Side Effects of Plavix (clopidogrel bisulfate)

Medically Reviewed on 8/4/2021

What is Plavix (clopidogrel bisulfate)?

Plavix (clopidogrel bisulfate) is an antiplatelet drug used to prevent strokes, heart attacks, and death in individuals who have had a previous stroke, unstable angina, heart attack or have peripheral arterial disease (PAD). 

The combination of Plavix and aspirin is better than aspirin or Plavix alone in preventing another heart attack but the risk of bleeding is higher. Plavix prevents blood clots by irreversibly binding to the P2Y12 receptor on platelets, preventing adenosine diphosphate (ADP) from activating platelets. 

Plavix is similar to ticlopidine in chemical structure and in the way it works. Unlike ticlopidine, Plavix 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. Plavix is used to reduce the risk of heart attacks and strokes in these patients. 

Drug interactions of Plavix include nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, naproxen, diclofenac, etodolac, nabumetone, fenoprofen, flurbiprofen, indomethacin, ketoprofen, oxaprozin, piroxicam, sulindac, tolmetin, and mefenamic acid, because the combination may increase the risk of stomach and intestinal bleeding.

There are no adequate studies of Plavix in pregnant women. It is unknown if Plavix appears in 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 Plavix to breastfeeding mothers.

What are the side effects of Plavix?

What are the common side effects of Plavix?

Common side effects of Plavix include

What are the serious side effects of Plavix?

Serious side effects of Plavix include

  • severe bleeding,
  • allergic reactions,
  • pancreatitis,
  • liver failure, and rarely,
  • severe reduction in white blood cell count and thrombotic thrombocytopenic purpura (TTP).

Is Plavix addictive?

No information provided

What drugs interact with Plavix?

CYP2C19 Inhibitors

  • Clopidogrel is metabolized to its active metabolite in part by CYP2C19. Concomitant use of drugs that inhibit the activity of this enzyme results in reduced plasma concentrations of the active metabolite of clopidogrel and a reduction in platelet inhibition.
Omeprazole Or Esomeprazole
  • Avoid concomitant use of Plavix with omeprazole or esomeprazole. In clinical studies, omeprazole was shown to reduce significantly the antiplatelet activity of Plavix when given concomitantly or 12 hours apart.
  • A similar reduction in antiplatelet activity was observed with esomeprazole when given concomitantly with Plavix.
  • Dexlansoprazole, lansoprazole, and pantoprazole had less effect on the antiplatelet activity of Plavix than did omeprazole or esomeprazole.


  • As with other oral P2Y12 inhibitors, coadministration of opioid agonists delay and reduce the absorption of clopidogrel, presumably because of slowed gastric emptying, resulting in reduced exposure to its metabolites.
  •  Consider the use of a parenteral antiplatelet agent in acute coronary syndrome patients requiring coadministration of morphine or other opioid agonists.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)

  • Coadministration of Plavix and NSAIDs increases the risk of gastrointestinal bleeding.

Warfarin (CYP2C9 Substrates)

  • Although the administration of clopidogrel 75 mg per day did not modify the pharmacokinetics of S-warfarin (a CYP2C9 substrate) or INR in patients receiving long-term warfarin therapy, coadministration of Plavix with warfarin increases the risk of bleeding because of independent effects on hemostasis.
  • However, at high concentrations in vitro, clopidogrel inhibits CYP2C9.


  • Since selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) affect platelet activation, the concomitant administration of SSRIs and SNRIs with clopidogrel may increase the risk of bleeding.

Repaglinide (CYP2C8 Substrates)

  • The acyl-β-glucuronide metabolite of clopidogrel is a strong inhibitor of CYP2C8. Plavix can increase the systemic exposure to drugs that are primarily cleared by CYP2C8, thereby needing dose adjustment and appropriate monitoring.
  • Plavix increased repaglinide exposures by 3.9-fold to 5.1-fold.
  • Avoid concomitant use of repaglinide with Plavix. If concomitant use cannot be avoided, initiate repaglinide at 0.5 mg before each meal and do not exceed a total daily dose of 4 mg. Increased frequency of glucose monitoring may be required during concomitant use.

