Kinder- und Jugendmedizin 2022; 22(05): 352-361
DOI: 10.1055/a-1911-4872
Schwerpunkt

Antikonvulsiva

Wahrnehmung von unerwünschten ArzneimittelwirkungenAnti-seizure medicationsPerceptions of adverse drug reactions
Martina P. Neininger
1   Klinische Pharmazie, Institut für Pharmazie, Medizinische Fakultät, Universität Leipzig und Zentrum für Arzneimittelsicherheit, Universität Leipzig und Universitätsklinikum Leipzig
,
Sarah Jeschke
2   Universitätsmedizin Greifswald, Klinik und Poliklinik für Kinder- und Jugendmedizin, Funktionsbereich Neuropädiatrie
,
Thilo Bertsche
1   Klinische Pharmazie, Institut für Pharmazie, Medizinische Fakultät, Universität Leipzig und Zentrum für Arzneimittelsicherheit, Universität Leipzig und Universitätsklinikum Leipzig
,
Astrid Bertsche
2   Universitätsmedizin Greifswald, Klinik und Poliklinik für Kinder- und Jugendmedizin, Funktionsbereich Neuropädiatrie
› Author Affiliations

ZUSAMMENFASSUNG

Antikonvulsiva haben ein großes Risikopotenzial für unerwünschte Arzneimittelwirkungen (UAW). Im ersten Abschnitt des Artikels werden die UAW-Profile in der Pädiatrie wichtiger Antikonvulsiva vorgestellt. Beispielsweise können unter Valproattherapie zwar seltene, aber potenziell lebensbedrohliche Organopathien auftreten. Bei anderen Antikonvulsiva stehen UAW im Vordergrund, die den Alltag beeinflussen können, wie etwa aggressives Verhalten bei Levetiracetam. Diese können die Lebensqualität und den Alltag pädiatrischer Patienten und deren Familien beeinträchtigen. Daher wird im zweiten Teil des Artikels auf die Wahrnehmung der Betroffenen eingegangen. Eltern befürchten eher schwerwiegende UAW wie Organversagen, pädiatrische Patienten eher neurologische und psychiatrische Symptome. Diese Symptome werden auch am häufigsten von pädiatrischen Patienten erlebt. Als besonders negativ werden die emotionale Belastung sowie erlebte Einschränkungen bei Aktivitäten in Schule und Freizeit beschrieben. Daher sollten neben der Effektivität des Arzneistoffs bei der jeweiligen Epilepsieform auch die Wünsche der pädiatrischen Patienten und deren Eltern bei der Therapieauswahl berücksichtigt werden.

ABSTRACT

Anti-seizure medications have a high risk potential for adverse drug reactions (ADRs). The first section of this article presents the ADR profiles of anti-seizure medications important in pediatrics. For example, although rare, potentially life-threatening organopathies can occur with valproate therapy. For other anti-seizure medications, the focus is on ADRs that can affect daily life, such as aggressive behavior with levetiracetam. Those ADRs can affect the quality of life and daily routine of pediatric patients and their families. Therefore, the second part of this article focuses on the perceptions of the affected pediatric patients and their families. While parents tend to fear serious ADRs such as organ failure, pediatric patients fear neurological and psychiatric symptoms. Those symptoms are also most commonly experienced by pediatric patients. Emotional distress and experienced limitations in school and leisure activities are described as particularly negative. Therefore, in addition to the effectiveness of the drug in the particular type of epilepsy, the wishes of the pediatric patients and their parents should also be taken into account in the choice of therapy.



