Allopurinol‐induced severe cutaneous adverse drug reactions: Risk minimization measures in Malaysia

Abstract

Purpose To describe risk minimization measures (RMMs) implemented in Malaysia for allopurinol‐induced severe cutaneous adverse drug reactions (SCARs) and examine their impact using real‐world data on allopurinol usage and adverse drug reaction (ADR) reports associated with allopurinol. Methods Data on allopurinol ADR reports (2000‐2018) were extracted from the Malaysian ADR database. We identified RMMs implemented between 2000 and 2018 from the minutes of relevant meetings and the national pharmacovigilance newsletter. We obtained allopurinol utilization data (2004‐2018) from the Pharmaceutical Services Programme. To determine the impact of RMMs on ADR reporting, we considered ADR reports received within 1 year of RMM implementation. We used the Pearson χ2 test to examine the relation between the implementation of RMMs and allopurinol ADR reports. Results The 16 RMMs for allopurinol‐related SCARs implemented in Malaysia involved nine risk communications, four prescriber or patient educational material, and three health system innovations. Allopurinol utilization decreased by 21.5% from 2004 to 2018. ADR reporting rates for all drugs (n = 144 507) and allopurinol (n = 1747) increased. ADR reports involving off‐label use decreased by 6% from 2011. SCARs cases remained between 20% and 50%. RMMs implemented showed statistically significant reduction in ADR reports involving off‐label use for August 2014 [χ2 (1, N = 258) = 5.32, P = .021] and October 2016 [χ2 (1, N = 349) = 3.85, P = .0499]. Conclusions RMMs to promote the appropriate use of allopurinol and prescriber education have a positive impact. We need further measures to reduce the incidence and severity of allopurinol‐induced SCARs, such as patient education and more research into pharmacogenetic screening.

Incidence of allopurinol‐induced severe cutaneous adverse drug reaction in Malaysia

“…This may be due to the risk minimisation measures implemented in the early 2010s, namely the restriction of allopurinol initiation only to specialists in the public health sector, removal of uric acid as a routine blood test to prevent allopurinol initiation for asymptomatic hyperuricaemia and various awareness programmes such as reminder letters to prescribers on asymptomatic hyperuricaemia, publications in the Malaysian Adverse Drug Reaction Advisory Committee bulletin. 36 We found that the average incidence of allopurinol-induced SCAR in Malaysia over 5 years (2015-2019) was 2.5 cases in every 1000 new users. Our findings were consistent with a Taiwan study that reported an incidence rate of 3-4.68 per 1000 users.…”

“…However, for allopurinol‐induced SCARs, the majority of reports came from healthcare professionals as these severe cases usually required hospitalisation. We expect the under‐reporting rate would be low, as many awareness measures including ADR reporting for allopurinol have been carried out for this issue 36 . The findings of our study enabled us to address this challenge and determine the estimated incidence rate for allopurinol‐induced SCARs from drug utilisation data as a denominator.…”

“…Despite the increase in allopurinol utilisation, incident users and reporting rates, a slight reduction in the incidence of allopurinol‐induced SCAR was observed from 2015 to 2019 from 3 to 2 cases per 1000 new users. This may be due to the risk minimisation measures implemented in the early 2010s, namely the restriction of allopurinol initiation only to specialists in the public health sector, removal of uric acid as a routine blood test to prevent allopurinol initiation for asymptomatic hyperuricaemia and various awareness programmes such as reminder letters to prescribers on asymptomatic hyperuricaemia, publications in the Malaysian Adverse Drug Reaction Advisory Committee bulletin 36 …”

Enhancing Medication Risk Communication in Developing Countries: A Mixed Method Survey Among Doctors and Pharmacists in Malaysia

“…[13] Initially producing printed material solely targeting healthcare professionals, NPRA now utilizes electronic communication as well as social media, and disseminates information to consumers. [13] The quality of risk communication content may be enhanced through multidisciplinary collaboration, by inviting nonregulatory healthcare professionals and in the future, consumer group representatives or patients to contribute articles and commentaries. Involvement of different stakeholders with various perspectives would result in communication which appeals to a broader audience.…”

“…[12] Various risk communication methods have been used in Malaysia over the past 30 years, including press releases, a national bulletin, safety alerts via email or social media, product package inserts, Direct Healthcare Professional Communication (DHPC) letters, and educational materials. However, our previous study [13] revealed that the risk communication methods, speci cally related to allopurinol, did not have a signi cant impact on ADR reporting and prescribing practice.…”