Cutaneous Adverse Reactions Reported with Antiepileptic Drugs in Tunisian Pediatric Population

Introduction: Antiepileptic drugs (AED) are widely used in pediatric population (PP). They are mainly indicated in the treatment of epilepsy and some psychiatric pathologies and behavioral disorders. AED are among the drugs most frequently associated with cutaneous adverse reactions (CAR) in children. These CAR are usually mild and disappear spontaneously after the AED withdrawal. However, severe life-threatening reactions can sometimes occur [1]. Objective: To study the epidemiological and clinical features of CAR occurring in PP and to identify the most implicated AED. Methods: We conducted a descriptive retrospective study over a period of seven years from January 2014 to December 2020 about CAR of AED in PP (aged under or equal to 16 years-old) notified to The Tunisian National Center of Pharmacovigilance. All cases were analyzed according to the updated French method of imputability [2]. Results: We collected 41 cases of CAR associated to AED. The age varied from 2 to 16 years old (mean = 9.5 years old) with a sex ratio (H/F) = 0.5. AED were indicated for neurological pathology (epilepsy) in 98% of cases and for psychiatric disorder (attention deficit hyperactivity disorder) in 2% of cases. Notified CAR in our study are summarized in table 1. Incriminated AED were lamotrigine (LMG) (41%), carbamazepin (27%), valproic acid (22%), phenobarbital (7%), phenytoin (2%) and levetiracetam (2%). These AED was prescribed in monotherapy in 56% of cases and in polytherapy in 44% of cases. Severe cutaneous adverse reactions (SCARs) accounted for 24% of all CAR. There was no statistically significant difference in occurrence of SCARs according to the number of prescribed AED (p = 0.72) or their aromatic nature (p = 0.1). LMG dose-escalation guidelines was not respected in one case. It was a patient who developed a maculopapular exanthema 3 days after initiating LMG treatment with 150mg/day. Therapeutic drug monitoring was performed in three cases of hair loss with VPA. The VPA plasma concentration was supra-therapeutic in two cases and within the therapeutic range in one case. Conclusion: Thus, according to this retrospective study, maculopapular exanthema was the most frequently reported CAR with AED in PP. Also, LMG was the most incriminated AED. However, a comparative study could be considered in order to specify the risk factors for the occurrence of AED-induced CAR.