Publication History

Article published online:
08 November 2022

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  • Literatur

  • 1 Davis T. Paediatric prescribing errors. Arch Dis Child 2011; 96: 489-491
  • 2 Kaushal R, Bates DW, Landrigan C. et al Medication errors and adverse drug events in pediatric inpatients. JAMA 2001; 285: 2114-2120
  • 3 Rieder M. Adverse Drug Reactions in Children: Pediatric Pharmacy and Drug Safety. J Pediatr Pharmacol Ther 2019; 24: 4-9
  • 4 Smyth RM, Gargon E, Kirkham J. et al Adverse drug reactions in children — a systematic review. PLoS One 2012; 07: e24061
  • 5 Kearns GL, Abdel-Rahman SM, Alander SW. et al Developmental pharmacology – drug disposition, action, and therapy in infants and children. N Engl J Med 2003; 349: 1157-1567
  • 6 Joseph PD, Craig JC, Caldwell PH. Clinical trials in children. Br J Clin Pharmacol 2015; 79: 357-369
  • 7 Kaushal R, Goldmann DA, Keohane CA. et al Adverse drug events in pediatric outpatients. Ambul Pediatr 2007; 07: 383-389
  • 8 Knopf H, Du Y. Perceived adverse drug reactions among non-institutionalized children and adolescents in Germany. Br J Clin Pharmacol 2010; 70: 409-417
  • 9 Wimmer S, Neubert A, Rascher W. The Safety of Drug Therapy in Children. Dtsch Arztebl Int 2015; 112: 781-787
  • 10 Cohen AL, Budnitz DS, Weidenbach KN. et al National surveillance of emergency department visits for outpatient adverse drug events in children and adolescents. J Pediatr 2008; 152: 416-421
  • 11 Smyth RL, Peak M, Turner MA. et al ADRIC: Adverse Drug Reactions In Children – a programme of research using mixed methods. Southampton (UK): NIHR Journals Library; 2014.
  • 12 Neininger MP, Jeschke S, Kiesel LM. et al Physicians’ perspectives on adverse drug reactions in pediatric routine care: a survey. World J Pediatr 2022; 18: 50-58
  • 13 Bertsche A, Neininger MP, Dahse AJ. et al Initial anticonvulsant monotherapy in routine care of children and adolescents: levetiracetam fails more frequently than valproate and oxcarbazepine due to a lack of effectiveness. Eur J Pediatr 2014; 173: 87-92
  • 14 Gaitatzis A, Sander JW. The long-term safety of antiepileptic drugs. CNS Drugs 2013; 27: 435-455
  • 15 Gerstner T, Buesing D, Longin E. et al Valproic acid induced encephalopathy – 19 new cases in Germany from 1994 to 2003 – a side effect associated to VPA therapy not only in young children. Seizure 2006; 15: 443-448
  • 16 Koenig SA, Buesing D, Longin E. et al Valproic acid-induced hepatopathy: nine new fatalities in Germany from 1994 to 2003. Epilepsia 2006; 47: 2027-2031
  • 17 Nicolai J, Aldenkamp AP, Huizenga JR. et al Cognitive side effects of valproic acid-induced hyperammonemia in children with epilepsy. J Clin Psychopharmacol 2007; 27: 221-224
  • 18 Koenig S, Gerstner T, Keller A. et al High incidence of valproate-induced coagulation disorders in children receiving valproic acid: a prospective study. Blood Coagul Fibrinolysis 2008; 19: 375-382
  • 19 Hakami T. Neuropharmacology of Antiseizure Drugs. Neuropsychopharmacol Rep 2021; 41: 336-351
  • 20 Thomé-Souza S, Freitas A, Fiore LA. et al Lamotrigine and valproate: efficacy of co-administration in a pediatric population. Pediatr Neurol 2003; 28: 360-364
  • 21 McVearry KM, Gaillard WD, VanMeter J. et al A prospective study of cognitive fluency and originality in children exposed in utero to carbamazepine, lamotrigine, or valproate monotherapy. Epilepsy Behav 2009; 16: 609-616
  • 22 Meador KJ, Baker GA, Browning N. et al Cognitive function at 3 years of age after fetal exposure to antiepileptic drugs. N Engl J Med 2009; 16: 1597-1605
  • 23 Meador KJ, Baker GA, Browning N. et al Foetal antiepileptic drug exposure and verbal versus non-verbal abilities at three years of age. Brain 2011; 134: 396-404
  • 24 Meador KJ, Baker GA, Browning N. et al Effects of fetal antiepileptic drug exposure: outcomes at age 4.5 years. Neurology 2012; 78: 1207-1214
