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Label Changes for:

Plavix (clopidogrel bisulfate) 75 mg Tablets

September 2013

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

Detailed View: Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER)  


September 2013


5.6 Allergic Cross-Reactivity
  • Patients should be evaluated for history of hypersensitivity to another thienopyridine (such as ticlopidine, prasugrel) since allergic cross-reactivity among thienopyridines has been reported.


6.2 Postmarketing Experience
  • added ...Respiratory, thoracic and mediastinal disorders: eosinophilic pneumonia
  • added ...Skin and subcutaneous tissue disorders: drug-induced hypersensitivity syndrome, drug rash with eosinophilia and systemic symptoms (DRESS)


 “What should I tell my doctor before taking Plavix?”

  • added ...“have had an allergy or reaction to any medicine used to treat your disease.”

“What are the possible side effects of Plavix?”

  • added ...“Tell your doctor if you develop an allergic reaction while taking Plavix.”


December 2011


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



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


  • REMS consists of a comprehensive Medication Guide


August 2010


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.


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).