Plavix
- Generic Name: clopidogrel bisulfate
- Brand Name: Plavix
- Drug Class:
Plavix (Clopidogrel Bisulfate) side effects drug center
Plavix Side Effects Center
What Is Plavix?
Plavix (clopidogrel bisulfate) is a thienopyridine class of drug that inhibits platelet aggregation and thus inhibits aspects of blood clotting used to treat patients with acute coronary syndrome, myocardial infarction (MI), peripheral vascular disease and some stroke (ischemic type) patients. Plavix is available in generic form.
What Are Side Effects of Plavix?
Common side effects of Plavix include:
- increased bleeding,
- nosebleeds,
- headaches,
- itching, and
- bruising.
Tell your doctor if you have serious side effects of Plavix including:
- bleeding that will not stop;
- bloody or tarry stools, blood in your urine;
- coughing up blood or vomit that looks like coffee grounds;
- chest pain or heavy feeling, pain spreading to the arm or shoulder, nausea, sweating, general ill feeling;
- sudden numbness or weakness, especially on one side of the body;
- sudden headache, confusion, problems with vision, speech, or balance;
- pale skin, weakness, fever, or jaundice (yellowing of the skin or eyes);
- unusual bleeding (nose, mouth, vagina, or rectum), or
- purple or red pinpoint spots under your skin.
Dosage for Plavix
Plavix is supplied as 75 and 300 mg tablets. For acute coronary syndrome with a non-ST elevation MI, the initial recommended dose is 300 mg, followed by a 75 mg dose per day; for ST elevation MIs, the initial and continuing dose is 75 mg per day. The recommended dose is 75 mg per day for patient with a history of MI, stroke, or peripheral vascular disease. Many doctors may choose to add an aspirin per day along with the Plavix dose in both non-ST elevation and ST elevation MIs as well as to stroke and peripheral vascular disease patients.
What Drugs, Substances, or Supplements Interact with Plavix?
Plavix may interact with aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), other medicines to prevent blood clots, armodafinil, modafinil, fluoxetine, fluvoxamine, gemfibrozil, isoniazid, cancer medications, stomach acid reducers, antifungals, HIV medications, or seizure medications. Tell your doctor all medications and supplements you use.
Plavix During Pregnancy and Breastfeeding
Tell your doctor if you are pregnant or plan to become pregnant during treatment with Plavix. Plavix is not expected to be harmful to a fetus. It is unknown if Plavix passes into breast milk or if it could harm a nursing baby. Breastfeeding while using Plavix is not recommended.
Additional Information
Our Plavix Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.
Plavix Consumer Information
Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.
Clopidogrel increases your risk of bleeding, which can be severe or life-threatening. Call your doctor or seek emergency medical attention if you have bleeding that will not stop, if you have blood in your urine, black or bloody stools, or if you cough up blood or vomit that looks like coffee grounds.
Also call your doctor at once if you have:
- nosebleeds, pale skin, easy bruising, purple spots under your skin or in your mouth;
- jaundice (yellowing of your skin or eyes);
- fast heartbeats, shortness of breath;
- headache, fever, weakness, feeling tired;
- little or no urination;
- a seizure;
- low blood sugar--headache, hunger, sweating, irritability, dizziness, fast heart rate, and feeling anxious or shaky; or
- signs of a blood clot--sudden numbness or weakness, confusion, problems with vision or speech.
Common side effects may include:
- bleeding.
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
Read the entire detailed patient monograph for Plavix (Clopidogrel Bisulfate)
Plavix Professional Information
SIDE EFFECTS
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 Trials Experience
Because clinical trials are conducted under widely varying conditions and durations of followup, 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.
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) (n=6259) |
Placebo (+ aspirin) (n=6303) |
| 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. |
||
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* 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.
- Blood and lymphatic system disorders: Agranulocytosis, aplastic anemia/pancytopenia, thrombotic thrombocytopenic purpura (TTP), acquired hemophilia A
- Gastrointestinal disorders: Colitis (including ulcerative or lymphocytic colitis), pancreatitis, stomatitis, gastric/duodenal ulcer, diarrhea
- General disorders and administration site condition: Fever
- Hepatobiliary disorders: Acute liver failure, hepatitis (noninfectious), abnormal liver function test
- Immune system disorders: Hypersensitivity reactions, anaphylactoid reactions, serum sickness, insulin autoimmune syndrome, which can lead to severe hypoglycemia
- Musculoskeletal, connective tissue and bone disorders: Myalgia, arthralgia, arthritis
- Nervous system disorders: Taste disorders, headache, ageusia
- Psychiatric disorders: Confusion, hallucinations
- Respiratory, thoracic and mediastinal disorders: Bronchospasm, interstitial pneumonitis, eosinophilic pneumonia
- Renal and urinary disorders: Increased creatinine levels
- Skin and subcutaneous tissue disorders: Maculopapular, erythematous or exfoliative rash, urticaria, bullous dermatitis, eczema, toxic epidermal necrolysis, Stevens-Johnson syndrome, acute generalized exanthematous pustulosis (AGEP), angioedema, drug-induced hypersensitivity syndrome, drug rash with eosinophilia and systemic symptoms (DRESS), erythema multiforme, lichen planus, generalized pruritus
- Vascular disorders: Vasculitis, hypotension
DRUG INTERACTIONS
CYP2C19 Inducers
Since clopidogrel is metabolized to its active metabolite partly by CYP2C19, use of drugs that induce the activity of this enzyme would be expected to result in increased drug levels of the active metabolite of clopidogrel.
Rifampin strongly induces CYP2C19 resulting to both an increase level of clopidogrel active metabolite and platelet inhibition, which in particular might potentiate the risk of bleeding. As a precaution, avoid concomitant use of strong CYP2C19 inducers [see WARNINGS AND PRECAUTIONS and CLINICAL PHARMACOLOGY].
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 [see WARNINGS AND PRECAUTIONS].
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 [see WARNINGS AND PRECAUTIONS and CLINICAL PHARMACOLOGY].
Opioids
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 [see CLINICAL PHARMACOLOGY]. 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.
SSRIs And SNRIs
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 [see CLINICAL PHARMACOLOGY]. 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.
Read the entire FDA prescribing information for Plavix (Clopidogrel Bisulfate)
IMAGES
See Images
&Copy; Plavix Patient Information is supplied by Cerner Multum, Inc. and Plavix Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.