Carbamazepine-Induced Severe Cutaneous Adverse Drug Reactions: A 21-Year Comparison Between Children and Adults in Malaysia.

Severe cutaneous adverse drug reactions (SCARs) are a life-threatening condition. We aimed to identify all carbamazepine-induced SCARs voluntarily reported to the Malaysian pharmacovigilance database and to compare between children and adults. Adverse drug reaction reports for carbamazepine were extracted from 2000 to 2020, and divided into 2 groups, that is, children (aged 0-17 years) and adults (aged 18 years and above). Age, sex, race, and carbamazepine dose were analyzed using multiple logistic regression. Of 1102 carbamazepine adverse drug reaction reports, 416 reports were SCARs (99 children, 317 adults). Stevens-Johnson syndrome and toxic epidermal necrolysis were the main SCAR types for both age groups. Median time-to-onset for any type of SCAR was 13 days, regardless of age. In children, Malay individuals were 3.6 times more likely to report SCARs (95% confidence interval, 1.356-9.546; P = .010) compared to the Chinese population. In adults, carbamazepine-induced SCARs were reported as 3.6 times higher in those with a daily dose of 200 mg or less as compared to a daily dose of 400 mg or more. (95% confidence interval, 2.257-5.758; P < .001) Carbamazepine-induced SCARs reported in Malaysia were predominantly Stevens-Johnson syndrome or toxic epidermal necrolysis, with the majority in Malay individuals. Initiation therapy needs close monitoring between 2 weeks and 1 month.

Incidence of Antiseizure Medication-Induced Severe Cutaneous Adverse Reactions in Malaysia.

Antiseizure medication can potentially cause severe cutaneous adverse reactions, and certain antiseizure medication-induced severe cutaneous adverse reactions are associated with specific human leukocyte antigen alleles. This caused a change in antiseizure medication prescribing patterns, which may influence the incidence of antiseizure medication-induced severe cutaneous adverse reactions. Thus, we aimed to determine the incidence of antiseizure medication-induced severe cutaneous adverse reactions and its change over 15 years (2006-2019) in Malaysia. This retrospective analysis combined antiseizure medication-induced SCAR cases from the national adverse drug reaction database in the National Pharmaceutical Regulatory Agency, antiseizure medication usage data from the Malaysian Statistics of Medicine, and prescribing data from University Malaya Medical Centre, a national-level tertiary hospital to calculate antiseizure medication-induced SCAR incidence in Malaysia. We observed an upward trend in reported antiseizure medication-induced SCAR cases from 28 cases in 2006 to 92 in 2016. The incidence of carbamazepine (CBZ)-induced severe cutaneous adverse reactions increased from 7.5 per 1000 person-years (2006) to 17.8 per 1000 person-years (2016) but dropped to 7.2 per 1000 person-years subsequently (2019). Concurrently, there was an increase in the incidence of severe cutaneous adverse reactions secondary to phenytoin and lamotrigine. The prevalent users of CBZ had reduced from 22.8% (2006) to 14.1% (2016), whereas the levetiracetam and sodium valproate users increased by 5.5% and 4.8%, respectively. The incidence of CBZ-induced severe cutaneous adverse reactions had reduced since 2016, probably related to the implementation of human leukocyte antigen-B*1502 screening in Malaysia or substitution of CBZ with other antiseizure medications. However, this was accompanied by an increase in SCAR incidence related to phenytoin and lamotrigine.

Incidence of allopurinol-induced severe cutaneous adverse drug reaction in Malaysia.

AIMS: Allopurinol is known to cause severe cutaneous adverse drug reactions (SCAR) in Malaysia. However, the incidence of allopurinol-induced SCAR is unknown. Therefore, we aimed to determine the incidence of allopurinol-induced SCAR in Malaysia over 5 years from 2015 to 2019. METHODS: This retrospective analysis was done in collaboration with the National Pharmaceutical Regulatory Agency (NPRA). All allopurinol-induced adverse drug reaction cases reported to NPRA from 2015 to 2019 were extracted. Allopurinol-induced SCAR cases were identified and the incidence over the 5 years was calculated. RESULTS: Incidence of allopurinol-induced SCAR averaged at 2.5 cases per 1000 new users over the 5-year period, with a reducing trend from 3.2 per 1000 new users in 2015 to 2.25 per 1000 in 2019; despite the increasing number of adverse drug reaction cases being reported over the years. Stevens-Johnson syndrome was the commonest form of allopurinol-induced SCAR reported, at 143 cases (46.8% of total SCAR reported). Among Malaysia's 3 main ethnicities, the Chinese had the highest percentages of allopurinol-induced SCAR when compared to the Bumiputera and Indians (3.18 × 10-4 %). CONCLUSION: The estimated incidence of allopurinol-induced SCAR in Malaysia from 2015 to 2019 was 2.5 cases per 1000 new users. This figure is consistent with the incidence reported in other Asian countries, namely Taiwan and Thailand.

