The incidence of recurrent cardiovascular events among acute coronary syndrome patients treated with generic or original clopidogrel in relation to their sociodemographic and clinical characteristics. The Aegean study.

INTRODUCTION: The use of generic drugs is continuously growing; however, there are limited epidemiological data regarding the therapeutic equivalence of each original drug formulation with its generic counterparts. We evaluated the 12-month composite endpoint of recurrent acute myocardial infarction, ischaemic stroke, cardiac deaths, or hospitalisation due to a major bleeding in acute coronary syndrome (ACS) patients treated with original clopidogrel or a generic clopidogrel formulation, in relation to sociodemographic and clinical characteristics. MATERIAL AND METHODS: Consecutive Greek ACS patients (n = 1194) hospitalised in the Aegean islands and the Attica region were enrolled. Clopidogrel treatment was recorded either as original clopidogrel hydrogen sulphate (Plavix®/Iscover®) or as a generic clopidogrel besylate formulation (Clovelen®). The composite endpoint was recorded at 12-month follow-up. RESULTS: The 12-month composite endpoint was 3.9% (4.6% in the Aegean islands and 3.5% in the Attica area, p > 0.05). The respective incidence in men was 4.0% and in women 3.8% (p > 0.05). Overall, generic and original clopidogrel use was 87% and 13% of patients, respectively. No significant differences were observed between original and generic clopidogrel use and 12-month composite endpoint incidence. Subgroup analysis with gender, region of residence, and clinical and lifestyle factors as strata did not reveal any significant outcomes. Haemorrhage incidence did not exceed 1% in the total sample. CONCLUSIONS: The use of a generic clopidogrel besylate formulation was quite high in both urban and insular areas of Greece and had similar efficacy and safety profile with the original clopidogrel salt, supporting the routine use of this low-cost generic clopidogrel in the management of cardiovascular disease patients.

[Clinical and economic consequences in patients initiating therapy with clopidogrel brand-name vs. generic: A real-life retrospective study]. / Consecuencias clínicas y económicas en pacientes que inician tratamiento con clopidogrel de marca vs. genérico: estudio retrospectivo de vida real.

OBJECTIVE: To evaluate the adherence to treatment, resource use, and costs in subjects initiating treatment with brand-name versus generic clopidogrel for acute coronary syndrome (ACS) and peripheral arterial disease (PAD). PATIENTS AND METHODS: Observational, retrospective study based on the medical records of patients aged ≥18 years who initiated treatment with clopidogrel (brand-name vs. generic) between 4 April 2015 and 31 March 2017. Four study groups were compared, and the follow-up was one year. The main measurements were: comorbidity, treatment adherence, medication possession ratio (MPR), resource use, and costs. The results were analysed using multivariate analysis. The level of statistical significance was P<.05. RESULTS: Four groups were compared: a) ACS: brand-name clopidogrel (N=1,067) vs. generic (N=3,504), and b) PAD: brand-name clopidogrel (N=425) vs. generic (N=994). In the ACS comparison (mean age: 69.7 years, 61.4% male), adherence (65.3% vs. 61.0%, P<.001), adjusted hazard ratio 0.85 and MPR (89.8% vs. 86.7%, P=.045) were more superior with brand-name clopidogrel than with the generic and with a lower mean cost per unit (€2,890 vs. €3,865, P=.001). In the PAD comparison, similar results were observed: persistence (64.7% vs. 58.9%, P=.039); adjusted hazard-ratio 0.86 and MPR (88.6% vs. 81.7%; P=.013) were more superior with brand-name clopidogrel than for the generic, with a lower mean cost per unit (€2,880 vs. €3,532, P=.044). CONCLUSIONS: There was better treatment adherence in patients initiating treatment with brand-name compared with generic clopidogrel for ACS and PAD, resulting in lower health costs for the Spanish National Health System.

Pivotal Bioequivalence Study of Clopacin®, a Generic Formulation of Clopidogrel 75 mg Film-Coated Tablets.

INTRODUCTION: Clopacin(®) (Acino Pharma AG) is a proprietary, besylate salt and lactose-free formulation of the widely-used anti-platelet treatment, clopidogrel. This study aimed to evaluate the bioequivalence of Clopacin(®) with the originator as reference drug, using a guideline-compliant trial design: open-labeled, randomized, single-dose (clopidogrel 75 mg tablet), two-period, crossover trial in 48 healthy male volunteers, with a 7 day wash-out period. METHODS: Plasma samples were collected at intervals and extracted before quantifying clopidogrel concentrations using a fully validated LC-MS/MS method. Bioequivalence of Clopacin(®) and the reference drug was established by comparison of the primary pharmacokinetic parameters, C max, AUC0-t, and AUC0-∞. RESULTS: The parameter values were similar for the two products (analysis of variance) and provided Clopacin/reference ratios (least squares means) of >90% and 90% confidence intervals (CIs 84.64-105.50%, 90.43-111.22%, 88.75-110.71%, respectively) that were well within the limits set for defining bioequivalence, according to international guidelines. The respective Clopacin(®) and reference drug values for mean time to maximal plasma clopidogrel concentration (t max) were 0.83 and 0.91 h, and for terminal elimination half-life were 3.99 and 3.51 h. The intra-subject coefficients of variability for maximal plasma clopidogrel concentration (C max), area under the plasma clopidogrel concentration versus time curve, at 48 h (AUC0-t) and extrapolated to infinity (AUC0-∞) were 32.2%, 30.2%, and 28.9% (least square means), respectively, and the respective power values were 99.5%, 97.1%, and 95.3%. CONCLUSION: This bioequivalence study provided robust clopidogrel pharmacokinetic data that established the bioequivalence of Clopacin(®) and the reference originator drug. FUNDING: Acino Pharma AG (formerly Cimex AG).

Salts of Clopidogrel: Investigation to Ensure Clinical Equivalence: A 12-Month Randomized Clinical Trial.

BACKGROUND: In the present clinical trial, we compared the efficacy and safety of the generic clopidogrel besylate (CB) with the innovator clopidogrel hydrogen sulfate (CHS) salt in patients eligible to receive clopidogrel. METHODS: A prospective 2-arm, multicenter, open-label, phase 4 clinical trial. Consecutive patients (n = 1864) were screened and 1800 were enrolled in the trial and randomized to CHS or CB. Primary efficacy end point was the composite of myocardial infarction, stroke, or death from vascular causes, and primary safety end point was rate of bleeding events as defined by Bleeding Academic Research Consortium criteria. RESULTS: At 12-month follow-up, no differences were observed between CB (n = 759) and CHS (n = 798) in primary efficacy and safety end points (age, sex, history of percutaneous coronary intervention adjusted odds ratio [OR], 0.70; 95% confidence interval [CI], 0.41-1.21 and OR, 0.81; 95% CI, 0.51-1.29, respectively) between CHS and CB. Analyses of efficacy and safety in subgroups that were defined according to the qualifying diagnosis revealed that there was no difference between CHS and CB. CONCLUSION: The efficacy and safety of CB administered for 12 months for the secondary prevention of atherothrombotic events are similar to that of CHS. (Salts of Clopidogrel: Investigation to ENsure Clinical Equivalence, SCIENCE trial; ClinicalTrials.gov Identifier:NCT02126982).