Plavix is an oral by anamaulida


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        <p>plavix is an oral, thienopyridine class antiplatelet agent
used to inhibit blood clots in coronary artery disease, peripheral
vascular disease, and cerebrovascular disease. It is marketed by Bristol-
Myers Squibb and Sanofi-Aventis. The drug works by irreversibly
inhibiting a receptor called P2Y12, an adenosine diphosphate ADP
chemoreceptor. Adverse effects include hemorrhage, severe neutropenia,
and Thrombotic thrombocytopenic purpura (TTP).</p>
<p>Â </p>
<p>1 Pharmacology</p>
<p>2 Clinical use</p>
<p>3 Indications</p>
<p>4 Dosage forms</p>
<p>5 Pharmacokinetics and metabolism</p>
<p>6 Pharmacogenetics</p>
<p>7 Adverse effects</p>
<p>8 Interactions</p>
<p>9 Marketing and litigation</p>
<p>10 References</p>
<p>11 External links</p>
<p>Â </p>
<p>Clopidogrel is a pro-drug whose action may be related to an adenosine
diphosphate (ADP) receptor on platelet cell membranes. The drug
specifically and irreversibly inhibits the P2Y12 subtype of ADP receptor,
which is important in aggregation of platelets and cross-linking by the
protein fibrin. The blockade of this receptor inhibits platelet
aggregation by blocking activation of the glycoprotein IIb/IIIa pathway.
The IIb/IIIa complex functions as a receptor mainly for fibrinogen and
vitronectin but also for fibronectin and von Willebrand factor.
Activation of this receptor complex is the "final common pathway" for
platelet aggregation, and is important in the cross-linking of platelets
by fibrin.</p>
<p>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 of 300–600mg is usually administered.</p>
<p>Clinical use</p>
<p>Clopidogrel is indicated for</p>
<p>Prevention of vascular ischaemic events in patients with symptomatic
<p>Acute coronary syndrome without ST-segment elevation (NSTEMI),</p>
<p>ST elevation MI (STEMI)</p>
<p>It is also used, along with aspirin, for the prevention of thrombosis
after placement of intracoronary stent or as an alternative antiplatelet
drug for patients who are intolerant to aspirin.</p>
<p>International guidelines granted the highest grade of recommendation
for NSTE-ACS, PCI and stent,for clopidogrel in addition to aspirin.
Consensus-based therapeutic guidelines recommend also the use of
clopidogrel, instead of aspirin, in patients requiring antiplatelet
therapy but with a history of gastric ulceration, as inhibition of the
synthesis of prostaglandins by aspirin (acetylsalicylic acid) can
exacerbate this condition. A study has shown that in patients with healed
aspirin-induced ulcers, however, patients receiving aspirin plus the
proton pump inhibitor esomeprazole had a lower incidence of recurrent
ulcer bleeding than patients receiving clopidogrel.However, a more recent
study suggested that prophylaxis with proton pump inhibitors along with
clopidogrel following acute coronary syndrome may increase adverse
cardiac outcomes, possibly due to inhibition of CYP2C19 which is required
for the conversion of clopidogrel to its active form.</p>
<p>Dosage forms</p>
<p>Clopidogrel is marketed as clopidogrel bisulfate (clopidogrel hydrogen
sulfate), most commonly under the trade names Plavix, as 75 mg oral
<p>Pharmacokinetics and metabolism</p>
<p>The active metabolite of clopidogrel</p>
<p>After repeated 75-mg oral doses of clopidogrel (base), plasma
concentrations of the parent compound, which has no platelet inhibiting
effect, are very low and are generally below the quantification limit
(0.000258 mg/L) beyond two hours after dosing.</p>
<p>Clopidogrel is a pro-drug activated in the liver by cytochrome P450
enzymes, including CYP2C19. The active metabolite has an elimination
half-life of about eight hours and acts by forming a disulfide bridge
with the platelet ADP receptor. Patients with a variant allele of CYP2C19
are 1.5 to 3.5 times more likely to die or have complications than
patients with the high-functioning allele.</p>
<p>Following an oral dose of 14C-labeled clopidogrel in humans,
approximately 50% was excreted in the urine and approximately 46% in the
feces in the five days after dosing.</p>
<p>Effect of Food: Administration of clopidogrel bisulfate with meals did
not significantly modify the bioavailability of clopidogrel as assessed
by the pharmacokinetics of the main circulating metabolite.</p>
<p>Absorption and Distribution: Clopidogrel is rapidly absorbed after
oral administration of repeated doses of 75 mg clopidogrel (base), with
peak plasma levels (appx. 3 mg/L) of the main circulating metabolite
occurring approximately one hour after dosing. The pharmacokinetics of
the main circulating metabolite are linear (plasma concentrations
increased in proportion to dose) in the dose range of 50 to 150 mg of
