INSTRUCTIONS

for medical use of the medicinal product

 

CLOPIDOGREL

 

 

Composition:

active substance: clopidogrel;

1 film-coated tablet contains clopidogrel bisulphate equivalent to clopidogrel 75 mg;

excipients: microcrystalline cellulose, lactose monohydrate, croscarmellose sodium, low-substituted hydroxypropyl cellulose, magnesium stearate, talc, colloidal silicon dioxide, hydrogenated castor oil, film coating SOL Code IC-S-279 (Brown) (contains titanium dioxide (E 171) and red iron oxide (E 172)), isopropyl alcohol, dichloromethane.

 

Pharmaceutical form. Film-coated tablets.

Basic physical and chemical properties: orange, round, biconvex film-coated tablets.

 

Pharmacotherapeutic group. Antithrombotic agents, ATC code: B01A C04.

 

Pharmacological properties.

Pharmacodynamics.

Mechanism of action. Clopidogrel selectively inhibits the binding of adenosine diphosphate (ADP) to its receptor on the platelet surface and the subsequent activation of the GPIIb/IIIa complex induced by ADP, thereby inhibiting platelet aggregation. Biotransformation of clopidogrel is necessary to produce active inhibition of platelet aggregation. Clopidogrel also inhibits platelet aggregation induced by other agonists by blocking the amplification of platelet activation by released ADP. Clopidogrel irreversibly modifies the ADP receptors of platelets. Thus, platelets that have interacted with clopidogrel remain affected for the rest of their lifespan. Normal platelet function returns at a rate corresponding to platelet turnover.

Pharmacodynamic effects. From the first day of administration at repeated daily doses of 75 mg, a significant inhibition of ADP-induced platelet aggregation is observed. This effect progressively increases and stabilizes between days 3 and 7. At steady state, the average level of aggregation inhibition under a 75 mg daily dose ranges from 40% to 60%. Platelet aggregation and bleeding time return to baseline on average within 5 days after discontinuation of treatment.

Pharmacokinetics.

Absorption

After oral administration of a single dose or repeated daily doses of 75 mg, clopidogrel is rapidly absorbed. Mean maximum plasma concentrations of unchanged clopidogrel (approximately 2.2–2.5 ng/mL after a single dose of 75 mg) were reached approximately 45 minutes after dosing. Absorption is at least 50%, as shown by urinary excretion of clopidogrel metabolites.

Distribution

Clopidogrel and the main circulating (inactive) metabolite bind reversibly in vitro to human plasma proteins (98% and 94%, respectively). This binding is non-saturable in vitro over a wide range of concentrations.

Metabolism

Clopidogrel is extensively metabolized in the liver. In vitro and in vivo, there are two main metabolic pathways: one involves esterases and leads to hydrolysis forming an inactive carboxylic acid derivative (accounting for 85% of circulating plasma metabolites), and the other involves cytochrome P450 enzymes. Clopidogrel is first converted to the intermediate metabolite 2-oxo-clopidogrel. Further metabolism of 2-oxo-clopidogrel results in the formation of a thiol derivative — the active metabolite. This active metabolite is mainly formed by the CYP2C19 enzyme, with participation of several other CYP enzymes such as CYP1A2, CYP2B6, and CYP3A4. The active thiol metabolite of clopidogrel, which was isolated in vitro, binds rapidly and irreversibly to platelet receptors, thereby preventing platelet aggregation.

Elimination

Within 120 hours after oral administration of 14C-labeled clopidogrel in humans, approximately 50% of the radioactivity is excreted in urine and about 46% in feces. After oral administration of a single 75 mg dose, the elimination half-life of clopidogrel is approximately 6 hours. The elimination half-life of the main circulating (inactive) metabolite is 8 hours after single and repeated doses.

Pharmacogenetics. CYP2C19 is involved in the formation of both the active metabolite and the intermediate 2-oxo-clopidogrel metabolite. The pharmacokinetics of the active clopidogrel metabolite and the antiplatelet effects, based on ex vivo platelet aggregation measurements, differ depending on CYP2C19 genotype.

