Antiepileptic combination therapy with Stevens-Johnson syndrome and toxic epidermal necrolysis: Analysis of a Japanese pharmacovigilance database.

OBJECTIVE: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are immune-mediated diseases characterized by an extensive loss of the epidermal skin layer, often resulting in death. SJS and TEN are often triggered by certain drugs, including antiepileptic drugs (AEDs). Epilepsy is very difficult to treat and often involves the combination of two or more AEDs. In this study, we quantified not only the risk of SJS or TEN associated with single-AED therapy but also the risk related to concomitant AED treatment using reporting-derived signals. METHODS: An analysis of the Japanese Adverse Drug Event Report (JADER) database was performed from the first quarter of 2004 to the fourth quarter of 2018. The single-AED signals were evaluated using the proportional reporting ratio (PRR), and the combination therapy signals were evaluated using Ω shrinkage measure and combination risk ratio (CRR). RESULTS: SJS signals were associated with 11 AEDs, and TEN signals were related to 12 AEDs. Moreover, the following AED combinations were associated with SJS signals: carbamazepine-lorazepam (Ω025 : 0.33, CRR: 2.18) and fosphenytoin-lorazepam (Ω025 : 0.99, CRR: 39.20). The TEN signals were related to the following combinations: clobazam-gabapentin (Ω025 : 0.35, CRR: 3.14), phenytoin-gabapentin (Ω025 : 0.03, CRR: 2.18), valproic acid-gabapentin (Ω025 : 0.15, CRR: 2.25), clobazam-clonazepam (Ω025 : 0.03, CRR: 2.93), clobazam-valproic acid (Ω025 : 0.29, CRR: 1.55), fosphenytoin-lamotrigine (Ω025 : 0.05, CRR: 7.37), and lacosamide-levetiracetam (Ω025 : 0.74, CRR: 1.85). SIGNIFICANCE: This study identified two AED combinations that increased the SJS signals and seven combinations that increased the TEN signals. Although AED monotherapies require attention for SJS and TEN, some AED combinations require extra caution.

[Multivariate and Bayesian Network Analyses of the Factors Causing Belief Conflicts That Deteriorate Teamwork and Cause Stress among Pharmacists during Proposals and Inquiries of Prescription].

Pharmacists working in collaboration with doctors are mainly involved in proposals and inquiries of prescription. At such times, belief conflicts are expected to deteriorate teamwork and induce stress. However, there is no strong evidence for this. To clarify factors resulting in belief conflicts, we conducted a survey among 594 pharmacists working at medical institutions in Gifu City and belonging to Gifu Pharmaceutical Association or Gifu Prefectural Society of Hospital Pharmacists between January 2019 and April 2019. The items of the survey were gender, place of employment, pharmacist working experience (years), awareness of "professional competencies for pharmacists" stated in Model Core Curriculum for Pharmacy Education -2015 version-, whether each item of "professional competencies for pharmacists" is applicable to himself/herself or not, whether teamwork deteriorates and stress occurs due to proposals and inquiries of prescription or not, and Assessment of Belief Conflict in Relationship-14 (ABCR-14). The recovery rate of the questionnaire was 50.3% and the valid response rate was 77.6%. Multiple logistic regression and Bayesian network analyses revealed that "I can empathize with a patient's feelings and emotions, but I experience difficulty with unfair criticism" commonly resulted in teamwork deterioration due to proposals of prescription. "Pharmacist working experience years (more than 10 years)" and "The other staff make unreasonable demands of me in the work" commonly resulted in stress. Thus, belief conflicts in therapeutic relationships result in teamwork deterioration and stress in prescription proposals.