PLAVIX GENERIC

Thromb Haemost. 2005 Mar;93(3):527-34.
Effects of aspirin, clopidogrel and dipyridamole administered singly and in combination on platelet and leucocyte function in normal volunteers and patients with prior ischaemic stroke.
Zhao L, Fletcher S, Weaver C, Leonardi-Bee J, May J, Fox S, Willmot M, Heptinstal S, Bath P.
Division of Stroke Medicine, South Block, D Floor, Queen's Medical Centre, Nottingham NG7 2UH UK, E-mail: philip.bath@nottingham.ac.uk.

The aim of this study was to assess whether triple antiplatelet therapy is superior to dual and mono therapy in attenuating platelet and leucocyte function. Aspirin (A), clopidogrel (C), and dipyridamole (D) were administered singly and in various combinations (A, C, D,AC,AD, CD,ACD), each for two weeks (without washout) to 11 healthy subjects and to 11 patients with previous ischaemic stroke in two randomised multiway crossover trials. At the end of each two-week period platelet aggregation, platelet-leucocyte conjugate formation and leucocyte activation were measured ex vivo blinded to treatment. Platelets were stimulated with collagen; additional measurements were made with adenosine diphosphate (ADP), platelet activating factor (PAF), adrenaline and the combination of, ADP, PAF and adrenaline. Results show that in the presence of collagen, ACD was superior to all antagonists or combinations, except AC, in reducing aggregation, platelet-leucocyte conjugate formation, and monocyte activation (all p<0.05). ACD was also more potent than other treatments, except AC, in inhibiting the aggregation and platelet-monocyte conjugate formation induced by the combination of ADP, PAF and adrenaline. The effects were similar in both volunteers and stroke patients. No serious adverse events or major bleeding events occurred. Triple antiplatelet therapy did not appear to be more effective than combined aspirin and clopidogrel in moderating platelet and leucocyte function. Any additional clinical benefit provided by dipyridamole may be through other mechanisms of action.

Circulation. 2005 Mar 8;111(9):1153-9. Epub 2005 Feb 28.
Clopidogrel loading with eptifibatide to arrest the reactivity of platelets: results of the Clopidogrel Loading With Eptifibatide to Arrest the Reactivity of Platelets (CLEAR PLATELETS) study.
Gurbel PA, Bliden KP, Zaman KA, Yoho JA, Hayes KM, Tantry US.
Sinai Center for Thrombosis Research, Hoffberger Bldg, Suite 56, 2401 W Belvedere Ave, Baltimore, MD 21215, USA.

BACKGROUND: Pretreatment is not the most common strategy practiced for clopidogrel administration in elective coronary stenting. Moreover, limited information is available on the antiplatelet pharmacodynamics of a 300-mg versus a 600-mg clopidogrel loading dose, and the comparative effect of eptifibatide with these regimens is unknown. METHODS AND RESULTS: Patients undergoing elective stenting (n=120) were enrolled in a 2x2 factorial study (300 mg clopidogrel with or without eptifibatide; 600 mg clopidogrel with or without eptifibatide) (Clopidogrel Loading With Eptifibatide to Arrest the Reactivity of Platelets [CLEAR PLATELETS] Study). Clopidogrel was administered immediately after stenting. Aggregometry and flow cytometry were used to assess platelet reactivity. Eptifibatide added a > or =2-fold increase in platelet inhibition to 600 mg clopidogrel alone at 3, 8, and 18 to 24 hours after stenting as measured by 5 micromol/L ADP-induced aggregation (P<0.001). Without eptifibatide, 600 mg clopidogrel produced better inhibition than 300 mg clopidogrel at all time points (P<0.001). Glycoprotein IIb/IIIa (GPIIb/IIIa) blockade was associated with lower cardiac marker release. Active GPIIb/IIIa expression was inhibited most in the groups treated with eptifibatide (P<0.05). CONCLUSIONS: In elective stenting without clopidogrel pretreatment, use of a GPIIb/IIIa inhibitor produces superior platelet inhibition and lower myocardial necrosis compared with high-dose (600 mg) or standard-dose (300 mg) clopidogrel loading alone. In the absence of a GPIIb/IIIa inhibitor, 600 mg clopidogrel provides better platelet inhibition than the standard 300-mg dose. These results require confirmation in a large-scale clinical trial.