The CYP2C191 allele corresponds to fully functional metabolism, whereas the CYP2C192 and CYP2C193 alleles correspond to non-functional metabolism. The CYP2C192 and CYP2C193 alleles account for the majority of reduced-function alleles in Caucasian (85%) and Asian (99%) populations with reduced metabolism. Other alleles associated with absent or reduced metabolism occur much less frequently. These include CYP2C194, *5, *6, *7, and *8. A poor metabolizer is a patient carrying two non-functional alleles, as listed above. According to published data, CYP2C19 genotypes associated with reduced metabolism occur in approximately 2% of Caucasians, 4% of African-Americans, and 14% of Chinese. Tests are now available to identify the CYP2C19 genotype.

Special populations. The pharmacokinetics of the active clopidogrel metabolite have not been studied in the special patient populations described below.

Renal impairment. After repeated administration of 75 mg of clopidogrel daily to patients with severe renal impairment (creatinine clearance 5–15 mL/min), ADP-induced platelet aggregation inhibition was lower (25%) than in healthy volunteers, while bleeding time was similarly prolonged as in healthy volunteers receiving 75 mg clopidogrel daily. Clinical tolerability was good in all patients.

Hepatic impairment. After repeated administration of 75 mg of clopidogrel daily for 10 days in patients with severe hepatic impairment, ADP-induced platelet aggregation inhibition was similar to that observed in healthy volunteers. The average prolongation of bleeding time was also similar in both groups.

Ethnicity. The prevalence of CYP2C19 alleles resulting in intermediate and poor metabolism of CYP2C19 varies among ethnic/racial groups (see section “Pharmacogenetics”). There are limited data for Asian patients available to evaluate the clinical significance of CYP genotyping in terms of clinical outcomes.

 

Clinical particulars.

Indications.

Prevention of atherothrombotic events in adults:

• in patients who have experienced myocardial infarction (treatment initiation – a few days after the event but no later than 35 days after its occurrence), ischemic stroke (treatment initiation – 7 days after the event but no later than 6 months after its occurrence), or in patients diagnosed with peripheral arterial disease (arterial lesions and atherothrombosis of the lower limb vessels);
• in patients with acute coronary syndrome:

– with acute coronary syndrome without ST-segment elevation (unstable angina or non-Q-wave myocardial infarction), including patients undergoing stent placement during percutaneous coronary intervention, in combination with acetylsalicylic acid;

– with acute ST-segment elevation myocardial infarction in combination with acetylsalicylic acid (in patients receiving standard medical treatment and those eligible for thrombolytic therapy).

Prevention of atherothrombotic and thromboembolic events in atrial fibrillation

Clopidogrel in combination with acetylsalicylic acid is indicated in adult patients with atrial fibrillation who have at least one risk factor for vascular events, who have contraindications to treatment with vitamin K antagonists, and who have a low risk of bleeding, for the prevention of atherothrombotic and thromboembolic events, including stroke.

For further information, see section "Pharmacological properties".

 

Contraindications.

Hypersensitivity to the active substance or to any of the excipients. Severe hepatic impairment.

Active bleeding (e.g., peptic ulcer or intracranial hemorrhage).

 

Interaction with other medicinal products and other forms of interaction.

Medicinal products associated with increased risk of bleeding. Due to a potential additive effect, there is an increased risk of hemorrhagic complications; therefore, concomitant use of such medicinal products with clopidogrel requires caution (see section "Precautions for use").

Oral anticoagulants. Concomitant use of Clopidogrel with oral anticoagulants is not recommended, as this combination may increase bleeding intensity. Although clopidogrel 75 mg daily does not alter the pharmacokinetics of S-warfarin or the international normalized ratio (INR) in patients receiving long-term warfarin therapy, the concomitant administration of clopidogrel and warfarin increases the risk of bleeding due to independent effects on hemostasis.

Glycoprotein IIb/IIIa receptor inhibitors. Clopidogrel should be used with caution in patients receiving glycoprotein IIb/IIIa receptor inhibitors.

Acetylsalicylic acid. Acetylsalicylic acid does not alter the inhibitory effect of clopidogrel on ADP-induced platelet aggregation, but clopidogrel enhances the effect of acetylsalicylic acid on collagen-induced platelet aggregation. However, the concomitant use of 500 mg acetylsalicylic acid twice daily for one day did not significantly prolong bleeding time already prolonged by clopidogrel. Since a possible pharmacodynamic interaction between clopidogrel and acetylsalicylic acid may increase the risk of bleeding, concomitant use requires caution. Nevertheless, clopidogrel and acetylsalicylic acid were co-administered for up to 1 year.