  • 25 Meador KJ, Baker GA, Browning N. et al Fetal antiepileptic drug exposure and cognitive outcomes at age 6 years (NEAD study): a prospective observational study. Lancet Neurol 2013; 12: 244-252
  • 26 Nadebaum C, Anderson V, Vajda F. et al The Australian brain and cognition and antiepileptic drugs study: IQ in school-aged children exposed to sodium valproate and polytherapy. J Int Neuropsychol Soc 2011; 17: 133-142
  • 27 Shallcross R, Bromley RL, Irwin B. et al Child development following in utero exposure: levetiracetam vs sodium valproate Neurol. Neurology 2011; 76: 383-389
  • 28 Koren G, Nava-Ocampo AA, Moretti ME. et al Major malformations with valproic acid. Can Fam Physician 2006; 52: 441-442 444, 447
  • 29 Christensen J, Grønborg TK, Sørensen MJ. et al Prenatal valproate exposure and risk of autism spectrum disorders and childhood autism. JAMA 2013; 309: 1696-1703
  • 30 Cohen MJ, Meador KJ, Browning N. et al Fetal antiepileptic drug exposure: motor, adaptive, and emotional/behavioral functioning at age 3 years. Epilepsy Behav 2011; 22: 240-246
  • 31 Zaccara G, Perucca E. Interactions between antiepileptic drugs, and between antiepileptic drugs and other drugs. Epileptic Disord 2014; 16: 409-431
  • 32 Veroniki AA, Cogo E, Rios P. et al Comparative safety of anti-epileptic drugs during pregnancy: a systematic review and network meta-analysis of congenital malformations and prenatal outcomes. BMC Med 2017; 15: 95
  • 33 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 Neurol 2018; 17: 530-538
  • 34 Mula M, Trimble MR, Sander JW. Psychiatric adverse events in patients with epilepsy and learning disabilities taking levetiracetam. Seizure 2004; 13: 55-57
  • 35 Mula M, Trimble MR, Yuen A. et al Psychiatric adverse events during levetiracetam therapy. Neurology 2003; 61: 704-706
  • 36 Wood H. Epilepsy: psychiatric adverse effects of levetiracetam linked to genetic variation in dopamine signaling. Nat Rev Neurol 2012; 08: 532
  • 37 Opp J, Tuxhorn I, May T. et al Levetiracetam in children with refractory epilepsy: a multicenter open label study in Germany. Seizure 2005; 14: 476-484
  • 38 Verrotti A, Prezioso G, Di Sabatino F. et al The adverse event profile of levetiracetam: A meta-analysis on children and adults. Seizure 2015; 31: 49-55
  • 39 Kuba R, Novotná I, Brázdil M. et al Longterm levetiracetam treatment in patients with epilepsy: 3-year follow up. Acta Neurol Scand 2010; 121: 83-88
  • 40 Institute for Safe Medication Practices, USA. Quarter Watch. Monitoring FDA MedWatch Reports. Special Report on Children 2014
  • 41 Marson A, Burnside G, Appleton R. et al The SANAD II study of the effectiveness and cost-effectiveness of valproate versus levetiracetam for newly diagnosed generalised and unclassifiable epilepsy: an open-label, non-inferiority, multicentre, phase 4, randomised controlled trial. Lancet 2021; 397: 1375-1386
  • 42 Levi N, Bastuji-Garin S, Mockenhaupt M. et al Medications as risk factors of Stevens-Johnson syndrome and toxic epidermal necrolysis in children: a pooled analysis. Pediatrics 2009; 123: e297-304
  • 43 Sabers A, Ohman I, Christensen J. et al Oral contraceptives reduce lamotrigine plasma levels. Neurology 2003; 61: 570-571
  • 44 Reimers A, Helde G, Brodtkorb E. Ethinyl estradiol, not progestogens, reduces lamotrigine serum concentrations. Epilepsia 2005; 46: 1414-1417
  • 45 Reddy DS. Clinical pharmacokinetic interactions between antiepileptic drugs and hormonal contraceptives. Expert Rev Clin Pharmacol 2010; 03: 183-192
  • 46 Sidhu J, Job S, Singh S. et al The pharmacokinetic and pharmacodynamic consequences of the co-administration of lamotrigine and a combined oral contraceptive in healthy female subjects. Br J Clin Pharmacol 2006; 61: 191-199
  • 47 Ben-Zeev B, Watemberg N, Lerman P. et al Sulthiame in childhood epilepsy. Pediatr Int 2004; 46: 521-524
  • 48 Verrotti A, Scaparrotta A, Agostinelli S. et al Topiramate-induced weight loss: a review. Epilepsy Res 2011; 95: 189-199
  • 49 Corbin Bush N, Twombley K, Ahn J. et al Prevalence and spot urine risk factors for renal stones in children taking topiramate. J Pediatr Urol 2013; 09: 884-889
