Implementing HLA-B*58:01 testing prior to allopurinol initiation in Malaysian primary care setting: A qualitative study from doctors' and patients' perspective.

INTRODUCTION: Allopurinol, the first-line treatment for chronic gout, is a common causative drug for severe cutaneous adverse reactions (SCAR). HLA-B*58:01 allele was strongly associated with allopurinol-induced SCAR in Asian countries such as Taiwan, Japan, Thailand and Malaysia. HLA-B*58:01 screening before allopurinol initiation is conditionally recommended in the Southeast-Asian population, but the uptake of this screening is slow in primary care settings, including Malaysia. This study aimed to explore the views and experiences of primary care doctors and patients with gout on implementing HLA-B*58:01 testing in Malaysia as part of a more extensive study exploring the feasibility of implementing it routinely. METHODS: This qualitative study used in-depth interviews and focus group discussions to obtain information from patients with gout under follow-up in primary care and doctors who cared for them. Patients and doctors shared their gout management experiences and views on implementing HLA-B*58:01 screening in primary care. Data were coded and analysed using thematic analysis. RESULTS: 18 patients and 18 doctors from three different healthcare settings (university hospital, public health clinics, private general practitioner clinics) participated. The acceptability to HLA-B*58:01 screening was good among the doctors and patients. We discovered inadequate disclosure of severe side effects of allopurinol by doctors due to concerns about medication refusal by patients, which could potentially be improved by introducing HLA-B*58:01 testing. Barriers to implementation included out-of-pocket costs for patients, the cost-effectiveness of this implementation, lack of established alternative treatment pathway besides allopurinol, counselling burden and concern about genetic data security. Our participants preferred targeted screening for high-risk populations instead of universal screening. CONCLUSION: Implementing HLA-B*58:01 testing in primary care is potentially feasible if a cost-effective, targeted screening policy on high-risk groups can be developed. A clear treatment pathway for patients who test positive should be made available.

Approaches to management of rhabdomyolysis as the adverse effect of drug interaction between atorvastatin and sacubitril/valsartan: a case report.

Background: Atorvastatin and sacubitril/valsartan (Entresto™) have been cornerstones in managing patients with coronary artery disease and heart failure (HF). We report a case of life-threatening rhabdomyolysis associated with the co-administration of atorvastatin and sacubitril/valsartan. Case summary: A 58-year-old male with coronary heart disease and chronic HF treated with the optimal dose of atorvastatin and other cardiovascular medications was frequently admitted for acute decompensation of HF. We decided to optimize his condition by adding sacubitril/valsartan to his treatment regime. He presented to our outpatient clinic with worsening myalgia and oliguria 6 days later. He was readmitted with markedly elevated serum creatinine kinase (CK) (94 850 U/L; normal range 32-294 U/L), deranged liver function tests, and acute kidney injury. We withheld atorvastatin and sacubitril/valsartan and treated him with renal replacement therapy. Discussion: Sacubitril inhibits the excretion of statins, thereby elevating serum statin concentration and increasing the likelihood of developing muscle-related toxicity. Co-administration of atorvastatin and sacubitril/valsartan should be monitored closely with laboratory investigations of CK and liver and renal function. The physician may consider starting low-dose atorvastatin at 20 mg daily in combination with sacubitril/valsartan 24 mg/26 mg twice daily and titrating accordingly to optimal doses. Rosuvastatin could be an alternative to atorvastatin, as it has less drug-drug interaction with sacubitril, thereby reducing the adverse effect.