Muhamad Ali Sk Abdul Kader

Knowledge and perceptions of physicians from private medical centres towards generic medicines: a nationwide survey from Malaysia

ObjectivesGeneric medicine prescribing has become a common practice in public hospitals. However, the trend in private medical centres seems to be different. The objective of this study was to investigate knowledge, perceptions and behavior of physicians from private medical centres in Malaysia regarding generic medicines.MethodsThis study was a cross-sectional nationwide survey targeting physicians from private medical centres in Malaysia. The survey was conducted using questionnaire having (i) background and demographic data of the physicians, volume of prescription in a day, stock of generic medicines in their hospital pharmacy etc. (ii) their knowledge about bioequivalence (iii) prescribing behavior (iv) physicians’ knowledge of quality, safety and efficacy of generic medicines, and their cost (v) perceptions of physicians towards issues pertaining to generic medicines utilization.ResultsA total of 263 questionnaires out of 735 were received, giving a response rate of 35.8%. Of the respondents, 214 (81.4%) were male and 49 (18.6%) were females. The majority of the participants were in the age range of 41–50 years and comprised 49.0% of the respondents. Only 2.3% of physicians were aware of the regulatory limits of bioequivalence standards in Malaysia. Of the respondents, 23.2% agreed that they ‘always’ write their prescriptions using originator product name whereas 50.2% do it ‘usually’. A number of significant associations were found between their knowledge, perceptions about generic medicines and their demographic characteristics.ConclusionsThe majority of the physicians from private medical centres in Malaysia had negative perceptions about safety, quality and the efficacy of generic medicines. These negative perceptions could be the cause of the limited use of generic medicines in the private medical centres. Therefore, in order to facilitate their use, it is recommended that the physicians need to be reassured and educated about the drug regulatory authority approval system of generic medicines with regard to their bioequivalence, quality, efficacy and safety. Apart from the policy on generic substitution, it would also be recommended to have a national medicine pricing policy, which controls drug prices, in both the public and private sector. These efforts are worthwhile to reduce the drug expenditure and improve the medicine affordability in Malaysia.

The Personalization of Clopidogrel Antiplatelet Therapy: The Role of Integrative Pharmacogenetics and Pharmacometabolomics

Dual antiplatelet therapy of aspirin and clopidogrel is pivotal for patients undergoing percutaneous coronary intervention. However, the variable platelets reactivity response to clopidogrel may lead to outcome failure and recurrence of cardiovascular events. Although many genetic and nongenetic factors are known, great portion of clopidogrel variable platelets reactivity remain unexplained which challenges the personalization of clopidogrel therapy. Current methods for clopidogrel personalization include CYP2C19 genotyping, pharmacokinetics, and platelets function testing. However, these methods lack precise prediction of clopidogrel outcome, often leading to insufficient prediction. Pharmacometabolomics which is an approach to identify novel biomarkers of drug response or toxicity in biofluids has been investigated to predict drug response. The advantage of pharmacometabolomics is that it does not only predict the response but also provide extensive information on the metabolic pathways implicated with the response. Integrating pharmacogenetics with pharmacometabolomics can give insight on unknown genetic and nongenetic factors associated with the response. This review aimed to review the literature on factors associated with the variable platelets reactivity response to clopidogrel, as well as appraising current methods for the personalization of clopidogrel therapy. We also aimed to review the literature on using pharmacometabolomics approach to predict drug response, as well as discussing the plausibility of using it to predict clopidogrel outcome.

The effect of CYP2C19 genetic polymorphism and non-genetic factors on clopidogrel platelets inhibition in East Asian coronary artery disease patients

Clopidogrel has essential role in dual antiplatelet therapy (DAPT). However, some patients suffer high on treatment platelets reactivity (HTPR) which may lead to recurrence of cardiac events. Among several genetic variabilities, the CYP2C19*2 and CYP2C19*3 alleles were significantly associated with clopidogrel HTPR [1]. Both alleles are more prevalent in East Asians compared to Caucasian and African Americas. In Malaysia, an East Asian population, clopidogrel HTPR and CYP2C19*2 are frequent [2,3]. However, CYP2C19*2 had modest role in clopidogrel HTPR, suggesting the interference of other clinical variables. In these reports, platelets function testing (PFT) were measured after standard clopidogrel loading dose (LD) (300 mg) or after at least 4 days of maintenance dose (MD) (75 mg). It has been suggested that high LD of clopidogrel (600 mg) can reduce clopidogrel HTPR [4]. The use of clopidogrel 600 mg LD is uncommon in Malaysian clinical practice [5]. To date, clopidogrel HTPR for LD 600 mg has not been reported in Malaysia. To that end, we investigated clopidogrel HTPR frequency post LD 600 mg and evaluated the effect of CYP2C19*2 and CYP2C19*3, as well as other clinical variables on platelets reactivity.