Heparin. In a clinical study involving healthy volunteers, clopidogrel did not require dose adjustment of heparin and did not alter the effect of heparin on coagulation. Concomitant administration of heparin did not change clopidogrel’s inhibition of platelet aggregation. Since a pharmacodynamic interaction between clopidogrel and heparin may increase the risk of bleeding, concomitant use requires caution.

Thrombolytic agents. The safety of concomitant use of clopidogrel, fibrin-specific or non-fibrin-specific thrombolytic agents, and heparin was studied in patients with acute myocardial infarction. The incidence of clinically significant bleeding was similar to that observed with concomitant use of thrombolytics and heparin with acetylsalicylic acid.

Non-steroidal anti-inflammatory drugs (NSAIDs). In a clinical study involving healthy volunteers, concomitant administration of clopidogrel and naproxen increased the incidence of occult gastrointestinal blood loss. However, due to the lack of interaction studies with other NSAIDs, it is currently unclear whether gastrointestinal bleeding risk increases with all NSAIDs. Therefore, caution is advised when NSAIDs, particularly COX-2 inhibitors, are used together with clopidogrel.

Other antiplatelet agents. Concomitant use of antiplatelet medicinal products increases the risk of bleeding due to an additive effect. If a patient is being treated concurrently with other antiplatelet agents, any signs or symptoms of bleeding must be promptly evaluated (see section "Precautions for use").

Selective serotonin reuptake inhibitors (SSRIs). SSRIs should be used with caution together with clopidogrel, as they affect platelet activation and increase the risk of bleeding.

Concomitant use of other drugs.

Since clopidogrel is partially metabolized into its active metabolite by CYP2C19, use of drugs that inhibit this enzyme may lead to a decrease in plasma levels of the active clopidogrel metabolite. The clinical significance of this interaction is unclear. As a precaution, concomitant use of strong and moderate CYP2C19 inhibitors should be avoided (see sections "Precautions for use" and "Pharmacokinetics").

Drugs that inhibit CYP2C19 activity include omeprazole, esomeprazole, fluvoxamine, fluoxetine, moclobemide, voriconazole, fluconazole, ticlopidine, carbamazepine, and efavirenz.

Proton pump inhibitors (PPIs). Omeprazole at a dose of 80 mg once daily, when co-administered with clopidogrel or taken within 12 hours of clopidogrel, reduced plasma levels of the active metabolite by 45% (loading dose) and 40% (maintenance dose). This reduction was accompanied by a 39% decrease in platelet aggregation inhibition (loading dose) and 21% (maintenance dose). Esomeprazole is expected to have a similar interaction with clopidogrel.

Results from observational and clinical studies have produced conflicting data regarding the clinical consequences of these pharmacokinetic and pharmacodynamic interactions in terms of major cardiovascular events. As a precaution, concomitant use of omeprazole or esomeprazole with clopidogrel should be avoided (see section "Precautions for use").

A lesser decrease in metabolite concentration was observed with pantoprazole or lansoprazole.

When pantoprazole was co-administered at 80 mg once daily, plasma concentrations of the active metabolite decreased by 20% (loading dose) and 14% (maintenance dose). This reduction was accompanied by a decrease in the mean platelet aggregation inhibition rate by 15% and 11%, respectively. The findings suggest that clopidogrel and pantoprazole can be used concomitantly.

There is no evidence that other drugs that reduce stomach acid production, such as H₂-receptor antagonists or antacids, affect the antiplatelet activity of clopidogrel.

Combination with other medicinal products. A number of clinical studies were conducted with clopidogrel in combination with other drugs to investigate potential pharmacodynamic and pharmacokinetic interactions. No clinically significant pharmacodynamic interactions were observed when clopidogrel was co-administered with atenolol, nifedipine, or both. Furthermore, the pharmacodynamic activity of clopidogrel remained essentially unchanged when co-administered with phenobarbital and estrogen.

The pharmacokinetics of digoxin or theophylline were not altered by co-administration with clopidogrel.

Antacid agents did not affect the absorption of clopidogrel.

Data from studies using human liver microsomes suggest that clopidogrel's carboxylic acid metabolite may inhibit CYP2C9 activity. This could potentially increase plasma levels of drugs such as phenytoin and tolbutamide and NSAIDs that are metabolized by CYP2C9. However, results from the CAPRIE study indicate that phenytoin and tolbutamide can be used safely with clopidogrel.

