Clopidogrel Mylan

ANNEX I 

 

SUMMARY OF PRODUCT CHARACTERISTICS 

 



1. NAME OF THE MEDICINAL PRODUCT 

 

Clopidogrel Mylan 75 mg film-coated tablets 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 

 

Each film-coated tablet contains 75 mg of clopidogrel (as hydrochloride). 

 

Excipient with known effect: 

Each film-coated tablet contains 13 mg hydrogenated castor oil.  

 

For the full list of excipients, see section 6.1. 

 

 

3. PHARMACEUTICAL FORM 

 

Film-coated tablet. 

Pink, round and biconvex film-coated tablets. 

 

 

4. CLINICAL PARTICULARS 

 

4.1 Therapeutic indications 

 

Secondary prevention of atherothrombotic events 

 

Clopidogrel is indicated in:   

• Adult patients suffering from myocardial infarction (from a few days until less than 35 days), 

ischaemic stroke (from 7 days until less than 6 months) or established peripheral arterial 

disease. 

• Adult patients suffering from acute coronary syndrome: 

- Non-ST segment elevation acute coronary syndrome (unstable angina or non-Q-wave 

myocardial infarction), including patients undergoing a stent placement following 

percutaneous coronary intervention, in combination with acetylsalicylic acid (ASA). 

- ST segment elevation acute myocardial infarction, in combination with ASA in medically 

treated patients eligible for thrombolytic therapy. 

 

Prevention of atherothrombotic and thromboembolic events in atrial fibrillation 

In adult patients with atrial fibrillation who have at least one risk factor for vascular events, are not 

suitable for treatment with Vitamin K antagonists (VKA) and who have a low bleeding risk, 

clopidogrel is indicated in combination with ASA for the prevention of atherothrombotic and 

thromboembolic events, including stroke. 

 

For further information please refer to section 5.1. 

 

4.2 Posology and method of administration 

 

Posology 

 

• Adults and elderly 

Clopidogrel should be given as a single daily dose of 75 mg.  

 

In patients suffering from acute coronary syndrome: 



- Non-ST segment elevation acute coronary syndrome (unstable angina or non-Q-wave 

myocardial infarction): clopidogrel treatment should be initiated with a single 300 mg loading 

dose and then continued at 75 mg once a day (with acetylsalicylic acid (ASA) 75 mg-325 mg 

daily). Since higher doses of ASA were associated with higher bleeding risk it is 

recommended that the dose of ASA should not be higher than 100 mg. The optimal duration 

of treatment has not been formally established. Clinical trial data support use up to 12 months, 

and the maximum benefit was seen at 3 months (see section 5.1). 

- ST segment elevation acute myocardial infarction: clopidogrel should be given as a single 

daily dose of 75 mg initiated with a 300 mg loading dose in combination with ASA and with 

or without thrombolytics. For patients over 75 years of age clopidogrel should be initiated 

without a loading dose. Combined therapy should be started as early as possible after 

symptoms start and continued for at least four weeks. The benefit of the combination of 

clopidogrel with ASA beyond four weeks has not been studied in this setting (see section 5.1). 

 

In patients with atrial fibrillation, clopidogrel should be given as a single daily dose of 75 mg. ASA 

(75 - 100 mg daily) should be initiated and continued in combination with clopidogrel (see section 

5.1). 

 

If a dose is missed: 

- Within less than 12 hours after regular scheduled time: patients should take the dose 

immediately and then take the next dose at the regular scheduled time. 

- For more than 12 hours: patients should take the next dose at the regular scheduled time and 

should not double the dose. 

 

• Paediatric population  

 Clopidogrel should not be used in children because of efficacy concerns (see section 5.1). 

 

• Renal impairment 

Therapeutic experience is limited in patients with renal impairment (see section 4.4). 

 

• Hepatic impairment 

Therapeutic experience is limited in patients with moderate hepatic disease who may have 

bleeding diatheses (see section 4.4). 

 

Method of administration 

For oral use 

It may be given with or without food. 

 

4.3 Contraindications 

 

• Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 

• Severe hepatic impairment. 

• Active pathological bleeding such as peptic ulcer or intracranial haemorrhage. 

 

4.4 Special warnings and precautions for use 

 

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 section 4.8). As with other antiplatelet 

agents, clopidogrel 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 ASA, 

heparin, glycoprotein IIb/IIIa inhibitors or non-steroidal anti-inflammatory drugs (NSAIDs) including 

Cox-2 inhibitors, or selective serotonin reuptake inhibitors (SSRIs), or CYP2C19 strong inducers or 



other medicinal products associated with bleeding risk such as pentoxifylline (see section 4.5). 

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 with oral anticoagulants is not recommended since it may 

increase the intensity of bleedings (see section 4.5). 

 

If a patient is to undergo elective surgery and antiplatelet effect is temporarily not desirable, 

clopidogrel should be discontinued 7 days prior to surgery. Patients should inform physicians and 

dentists that they are taking clopidogrel before any surgery is scheduled and before any new medicinal 

product is taken. Clopidogrel 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 be told that it might take longer than usual to stop bleeding when they take clopidogrel 

(alone or in combination with ASA), 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 ischaemic stroke 

In view of the lack of data, clopidogrel cannot be recommended during the first 7 days after acute 

ischaemic stroke. 

 

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 

section 4.5 for a list of CYP2C19 inhibitors, see also section 5.2).  

 

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 section 4.5). 

 

CYP2C8 substrates 

Caution is required in patients treated concomitantly with clopidogrel and CYP2C8 substrate 

medicinal products (see section 4.5). 

 

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 section 

4.8). 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. 

 

Renal impairment 

Therapeutic experience with clopidogrel is limited in patients with renal impairment. Therefore 

clopidogrel should be used with caution in these patients (see section 4.2). 

 

Hepatic impairment 

Experience is limited in patients with moderate hepatic disease who may have bleeding diatheses. 

Clopidogrel should therefore be used with caution in this population (see section 4.2). 

 

Excipients 

This medicinal product contains hydrogenated castor oil which may cause stomach upset and 

diarrhoea. 

 

4.5 Interaction with other medicinal products and other forms of interaction 

 

Medicinal products associated with bleeding risk: There is an increased risk of bleeding due to the 

potential additive effect. The concomitant administration of medicinal products associated with 

bleeding risk should be undertaken with caution (see section 4.4). 

 

Oral anticoagulants: the concomitant administration of clopidogrel with oral anticoagulants is not 

recommended since it may increase the intensity of bleedings (see section 4.4). Although the 

administration of clopidogrel 75 mg/day did not modify the pharmacokinetics of S-warfarin or 

International Normalised Ratio (INR) in patients receiving long-term warfarin therapy, 

coadministration of clopidogrel with warfarin increases the risk of bleeding because of independent 

effects on hemostasis. 

 

Glycoprotein IIb/IIIa inhibitors: clopidogrel should be used with caution in patients who receive 

concomitant glycoprotein IIb/IIIa inhibitors (see section 4.4). 

 

Acetylsalicylic acid (ASA): ASA did not modify the clopidogrel-mediated inhibition of ADP-induced 

platelet aggregation, but clopidogrel potentiated the effect of ASA on collagen-induced platelet 

aggregation. However, concomitant administration of 500 mg of ASA twice a day for one day did not 

significantly increase the prolongation of bleeding time induced by clopidogrel intake. A 

pharmacodynamic interaction between clopidogrel and acetylsalicylic acid is possible, leading to 

increased risk of bleeding. Therefore, concomitant use should be undertaken with caution (see 

section 4.4). However, clopidogrel and ASA have been administered together for up to one year 

(see section 5.1). 

 

Heparin: in a clinical study conducted in healthy subjects, clopidogrel did not necessitate 

modification of the heparin dose or alter the effect of heparin on coagulation. Co-administration of 

heparin had no effect on the inhibition of platelet aggregation induced by clopidogrel. A 

pharmacodynamic interaction between clopidogrel and heparin is possible, leading to increased risk of 

bleeding. Therefore, concomitant use should be undertaken with caution (see section 4.4). 

