Retrospective review of paediatric case reports of Stevens-Johnson syndrome and toxic epidermal necrolysis with lamotrigine from an international pharmacovigilance database

Abstract

ObjectivesThis study aims to characterise paediatric reports with lamotrigine (LTG) and Stevens-Johnson syndrome or toxic epidermal necrolysis (SJS/TEN), and to explore whether potential risk factors can be identified.DesignThis is a retrospective review of suspected adverse drug reaction (ADR) reports. Reported time from LTG start to SJS/TEN onset, indication for use and dose was explored. To identify potential risk groups, report features (eg, ages, patient sex, co-reported drugs) for LTG and SJS/TEN were contrasted with two reference groups in the same database, using shrinkage logOR.SettingReports were retrieved from VigiBase, the WHO global database of individual case safety reports, in January 2015.PatientsData for patients aged ≤17 years old were extracted.ResultsThere were 486 reports of SJS/TEN in LTG-treated paediatric patients. Ninety-seven per cent of the cases with complete information on time to onset of SJS/TEN occurred within 8 weeks of initiation of LTG therapy. The median time to onset was 15 days (IQR: 10–22 days). The proportion of SJS/TEN with LTG and valproic acid (VPA) co-reporting was significantly more than non-cutaneous ADRs (43% vs 19%, (logOR: 1.60 (99% CI: 1.33 to 1.84)).ConclusionsThe results suggest that VPA co-medication with LTG therapy is a risk factor for SJS/TEN in the paediatric population. Although this relationship has been identified from individual case reports, this is the first supportive study from a large compilation of cases. SJS/TEN risk is highest in first 8 weeks of treatment with LTG in children and clinicians should be aware of this risk during this period.

Anti-Epileptic Drug Toxicity in Children

“…For example, patients due to commence treatment with carbamazepine or lamotrigine (especially lamotrigine in combination with valproic acid) should be warned of the risk of developing an allergic reaction. Allergic reactions are not uncommon with either carbamazepine or lamotrigine, but can lead on to Stevens-Johnson syndrome, which can be fatal [ 6 ]. Parents and older children should be informed that if they develop a rash that they should contact a health professional that day.…”

Studying the Evolving Knowledge of Adverse Drug Reactions in Order to Facilitate the Rational Use of Medicines in Paediatric Patients

“…These sources can be used to identify possible new ADRs in paediatric patients such as acute renal impairment in association with levetiracetam [49]. Case series and pharmacovigilance reporting systems are useful for identifying possible risk factors for severe but uncommon ADRs [40]. Well-documented case series can give insights into the nature of ADRs such as when the event is expected to occur in relation to the commencement of treatment with a medicine and inform about the chronology of signs and symptoms leading up to the diagnosis of an ADR, as well as the outcome and time to recovery.…”

“…A review of paediatric case reports of Stevens–Johnson syndrome and toxic epidermal necrolysis in association with lamotrigine in VigiBase identified 486 reports. Co-medication with valproic acid was reported in 207 of the 486 cases (43%), which was significantly more than for cases with these co-medications reported without skin reactions [40].…”

The use of drug calendars for the diagnosis of cutaneous drug eruptions in the age of electronic medical records

“…The drug calendar would also include the start and stoppage of medications and the change of dosage of medications. Stevens-Johnson syndrome and toxic epidermal necrolysis are well known to develop with a rapid escalation of the dose of lamotrigine (Lamictal), [12,13]. In addition, the co-administration of certain medications, such as valproate and lamotrigine, increases the risk of hypersensitivity reaction to lamotrigine [13,14].…”