Drugs that are CYP2C8 substrates. Clopidogrel has been shown to increase repaglinide exposure in healthy volunteers. In vitro studies demonstrated that this increase is due to inhibition of CYP2C8 by clopidogrel’s glucuronide metabolite. Due to the risk of increased plasma levels, concomitant use of clopidogrel with drugs primarily eliminated by CYP2C8 metabolism (e.g., repaglinide, paclitaxel) requires caution (see section "Precautions for use").

With the exception of the drug interactions described above, no interaction studies of clopidogrel with drugs commonly used in patients with atherothrombosis have been conducted. However, patients in clopidogrel clinical trials commonly received other medications, including diuretics, beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, calcium antagonists, lipid-lowering agents, coronary vasodilators, antidiabetic agents (including insulin), antiepileptic agents, and GPIIb/IIIa antagonists, without evidence of clinically significant adverse interactions.

In HIV-infected patients receiving antiretroviral therapy (ART) with ritonavir or cobicistat, reduced exposure to the active clopidogrel metabolite and diminished platelet inhibition have been observed. Although the clinical significance of these findings is uncertain, spontaneous reports have been received of HIV-infected patients on boosted ART who experienced recurrent occlusive events after de-obstruction or thrombotic events during clopidogrel therapy. Clopidogrel efficacy and average platelet inhibition may be reduced when co-administered with ritonavir. Therefore, concomitant use of clopidogrel with the above-mentioned ART is not recommended.

 

Precautions for use.

Bleeding and hematological disorders.

Due to the risk of bleeding and hematological adverse reactions, a complete blood count and/or other appropriate tests should be performed immediately if symptoms suggestive of bleeding appear during treatment (see section "Adverse reactions"). As with other antiplatelet agents, clopidogrel should be used with caution in patients at increased risk of bleeding due to trauma, surgical intervention, or other pathological conditions, as well as in patients receiving anticoagulants, antiplatelet agents, acetylsalicylic acid, heparin, glycoprotein IIb/IIIa inhibitors, or NSAIDs (used on a regular basis), including COX-2 inhibitors, selective serotonin reuptake inhibitors (SSRIs), or other drugs such as pentoxifylline, which are associated with an increased risk of hemorrhagic events (see section "Interaction with other medicinal products and other forms of interaction"). Patients should be carefully monitored for signs of bleeding, including occult bleeding, especially during the first weeks of treatment and/or after invasive cardiac procedures or surgical interventions. Concomitant use of clopidogrel with oral anticoagulants is not recommended, as it may increase bleeding intensity (see section "Interaction with other medicinal products and other forms of interaction").

In the case of planned surgery where an antiplatelet effect is temporarily undesirable, treatment with clopidogrel should be discontinued 7 days prior to surgery.

Patients should inform their doctor (including their dentist) that they are taking clopidogrel before any surgical procedure or before starting any new medication.

Clopidogrel prolongs bleeding time; therefore, it should be used with caution in patients with increased bleeding risk (especially gastrointestinal and intraocular bleeding).

 

Patients should be warned that while taking clopidogrel (alone or in combination with acetylsalicylic acid), bleeding may take longer to stop than usual, and that they should inform their doctor of any unusual bleeding (in terms of location or duration).

Thrombotic thrombocytopenic purpura (TTP).

Cases of TTP have been reported very rarely following clopidogrel administration, sometimes after a short course of treatment. TTP is characterized by thrombocytopenia and microangiopathic hemolytic anemia, accompanied by neurological symptoms, renal dysfunction, or fever. TTP is a potentially life-threatening condition that requires urgent treatment, including plasma exchange.

Acquired hemophilia. Cases of acquired hemophilia have been reported following clopidogrel use. In patients with confirmed isolated prolongation of activated partial thromboplastin time (aPTT), with or without bleeding, acquired hemophilia should be considered. Patients with confirmed acquired hemophilia should be managed by specialists and treated appropriately; clopidogrel should be discontinued.

Recent ischemic stroke.

Due to insufficient data, clopidogrel is not recommended during the first 7 days after an acute ischemic stroke.

Cytochrome P450 2C19 (CYP2C19).

Pharmacogenetics: In patients with genetically reduced CYP2C19 function, lower plasma concentrations of the active clopidogrel metabolite and reduced antiplatelet effects are observed when using the recommended doses of clopidogrel. Tests are now available to identify the CYP2C19 genotype in patients.

