CoPlavix Special Precautions

Bleeding and haematological disorders: Due to the risk of bleeding and haematological adverse reactions, blood cell count determination and/or other appropriate testing should be promptly considered whenever clinical symptoms suggestive of bleeding arise during the course of treatment (see Adverse Reactions). As a dual antiplatelet agent, Clopidogrel bisulfate + Aspirin (CoPlavix) should be used with caution in patients who may be at risk of increased bleeding from trauma, surgery or other pathological conditions, and in patients receiving treatment with other NSAIDs including COX-2 inhibitors, heparin, glycoprotein IIb/IIIa inhibitors, selective serotonin reuptake inhibitors (SSRIs), CYP2C19 strong inducers, thrombolytics or other medicinal products associated with bleeding risk such as pentoxifylline (see Interactions). Due to the increased risk of haemorrhage, triple antiplatelet therapy (clopidogrel + ASA + dipyridamole) for stroke secondary prevention is not recommended in patients with acute non-cardioembolic ischemic stroke or TIA (see Interactions and Adverse Reactions). Patients should be followed carefully for any signs of bleeding including occult bleeding, especially during the first weeks of treatment and/or after invasive cardiac procedures or surgery. The concomitant administration of Clopidogrel bisulfate + Aspirin (CoPlavix) with oral anticoagulants is not recommended since it may increase the intensity of bleeding (see Interactions).
Patients should inform physicians and dentists that they are taking Clopidogrel bisulfate + Aspirin (CoPlavix) before any surgery is scheduled and before any new medicinal product is taken. Where elective surgery is being considered, the need for dual antiplatelet therapy should be reviewed and consideration given to the use of a single antiplatelet agent. If patients must temporarily stop antiplatelet therapy, Clopidogrel bisulfate + Aspirin (CoPlavix) should be discontinued 7 days prior to surgery.
Clopidogrel bisulfate + Aspirin (CoPlavix) prolongs bleeding time and should be used with caution in patients who have lesions with a propensity to bleed (particularly gastrointestinal and intraocular).
Patients should also be told that it might take longer than usual to stop bleeding when they take Clopidogrel bisulfate + Aspirin (CoPlavix), and that they should report any unusual bleeding (site or duration) to their physician.
Thrombotic Thrombocytopenic Purpura (TTP): Thrombotic Thrombocytopenic Purpura (TTP) has been reported very rarely following the use of clopidogrel, sometimes after a short exposure. It is characterised by thrombocytopenia and microangiopathic haemolytic anaemia associated with either neurological findings, renal dysfunction or fever.
TTP is a potentially fatal condition requiring prompt treatment including plasmapheresis.
Acquired haemophilia: Acquired haemophilia has been reported following use of clopidogrel. In cases of confirmed isolated activated Partial Thromboplastin Time (aPTT) prolongation with or without bleeding, acquired haemophilia should be considered. Patients with a confirmed diagnosis of acquired haemophilia should be managed and treated by specialists, and clopidogrel should be discontinued.
Recent transient ischaemic attack or stroke: In patients with recent transient ischaemic attack or stroke who are at high risk of recurrent ischaemic events, the combination of Aspirin and clopidogrel has been shown to increase major bleeding. Therefore, such addition should be undertaken with caution outside of clinical situations where the combination has proven to be beneficial.
Cytochrome P450 2C19 (CYP2C19): Pharmacogenetics: In patients who are poor CYP2C19 metabolisers, clopidogrel at recommended doses forms less of the active metabolite of clopidogrel and has a smaller effect on platelet function. Tests are available to identify a patient's CYP2C19 genotype.
Since clopidogrel is metabolised to its active metabolite partly by CYP2C19, use of medicinal products that inhibit the activity of this enzyme would be expected to result in reduced drug levels of the active metabolite of clopidogrel. The clinical relevance of this interaction is uncertain. As a precaution, concomitant use of strong or moderate CYP2C19 inhibitors should be discouraged (see Interactions for a list of CYP2C19 inhibitors; see also Pharmacology: Pharmacokinetics under Actions).