 

Thrombolytics: the safety of the concomitant administration of clopidogrel, fibrin or non-fibrin 

specific thrombolytic agents and heparins was assessed in patients with acute myocardial infarction. 

The incidence of clinically significant bleeding was similar to that observed when thrombolytic agents 

and heparin are co-administered with ASA (see section 4.8). 

 

NSAIDs: in a clinical study conducted in healthy volunteers, the concomitant administration of 

clopidogrel and naproxen increased occult gastrointestinal blood loss. However, due to the lack of 



interaction studies with other NSAIDs it is presently unclear whether there is an increased risk of 

gastrointestinal bleeding with all NSAIDs. Consequently, NSAIDs including Cox-2 inhibitors and 

clopidogrel should be co-administered with caution (see section 4.4). 

 

SSRIs: since SSRIs affect platelet activation and increase the risk of bleeding, the concomitant 

administration of SSRIs with clopidogrel should be undertaken with caution. 

 

 

Other concomitant therapy:  

 

Inducers of CYP2C19 

Since clopidogrel is metabolised to its active metabolite partly by CYP2C19, use of medicinal 

products that induce the activity of this enzyme would be expected to result in increased drug levels of 

the active metabolite of clopidogrel. 

 

Rifampicin strongly induces CYP2C19, resulting in both an increased level of clopidogrel active 

metabolite and platelet inhibition, which in particular might potentiate the risk of bleeding. As a 

precaution, concomitant use of strong CYP2C19 inducers should be discouraged (see section 4.4). 

 

Inhibitors of CYP2C19 

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 

sections 4.4 and 5.2). 

 

Medicinal products that are strong or moderate CYP2C19 inhibitors include, for example, omeprazole 

and esomeprazole, fluvoxamine, fluoxetine, moclobemide, voriconazole, fluconazole, ticlopidine, 

carbamazepine, and efavirenz. 

 

Proton Pump Inhibitors (PPI):  

Omeprazole 80 mg once daily administered either at the same time as clopidogrel or with 12 hours 

between the administrations of the two drugs decreased the exposure of the active metabolite by 45% 

(loading dose) and 40% (maintenance dose). The decrease was associated with a 39% (loading dose) 

and 21% (maintenance dose) reduction of inhibition of platelet aggregation. Esomeprazole is expected 

to give a similar interaction with clopidogrel. 

 

Inconsistent data on the clinical implications of this pharmacokinetic (PK)/pharmacodynamic (PD) 

interaction in terms of major cardiovascular events have been reported from both observational and 

clinical studies. As a precaution, concomitant use of omeprazole or esomeprazole should be 

discouraged (see section 4.4).  

 

Less pronounced reductions of metabolite exposure has been observed with pantoprazole or 

lansoprazole. 

 

The plasma concentrations of the active metabolite was 20% reduced (loading dose) and 14% reduced 

(maintenance dose) during concomitant treatment with pantoprazole 80 mg once daily. This was 

associated with a reduction of the mean inhibition of platelet aggregation by 15% and 11%, 

respectively. These results indicate that clopidogrel can be administered with pantoprazole. 

 

There is no evidence that other medicinal products that reduce stomach acid such as H2 blockers or 

antacids interfere with antiplatelet activity of clopidogrel. 

 

Boosted anti-retroviral therapy (ART): 

HIV patients treated with boosted anti-retroviral therapies (ART) are at high risk of vascular events. 



 

A significantly reduced platelet inhibition has been shown in HIV patients treated with ritonavir-or 

cobicistat-boosted ART. Although the clinical relevance of these findings is uncertain, there have been 

spontaneous reports of HIV-infected patients treated with ritonavir boosted ART, who have 

experienced re-occlusive events after de-obstruction or have suffered thrombotic events under a 

clopidogrel loading treatment schedule. Average platelet inhibition can be decreased with concomitant 

use of clopidogrel and ritonavir. Therefore, concomitant use of clopidogrel with ART boosted 

therapies should be discouraged. 

 

Other medicinal products: A number of other clinical studies have been conducted with clopidogrel 

and other concomitant medicinal products to investigate the potential for pharmacodynamic and 

pharmacokinetic interactions. No clinically significant pharmacodynamic interactions were observed 

when clopidogrel was co-administered with atenolol, nifedipine, or both atenolol and nifedipine. 

Furthermore, the pharmacodynamic activity of clopidogrel was not significantly influenced by the 

co-administration of phenobarbital, or oestrogen. 

 

The pharmacokinetics of digoxin or theophylline were not modified by the co-administration of 

clopidogrel. Antacids did not modify the extent of clopidogrel absorption. 

 

Data from the CAPRIE study indicate that phenytoin and tolbutamide which are metabolised by 

CYP2C9 can be safely co-administered with clopidogrel. 

 

CYP2C8 substrate medicinal products: Clopidogrel has been shown to increase repaglinide exposure 

in healthy volunteers. In vitro studies have shown the increase in repaglinide exposure is due to 

inhibition of CYP2C8 by the glucuronide metabolite of clopidogrel. Due to the risk of increased 

plasma concentrations, concomitant administration of clopidogrel and drugs primarily cleared by 

CYP2C8 metabolism (e.g., repaglinide, paclitaxel) should be undertaken with caution (see section 

4.4). 

 

Apart from the specific medicinal product interaction information described above, interaction studies 

with clopidogrel and some medicinal products commonly administered in patients with 

atherothrombotic disease have not been performed. However, patients entered into clinical trials with 

clopidogrel received a variety of concomitant medicinal products including diuretics, beta blockers, 

ACEI, calcium antagonists, cholesterol lowering agents, coronary vasodilators, antidiabetic agents 

(including insulin), antiepileptic agents, and GPIIb/IIIa antagonists without evidence of clinically 

significant adverse interactions. 

 

As with other oral P2Y12 inhibitors, co-administration of opioid agonists has the potential to delay 

and reduce the absorption of clopidogrel presumably because of slowed gastric emptying. The clinical 

relevance is unknown. Consider the use of a parenteral antiplatelet agent in acute coronary syndrome 

patients requiring co-administration of morphine or other opioid agonists 

 

4.6 Fertility, pregnancy and lactation 

 

Pregnancy 

As no clinical data on exposure to clopidogrel during pregnancy are available, it is preferable not to 

use clopidogrel during pregnancy as a precautionary measure.  

 

Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, 

embryonal/foetal development, parturition or postnatal development (see section 5.3). 

 

Breast-feeding 

It is unknown whether clopidogrel is excreted in human breast milk. Animal studies have shown 

excretion of clopidogrel in breast milk. As a precautionary measure, breast-feeding should not be 

continued during treatment with Clopidogrel Mylan. 



 

Fertility 

Clopidogrel was not shown to alter fertility in animal studies. 

 

4.7 Effects on ability to drive and use machines 

 

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

 

4.8 Undesirable effects 

 

Summary of the safety profile 

 

Clopidogrel has been evaluated for safety in more than 44,000 patients, who have participated in 

clinical studies, including over 12,000 patients treated for 1 year or more. Overall, clopidogrel 

75 mg/day was comparable to ASA 325 mg/day in CAPRIE regardless of age, gender and race. The 

clinically relevant adverse reactions observed in the CAPRIE, CURE, CLARITY, COMMIT and 

ACTIVE-A studies are discussed below. In addition to clinical studies experience, adverse reactions 

have been spontaneously reported. 

 

Bleeding is the most common reaction reported both in clinical studies as well as in post-marketing 

experience where it was mostly reported during the first month of treatment. 

 

In CAPRIE, in patients treated with either clopidogrel or ASA, the overall incidence of any bleeding 

was 9.3%. The incidence of severe cases was similar for clopidogrel and ASA.  