  • 50 Ishikawa N, Tani H, Kobayashi Y. et al High Incidence of Renal Stones in Severely Disabled Children with Epilepsy Treated with Topiramate. Neuropediatrics 2019; 50: 160-163
  • 51 Thompson PJ, Baxendale SA, Duncan JS. et al Effects of topiramate on cognitive function. J Neurol Neurosurg Psychiatry 2000; 69: 636-641
  • 52 Coppola G, Verrotti A, Resicato G. et al Topiramate in children and adolescents with epilepsy and mental retardation: a prospective study on behavior and cognitive effects. Epilepsy Behav 2008; 12: 253-256
  • 53 Mirza N, Marson AG, Pirmohamed M. Effect of topiramate on acid-base balance: extent, mechanism and effects. Br J Clin Pharmacol 2009; 68: 655-661
  • 54 Johnston CA, Crawford PM. Anti-epileptic drugs and hormonal treatments. Curr Treat Options Neurol 2014; 16: 288
  • 55 Taylor J, Jacoby A, Baker GA. et al Self-reported and parent-reported quality of life of children and adolescents with new-onset epilepsy. Epilepsia 2011; 52: 1489-1498
  • 56 Cianchetti C, Messina P, Pupillo E. et al The perceived burden of epilepsy: impact on the quality of life of children and adolescents and their families. Seizure 2015; 24: 93-101
  • 57 Fisch SM, Neininger MP, Prenzel F. et al Experiences, expectations, and fears of adolescents with epilepsy or bronchial asthma. Eur J Pediatr 2018; 177: 1451-1457
  • 58 Hackel K, Neininger MP, Kiess W. et al Epilepsy: knowledge and attitudes of physiotherapists, occupational therapists, and speech therapists. Eur J Pediatr 2019; 178: 1485-1491
  • 59 Spindler UP, Hotopp LC, Bach VA. et al Seizure disorders and developmental disorders: impact on life of affected families-a structured interview. Eur J Pediatr 2017; 176: 1121-1129
  • 60 Junger KW, Morita D, Modi AC. The pediatric epilepsy side effects questionnaire: establishing clinically meaningful change. Epilepsy Behav 2015; 45: 101-104
  • 61 Wu YP, Follansbee-Junger K, Rausch J. et al Parent and family stress factors predict health-related quality in pediatric patients with new-onset epilepsy. Epilepsia 2014; 55: 866-877
  • 62 Kowski AB, Weissinger F, Gaus V. et al Specific adverse effects of antiepileptic drugs – A true-to-life monotherapy study. Epilepsy Behav 2016; 54: 150-157
  • 63 Bach VA, Neininger MP, Spindler UP. et al How do parents perceive adverse drug events of their children’s anticonvulsant medication?. Eur J Paediatr Neurol 2018; 22: 427-433
  • 64 Raspall-Chaure M, Neville BG, Scott RC. The medical management of the epilepsies in children: conceptual and practical considerations. Lancet Neurol 2008; 07: 57-69
  • 65 Niriayo YL, Mamo A, Gidey K. et al Medication belief and adherence among patients with epilepsy. Behav Neurol 2019; 2019: 2806341
  • 66 da Mota Gomes M, Navarro T, Keepanasseril A. et al Increasing adherence to treatment in epilepsy: what do the strongest trials show?. Acta Neurol Scand 2017; 135: 266-272
  • 67 Hartmann N, Neininger MP, Bernhard MK. et al Use of complementary and alternative medicine (CAM) by parents in their children and adolescents with epilepsy – Prevalence, predictors and parents’ assessment. Eur J Paediatr Neurol 2016; 20: 11-19
  • 68 Neininger MP, Woltermann S, Jeschke S. et al How do pediatric patients perceive adverse drug events of anticonvulsant drugs? A survey. Eur J Pediatr 2020; 179: 1413-1420
  • 69 Woltermann S, Jeschke S, Herziger B. et al Anticonvulsant long-term and rescue medication: The children’s perspective. Eur J Paediatr Neurol 2020; 28: 180-185
  • 70 Demir E, Aysun S. Weight gain associated with valproate in childhood. Pediatr Neurol 2000; 22: 361-364
  • 71 Garoufi A, Vartzelis G, Tsentidis C. et al Weight gain in children on oxcarbazepine monotherapy. Epilepsy Res 2016; 122: 110-113
  • 72 Slof-Op’t Landt MCT, van Furth EF, van Beijsterveldt CEM. et al Prevalence of dieting and fear of weight gain across ages: a community sample from adolescents to the elderly. Int J Public Health 2017; 62: 911-919