Pharmacometabolomics analysis of plasma to phenotype clopidogrel high on treatment platelets reactivity in coronary artery disease patients

&NA; Dual antiplatelet therapy (DAPT) of clopidogrel and aspirin is crucial for coronary artery disease (CAD) patients undergoing percutaneous coronary intervention (PCI). However, some patients may endure clopidogrel high on treatment platelets reactivity (HTPR) which may cause thromboembolic events. Clopidogrel HTPR is multifactorial with some genetic and non‐genetic factors contributing to it. We aimed to use nuclear magnetic resonance (1H NMR) pharmacometabolomics analysis of plasma to investigate this multifactorial and identify metabolic phenotypes and pathways associated with clopidogrel HTPR. Blood samples were collected from 71 CAD patients planned for interventional angiographic procedure (IAP) before the administration of clopidogrel 600 mg loading dose (LD) and 6 h after the LD. Platelets function testing was done 6 h post‐LD using VerifyNow® P2Y12 assay. Pre‐dose and post‐dose plasma samples were analysed using 1H NMR. Multivariate statistical analysis was used to indicate the discriminating metabolites. Two metabotypes, each with 34 metabolites (pre‐dose and post‐dose) were associated with clopidogrel HTPR. Pathway analysis of these metabotypes revealed that aminoacyl‐tRNA biosynthesis, nitrogen metabolism and glycine‐serine‐threonine metabolism are the most perturbed metabolic pathways associated with clopidogrel HTPR. Furthermore, the identified biomarkers indicated that clopidogrel HTPR is multifactorial where the metabolic phenotypes of insulin resistance, type two diabetes mellitus, obesity, gut‐microbiota and heart failure are associated with it. Pharmacometabolomics analysis of plasma revealed new insights on the implicated metabolic pathways and the predisposing factors of clopidogrel HTPR. Graphical abstract Figure. No caption available.

Use of ticagrelor alongside fibrinolytic therapy in patients with ST-segment elevation myocardial infarction: Practical perspectives based on data from the TREAT study

Primary percutaneous coronary intervention (PCI) is the preferred reperfusion method in patients with ST‐segment elevation myocardial infarction (STEMI). In patients with STEMI who cannot undergo timely primary PCI, pharmacoinvasive treatment is recommended, comprising immediate fibrinolytic therapy with subsequent coronary angiography and rescue PCI if needed. Improving clinical outcomes following fibrinolysis remains of great importance for the many patients globally for whom rapid treatment with primary PCI is not possible. For patients with acute coronary syndrome who underwent primary PCI, the PLATO trial demonstrated superior efficacy of ticagrelor relative to clopidogrel. Results in the predefined subgroup of patients with STEMI were consistent with the overall PLATO trial. Patients who received fibrinolytic therapy in the 24 hours before randomization were excluded from PLATO, and there is thus a lack of data on the safety of using ticagrelor in conjunction with fibrinolytic therapy in the first 24 hours after STEMI. The TREAT study addresses this knowledge gap; patients with STEMI who had symptom onset within the previous 24 hours and had received fibrinolytic therapy (of whom 89.4% had also received clopidogrel) were randomized to treatment with ticagrelor or clopidogrel (median time between fibrinolysis and randomization: 11.5 hours). At 30 days, ticagrelor was found to be non‐inferior to clopidogrel for the primary safety outcome of Thrombolysis in Myocardial Infarction (TIMI)‐defined first major bleeding. Considering together the results of the PLATO and TREAT studies, initiating or switching to treatment with ticagrelor within the first 24 hours after STEMI in patients receiving fibrinolysis is reasonable.