 

In CURE, there was no excess in major bleeds with clopidogrel plus ASA within 7 days after 

coronary bypass graft surgery in patients who stopped therapy more than five days prior to surgery. In 

patients who remained on therapy within five days of bypass graft surgery, the event rate was 9.6% 

for clopidogrel plus ASA, and 6.3% for placebo plus ASA. 

 

In CLARITY, there was an overall increase in bleeding in the clopidogrel plus ASA group vs. the 

placebo plus ASA group. The incidence of major bleeding was similar between groups. This was 

consistent across subgroups of patients defined by baseline characteristics, and type of fibrinolytic or 

heparin therapy.  

 

In COMMIT, the overall rate of noncerebral major bleeding or cerebral bleeding was low and similar 

in both groups.  

 

In ACTIVE A, the rate of major bleeding was greater in the clopidogrel + ASA group than in the 

placebo + ASA group (6.7% versus 4.3%). Major bleeding was mostly of extracranial origin in both 

groups (5.3% in the clopidogrel + ASA group; 3.5% in the placebo +ASA group), mainly from the 

gastrointestinal tract (3.5% vs. 1.8%). There was an excess of intracranial bleeding in the clopidogrel 

+ ASA treatment group compared to the placebo + ASA group (1.4% versus 0.8%, respectively). 

There was no statistically significant difference in the rates of fatal bleeding (1.1% in the clopidogrel 

+ ASA group and 0.7% in the placebo +ASA group) and haemorrhagic stroke (0.8% and 0.6%, 

respectively) between groups. 

 

Tabulated list of adverse reactions 

 

Adverse reactions that occurred either during clinical studies or that were spontaneously reported are 

presented in the table below. Their frequency is defined using the following conventions: 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), not known (cannot be estimated from the available data). Within each system organ 

class, adverse reactions are presented in order of decreasing seriousness. 



System Organ 

Class 

Common Uncommon Rare Very rare, not known* 

Blood and the 

lymphatic 

system disorders 

 Thrombocytopenia, 

leucopenia, 

eosinophilia 

Neutropenia, 

including 

severe 

neutropenia 

Thrombotic 

thrombocytopenic purpura 

(TTP) (see section 4.4), 

aplastic anaemia, 

pancytopenia, 

agranulocytosis, severe 

thrombocytopenia, acquired 

haemophilia A, 

granulocytopenia, anaemia 

Cardiac 

disorders 

   Kounis syndrome 

(vasospastic allergic angina / 

allergic myocardial 

infarction) in the context of a 

hypersensitivity reaction due 

to clopidogrel* 

Immune system 

disorders 

   Serum sickness, 

anaphylactoid reactions, 

cross-reactive drug 

hypersensitivity among 

thienopyridines (such as 

ticlopidine, prasugrel) (see 

section 4.4), insulin 

autoimmune syndrome, which 

can lead to severe 

hypoglycemia, particularly in 

patients with HLA DRA4 

subtype (more frequent in the 

Japanese population)* 

Psychiatric 

disorders 

   Hallucinations, confusion 

Nervous system 

disorders 

 Intracranial 

bleeding (some 

cases were 

reported with fatal 

outcome), 

headache, 

paraesthesia, 

dizziness 

 Taste disturbances, ageusia 

Eye disorders  Eye bleeding 

(conjunctival, 

ocular, retinal) 

  

Ear and labyrinth 

disorders 

  Vertigo  

Vascular 

disorders 

Haematoma   Serious haemorrhage, 

haemorrhage of operative 

wound, vasculitis, 

hypotension 

Respiratory, 

thoracic and 

mediastinal 

disorders 

Epistaxis   Respiratory tract bleeding 

(haemoptysis, pulmonary 

haemorrhage), bronchospasm, 

interstitial pneumonitis, 

eosinophilic pneumonia 



System Organ 

Class 

Common Uncommon Rare Very rare, not known* 

Gastrointestinal 

disorders 

Gastrointestinal 

haemorrhage, 

diarrhoea, 

abdominal pain, 

dyspepsia 

Gastric ulcer and 

duodenal ulcer, 

gastritis, vomiting, 

nausea, 

constipation, 

flatulence 

Retroperitoneal 

haemorrhage 

Gastrointestinal and 

retroperitoneal haemorrhage 

with fatal outcome, 

pancreatitis, colitis (including 

ulcerative or lymphocytic 

colitis), stomatitis 

Hepato-biliary 

disorders 

   Acute liver failure, hepatitis, 

abnormal liver function test 

Skin and 

subcutaneous 

tissue disorders 

Bruising Rash, pruritus, skin 

bleeding (purpura) 

 Bullous dermatitis (toxic 

epidermal necrolysis, Stevens 

Johnson Syndrome, erythema 

multiforme, acute generalised 

exanthematous pustulosis 

(AGEP)), angioedema, drug 

induced hypersensitivity 

syndrome, drug rash with 

eosinophilia and systemic 

symptoms (DRESS), rash 

erythematous or exfoliative, 

urticaria, eczema, lichen 

planus 

Reproductive 

system and 

breast disorders 

  Gynaecomastia  

Musculoskeletal, 

connective tissue 

and bone 

disorders 

   Musculoskeletal bleeding 

(haemarthrosis), arthritis, 

arthralgia, myalgia 

Renal and 

urinary disorders 

 Haematuria  Glomerulonephritis, blood 

creatinine increased 

General 

disorders and 

administration 

site conditions 

Bleeding at 

puncture site 

  Fever 

Investigations  Bleeding time 

prolonged, 

neutrophil count 

decreased, platelet 

count decreased 

  

* Information related to clopidogrel with frequency “not known”. 

 

Reporting of suspected adverse reactions  

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 

allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 

professionals are asked to report any suspected adverse reactions via the national reporting system 

listed in Appendix V. 

 

4.9 Overdose 

 

Overdose following clopidogrel administration may lead to prolonged bleeding time and subsequent 

bleeding complications. Appropriate therapy should be considered if bleedings are observed. No 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


antidote to the pharmacological activity of clopidogrel has been found. If prompt correction of 

prolonged bleeding time is required, platelet transfusion may reverse the effects of clopidogrel. 

 

 

5. PHARMACOLOGICAL PROPERTIES 

 

5.1  Pharmacodynamic properties 

 

Pharmacotherapeutic group: Antithrombotic agents, platelet aggregation inhibitors excl. heparin, ATC 

code: B01AC04.  

 

Mechanism of action 

 

Clopidogrel is a prodrug, one of whose metabolites is an inhibitor of platelet aggregation. Clopidogrel 

must be metabolised by CYP450 enzymes to produce the active metabolite that inhibits platelet 

aggregation. The active metabolite of clopidogrel selectively inhibits the binding of adenosine 

diphosphate (ADP) to its platelet P2Y12 receptor and the subsequent ADP-mediated activation of the 

glycoprotein GPIIb/IIIa complex, thereby inhibiting platelet aggregation. Due to the irreversible 

binding, platelets exposed are affected for the remainder of their lifespan (approximately 7-10 days) 

and recovery of normal platelet function occurs at a rate consistent with platelet turnover. Platelet 

aggregation induced by agonists other than ADP is also inhibited by blocking the amplification of 

platelet activation by released ADP. 

 

Because the active metabolite is formed by CYP450 enzymes, some of which are polymorphic or 

subject to inhibition by other medicinal products, not all patients will have adequate platelet inhibition. 

 

Pharmacodynamic effects 

 

Repeated doses of 75 mg per day produced substantial inhibition of ADP-induced platelet aggregation 

from the first day; this increased progressively and reached steady state between Day 3 and Day 7. At 

steady state, the average inhibition level observed with a dose of 75 mg per day was between 40% and 

60%. Platelet aggregation and bleeding time gradually returned to baseline values, generally within 

5 days after treatment was discontinued. 

