drug adverse effects of anticonvulsants
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Adverse effects
- suicide, 2-fold risk of suicidal behavior or ideation compared to patients receiving placebo[1][2][4]
- levetiracetam & topiramate increase risk 3-fold[5]
- carbamazepine, phenytoin, valproate, gabapentin & lamotrigine did not increase risk[5]
- withdrawal effects with abrupt discontinuation[3]
- Stevens-Johnson syndrome -> toxic epidermal necrolysis
- birth defects:
- may be associated with use of older anticonvulsants
- lamotrigine, oxcarbazine, gabapentin & leveriacetam not associated with increased risk of birth defects[6]
- topiramate results mixed
- association with cleft lip & cleft palate[7]
- classified as pregnancy category D
- ref[6] finds no association with birth defects
- major congenital malformations
- valproate with highest risk (25% >1450 mg/day)
- lamotrigine with lowest risk (2.5% < 326 mg/day)[9]
- probably not associated with increased risk for miscarriage or stillbirth [8]
- may increase bone catabolism & osteoporosis
- increased risk of vertebral compression fractures[12]
- supplement vitamin D & calcium[10]
- osteopenia & osteoporosis less with lamotrigine or levetiracetam than carbamazepine, phenytoin, phenobarbital, valproic acid
- association between epilepsy & cardiovascular events in elderly largely due to enzyme-inducing anticonvulsants [11]
- strong enzyme-inducing anticonvulsants include:
- weak enzyme-inducing anticonvulsants include:
- of the cardiovascular events, strong enzyme-inducing anticonvulsant appear to have the largest effect on myocardial infarction (59%)[11]
More general terms
References
- ↑ Jump up to: 1.0 1.1 FDA MedWatch http://www.fda.gov/medwatch/safety/2008/safety08.htm#Antiepileptic
- ↑ Jump up to: 2.0 2.1 Prescriber's Letter 15(3): 2008 Drugs and Suicidality Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=240313&pb=PRL (subscription needed) http://www.prescribersletter.com
FDA alert concerning suicidality of antiepileptic drugs http://www.fda.gov/cder/drug/InfoSheets/HCP/antiepilepticsHCP.htm - ↑ Jump up to: 3.0 3.1 Prescriber's Letter 15(12): 2008 Common Oral Medications that May Need Tapering Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=241208&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ Jump up to: 4.0 4.1 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
- ↑ Jump up to: 5.0 5.1 5.2 Andersohn F et al, Use of antiepileptic drugs in epilepsy and the risk of self-harm or suicidal behavior Neurology 2010;75:335-340 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/20660863 <Internet> http://www.neurology.org/cgi/content/abstract/75/4/335
- ↑ Jump up to: 6.0 6.1 6.2 Molgaard-Nielsen D and Hivid A Newer-Generation Antiepileptic Drugs and the Risk of Major Birth Defects JAMA. 2011;305(19):1996-2002. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/21586715 <Internet> http://jama.ama-assn.org/content/305/19/1996.short
- ↑ Jump up to: 7.0 7.1 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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/18645165 <Internet> http://www.neurology.org/content/71/4/272.abstract - ↑ Jump up to: 8.0 8.1 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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25150301 <Internet> http://www.bmj.com/content/349/bmj.g5159
- ↑ Jump up to: 9.0 9.1 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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/29680205 <Internet> 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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/29680207 <Internet> http://www.thelancet.com/journals/laneur/article/PIIS1474-4422(18)30154-6/fulltext - ↑ Jump up to: 10.0 10.1 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 - ↑ Jump up to: 11.0 11.1 11.2 Li J, Shlobin NA, Thijs RD et al Antiseizure Medications and Cardiovascular Events in Older People With Epilepsy. JAMA Neurol. 2024 Sep 30. PMID: https://www.ncbi.nlm.nih.gov/pubmed/39348143 https://jamanetwork.com/journals/jamaneurology/fullarticle/2824203
- ↑ Jump up to: 12.0 12.1 Dussault PM, McCarthy D, Davis SA, Thakore-James M, Lazzari AA. High prevalence of vertebral fractures in seizure patients with normal bone density receiving chronic anti-epileptic drugs. Osteoporos Int. 2021 Oct;32(10):2051-2059. PMID: https://www.ncbi.nlm.nih.gov/pubmed/33822290