Clopidogrel indications

Aspirin decreases the risk of death, recurrent infarction, and stroke following myocardial infarction. Aspirin prescription at hospital discharge is a quality care indicator in MI patients.3 All patients should receive aspirin indefinitely those patients with a contraindication to aspirin should receive clopidogrel.2,3... 

According to ACC/AHA 2007 guidelines, clopidogrel is indicated for up to 12 months in NSTE ACS patients, with a minimum treatment duration of 1 month after placement of a bare-metal stent and 12 months after placement of a sirolimus- or paclitaxel-coated stent. 

Tirofiban and eptifibatide are also indicated in patients with continued or recurrent ischemia despite treatment with aspirin, clopidogrel, and an anticoagulant. 

Clopidogrel is indicated for prevention of vascular ischaemic events in patients with symptomatic atherosclerosis. It is also used, along with aspirin, for the prevention of thromboembolism after placement of an intracoronary stent. Platelet inhibition can be demonstrated two hours after a single dose of oral clopidogrel, but the onset of action is slow, so that a loading-dose is usually administered. Although rare, severe neutropenia and also thrombotic thrombocytopenic purpura may occur. 

Mohan et al. [8] used an NMR spectroscopic method to characterize impurity D in samples of clopidogrel bisulfate. The method entailed XH NMR (at 400.13 MHz) and 13C NMR (at 100.62 MHz), with a sample concentration of 1 mg/ml in DMSO-t/f, (this solvent also served as an internal chemical shift standard). It was found that the 1H NMR spectrum of impurity D exhibited one hydrogen band than did that of clopidogrel, while the 13C NMR and DEPT135 NMR spectra indicated the presence of one methyl carbon, two methylene carbons, eight methine carbons, and five quaternary carbons. This corresponded to a similar structure as for clopidogrel, but with one less methylene carbon and one more methine carbon. 

Quantitative and/or qualitative XRPD methods have been reported to determine the polymorphic content of clopidogrel bisulfate samples, and these have been summarized in Table 2.3. Koradia et al. [16] reported the qualitative analysis of clopidogrel bisulfate in both active pharmaceutical ingredients and tablet dosage forms. Based on the interplanar distances (d-spacing) associated with each polymorph, it was concluded that the molecular packing in Form-I was more dense than that of Form-II, indicating that Form-II would be less stable relative to Form-I. This result was similar with that reported by Bousquet [9]. 

Activation of platelets is considered an essential process for arterial thrombosis. Thus, treatment with platelet-inhibiting drugs such as aspirin and ticlopidine or clopidogrel is indicated in patients with transient ischemic attacks and strokes or unstable angina and acute myocardial infarction. In angina and infarction, these drugs are often used in conjunction with -blockers, calcium channel blockers, and fibrinolytic drugs. 

ADP receptor inhibitors might be used in patients with coronary artery disease, in neurology, and in angiology. This chapter will mainly consider indications of ticlopidine and clopidogrel since these are the only two drugs currently available in the market. 

Clopidogrel is indicated in the two types of ACS with or without persistent ST-segment elevation. 

This indication was considered in three trials. The first was the PCI-CURE study (44) (n = 2658 patients), a prespecified subgroup analysis of CURE. This trial studied the benefit of pretreatment with clopidogrel (median 10 days) before PCI. At one-month follow-up, there was a significant (P = 0.04) reduction of cardiovascular death and Ml (from 4.4% to 2.9%). 

Inhibitors obtained from in vitro data include a number of compounds with different selectivities and specificity toward this enzyme. Most of them have not been tested for their in vivo effects and some may also inhibit other enzymes (ticlopidine, fluvoxamine, miconazole, nefazodone, paroxetine, etc.). This query did not yield any additional inhibitors. A summary of substrates (including partial ones) and inhibitors is shown in Table 1 and indicates that clopidogrel and ticlopidine, whose effects have been well documented in vivo and in vitro, are effective inhibitors of CYP2B6 and can be used in an in vivo DI program. 

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