 

Clinical efficacy and safety 

 

The safety and efficacy of clopidogrel have been evaluated in 5 double-blind studies involving over 

88,000 patients: the CAPRIE study, a comparison of clopidogrel to ASA, and the CURE, CLARITY, 

COMMIT and ACTIVE-A studies comparing clopidogrel to placebo, both medicinal products given 

in combination with ASA and other standard therapy.  

 

Recent myocardial infarction (MI), recent stroke or established peripheral arterial disease 

 

The CAPRIE study included 19,185 patients with atherothrombosis as manifested by recent 

myocardial infarction (<35 days), recent ischaemic stroke (between 7 days and 6 months) or 

established peripheral arterial disease (PAD). Patients were randomised to clopidogrel 75 mg/day or 

ASA 325 mg/day, and were followed for 1 to 3 years. In the myocardial infarction subgroup, most of 

the patients received ASA for the first few days following the acute myocardial infarction. 

 

Clopidogrel significantly reduced the incidence of new ischaemic events (combined end point of 

myocardial infarction, ischaemic stroke and vascular death) when compared to ASA. In the intention 

to treat analysis, 939 events were observed in the clopidogrel group and 1,020 events with ASA 

(relative risk reduction (RRR) 8.7%, [95% CI: 0.2 to 16.4]; p = 0.045), which corresponds, for every 

1,000 patients treated for 2 years, to 10 [CI: 0 to 20] additional patients being prevented from 



experiencing a new ischaemic event. Analysis of total mortality as a secondary endpoint did not show 

any significant difference between clopidogrel (5.8%) and ASA (6.0%). 

 

In a subgroup analysis by qualifying condition (myocardial infarction, ischaemic stroke, and PAD) the 

benefit appeared to be strongest (achieving statistical significance at p = 0.003) in patients enrolled 

due to PAD (especially those who also had a history of myocardial infarction) (RRR = 23.7%; CI: 8.9 

to 36.2) and weaker (not significantly different from ASA) in stroke patients (RRR = 7.3%; CI: -5.7 to 

18.7 [p=0.258]). In patients who were enrolled in the trial on the sole basis of a recent myocardial 

infarction, clopidogrel was numerically inferior, but not statistically different from ASA (RRR = -

4.0%; CI: -22.5 to 11.7 [p=0.639]). In addition, a subgroup analysis by age suggested that the benefit 

of clopidogrel in patients over 75 years was less than that observed in patients ≤75 years. 

 

Since the CAPRIE trial was not powered to evaluate efficacy of individual subgroups, it is not clear 

whether the differences in relative risk reduction across qualifying conditions are real, or a result of 

chance. 

 

Acute coronary syndrome 

 

The CURE study included 12,562 patients with non-ST segment elevation acute coronary syndrome 

(unstable angina or non-Q-wave myocardial infarction), and presenting within 24 hours of onset of the 

most recent episode of chest pain or symptoms consistent with ischaemia. Patients were required to 

have either ECG changes compatible with new ischaemia or elevated cardiac enzymes or troponin I or 

T to at least twice the upper limit of normal. Patients were randomised to clopidogrel (300 mg loading 

dose followed by 75 mg/day, N=6,259) or placebo (N=6,303), both given in combination with ASA 

(75-325 mg once daily) and other standard therapies. Patients were treated for up to one year. In 

CURE, 823 (6.6%) patients received concomitant GPIIb/IIIa receptor antagonist therapy. Heparins 

were administered in more than 90% of the patients and the relative rate of bleeding between 

clopidogrel and placebo was not significantly affected by the concomitant heparin therapy.  

 

The number of patients experiencing the primary endpoint [cardiovascular (CV) death, myocardial 

infarction (MI), or stroke] was 582 (9.3%) in the clopidogrel-treated group and 719 (11.4%) in the 

placebo-treated group, a 20% relative risk reduction (95% CI of 10%-28%; p=0.00009) for the 

clopidogrel-treated group (17% relative risk reduction when patients were treated conservatively, 29% 

when they underwent percutaneous transluminal coronary angioplasty (PTCA) with or without stent 

and 10% when they underwent coronary artery bypass graft (CABG)). New cardiovascular events 

(primary endpoint) were prevented, with relative risk reductions of 22% (CI: 8.6, 33.4), 32% (CI: 

12.8, 46.4), 4% (CI: -26.9, 26.7), 6% (CI: -33.5, 34.3) and 14% (CI: -31.6, 44.2), during the 0-1, 1-3, 

3-6, 6-9 and 9-12 month study intervals, respectively. Thus, beyond 3 months of treatment, the benefit 

observed in the clopidogrel + ASA group was not further increased, whereas the risk of haemorrhage 

persisted (see section 4.4).  

 

The use of clopidogrel in CURE was associated with a decrease in the need of thrombolytic therapy 

(RRR = 43.3%; CI: 24.3%, 57.5%) and GPIIb/IIIa inhibitors (RRR = 18.2%; CI: 6.5%, 28.3%). The 

number of patients experiencing the co-primary endpoint (CV death, MI, stroke or refractory 

ischaemia) was 1,035 (16.5%) in the clopidogrel-treated group and 1,187 (18.8%) in the 

placebo-treated group, a 14% relative risk reduction (95% CI of 6%-21%, p=0.0005) for the 

clopidogrel-treated group. This benefit was mostly driven by the statistically significant reduction in 

the incidence of MI [287 (4.6%) in the clopidogrel treated group and 363 (5.8%) in the placebo 

treated group]. There was no observed effect on the rate of rehospitalisation for unstable angina. 

 

The results obtained in populations with different characteristics (e.g. unstable angina or non-Q-wave 

MI, low to high risk levels, diabetes, need for revascularisation, age, gender, etc.) were consistent with 

the results of the primary analysis. In particular, in a post-hoc analysis in 2,172 patients (17% of the 



total CURE population) who underwent stent placement (Stent-CURE), the data showed that 

clopidogrel compared to placebo, demonstrated a significant RRR of 26.2% favouring clopidogrel for 

the co-primary endpoint (CV death, MI, stroke) and also a significant RRR of 23.9% for the second 

co-primary endpoint (CV death, MI, stroke or refractory ischaemia). Moreover, the safety profile of 

clopidogrel in this subgroup of patients did not raise any particular concern. Thus, the results from this 

subset are in line with the overall trial results.  

 

The benefits observed with clopidogrel were independent of other acute and long-term cardiovascular 

therapies (such as heparin/LMWH, GPIIb/IIIa antagonists, lipid lowering medicinal products, beta 

blockers, and ACE-inhibitors). The efficacy of clopidogrel was observed independently of the dose of 

ASA (75-325 mg once daily). 

 

In patients with acute ST-segment elevation MI, safety and efficacy of clopidogrel have been 

evaluated in 2 randomised, placebo-controlled, double-blind studies, CLARITY and COMMIT. 

 

The CLARITY trial included 3,491 patients presenting within 12 hours of the onset of a ST elevation 

MI and planned for thrombolytic therapy. Patients received clopidogrel (300 mg loading dose, 

followed by 75 mg/day, n=1,752) or placebo (n=1,739), both in combination with ASA (150 to 

325 mg as a loading dose, followed by 75 to 162 mg/day), a fibrinolytic agent and, when appropriate, 

heparin. The patients were followed for 30 days. The primary endpoint was the occurrence of the 

composite of an occluded infarct-related artery on the predischarge angiogram, or death or recurrent 

MI before coronary angiography. For patients who did not undergo angiography, the primary endpoint 

was death or recurrent myocardial infarction by Day 8 or by hospital discharge. The patient 

population included 19.7% women and 29.2% patients ≥ 65 years. A total of 99.7% of patients 

received fibrinolytics (fibrin specific: 68.7%, non-fibrin specific: 31.1%), 89.5% heparin, 78.7% beta 

blockers, 54.7% ACE inhibitors and 63% statins. 