Allopurinol-Induced Severe Cutaneous Adverse Drug Reactions: An Analysis of Spontaneous Reports in Malaysia (2000-2018).

INTRODUCTION: Allopurinol-induced severe cutaneous adverse drug reactions (SCARs) are potentially debilitating and life-threatening reactions, which can cause a financial burden to the healthcare system. OBJECTIVES: We aimed to identify risk factors for allopurinol-induced SCARs and to assess their impact on fatality. METHODS: Adverse drug reaction (ADR) reports with allopurinol as suspected drug were extracted from the Malaysian pharmacovigilance database from year 2000 to 2018. Multiple logistic regression analysis was used to identify significant predictors of allopurinol-induced SCARs. We further analysed the association between covariates and SCARs-related fatality in a separate model. Level of significance was set at p value < 0.05. RESULTS: Out of 1747 allopurinol ADR reports, 612 involved SCARs (35%). The strongest predictors significantly associated with SCARs were underlying renal disease (odds ratio [OR] 2.02; 95% confidence interval [CI] 1.36, 3.00; p = 0.001), allopurinol-prescribed dose of 300 mg/day or higher (OR 1.72; 95% CI 1.38, 2.15; p < 0.001), females (OR 1.54; 95% CI 1.24, 1.93; p < 0.001), age 65 years and above (OR 1.31; 95% CI 1.04, 1.64; p = 0.020), and allopurinol-prescribed indication. SCARs cases were higher in patients who received allopurinol for unspecified hyperuricaemia (OR 1.87; 95% CI 1.29, 2.70; p = 0.001) and off-label indications (OR 3.45; 95% CI 2.20, 5.42; p < 0.001) compared to registered indications. Fatality was associated with older age and a diagnosis of Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) overlap or TEN. CONCLUSIONS: Malaysian pharmacovigilance data show that predictors of allopurinol-induced SCARs were elderly females, patients with underlying renal disease and high allopurinol doses. These patients need close monitoring and must be educated to stop allopurinol at the first signs of rash.

Patient Reporting of Adverse Drug Reactions (ADRs): Survey of Public Awareness and Predictors of Confidence to Report.

BACKGROUND: Many countries incorporate direct patient reporting of adverse drug reactions (ADRs) into their pharmacovigilance systems as patients provide a different insight into drug safety compared to health care professionals. This study aimed to examine public awareness about ADR reporting in Malaysia and patients' confidence in reporting ADRs. METHODS: Using a cross-sectional design and convenient sampling, data were collected in public areas within Kuala Lumpur, Malaysia, via face-to-face interview with a structured questionnaire. Multivariate logistic regression analysis was used to identify the significant predictors of patients' confidence in ADR reporting. RESULTS: Out of 860 consented respondents achieving a response rate of 73.5%, only 69 (8%) were aware of the Malaysian ADR monitoring system. The majority (60%) of the respondents indicated they had the confidence to report ADRs. Multivariate logistic regression analysis revealed that ease in completing the ADR reporting form was the strongest variable predictive of confidence to report ADRs (odds ratio [OR], 18.45; 95% confidence interval [CI], 10.55-32.25). Increased confidence in ADR reporting was also associated with education level. Respondents with a higher education level were more likely to be confident to report ADRs compared to those with primary or no formal education (OR, 2.49; 95% CI, 0.77-8.1). CONCLUSIONS: Lack of awareness of the ADR monitoring system is still prevalent among Malaysian patients. The ease of completing the ADR form and education level are predictive of patient confidence to report ADRs. These factors should be considered in designing public promotional activities to encourage patient contributions to pharmacovigilance.

Self-medication practices among adult population attending community pharmacies in Malaysia: an exploratory study.

OBJECTIVE: To assess the prevalence of self-medication among adults in an urban setting and to identify any factors contributing to self-medication in relation to consumer characteristics. SETTING: The study was carried out in Kuala Lumpur, the capital of Malaysia. METHODS: A cross-sectional study using a self administered questionnaire including adults above 21 years old as an exit survey was conducted in Kuala Lumpur. MAIN OUTCOME MEASURES: Number of medications taken in a day by participants, source of medication for the treatment of minor illnesses among participants, common illnesses chosen for self-medication by participants, and the sources of information of participants. RESULTS: Of 314 participants, 62.7% had taken at least one medication in the past week without prescription and 62.7% believed that over the counter medicines were just as effective as those prescribed by doctors. 69.4% would seek a healthcare professional's advice before purchasing any medication and 86.9% would consult a pharmacist prior to buying medication from the pharmacy. Only 86% checked the expiry dates on medications and 54.5% reported keeping leftover medication. CONCLUSIONS: Self-medication practice is prevalent in Kuala Lumpur but some practice might be harmful. Education on appropriate use of self-medication need to be emphasized in order to ensure quality use of medicines.