GENERIC NAME: clopidogrel
BRAND NAME: Plavix

DRUG CLASS AND MECHANISM: Clopidogrel is an anti-platelet drug, that is, a drug that inhibits the ability of platelets to clump together as part of a blood clot. It is similar to ticlopidine (Ticlid) in chemical structure and in the way it works. Unlike ticlopidine, clopidogrel does not cause serious reductions of white cells in the blood and, therefore, routine blood testing to determine if the white blood cell count is low is not necessary during treatment. The risk of heart attacks and strokes (which usually are caused by blood clots) is increased in patients with a recent history of stroke or heart attack and patients with peripheral vascular disease. (Peripheral vascular disease is the same as atherosclerotic arterial disease or "hardening" of the arteries in which the arteries become narrowed. It frequently occurs in the legs and often causes claudication or pain in the legs upon walking). Clopidogrel is used to reduce the risk of heart attacks and strokes in these patients. Clopidogrel was approved by the FDA in 1997.

PREPARATIONS: Tablets: 75mg.

STORAGE: Tablets should be stored at room temperature, 15-30°C (59-86°F).

PRESCRIBED FOR: Clopidogrel is used to prevent strokes and heart attacks in persons who are at high risk. In one large study, clopidogrel was more effective than aspirin in reducing heart attacks. The frequency of side effects of clopidogrel was similar to aspirin; however, stomach and intestinal bleeding probably occurs less often with clopidogrel than with aspirin.

DOSING: Clopidogrel usually is taken once daily. It can be taken with or without food.

DRUG INTERACTIONS: The combination of clopidogrel with nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen (Motrin; Advil; Nuprin), naproxen (Naprosyn, Aleve), diclofenac (Voltaren), etodolac (Lodine), nabumetone (Relafen), fenoprofen (Nalfon), flurbiprofen (Ansaid), indomethacin (Indocin), ketoprofen (Orudis; Oruvail), oxaprozin (), piroxicam (Feldene), sulindac (Clinoril), tolmetin (Tolectin), and mefenamic acid (Ponstel) may increase the risk of stomach and intestinal bleeding.

At high concentrations in the blood, clopidogrel inhibits the activity of the enzyme which metabolizes (eliminates) warfarin (Coumadin), a "blood thinner". This could lead to an increase in levels of warfarin and increase the risk of bleeding due to over-thinning of the blood. To date there have been no reports of an important interaction in humans between warfarin and clopidogrel. Nonetheless, because warfarin increases the risk of bleeding, blood tests to measure the degree to which the blood is anti-coagulated or thinned (prothrombin time; INR) may be ordered to assess the degree of blood-thinning when warfarin and clopidogrel are used together. The same enzyme also is responsible for the metabolism of phenytoin (Dilantin), tamoxifen (Nolvadex), tolbutamide (Orinase), torsemide (Demadex), and fluvastatin (Lescol). Although important interactions between clopidogrel and these drugs are unlikely, interactions should be looked for carefully.

PREGNANCY: There are no adequate studies of clopidogrel in pregnant women. Therefore, it can be used in pregnancy if the physician determines that it is needed.

NURSING MOTHERS: Studies in rats have shown that clopidogrel appears in breast milk; however, it is not known whether it also appears in human breast milk. Because of a potential for side effects in the nursing infant, the physician must weigh the potential benefits and possible risks before prescribing clopidogrel in nursing mothers.

SIDE EFFECTS: The tolerability of clopidogrel is similar to that of aspirin. Diarrhea, rash, or itching occurs in approximately 1 in 20 persons taking clopidogrel. Abdominal pain also occurs in about 1 in 20 persons, but it is less frequent than with aspirin.

Ticlopidine (Ticlid) is an antiplatelet medication quite similar to clopidogrel. It has been associated with a severe reduction in white blood cell count in between 0.8% and 1% of persons. The risk of this dangerous side effect with clopidogrel is about 0.04%, much less than with ticlopidine but twice that of aspirin

Clopidogrel rarely causes a condition called thrombotic thrombocytopenic purpura (TTP) in one out of every 250,000 people. TTP is a serious condition in which blood clots form throughout the body. Blood platelets, which participate in clotting, are consumed, and the result can be bleeding because enough platelets are no longer left to allow blood to clot normally. For comparison, the related drug, ticlodipine (Ticlid), causes TTP 17-50 times more frequently than clopidogrel.

Caution! Before starting to take this medicine, it is vital that you should consult your doctor! Do not use it on your own initiative, without medical advice.