 

Fifteen percent (15.0%) of patients in the clopidogrel group and 21.7% in the placebo group reached 

the primary endpoint, representing an absolute reduction of 6.7% and a 36 % odds reduction in favor 

of clopidogrel (95% CI: 24, 47%; p < 0.001), mainly related to a reduction in occluded infarct-related 

arteries. This benefit was consistent across all prespecified subgroups including patients’ age and 

gender, infarct location, and type of fibrinolytic or heparin used. 

 

The 2x2 factorial design COMMIT trial included 45,852 patients presenting within 24 hours of the 

onset of the symptoms of suspected MI with supporting ECG abnormalities (i.e. ST elevation, ST 

depression or left bundle-branch block). Patients received clopidogrel (75 mg/day, n=22,961) or 

placebo (n=22,891), in combination with ASA (162 mg/day), for 28 days or until hospital discharge. 

The co-primary endpoints were death from any cause and the first occurrence of re-infarction, stroke 

or death. The population included 27.8% women, 58.4% patients ≥ 60 years (26% ≥ 70 years) and 

54.5% patients who received fibrinolytics. 

 

Clopidogrel significantly reduced the relative risk of death from any cause by 7% (p=0.029), and the 

relative risk of the combination of re-infarction, stroke or death by 9% (p=0.002), representing an 

absolute reduction of 0.5% and 0.9%, respectively. This benefit was consistent across age, gender and 

with or without fibrinolytics, and was observed as early as 24 hours. 

 

De-escalation of P2Y12 Inhibitor Agents in ACS  

Switching from a more potent P2Y12 receptor inhibitor to clopidogrel in association with aspirin after 

acute phase in ACS has been evaluated in two randomized investigator-sponsored studies (ISS) – 

TOPIC and TROPICAL-ACS – with clinical outcome data. 

 

The clinical benefit provided by the more potent P2Y12 inhibitors, ticagrelor and prasugrel, in their 

pivotal studies is related to a significant reduction in recurrent ischaemic events (including acute and 

subacute stent thrombosis (ST), myocardial infarction (MI), and urgent revascularization). Although 

the ischaemic benefit was consistent throughout the first year, greater reduction in ischaemic 



recurrence after ACS was observed during the initial days following the treatment initiation.  In 

contrast, post-hoc analyses demonstrated statistically significant increases in the bleeding risk with the 

more potent P2Y12 inhibitors, occurring predominantly during the maintenance phase, after the first 

month post-ACS. TOPIC and TROPICAL-ACS were designed to study how to mitigate the bleeding 

events while maintaining efficacy. 

 

TOPIC (Timing Of Platelet Inhibition after acute Coronary syndrome) 

This randomized, open-label trial included ACS patients requiring PCI. Patients on aspirin and a more 

potent P2Y12 blocker and without adverse event at one month were assigned to switch to fixed-dose 

aspirin plus clopidogrel (de-escalated dual antiplatelet therapy (DAPT)) or continuation of their drug 

regimen (unchanged DAPT).   

 

Overall, 645 of 646 patients with STEMI or NSTEMI or unstable angina were analyzed (de-escalated 

DAPT (n=322); unchanged DAPT (n=323)). Follow-up at one year was performed for 316 patients 

(98.1%) in the de-escalated DAPT group and 318 patients (98.5%) in the unchanged DAPT group. 

The median follow-up for both groups was 359 days. The characteristics of the studied cohort were 

similar in the 2 groups. 

 

The primary outcome, a composite of cardiovascular death, stroke, urgent revascularization, and 

BARC (Bleeding Academic Research Consortium) bleeding ≥2 at 1 year post ACS, occurred in 

43 patients (13.4%) in the de-escalated DAPT group and in 85 patients (26.3%) in the unchanged 

DAPT group (p<0.01). This statistically significant difference was mainly driven by fewer bleeding 

events, with no difference reported in ischaemic endpoints (p=0.36), while BARC ≥2 bleeding 

occurred less frequently in the de-escalated DAPT group (4.0%) versus 14.9%  in the unchanged 

DAPT group (p<0.01). Bleeding events defined as all BARC occurred in 30 patients (9.3%) in the 

de-escalated DAPT group and in 76 patients (23.5%) in the unchanged DAPT group (p<0.01). 

 

TROPICAL-ACS (Testing Responsiveness to Platelet Inhibition on Chronic Antiplatelet Treatment 

for Acute Coronary Syndromes) 

This randomized, open-label trial included 2,610 biomarker-positive ACS patients after successful 

PCI. Patients were randomized to receive either prasugrel 5 or 10 mg/d (Days 0-14) (n=1306), or 

prasugrel 5 or 10 mg/d (Days 0-7) then de-escalated to clopidogrel 75 mg/d (Days 8-14) (n=1304), in 

combination with ASA (<100 mg/day).  At Day 14, platelet function testing (PFT) was performed. 

The prasugrel-only patients were continued on prasugrel for 11.5 months.   

 

The de-escalated patients underwent high platelet reactivity (HPR) testing.  If HPR≥46 units, the 

patients were escalated back to prasugrel 5 or 10 mg/d for 11.5 months; if HPR<46 units, the patients 

continued on clopidogrel 75 mg/d for 11.5 months.  Therefore, the guided de-escalation arm had 

patients on either prasugrel (40%) or clopidogrel (60%). All patients were continued on aspirin and 

were followed for one year.  

 

The primary endpoint (the combined incidence of CV death, MI, stroke and BARC bleeding grade ≥2 

at 12 months) was met showing non-inferiority. Ninety five patients (7%) in the guided de-escalation 

group and 118 patients (9%) in the control group (p non-inferiority=0.0004) had an event. The guided 

de-escalation did not result in an increased combined risk of ischemic events (2.5% in the de-

escalation group vs 3.2% in the control group; p non-inferiority=0.0115), nor in the key secondary 

endpoint of BARC bleeding ≥2 ((5%) in the de-escalation group versus 6% in the control group 

(p=0.23)). The cumulative incidence of all bleeding events (BARC class 1 to 5) was 9% (114 events) 

in the guided de-escalation group versus 11% (137 events) in the control group (p=0.14). 

 

Atrial fibrillation 

 

The ACTIVE-W and ACTIVE-A studies, separate trials in the ACTIVE program, included patients 

with atrial fibrillation (AF) who had at least one risk factor for vascular events. Based on enrollment 

criteria, physicians enrolled patients in ACTIVE-W if they were candidates for vitamin K antagonist 



(VKA) therapy (such as warfarin). The ACTIVE-A study included patients who could not receive 

VKA therapy because they were unable or unwilling to receive the treatment. 

 

The ACTIVE-W study demonstrated that anticoagulant treatment with vitamin K antagonists was 

more effective than with clopidogrel and ASA. 

 

The ACTIVE-A study (N=7,554) was a multicenter, randomized, double-blind, placebo-controlled 

study which compared clopidogrel 75 mg/day + ASA (N=3,772) to placebo + ASA (N=3,782). The 

recommended dose for ASA was 75 to 100 mg/day. Patients were treated for up to 5 years. 

 

Patients randomized in the ACTIVE program were those presenting with documented AF, i.e., either 

permanent AF or at least 2 episodes of intermittent AF in the past 6 months, and had at least one of 

the following risk factors: age 75 years or age 55 to 74 years and either diabetes mellitus requiring 

drug therapy, or documented previous MI or documented coronary artery disease; treated for systemic 

hypertension; prior stroke, transient ischaemic attack (TIA), or non-CNS systemic embolus; left 

ventricular dysfunction with left ventricular ejection fraction <45%; or documented peripheral 

vascular disease. The mean CHADS2 score was 2.0 (range 0-6). 

 

The major exclusion criteria for patients were documented peptic ulcer disease within the previous 

6 months; prior intracerebral hemorrhage; significant thrombocytopenia (platelet count < 50 x 109/l); 

requirement for clopidogrel or oral anticoagulants (OAC); or intolerance to any of the two 

compounds. 