Use of medicinal products that induce the activity of CYP2C19 would be expected to result in increased drug levels of the active metabolite of clopidogrel and might potentiate the bleeding risk. As a precaution, concomitant use of strong CYP2C19 inducers should be discouraged (see Interactions).
CYP2C8 substrates: Caution is required in patients treated concomitantly with clopidogrel and CYP2C8 substrate medicinal products (see Interactions).
Cross-reactions among thienopyridines: Patients should be evaluated for history of hypersensitivity to thienopyridines (such as clopidogrel, ticlopidine, prasugrel) since cross-reactivity among thienopyridines has been reported (see Adverse Reactions). Thienopyridines may cause mild to severe allergic reactions such as rash, angioedema, or haematological cross-reactions such as thrombocytopaenia and neutropaenia. Patients who had developed a previous allergic reaction and/or haematological reaction to one thienopyridine may have an increased risk of developing the same or another reaction to another thienopyridine. Monitoring for signs of hypersensitivity in patients with a known allergy to thienopyridines is advised.
Caution required due to Aspirin: In patients with a history of asthma or allergic disorders since they are at increased risk of hypersensitivity reactions.
In patients with gout since low doses of Aspirin increase urate concentrations.
In children under 18 years of age, there is a possible association between Aspirin and Reye's syndrome. Reye's syndrome is a very rare disease which can be fatal.
This medicinal product must be administered under close medical supervision in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency due to risk of hemolysis (see Adverse Reactions).
Alcohol may increase the risk of gastrointestinal injury when taken with Aspirin. Patients should be counselled about the risks of gastrointestinal injury and bleeding while taking clopidogrel plus Aspirin with alcohol, especially if alcohol consumption is chronic or heavy. (See Interactions.)
Drug reaction with eosinophilia and systemic symptoms (DRESS): Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) has been reported in patients taking NSAIDs such as ASA. Some of these events have been fatal or life-threatening. DRESS typically, although not exclusively, presents with fever, rash, lymphadenopathy, and/or facial swelling. Other clinical manifestations may include hepatitis, nephritis, hematological abnormalities, myocarditis, or myositis. Sometimes symptoms of DRESS may resemble an acute viral infection. Eosinophilia is often present. Because this disorder is variable in its presentation, other organ systems not noted here may be involved. It is important to note that early manifestations of hypersensitivity, such as fever or lymphadenopathy, may be present even though rash is not evident. If such signs or symptoms are present, ASA must be discontinued, and the patient must be evaluated immediately (see Adverse Reactions).
Gastrointestinal (GI): Clopidogrel bisulfate + Aspirin (CoPlavix) should be used with caution in patients with a history of peptic ulcer or gastroduodenal haemorrhage or minor upper GI symptoms as this may be due to gastric ulceration which may lead to gastric bleeding. GI undesirable effects including stomach pain, heartburn, nausea, vomiting, and GI bleeding may occur. Minor GI symptoms, such as dyspepsia, are common and can occur anytime during therapy. Physicians should remain alert for signs of GI ulceration and bleeding, even in the absence of previous GI symptoms. Patients should be told about the signs and symptoms of GI undesirable effects and what steps to take if they occur (see Adverse Reactions).
In patients concomitantly receiving nicorandil and NSAIDs including Aspirin and LAS, there is an increased risk for severe complications such as gastrointestinal ulceration, perforation and haemorrhage (see Interactions).
Excipients: Clopidogrel bisulfate + Aspirin (CoPlavix) contains lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.
This medicinal product also contains hydrogenated castor oil which may cause stomach upset and diarrhoea.
Effects on ability to drive and use machines: Clopidogrel bisulfate + Aspirin (CoPlavix) has no or negligible influence on the ability to drive and use machines.