Since clopidogrel is partly converted into its active metabolite by CYP2C19, use of drugs that inhibit this enzyme may lead to reduced plasma levels of the active metabolite. However, the clinical significance of this interaction is unclear. Therefore, as a precaution, concomitant use of strong and moderate CYP2C19 inhibitors should be avoided.

CYP2C8 substrates. Caution is advised in patients receiving clopidogrel concomitantly with medicinal products that are CYP2C8 substrates (see section "Interaction with other medicinal products and other forms of interaction").

Cross-reactivity among thienopyridines. Patients should be evaluated for a history of hypersensitivity to other thienopyridines (such as ticlopidine, prasugrel), as cross-reactivity among thienopyridines has been reported.

Use of thienopyridines may lead to mild to severe allergic reactions such as rash, angioedema, or hematologic reactions such as thrombocytopenia and neutropenia. Patients who have previously had allergic and/or hematologic reactions to one thienopyridine may have an increased risk of developing a reaction to another thienopyridine. Monitoring for cross-reactivity is recommended.

Renal impairment.

Experience with clopidogrel in patients with renal impairment is limited; therefore, it should be used with caution in these patients.

Hepatic impairment.

Experience with clopidogrel in patients with moderate hepatic disease and a potential bleeding diathesis is limited; therefore, caution should be exercised in such patients.

Excipients.

Clopidogrel contains lactose; therefore, patients with rare hereditary problems of galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption should not take this medicinal product.

Clopidogrel contains hydrogenated castor oil, which may cause stomach upset and diarrhea.

Alcohol should not be consumed during treatment due to an increased risk of gastrointestinal bleeding.

Special precautions for disposal and other handling

Any unused product or waste material should be disposed of in accordance with local requirements.

 

Pregnancy and lactation.

Due to the absence of clinical data on the use of clopidogrel during pregnancy, administration of the drug to pregnant women is not recommended (precautionary measure).

Animal studies have not shown direct or indirect harmful effects of clopidogrel on pregnancy, embryo/foetal development, delivery, or postnatal development.

It is not known whether clopidogrel is excreted in human breast milk. Animal studies have shown that clopidogrel is excreted in breast milk; therefore, breastfeeding should be discontinued during treatment.

Fertility. Animal studies did not reveal any harmful effects of clopidogrel on fertility.

 

Effects on ability to drive and use machines.

Clopidogrel has no or negligible influence on the ability to drive or use machines.

 

Method of administration and dosage.

Adults and elderly patients. Clopidogrel is administered at a dose of 75 mg once daily, with or without food.

In patients with acute coronary syndrome without ST-segment elevation (unstable angina or non-Q-wave myocardial infarction), clopidogrel treatment should begin with a single loading dose of 300 mg, followed by 75 mg once daily (in combination with acetylsalicylic acid at a dose of 75–325 mg daily).

Since the use of higher doses of acetylsalicylic acid increases the risk of bleeding, a dose of acetylsalicylic acid above 100 mg is not recommended. The optimal duration of treatment has not been formally established. Clinical trial data support the use of the product for up to 12 months, with the greatest benefit observed at 3 months of treatment.

In patients with acute ST-segment elevation myocardial infarction, clopidogrel should be administered at a dose of 75 mg once daily, starting with a single loading dose of 300 mg, in combination with acetylsalicylic acid, with or without thrombolytic agents. In patients aged 75 years or older, clopidogrel treatment should be initiated without a loading dose. Combination therapy should be started as early as possible after the onset of symptoms and continued for at least 4 weeks. The benefit of combining clopidogrel with acetylsalicylic acid beyond 4 weeks in this setting has not been studied.

In patients with atrial fibrillation, clopidogrel is administered once daily at a dose of 75 mg.

Acetylsalicylic acid (at a dose of 75–100 mg daily) should be initiated and continued concurrently with clopidogrel.

In case of a missed dose:

- if less than 12 hours have passed since the scheduled time, the patient should take the missed dose immediately and continue with the next dose at the usual time;

- if more than 12 hours have passed, the patient should skip the missed dose and take the next dose at the regular scheduled time. The dose should not be doubled to make up for a missed dose.

Children and adolescents. Clopidogrel should not be used in children, as there are no data on the effectiveness of the product in this population.

