Clinical Bioequivalence of a Dose of Clopidogrel Leti Cravid Tablets 75 mg Versus Clopidogrel Sanofi Plavix Tablets 75 mg Administered on a Daily Dose for 7 Days on Healthy Volunteers: A Clinical Trial

Abstract

Patients undergoing percutaneous coronary intervention procedures, as in patients with coronary disease, should receive treatment indefinitely with acetylsalicylic acid and clopidogrel. New brands of clopidogrel have been developed at lower costs, for helping to avoid premature suspension of antiplatelet therapy, as Cravid Leti Laboratories clopidogrel. Its effectiveness and safety must be compared with Plavix international standard. A prospective, comparative, cross-over, and randomized study was conducted in healthy volunteers. Each group received 1 tablet of Clopidogrel Leti or Clopidogrel Sanofi, 75 mg in a single dose daily for 7 days, followed by 7-day washout period before administration of second treatment. Platelet aggregation was measured at the start of each period and at 7 days of treatment through optical aggregometry, using an optical aggregometer 490-2D Chrono-Log, with a self-calibration system working with platelet-rich plasma with readings 0%-100% of light transmission. An important decrease of platelet aggregation was observed in both groups at 7 days of treatment of more than 50%, independent of adenosine diphosphate reactive (Helena and Chrono-Log) used for aggregation (P < 0.05). The relationship between the mean and 90% confidence interval ratio obtained with the 2 different adenosine diphosphate brands were between 80% and 125%, therefore, it can be considered that both brands are bioequivalent and perfectly exchangeable.

Generic versus brand-name drugs used in cardiovascular diseases

“…inhibition (E), mAEs (S), sAEs (S) Industry (other) No Kim (P) [ 55 ] 2009 Korea Clopidogrel Healthy 24 7 days (13 days) Cross-over 44 (44) Platelet aggr. inhibition (E), mAEs (S), sAEs (S) Generic manufacturer No Di Girolamo [ 70 ] 2010 Argentina Clopidogrel Healthy 34 12 h Cross-over 24 (24) sAEs (S) Generic manufacturer No Müller [ 74 ] 2010 Venezuela Clopidogrel Healthy 23 7 days Cross-over 20 (20) Platelet aggr. inhibition (E) Not reported No Shim [ 95 ] 2010 Korea Clopidogrel Healthy 29 1 week Cross-over 29 (29) Bleeding time (E), sAEs (S) Generic manufacturer No Khosravi [ 71 ] 2011 Iran Clopidogrel PCI 59 6 months <...>…”

“…The only other published meta-analysis to-date on this topic, although rigorously done, only included 50, 23 and 71 subjects in the evaluation of antiplatelet agents, ACE inhibitors and statins, respectively [ 4 ]. Also, most of these subjects had been followed for <2 days, only efficacy outcomes were combined, and many trials have been published later on [ 32 , 54 , 55 , 63 , 64 , 67 – 72 , 74 – 81 , 83 , 84 , 86 – 96 ]. In the present meta-analysis all 53 RCTs evaluating efficacy outcomes found no significant differences between generic and brand-name cardiovascular drugs.…”