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Plavix (Clopidogrel Bisulfate) - Side Effects and Adverse Reactions

 
 



ADVERSE REACTIONS

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

  • Bleeding [see Warnings and Precautions]
  • Thrombotic thrombocytopenic purpura [see Warnings and Precautions]

Clinical Studies 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 1 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.

Bleeding

CURE

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) 1
Placebo
(+ aspirin)
p-value
(n=6259) (n=6303)
Major bleeding 2 3.7 3 2.7 4 0.001
  Life-threatening bleeding 2.2 1.8 0.13
    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 0.005
    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 5.1 2.4 < 0.001

1 Other standard therapies were used as appropriate.
2 Life-threatening and other major bleeding.
3 Major bleeding event rate for Plavix + aspirin was dose-dependent on aspirin: <100 mg = 2.6%; 100–200 mg = 3.5%; >200 mg = 4.9%
Major bleeding event rates for Plavix + aspirin by age were: <65 years = 2.5%, ≥65 to <75 years = 4.1%, ≥75 years = 5.9%
4 Major bleeding event rate for placebo + aspirin was dose-dependent on aspirin: <100 mg = 2.0%; 100–200 mg = 2.3%; >200 mg = 4.0%
Major bleeding event rates for placebo + aspirin by age were: <65 years = 2.1%, ≥65 to <75 years = 3.1%, ≥75 years = 3.6%
5 Led to interruption of study medication.

Ninety-two percent (92%) of the patients in the CURE study received heparin or low molecular weight heparin (LMWH), and the rate of bleeding in these patients was similar to the overall results.

COMMIT

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)
(n=22961)
Placebo
(+ aspirin)
(n=22891)
p-value
Major 1 noncerebral or cerebral bleeding 2 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 (non-major) 3.6 3.1 0.005
Any noncerebral bleeding 3.9 3.4 0.004

1 Major bleeds were cerebral bleeds or non-cerebral bleeds thought to have caused death or that required transfusion.
2 The relative rate of major noncerebral or cerebral bleeding was independent of age. Event rates for Plavix + aspirin by age were: <60 years = 0.3%, ≥60 to <70 years = 0.7%, ≥70 years = 0.8%. Event rates for placebo + aspirin by age were: <60 years = 0.4%, ≥60 to <70 years = 0.6%, ≥70 years = 0.7%.

CAPRIE (Plavix vs. Aspirin)

In CAPRIE, gastrointestinal hemorrhage occurred at a rate of 2.0% in those taking Plavix vs. 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 post-approval 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.

  • Blood and lymphatic system disorders: Agranulocytosis, aplastic anemia/pancytopenia, thrombotic thrombocytopenic purpura (TTP)
  • Gastrointestinal disorders: Gastrointestinal and retroperitoneal hemorrhage with fatal outcome, colitis (including ulcerative or lymphocytic colitis), pancreatitis, stomatitis
  • General disorders and administration site condition: Fever, hemorrhage of operative wound
  • Hepato-biliary disorders: Acute liver failure, hepatitis (non-infectious), abnormal liver function test
  • Immune system disorders: Hypersensitivity reactions, anaphylactoid reactions, serum sickness
  • Musculoskeletal, connective tissue and bone disorders: Musculoskeletal bleeding, myalgia, arthralgia, arthritis
  • Nervous system disorders: Taste disorders, fatal intracranial bleeding
  • Eye disorders: Eye (conjunctival, ocular, retinal) bleeding
  • Psychiatric disorders: Confusion, hallucinations
  • Respiratory, thoracic and mediastinal disorders: Bronchospasm, interstitial pneumonitis, respiratory tract bleeding
  • Renal and urinary disorders: Glomerulopathy, increased creatinine levels
  • Skin and subcutaneous tissue disorders: Maculopapular or erythematous rash, urticaria, bullous dermatitis, eczema, toxic epidermal necrolysis, Stevens-Johnson syndrome, angioedema, erythema multiforme, skin bleeding, lichen planus
  • Vascular disorders: Vasculitis, hypotension


REPORTS OF SUSPECTED PLAVIX SIDE EFFECTS / ADVERSE REACTIONS

Below is a sample of reports where side effects / adverse reactions may be related to Plavix. The information is not vetted and should not be considered as verified clinical evidence.

Possible Plavix side effects / adverse reactions in 59 year old male

Reported by a consumer/non-health professional from United States on 2011-10-03

Patient: 59 year old male

Reactions: Coronary Artery Occlusion

Adverse event resulted in: hospitalization

Suspect drug(s):
Plavix



Possible Plavix side effects / adverse reactions in 85 year old male

Reported by a consumer/non-health professional from United States on 2011-10-03

Patient: 85 year old male

Reactions: Rash

Suspect drug(s):
Ibuprofen (Advil)
    Dosage: unk

Plavix
    Dosage: 75 mg, unk



Possible Plavix side effects / adverse reactions in 69 year old female

Reported by a physician from United States on 2011-10-03

Patient: 69 year old female

Reactions: Hypertensive Encephalopathy, Drug Ineffective, Transient Ischaemic Attack, Hypertension

Suspect drug(s):
Plavix
    Administration route: Oral
    Start date: 2008-06-23
    End date: 2011-05-03

Plavix
    Administration route: Oral
    Indication: Cerebrovascular Accident Prophylaxis
    Start date: 2008-06-23
    End date: 2011-05-03

Other drugs received by patient: Clonidine; Amlodipine; Zocor; Coreg; Hydrochlorothiazide



See index of all Plavix side effect reports >>

Drug label data at the top of this Page last updated: 2010-08-19

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