 

Seventy-three percent (73%) of patients enrolled into the ACTIVE-A study were unable to take VKA 

due to physician assessment, inability to comply with INR (international normalised ratio) 

monitoring, predisposition to falling or head trauma, or specific risk of bleeding; for 26% of the 

patients, the physician’s decision was based on the patient’s unwillingness to take VKA.  

 

The patient population included 41.8 % women. The mean age was 71 years, 41.6% of patients were 

≥75 years. A total of 23.0% of patients received anti-arrhythmics, 52.1% beta-blockers, 54.6% ACE 

inhibitors, and 25.4% statins. 

 

The number of patients who reached the primary endpoint (time to first occurrence of stroke, MI, 

non-CNS systemic embolism or vascular death) was 832 (22.1%) in the group treated with 

clopidogrel + ASA and 924 (24.4%) in the placebo + ASA group (relative risk reduction of 11.1%; 

95% CI of 2.4% to 19.1%; p=0.013), primarily due to a large reduction in the incidence of strokes. 

Strokes occurred in 296 (7.8%) patients receiving clopidogrel + ASA and 408 (10.8%) patients 

receiving placebo + ASA (relative risk reduction, 28.4%; 95% CI, 16.8% to 38.3%; p=0.00001).  

 

Paediatric population 

 

In a dose escalation study of 86 neonates or infants up to 24 months of age at risk for thrombosis 

(PICOLO), clopidogrel was evaluated at consecutive doses of 0.01, 0.1 and 0.2 mg/kg in neonates and 

infants and 0.15 mg/kg only in neonates. The dose of 0.2 mg/kg achieved the mean percent inhibition 

of 49.3% (5 µM ADP-induced platelet aggregation) which was comparable to that of adults taking 

clopidogrel 75 mg/day. 

 

In a randomised, double-blind, parallel-group study (CLARINET), 906 paediatric patients (neonates 

and infants) with cyanotic congenital heart disease palliated with a systemic-to-pulmonary arterial 

shunt were randomised to receive clopidogrel 0.2 mg/kg (n=467) or placebo (n=439) along with 

concomitant background therapy up to the time of second stage surgery. The mean time between shunt 

palliation and first administration of study medicinal product was 20 days. Approximately 88% of 

patients received concomitant ASA (range of 1 to 23 mg/kg/day). There was no significant difference 

between groups in the primary composite endpoint of death, shunt thrombosis or cardiac-related 

intervention prior to 120 days of age following an event considered of thrombotic nature (89 [19.1%] 



for the clopidogrel group and 90 [20.5%] for the placebo group) (see section 4.2). Bleeding was the 

most frequently reported adverse reaction in both clopidogrel and placebo groups; however, there was 

no significant difference in the bleeding rate between groups. In the long-term safety follow-up of this 

study, 26 patients with the shunt still in place at one year of age received clopidogrel up to 18 months 

of age. No new safety concerns were noted during this long-term follow-up. 

 

The CLARINET and the PICOLO trials were conducted using a constituted solution of clopidogrel. In 

a relative bioavailability study in adults, the constituted solution of clopidogrel showed a similar 

extent and slightly higher rate of absorption of the main circulating (inactive) metabolite compared to 

the authorised tablet. 

 

5.2 Pharmacokinetic properties 

 

Absorption 

After single and repeated oral doses of 75 mg per day, clopidogrel is rapidly absorbed. Mean peak 

plasma levels of unchanged clopidogrel (approximately 2.2-2.5 ng/ml after a single 75 mg oral dose) 

occurred approximately 45 minutes after dosing. Absorption is at least 50%, based on 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). The binding is non-saturable in vitro over a wide concentration 

range.  

 

Biotransformation 

Clopidogrel is extensively metabolised by the liver. In vitro and in vivo, clopidogrel is metabolised 

according to two main metabolic pathways: one mediated by esterases and leading to hydrolysis into 

its inactive carboxylic acid derivative (85% of circulating metabolites), and one mediated by multiple 

cytochromes P450. Clopidogrel is first metabolised to a 2-oxo-clopidogrel intermediate metabolite. 

Subsequent metabolism of the 2-oxo-clopidogrel intermediate metabolite results in formation of the 

active metabolite, a thiol derivative of clopidogrel. The active metabolite is formed mostly by 

CYP2C19 with contributions from several other CYP enzymes, including CYP1A2, CYP2B6 and 

CYP3A4. The active thiol metabolite which has been isolated in vitro, binds rapidly and irreversibly 

to platelet receptors, thus inhibiting platelet aggregation. 

 

The Cmax of the active metabolite is twice as high following a single 300 mg clopidogrel loading dose 

as it is after four days of 75 mg maintenance dose. Cmax occurs approximately 30 to 60 minutes after 

dosing.  

 

Elimination 

Following an oral dose of 14C-labelled clopidogrel in man, approximately 50% was excreted in the 

urine and approximately 46% in the faeces in the 120-hour interval after dosing. After a single oral 

dose of 75 mg, clopidogrel has a half-life of approximately 6 hours. The elimination half-life of the 

main circulating (inactive) metabolite was 8 hours after single and repeated administration. 

 

Pharmacogenetics 

CYP2C19 is involved in the formation of both the active metabolite and the 2-oxo-clopidogrel 

intermediate metabolite. Clopidogrel active metabolite pharmacokinetics and antiplatelet effects, as 

measured by ex vivo platelet aggregation assays, differ according to CYP2C19 genotype.  

 

The CYP2C19*1 allele corresponds to fully functional metabolism while the CYP2C19*2 and 

CYP2C19*3 alleles are nonfunctional. The CYP2C19*2 and CYP2C19*3 alleles account for the 

majority of reduced function alleles in Caucasian (85%) and Asian (99%) poor metabolisers. Other 

alleles associated with absent or reduced metabolism are less frequent and include CYP2C19*4, *5, 

*6, *7, and *8. A patient with poor metaboliser status will possess two loss-of-function alleles as 



defined above. Published frequencies for the poor CYP2C19 metaboliser genotypes are approximately 

2% for Caucasians, 4% for Blacks and 14% for Chinese. Tests are available to determine a patient’s 

CYP2C19 genotype.  

 

A crossover study in 40 healthy subjects, 10 each in the four CYP2C19 metaboliser groups (ultrarapid, 

extensive, intermediate and poor), evaluated pharmacokinetic and antiplatelet responses using 300 mg 

followed by 75 mg/day and 600 mg followed by 150 mg/day, each for a total of 5 days (steady state). 

No substantial differences in active metabolite exposure and mean inhibition of platelet aggregation 

(IPA) were observed between ultrarapid, extensive and intermediate metabolisers. In poor 

metabolisers, active metabolite exposure was decreased by 63-71% compared to extensive 

metabolisers. After the 300 mg/75 mg dose regimen, antiplatelet responses were decreased in the poor 

metabolisers with mean IPA (5 μM ADP) of 24% (24 hours) and 37% (Day 5) as compared to IPA of 

39% (24 hours) and 58% (Day 5) in the extensive metabolisers and 37% (24 hours) and 60% (Day 5) 

in the intermediate metabolisers. When poor metabolisers received the 600 mg/150 mg regimen, 

active metabolite exposure was greater than with the 300 mg/75 mg regimen. In addition, IPA was 

32% (24 hours) and 61% (Day 5), which were greater than in the poor metabolisers receiving the 

300 mg/75 mg regimen, and were similar to the other CYP2C19 metaboliser groups receiving the 

300 mg/75 mg regimen. An appropriate dose regimen for this patient population has not been 

established in clinical outcome trials. 

 

Consistent with the above results, in a meta-analysis including 6 studies of 335 clopidogrel-treated 

subjects at steady state, it was shown that active metabolite exposure was decreased by 28% for 

intermediate metabolisers, and 72% for poor metabolisers while platelet aggregation inhibition (5 μM 

ADP) was decreased with differences in IPA of 5.9% and 21.4%, respectively, when compared to 

extensive metabolisers. 

