Label Changes for:

Plavix (clopidogrel bisulfate) tablets

December 2011

Changes have been made to the WARNINGS and PRECAUTIONS sections of the safety label.

Detailed View: Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER) – August 2010, February and December 2011

 

December 2011

 

WARNINGS AND PRECAUTIONS

Diminished Antiplatelet Activity Due to Impaired CYP2C19 Function
  • Proton Pump Inhibitors- Avoid concomitant use of Plavix with omeprazole or esomeprazole because both significantly reduce the antiplatelet activity of Plavix

 

DRUG INTERACTIONS

CYP2C19 Inhibitors

  • Proton Pump Inhibitors: A higher dose regimen of clopidogrel concomitantly administered with omeprazole increases antiplatelet response; an appropriate dose regimen has not been established

 

February 2011

MEDICATION GUIDE

  • REMS consists of a comprehensive Medication Guide

 

August 2010

WARNINGS and PRECAUTIONS

Diminished Antiplatelet Activity Due to Impaired CYP2C19 Function
  • Clopidogrel is a prodrug. Inhibition of platelet aggregation by clopidogrel is due to an active metabolite. The metabolism of clopidogrel to its active metabolite can be impaired by genetic variations in CYP2C19 [see Boxed Warning] and by concomitant medications that interfere with CYP2C19. Avoid concomitant use of Plavix and strong or moderate CYP2C19 inhibitors.
  • Omeprazole, a moderate CYP2C19 inhibitor, has been shown to reduce the pharmacological activity of Plavix if given concomitantly or if given 12 hours apart. Consider using another acid-reducing agent with less CYP2C19 inhibitory activity. Pantoprazole, a weak CYP2C19 inhibitor, had less effect on the pharmacological activity of Plavix than omeprazole.

DRUG INTERACTIONS

Proton Pump Inhibitors (PPI)
  • A study was conducted with Plavix (300 mg loading dose followed by 75 mg/day) administered with a high dose (80 mg/day) of omeprazole...
  • There are no adequate studies of a lower dose of omeprazole or a higher dose of Plavix in comparison with the approved dose of Plavix.
  • A study was conducted using Plavix (300 mg loading dose followed by 75 mg/day) and a high dose (80 mg/day) of pantoprazole, a PPI with less CYP2C19 inhibitory activity than omeprazole. The plasma concentrations of the clopidogrel active metabolite and the degree of platelet inhibition were less than observed with Plavix alone but were greater than observed when omeprazole 80 mg was co-administered with 300 mg loading dose followed by 75 mg/day of Plavix (Table 3).

 

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