clopidogrel. Absorption is at least 50% based on urinary excretion of
clopidogrel-related metabolites. Clopidogrel and the main circulating
metabolite bind reversibly in vitro to human plasma proteins (98% and
94%, respectively). The binding is nonsaturable in vitro up to a
concentration of 110 μg/mL.</p>
<p>Metabolism and Elimination: In vitro and in vivo, clopidogrel
undergoes rapid hydrolysis into its carboxylic acid derivative. In plasma
and urine, the glucuronide of the carboxylic acid derivative is also
<p>In March 2010, the U.S. Food and Drug Administration (FDA) added a
boxed warning to Plavix alerting that the drug can be less effective in
people who cannot metabolize the drug to convert it to its active
<p>CYP2C19 is an important drug-metabolizing enzyme that catalyzes the
biotransformation of many clinically useful drugs including
antidepressants, barbiturates, proton pump inhibitors, antimalarial and
antitumor drugs. Clopidogrel is one of the drugs metabolized by this
<p>Several recent landmark studies have proven the importance of 2C19
genotyping in treatment using clopidogrel or Plavix. In March of 2010,
the FDA put a black box warning on Plavix to make patients and healthcare
providers aware that CYP2C19 poor metabolizers, representing up to 14% of
patients, are at high risk of treatment failure and that testing is
available.Researchers have found that patients with variants in
cytochrome P-450 2C19 (CYP2C19) have lower levels of the active
metabolite of clopidogrel, less inhibition of platelets, and a 3.58 times
greater risk for major adverse cardiovascular events such as death, heart
attack, and stroke; the risk was greatest in CYP2C19 poor
<p>Adverse effects</p>
<p>Serious adverse drug reactions associated with clopidogrel therapy
<p>Severe neutropenia (low white blood cells) (Incidence: 1/2,000)</p>
<p>Thrombotic thrombocytopenic purpura (TTP) (Incidence: 4/1,000,000
patients treated)</p>
<p>Hemorrhage - The annual incidence of hemorrhage may be increased by
the co-administration of aspirin.</p>
<p>Gastrointestinal Hemorrhage (Incidence: 2.0% annually)</p>
<p>Cerebral Hemorrhage (Incidence: 0.1 to 0.4% annually)</p>
<p>Use of non-steroidal anti-inflammatory drugs is discouraged in those
taking clopidogrel due to increased risk of digestive tract
<p>Clopidogrel interacts with the following drugs: proton pump inhibitors
(except pantoprazole), phenytoin (Dilantin); tamoxifen (Nolvadex);
tolbutamide (Orinase); torsemide (Demadex); fluvastatin (Lescol); a blood
thinner such as warfarin (Coumadin), heparin, ardeparin (Normiflo),
dalteparin (Fragmin), danaparoid (Orgaran), enoxaparin (Lovenox), or
tinzaparin (Innohep); (Activase), anistreplase (Eminase), dipyridamole
(Persantine), streptokinase (Kabikinase, Streptase), ticlopidine
(Ticlid), and urokinase (Abbokinase). If you are using any of these
drugs, you may not be able to take Plavix, or you may need dosage
adjustments or special tests during treatment.</p>
<p>In November 2009, the FDA announced that clopidogrel should not be
taken with PPIs such as Prilosec (omeprazole) and Nexium
<p>Marketing and litigation</p>
<p>Â </p>
<p>A box of Plavix</p>
<p>Plavix is marketed worldwide in nearly 110 countries, with sales of
US$6.6 billion in 2009.It had been the 2nd top selling drug in the world
for a few years as of 2007and was still growing by over 20% in 2007. U.S.
sales were US$3.8 billion in 2008[</p>
<p>In 2006, generic clopidogrel was briefly marketed by Apotex, a
Canadian generic pharmaceutical company before a court order halted
further production until resolution of a patent infringement case brought
by Bristol-Myers Squibb.The court ruled that Bristol-Myers Squibb's
patent was valid and provided protection until November 2011.</p>
<p>Generic clopidogrel is also produced by several pharmaceutical
companies in India. Clopidogrel is marketed by Sun Pharmaceuticals under
the trade name Clopilet, by Ranbaxy Laboratories under the trade name
Ceruvin, and under the name "Clavix" by Intas Pharmaceuticals and under
the name "deplatt" by torrent pharmaceuticals. In India, it is sold as
Clopigrel, Clopitab, Clopijoy, and Clasprin (mixed with aspirin).</p>
<p>Counterfeit Plavix is in circulation, as with many popular
<p>Â </p>
<p>You can buy online <a rel="nofollow"
'/outgoing/article_exit_link/3092860']);" href="http://www.meds-">Plavix</a> at <a
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'/outgoing/article_exit_link/3092860']);" href="http://www.meds-">http://www.meds-</a></p>
<p>Â </p>
<p>Visit <a rel="nofollow"
'/outgoing/article_exit_link/3092860']);" href="http://www.meds-"></a> for more details</p>        <!--

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