 

The influence of CYP2C19 genotype on clinical outcomes in patients treated with clopidogrel has not 

been evaluated in prospective, randomised, controlled trials. There have been a number of 

retrospective analyses, however, to evaluate this effect in patients treated with clopidogrel for whom 

there are genotyping results: CURE (n=2721), CHARISMA (n=2428), CLARITY-TIMI 28 (n=227), 

TRITON-TIMI 38 (n=1477), and ACTIVE-A (n=601), as well as a number of published cohort 

studies. 

 

In TRITON-TIMI 38 and 3 of the cohort studies (Collet, Sibbing, Giusti) the combined group of 

patients with either intermediate or poor metaboliser status had a higher rate of cardiovascular events 

(death, myocardial infarction, and stroke) or stent thrombosis compared to extensive metabolisers. 

 

In CHARISMA and one cohort study (Simon), an increased event rate was observed only in poor 

metabolisers when compared to extensive metabolisers. 

 

In CURE, CLARITY, ACTIVE-A and one of the cohort studies (Trenk), no increased event rate was 

observed based on metaboliser status. 

 

None of these analyses were adequately sized to detect differences in outcome in poor metabolisers. 

 

Special populations 

 

The pharmacokinetics of the active metabolite of clopidogrel is not known in these special 

populations. 

 

Renal impairment 

After repeated doses of 75 mg clopidogrel per day in subjects with severe renal disease (creatinine 

clearance from 5 to 15 ml/min) inhibition of ADP-induced platelet aggregation was lower (25%) than 

that observed in healthy subjects, however, the prolongation of bleeding time was similar to that seen 



in healthy subjects receiving 75 mg of clopidogrel per day. In addition, clinical tolerance was good in 

all patients. 

 

Hepatic impairment 

After repeated doses of 75 mg clopidogrel per day for 10 days in patients with severe hepatic 

impairment, inhibition of ADP-induced platelet aggregation was similar to that observed in healthy 

subjects. The mean bleeding time prolongation was also similar in the two groups.  

 

Race 

The prevalence of CYP2C19 alleles that result in intermediate and poor CYP2C19 metabolism differs 

according to race/ethnicity (see Pharmacogenetics). From literature, limited data in Asian populations 

are available to assess the clinical implication of genotyping of this CYP on clinical outcome events. 

 

5.3 Preclinical safety data 

 

During non clinical studies in rat and baboon, the most frequently observed effects were liver 

changes. These occurred at doses representing at least 25 times the exposure seen in humans receiving 

the clinical dose of 75 mg/day and were a consequence of an effect on hepatic metabolising enzymes. 

No effect on hepatic metabolising enzymes was observed in humans receiving clopidogrel at the 

therapeutic dose. 

 

At very high doses, a poor gastric tolerability (gastritis, gastric erosions and/or vomiting) of 

clopidogrel was also reported in rat and baboon.  

 

There was no evidence of carcinogenic effect when clopidogrel was administered for 78 weeks to 

mice and 104 weeks to rats when given at doses up to 77 mg/kg per day (representing at least 25 times 

the exposure seen in humans receiving the clinical dose of 75 mg/day). 

 

Clopidogrel has been tested in a range of in vitro and in vivo genotoxicity studies, and showed no 

genotoxic activity.  

 

Clopidogrel was found to have no effect on the fertility of male and female rats and was not 

teratogenic in either rats or rabbits. When given to lactating rats, clopidogrel caused a slight delay in 

the development of the offspring. Specific pharmacokinetic studies performed with radiolabelled 

clopidogrel have shown that the parent compound or its metabolites are excreted in the milk. 

Consequently, a direct effect (slight toxicity), or an indirect effect (low palatability) cannot be 

excluded. 

 

 

6. PHARMACEUTICAL PARTICULARS 

 

6.1 List of excipients 

 

Tablet core: 

Cellulose, microcrystalline 

Colloidal anhydrous silica 

Crospovidone (type A) 

Macrogol 6000 

Hydrogenated castor oil 

 

Film coating: 

Polyvinyl alcohol 

Titanium dioxide (E171) 

Red iron oxide (E172) 

Yellow iron oxide (E172) 



Talc 

Macrogol 3000 (Polyethyleneglycol) 

 

6.2 Incompatibilities 

 

Not applicable. 

 

6.3 Shelf life 

 

3 years. 

 

6.4 Special precautions for storage 

 

Store in the original package in order to protect from moisture and light. 

 

6.5 Nature and contents of container 

 

Blister of OPA/Al/PVC-Al containing 7, 14, 28, 30, 50, 56, 84, 90 and 100 film-coated tablets in the 

box. 

Calendar Blister of OPA/Al/PVC-Al containing 7, 14, 28, 56, 84 film-coated tablets in the box. 

Perforated unit dose blister of OPA/Al/PVC-Al containing 30x1 and 50x1 film-coated tablets in the 

box. 

 

Not all pack sizes may be marketed. 

 

6.6 Special precautions for disposal  

 

No special requirements. 

 

 

7. MARKETING AUTHORISATION HOLDER 

 

Mylan S.A.S, 117 allée des Parcs, 69 800 Saint Priest, France 

 

 

8. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/09/559/001-016 

 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 

 

Date of first authorisation: 21 September 2009 

 

Date of latest renewal: 22 May 2014 

 

 

10. DATE OF REVISION OF THE TEXT 

 

Detailed information on this medicinal product is available on the website of the European Medicines 

Agency http://www.ema.europa.eu/ 

 

  



 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX II 

 

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH 

RELEASE 

 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 

AND USE 

 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE 

MARKETING AUTHORISATION 

 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO 

THE SAFE AND EFFECTIVE USE OF THE MEDICINAL 

PRODUCT 

 



A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 

 

Name and address of the manufacturer(s) responsible for batch release 

 

KRKA, d.d., Novo mesto 

Šmarješka cesta 6 

8501 Novo mesto 

Slovenia 

 

TAD Pharma GmbH 

Heinz-Lohmann-Straße 5 

27472 Cuxhaven 

Germany 

 

The printed package leaflet of the medicinal product must state the name and address of the 

manufacturer responsible for the release of the concerned batch. 

 

 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 

 

 

Medicinal product subject to medical prescription. 

 

 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 

 

• Periodic Safety Update Reports 

 

The marketing authorisation holder shall submit periodic safety update reports for this product in 

accordance with the requirements set out in the list of Union reference dates (EURD list) ) provided 

for under Article 107c(7) of Directive 2001/83/EC and published on the European medicines web-

portal. 

 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 

 

• Risk Management Plan (RMP) 

 

Not applicable 

 

  



 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX III 

 

LABELLING AND PACKAGE LEAFLET 

  



 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

A. LABELLING 

  



PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

OUTER CARTON 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Clopidogrel Mylan 75 mg film-coated tablets 

 

clopidogrel 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each film-coated tablet contains 75 mg of clopidogrel (as hydrochloride). 

 

 

3. LIST OF EXCIPIENTS 

 

It also contains hydrogenated castor oil. 