Renal impairment. Therapeutic experience in patients with renal impairment is limited (see section "Special warnings and precautions for use").

Hepatic impairment. Therapeutic experience in patients with moderate hepatic disease and a potential bleeding diathesis is limited (see section "Precautions for use").

 

Children.

Clopidogrel should not be used for children, as there are no data on its efficacy.

  

Overdose.

In case of clopidogrel overdose, prolongation of bleeding time with subsequent complications may occur. In the event of bleeding, symptomatic treatment is recommended.

An antidote to the pharmacological activity of clopidogrel is not known. If immediate correction of prolonged bleeding time is necessary, the effect of clopidogrel can be reversed by platelet transfusion.

 

Adverse reactions.

Adverse reactions are classified by organ system, and their frequency is defined as follows: common (> 1/100 to <1/10), uncommon (> 1/1,000 to  <1/100), rare (> 1/10,000 to  <1/1,000), very rare (< 1/10,000), frequency unknown. Within each organ system class, adverse effects are listed in order of decreasing severity.

Blood and lymphatic system disorders: uncommon – thrombocytopenia, leukopenia, eosinophilia; rare – neutropenia, including severe neutropenia; very rare, frequency unknown* – thrombotic thrombocytopenic purpura (TTP), aplastic anemia, pancytopenia, agranulocytosis, severe thrombocytopenia, acquired hemophilia A, granulocytopenia, anemia

Immune system disorders: very rare, frequency unknown* – serum sickness, anaphylactoid reactions, cross-reactivity among thienopyridines (e.g., ticlopidine, prasugrel).

Psychic disorders: very rare, frequency unknown* – hallucinations, confusion.

Nervous system disorders: uncommon – intracranial haemorrhage (in some cases fatal), headache, paraesthesia, dizziness; very rare, frequency unknown* – change in taste perception.

Eye disorders: uncommon – bleeding in the eye (conjunctival, ocular, retinal).

Hearing and labyrinth disorders: rare – vertigo.

Vascular disorders: common – haematoma; very rare, frequency unknown* – severe haemorrhage, bleeding from the surgical wound, vasculitis, arterial hypotension.

Respiratory system, thoracic and mediastinal disorders: common – epistaxis; very rare, frequency unknown* – respiratory tract bleeding (haemoptysis, pulmonary haemorrhage), bronchospasm, interstitial pneumonitis, eosinophilic pneumonia.

Gastrointestinal tract disorders: common – gastrointestinal bleeding, diarrhoea, abdominal pain, dyspepsia; uncommon – gastric and duodenal ulcer, gastritis, vomiting, nausea, constipation, flatulence; rare – retroperitoneal haemorrhage; very rare, frequency unknown* – fatal gastrointestinal and retroperitoneal haemorrhages, pancreatitis, colitis (including ulcerative or lymphocytic), stomatitis.

Hepatobiliary system disorders: very rare, frequency unknown* – acute liver failure, hepatitis, abnormal liver function test results.

Skin and subcutaneous tissue disorders: common – subcutaneous haemorrhage; uncommon – rash, pruritus, intradermal haemorrhages (purpura); very rare, frequency unknown* – bullous dermatitis (toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, acute generalised exanthematous pustulosis (AGEP), angioedema, erythematous rash, urticaria, drug hypersensitivity syndrome, drug rash with eosinophilia and systemic symptoms (DRESS syndrome), eczema, lichen planus.

Reproductive system and mammary glands disorders: rare – gynaecomastia.

Musculoskeletal system and connective tissue disorders: very rare, frequency unknown* – bone and muscle haemorrhages (haemarthrosis), arthritis, arthralgia, myalgia.

Kidney and urinary tract disorders: uncommon – haematuria; very rare, frequency unknown* – glomerulonephritis, increased blood creatinine levels.

General disorders and reactions at the site of administration: common – bleeding at the injection site; very rare, frequency unknown* – fever.

Investigations: uncommon – prolonged bleeding time, decreased neutrophil and platelet counts.

* Information on clopidogrel with frequency ‘frequency unknown’.

 

Shelf life: 2 years.

 

Storage conditions: store in a dry place protected from light at a temperature not exceeding 30 °C. Keep out of reach of children,

 

Packaging: 10 tablets in a blister; 1, 3 or 10 blister in a box.

 

Terms of dispensing. On prescription.

 

Date of last update.

17.05.2024