Plavix Labeling Updated with Several Changes

The updates include additions to the boxed warning and indications
The updates include additions to the boxed warning and indications

The Food and Drug Administration (FDA) has approved several changes to the prescribing information for Plavix (clopidogrel bisulfate tablets; Bristol-Myers Squibb and Sanofi).

The new Boxed Warnings state the following: 

WARNING: DIMINISHED ANTIPLATELET EFFECT IN PATIENTS WITH TWO LOSS-OF-FUNCTION ALLELES OF THE CYP2C19 GENE 

  • Effectiveness of Plavix depends on conversion to an active metabolite by the cytochrome P450 (CYP) system, principally CYP2C19.
  • Tests are available to identify patients who are CYP2C19 poor metabolizers. 
  • Consider use of another platelet P2Y12 inhibitor in patients identified as CYP2C19 poor metabolizers. 

Previously, the Boxed Warnings included a statement regarding poor metabolizers treated with Plavix at recommended doses exhibiting higher cardiovascular event rates following acute coronary syndrome (ACS) or percutaneous coronary intervention (PCI) than patients with normal CYP2C19 function; this statement has since been removed.

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The new Indications state the following:

For ACS:

  • Plavix is indicated to reduce the rate of myocardial infarction (MI) and stroke in patients with non-ST-segment elevation ACS [unstable angina (UA)/non-ST-elevation myocardial infarction (NSTEMI)], including patients who are to be managed medically and those who are to be managed with coronary revascularization. Plavix should be administered in conjunction with aspirin. 
  • Plavix is indicated to reduce the rate of myocardial infarction and stroke in patients with acute ST elevation myocardial infarction (STEMI) who are to be managed medically. Plavix should be administered in conjunction with aspirin. 

For Recent MI, Stroke or Established Peripheral Artery Disease:

  • In patients with established peripheral arterial disease or with a history of recent MI or recent stroke Plavix is indicated to reduce the rate of MI and stroke. 

The Dosing and Administration section has been updated as well to include the following:

For ACS:

  • In patients who need an antiplatelet effect within hours, initiate Plavix with a single 300­mg oral loading dose and then continue at 75mg once daily. Initiating Plavix without a loading dose will delay establishment of an antiplatelet effect by several days.

For Recent MI, Recent Stroke, or Established Peripheral Artery Disease:

  • 75 mg once daily orally without a loading dose.

Although no longer mentioned in the Dosing and Administration section, regarding proton pump inhibitors, the Warnings and Precautions state that patients should avoid concomitant use of omeprazole or esomeprazole; however, dexlansoprazole, lansoprazole, and pantoprazole may have less pronounced effects on antiplatelet activity. In addition, the Dosing and Administration section no longer includes information on CYP2C19 poor metabolizers; this information is now located in the Warnings and Precautions section.

Clopidogrel is an inhibitor of platelet activation and aggregation through the irreversible binding of its active metabolite to the P2Y12 class of ADP receptors on platelets. It is available as 75mg and 300mg strength tablets.

For more information visit FDA.gov.

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