Plavix side effects list for healthcare professionals

The following serious adverse reactions are discussed below and elsewhere in the labeling:

  • Bleeding
  • Thrombotic thrombocytopenic purpura

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions and durations of follow-up, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Plavix has been evaluated for safety in more than 54,000 patients, including over 21,000 patients treated for one year or more. The clinically important adverse reactions observed in trials comparing Plavix plus aspirin to placebo plus aspirin and trials comparing Plavix alone to aspirin alone are discussed below.



In CURE, Plavix use with aspirin was associated with an increase in major bleeding (primarily gastrointestinal and at puncture sites) compared to placebo with aspirin (see Table 1).

The incidence of intracranial hemorrhage (0.1%) and fatal bleeding (0.2%) were the same in both groups. Other bleeding events that were reported more frequently in the clopidogrel group were epistaxis, hematuria, and bruise.

The overall incidence of bleeding is described in Table 1.

Table 1: CURE Incidence of Bleeding Complications (% patients)

Event Plavix
(+ aspirin)
(+ aspirin)
Major bleeding* 3.7 2.7
  Life-threatening bleeding 2.2 1.8
    Fatal 0.2 0.2
    5 g/dL hemoglobin drop 0.9 0.9
    Requiring surgical intervention 0.7 0.7
    Hemorrhagic strokes 0.1 0.1
    Requiring inotropes 0.5 0.5
    Requiring transfusion (≥4 units) 1.2 1.0
  Other major bleeding 1.6 1.0
    Significantly disabling 0.4 0.3
    Intraocular bleeding with significant loss of vision 0.05 0.03
    Requiring 2-3 units of blood 1.3 0.9
Minor bleeding 5.1 2.4
* Life-threatening and other major bleeding.
Led to interruption of study medication.


In COMMIT, similar rates of major bleeding were observed in the Plavix and placebo groups, both of which also received aspirin (see Table 2).

Table 2: Incidence of Bleeding Events in COMMIT (% patients)

Type of Bleeding Plavix
(+ aspirin)
(+ aspirin)
Major* noncerebral or cerebral bleeding 0.6 0.5 0.59
  Major noncerebral 0.4 0.3 0.48
  Fatal 0.2 0.2 0.90
Hemorrhagic stroke 0.2 0.2 0.91
  Fatal 0.2 0.2 0.81
Other noncerebral bleeding (nonmajor) 3.6 3.1 0.005
Any noncerebral bleeding 3.9 3.4 0.004
* Major bleeds were cerebral bleeds or noncerebral bleeds thought to have caused death or that required transfusion.

CAPRIE (Plavix Vs Aspirin)
  • In CAPRIE, gastrointestinal hemorrhage occurred at a rate of 2.0% in those taking Plavix versus 2.7% in those taking aspirin; bleeding requiring hospitalization occurred in 0.7% and 1.1%, respectively. The incidence of intracranial hemorrhage was 0.4% for Plavix compared to 0.5% for aspirin.
  • Other bleeding events that were reported more frequently in the Plavix group were epistaxis and hematoma.
Other Adverse Events
  • In CURE and CHARISMA, which compared Plavix plus aspirin to aspirin alone, there was no difference in the rate of adverse events (other than bleeding) between Plavix and placebo.
  • In CAPRIE, which compared Plavix to aspirin, pruritus was more frequently reported in those taking Plavix. No other difference in the rate of adverse events (other than bleeding) was reported.

Postmarketing Experience

The following adverse reactions have been identified during postapproval use of Plavix. Because these reactions are reported voluntarily from a population of an unknown size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Hemorrhages, including those with fatal outcome, have been reported in patients treated with Plavix.


Plavix (clopidogrel bisulfate) is an antiplatelet drug used to prevent strokes, heart attacks, and death in individuals who have had a previous stroke, unstable angina, heart attack or have peripheral arterial disease (PAD). Common side effects of Plavix include diarrhea, rash, itching, abdominal pain, headache, chest pain, muscle aches, dizziness. There are no adequate studies of Plavix in pregnant women. It is unknown if Plavix appears in breast milk.

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Medically Reviewed on 8/4/2021
FDA Prescribing Information

Professional side effects and drug interactions sections courtesy of the U.S. Food and Drug Administration.