetiracetam & topiramate increase risk 3-fold [5] b) carbamazepine, phenytoin, valproate, gabapentin & lamotrigine did not increase risk [5] 2) withdrawal effects with abrupt discontinuation [3] a) seizures may occur b) taper 20-25% of dose/week 3) Stevens-Johnson syndrome -> toxic epidermal necrolysis 4) birth defects: a) may be associated with use of older anticonvulsants b) lamotrigine, oxcarbazine, gabapentin & leveriacetam not associated with increased risk of birth defects [6] c) topiramate results mixed - association with cleft lip & cleft palate [7] - classified as pregnancy category D - ref [6] finds no association with birth defects d) major congenital malformations - valproate with highest risk (25% >1450 mg/day) - lamotrigine with lowest risk (2.5% < 326 mg/day) [9] 5) probably not associated with increased risk for miscarriage or stillbirth [8] 6) may increase bone catabolism (supplement vitamin D & calcium) [10] - carbamazepine, phenytoin, phenobarbital, valproic acid 7) association between epilepsy & cardiovascular events in elderly largely due to enzyme-inducing anticonvulsants [11] - strong enzyme-inducing anticonvulsants include: - carbamazepine, phenytoin, phenobarbital, & primidone - weak enzyme-inducing anticonvulsants include: - oxcarbazepine, eslicarbazepine, topiramate, & rufinamide - of the cardiovascular events, strong enzyme-inducing anticonvulsant appear to have the largest effect on myocardial infarction (59%) [11]

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DRUGS: anticonvulsant FORM: drug adverse effects anticonvulsant

References

  1. FDA MedWatch http://www.fda.gov/medwatch/safety/2008/safety08.htm#Antiepileptic
  2. Prescriber's Letter 15(3): 2008 Drugs and Suicidality Detail-Document#: 240313 (subscription needed) http://www.prescribersletter.com - FDA alert concerning suicidality of antiepileptic drugs http://www.fda.gov/cder/drug/InfoSheets/HCP/antiepilepticsHCP.htm
  3. Prescriber's Letter 15(12): 2008 Common Oral Medications that May Need Tapering Detail-Document#: 241208 (subscription needed) http://www.prescribersletter.com
  4. FDA News FDA Requires Warnings about Risk of Suicidal Thoughts and Behavior for Antiepileptic Medications Dec. 16, 2008 http://www.fda.gov/bbs/topics/NEWS/2008/NEW01927.html
  5. Andersohn F et al, Use of antiepileptic drugs in epilepsy and the risk of self-harm or suicidal behavior Neurology 2010;75:335-340 PMID: 20660863 http://www.neurology.org/cgi/content/abstract/75/4/335
  6. Molgaard-Nielsen D and Hivid A Newer-Generation Antiepileptic Drugs and the Risk of Major Birth Defects JAMA. 2011;305(19):1996-2002. PMID: 21586715 http://jama.ama-assn.org/content/305/19/1996.short
  7. FDA MedWatch: 3/3/2011 Topamax (topiramate): Label Change - Risk For Development of Cleft Lip and/or Cleft Palate in Newborns http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm245777.htm - FDA Drug Safety Communication: Risk of oral clefts in children born to mothers taking Topamax (topiramate 03-04-2011 http://www.fda.gov/Drugs/DrugSafety/ucm245085.htm - Hunt S et al Topiramate in pregnancy: Preliminary experience from the UK Epilepsy and Pregnancy Register Neurology 2008 71:272-276 PMID: 18645165 http://www.neurology.org/content/71/4/272.abstract
  8. Bech BH et al Use of antiepileptic drugs during pregnancy and risk of spontaneous abortion and stillbirth: population based cohort study. BMJ 2014;349:g5159 PMID: 25150301 http://www.bmj.com/content/349/bmj.g5159
  9. Tomson T, Battino D, Bonizzoni E, et al Comparative risk of major congenital malformations with eight different antiepileptic drugs: a prospective cohort study of the EURAP registry. Lancet Neurology. April 18, 2018 PMID: 29680205 http://www.thelancet.com/journals/laneur/article/PIIS1474-4422(18)30107-8/fulltext - Pennell PB Prescribing antiepileptic drugs to women of reproductive age. Lancet Neurology. April 18, 2018 PMID: 29680207 http://www.thelancet.com/journals/laneur/article/PIIS1474-4422(18)30154-6/fulltext
  10. Medical Knowledge Self Assessment Program (MKSAP) 18, American College of Physicians, Philadelphia 2018 - Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022
  11. Li J, Shlobin NA, Thijs RD et al Antiseizure Medications and Cardiovascular Events in Older People With Epilepsy. JAMA Neurol. 2024 Sep 30. PMID: 39348143 https://jamanetwork.com/journals/jamaneurology/fullarticle/2824203