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, 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) or thrombolytics. Patients should be followed carefully for any signs of bleeding including occult bleeding, especially during the 1st weeks of treatment and/or after invasive cardiac procedures or surgery. The concomitant administration of 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 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 a patient is to undergo elective surgery and an antiplatelet effect is not desired, CoPlavix should be discontinued 5-7 days prior to surgery.
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 CoPlavix and that they should report any unusual bleeding (site or duration) to their physician.
Thrombotic Thrombocytopenic Purpura (TTP): Thrombotic thrombocytopenic purpura 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. Thrombotic thrombocytopenic purpura is a potentially fatal condition requiring prompt treatment including plasmapheresis (plasma exchange).
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 ASA 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 P4502C19 (CYP2C19): Pharmacogenetics: In patients who are CYP2C19 poor metabolizers, clopidogrel at recommended doses forms less of the active metabolite of clopidogrel and has a smaller effect on platelet function. Poor metabolisers with acute coronary syndrome or undergoing percutaneous coronary intervention treated with clopidogrel at recommended doses may exhibit higher CV event rates than do patients with normal CYP2C19 function (see Pharmacology: Pharmacokinetics: Pharmacogenetics under Actions). Tests are available to identify a patient's CYP2C19 genotype; these tests can be used as an aid in determining therapeutic strategy. Consider the use of higher clopidogrel doses in patients who are known CYP2C19 poor metabolisers (see Pharmacology: Pharmacokinetics: Pharmacogenetics under Actions and Dosage & Administration).
Cross-Reactivity Among Thienopyridines: Patients should be evaluated for history of hypersensitivity to another thienopyridine (eg, ticlopidine, prasugrel) since cross-reactivity among thienopyridines has been reported (see Adverse Reactions). Thienopyridines may cause mild to severe allergic reactions eg, rash, angioedema or haematological reactions eg, 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 cross-reactivity is advised.
Caution Required Due to Acetylsalicylic Acid: Patients with a history of asthma or allergic disorders since they are at increased risk of hypersensitivity reactions; patients with gout since low doses of ASA increase urate concentrations; children <18 years since there is a possible association between ASA and Reye's syndrome. Reye's syndrome is a very rare disease which can be fatal.
Due to the presence of aspirin, patients should be counseled about the bleeding risks involved with chronic, heavy alcohol use while taking CoPlavix. CoPlavix must be administered under close medical supervision in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency due to risk of hemolysis (see Adverse Reactions).
Gastrointestinal: CoPlavix should be used with caution in patients with a history of peptic ulcer or gastroduodenal haemorrhage or minor upper gastrointestinal symptoms as this may be due to gastric ulceration which may lead to gastric bleeding. Gastrointestinal undesirable effects including stomach pain, heartburn, nausea, vomiting and gastrointestinal bleeding may occur. Minor upper gastrointestinal symptoms eg, dyspepsia, are common and can occur anytime during therapy. Physicians should remain alert for signs of gastrointestinal ulceration and bleeding, even in the absence of previous gastrointestinal symptoms. Patients should be told about the signs and symptoms of gastrointestinal undesirable effects and what steps to take if they occur (see Adverse Reactions).
Excipients: CoPlavix contains lactose. Patients with rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption should not take CoPlavix.
CoPlavix also contains hydrogenated castor oil which may cause stomach upset and diarrhoea.
Effects on the Ability to Drive or Operate Machinery: CoPlavix has no or negligible influence on the ability to drive and use machines.
Renal Impairment: CoPlavix must not be used in patients with severe renal impairment (see Contraindications). Therapeutic experience is limited in patients with mild to moderate renal impairment. Therefore, CoPlavix should be used with caution in these population.
Hepatic Impairment: CoPlavix must not be used in patients with severe hepatic impairment (see Contraindications). Therapeutic experience is limited in patients with moderate hepatic disease who may have bleeding diatheses. Therefore, CoPlavix should be used with caution in these population.
Impairment of Fertility: There are no fertility data with CoPlavix. Clopidogrel was not shown to alter fertility in animal studies.
For Acetylsalicylic Acid Doses ≥500 mg/day: There is some evidence that drugs which inhibit cyclooxygenase/prostaglandin synthesis may cause impairment of female fertility by an effect on ovulation. This is reversible on withdrawal of treatment.
Use in Pregnancy: No clinical data on exposure to CoPlavix during pregnancy are available. CoPlavix should not be used during the first 2 trimesters of pregnancy unless the clinical condition of the woman requires treatment with clopidogrel/ASA.
Due to the presence of ASA, CoPlavix is contraindicated during the 3rd trimester of pregnancy.
Clopidogrel: There are no adequate data from the use of clopidogrel in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see Pharmacology: Toxicology under Actions).
Acetylsalicylic Acid: Low doses (up to 100 mg/day): Clinical studies indicate that doses up to 100 mg/day for restricted obstetrical use, which require specialised monitoring, appear safe.
Doses of 100-500 mg/day: There is insufficient clinical experience regarding the use of doses >100 mg/day up to 500 mg/day. Therefore, the recommendations as follows for doses of ≥500 mg/day apply also for this dose range.
Doses of ≥500 mg/day: Inhibition of prostaglandin synthesis may adversely affect the pregnancy and/or the embryo/foetal development. Data from epidemiological studies suggest an increased risk of miscarriage and of cardiac malformation and gastroschisis after use of a prostaglandin synthesis inhibitor in early pregnancy. The absolute risk for CV malformation was increased from <1% up to approximately 1.5%. The risk is believed to increase with dose and duration of therapy. In animals, administration of a prostaglandin synthesis inhibitor has been shown to result in reproductive toxicity (see Pharmacology: Toxicology under Actions). Until the 24th amenorrhea week (5th month of pregnancy), ASA should not be given unless clearly necessary. If ASA is used by a woman attempting to conceive or until the 24th amenorrhea week (5th month of pregnancy), the dose should be kept as low and duration of treatment as short as possible.
From the beginning of the 6th month of pregnancy, all prostaglandin synthesis inhibitors may expose the foetus to cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension), renal dysfunction which may progress to renal failure with oligohydroamniosis. May also expose the mother and the neonate at the end of pregnancy to possible prolongation of bleeding time, an anti-aggregating effect which may occur even at very low doses; inhibition of uterine contractions resulting in delayed or prolonged labour.
Use in Lactation: It is unknown whether clopidogrel is excreted in human milk. Acetylsalicylic acid is known to be excreted in limited amounts in human milk. Breastfeeding should be discontinued during treatment with CoPlavix.
Use in Children: The safety and efficacy of CoPlavix in children and adolescents <18 years have not been established. CoPlavix is not recommended in this population.