See leaflet for further information. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

7 film-coated tablets 

14 film-coated tablets 

28 film-coated tablets 

30 film-coated tablets 

30x1 film-coated tablets 

50 film-coated tablets 

50x1 film-coated tablets 

56 film-coated tablets 

84 film-coated tablets 

90 film-coated tablets 

100 film-coated tablets 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Oral use 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 



 

8. EXPIRY DATE 

 

EXP 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Store in the original package in order to protect from moisture and light. 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Mylan S.A.S, 117 allée des Parcs, 69 800 Saint Priest, France 

 

 

12. MARKETING AUTHORISATION NUMBER(S)  

 

7 film-coated tablets: EU/1/09/559/001 

14 film-coated tablets: EU/1/09/559/002 

28 film-coated tablets: EU/1/09/559/003 

30 film-coated tablets: EU/1/09/559/004 

50 film-coated tablets: EU/1/09/559/005 

56 film-coated tablets: EU/1/09/559/006 

84 film-coated tablets: EU/1/09/559/007 

90 film-coated tablets: EU/1/09/559/008 

100 film-coated tablets: EU/1/09/559/009 

30x1 film-coated tablets EU/1/09/559/010 

50x1 film-coated tablets EU/1/09/559/011 

7 film-coated tablets - calendar blister: EU/1/09/559/012 

14 film-coated tablets - calendar blister: EU/1/09/559/013 

28 film-coated tablets - calendar blister: EU/1/09/559/014 

56 film-coated tablets - calendar blister: EU/1/09/559/015 

84 film-coated tablets - calendar blister: EU/1/09/559/016 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 



 

16. INFORMATION IN BRAILLE 

 

Clopidogrel Mylan 75 mg  

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC:  

SN:  

NN:



27 

 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

BLISTER (Boxes of 7, 14, 28, 30, 30x1, 50, 50x1, 56, 84, 90 and 100) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Clopidogrel Mylan 75 mg film-coated tablets 

 

clopidogrel 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Mylan S.A.S 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. OTHER 

 



28 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

CALENDAR BLISTER (boxes of 7, 14, 28, 56 or 84 tablets) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Clopidogrel Mylan 75 mg film-coated tablets 

 

clopidogrel 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Mylan S.A.S 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. OTHER 

 

Mon 

Tue 

Wed 

Thu 

Fri 

Sat 

Sun 

 

Week 1 

Week 2 (for boxes of 14, 28, 56, 84) 

Week 3 (for boxes of 28, 56, 84) 

Week 4 (for boxes of 28, 56, 84) 

  



 

29 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

B. PACKAGE LEAFLET 

 



 

30 

Package leaflet: Information for the user 

 

Clopidogrel Mylan 75 mg film-coated tablets 

clopidogrel 

 

Read all of this leaflet carefully before you start taking this medicine because it contains 

 important information for you. 

- Keep this leaflet. You may need to read it again. 

- If you have any further questions, ask your doctor or pharmacist. 

- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours. 

- If you get any side effects, talk to your doctor or pharmacist. This includes any possible side 

effects not listed in this leaflet. See section 4. 

 

 

What is in this leaflet:  

1. What Clopidogrel Mylan is and what it is used for 

2. What you need to know before you take Clopidogrel Mylan  

3. How to take Clopidogrel Mylan  

4. Possible side effects 

5. How to store Clopidogrel Mylan  

6. Contents of the pack and other information 

 

 

1. What Clopidogrel Mylan is and what it is used for 

 

Clopidogrel Mylan contains clopidogrel and belongs to a group of medicines called antiplatelet 

medicinal products. Platelets are very small structures in the blood, which clump together during blood 

clotting. By preventing this clumping, antiplatelet medicinal products reduce the chances of blood 

clots forming (a process called thrombosis). 

 

Clopidogrel Mylan is taken by adults to prevent blood clots (thrombi) forming in hardened blood 

vessels (arteries), a process known as atherothrombosis, which can lead to atherothrombotic events 

(such as stroke, heart attack, or death). 

 

You have been prescribed Clopidogrel Mylan to help prevent blood clots and reduce the risk of these 

severe events because: 

- You have a condition of hardening of arteries (also known as atherosclerosis), and 

- You have previously experienced a heart attack, stroke or have a condition known as peripheral 

arterial disease, or 

- You have experienced a severe type of chest pain known as ‘unstable angina’ or ‘myocardial 

infarction’ (heart attack). For the treatment of this condition your doctor may have placed a stent 

in the blocked or narrowed artery to restore effective blood flow. You should also be given 

acetylsalicylic acid (a substance present in many medicines used to relieve pain and lower fever 

as well as to prevent blood clotting) by your doctor. 

- You have an irregular heartbeat, a condition called ‘atrial fibrillation’, and you cannot take 

medicines known as ‘oral anticoagulants’ (vitamin K antagonists) which prevent new clots from 

forming and prevent existing clots from growing. You should have been told that ‘oral 

anticoagulants’ are more effective than acetylsalicylic acid or the combined use of Clopidogrel 

Mylan and acetylsalicylic acid for this condition. Your doctor should have prescribed 

Clopidogrel Mylan plus acetylsalicylic acid if you cannot take ‘oral anticoagulants’ and you do 

not have a risk of major bleeding. 

 

2. What you need to know before you take Clopidogrel Mylan  

 

Do not take Clopidogrel Mylan  



 

31 

• if you are allergic to clopidogrel or any of the other ingredients of this medicine (listed in 

section 6); 

• if you have a medical condition that is currently causing bleeding such as a stomach ulcer or 

bleeding within the brain; 

• if you suffer from severe liver disease; 

 

If you think any of these apply to you, or if you are in any doubt at all, consult your doctor before 

taking Clopidogrel Mylan. 

 

Warnings and precautions  

Talk to your doctor before taking Clopidogrel Mylan if any of the situations mentioned below apply to 

you: 

• if you have a risk of bleeding such as 

- a medical condition that puts you at risk of internal bleeding (such as a stomach ulcer) 

- a blood disorder that makes you prone to internal bleeding (bleeding inside any tissues, 

organs or joints of your body). 

- a recent serious injury 

- a recent surgery (including dental). 

- a planned surgery (including dental) in the next seven days. 

• if you have had a clot in an artery of your brain (ischaemic stroke) which occurred within the 

last seven days. 

• if you have kidney or liver disease. 

• if you have had an allergy or reaction to any medicine used to treat your disease. 

 

 

While you are taking Clopidogrel Mylan: 

• You should tell your doctor if a surgery (including dental) is planned. 

• You should also tell your doctor immediately if you develop a medical condition (also known as 

Thrombotic Thrombocytopenic Purpura or TTP) that includes fever and bruising under the skin 

that may appear as red pinpoint dots, with or without unexplained extreme tiredness, confusion, 

yellowing of the skin or eyes (jaundice) (see section 4 ‘Possible side effects’). 

• If you cut or injure yourself, it may take longer than usual for bleeding to stop. This is linked to 

the way your medicine works as it prevents the ability of blood clots to form. For minor cuts 

and injuries e.g., cutting yourself, shaving, this is usually of no concern. However, if you are 

concerned by your bleeding, you should contact your doctor straightaway (see section 4 

‘Possible side effects’). 

• Your doctor may order blood tests. 

 

Children and adolescents 

Do not give this medicine to children because it does not work. 

 

Other medicines and Clopidogrel Mylan 

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 

medicines, including medicines obtained without a prescription. 

Some other medicines may influence the use of Clopidogrel Mylan or vice versa. 

 

You should specifically tell your doctor if you take  

- medicines that may increase your risk of bleeding such as: 

o oral anticoagulants, medicines used to reduce blood clotting, 

o a non-steroidal anti-inflammatory medicine, usually used to treat painful and/or inflammatory 

conditions of muscle or joints,  

o heparin, or any other injectable medicine used to reduce blood clotting, 

o ticlopidine, other antiplatelet agent, 

o a selective serotonin reuptake inhibitor (including but not restricted to fluoxetine or 

fluvoxamine), medicines usually used to treat depression,  

o rifampicin (used to treat severe infections) 



 

32 

- omeprazole or esomeprazole, medicines to treat upset stomach, 

- fluconazole or voriconazole, medicines to treat fungal infections, 

- efavirenz, or other anti-retroviral medicines (used to treat HIV infections), 
- carbamazepine, a medicine to treat some forms of epilepsy, 

- moclobemide, medicine to treat depression, 

- repaglinide, medicine to treat diabetes, 

- paclitaxel, medicine to treat cancer, 

- opioids: while you are treated with clopidogrel, you should inform your doctor before being 

prescribed any opioid (used to treat severe pain). 

 

If you have experienced severe chest pain (unstable angina or heart attack), you may be prescribed 

Clopidogrel Mylan in combination with acetylsalicylic acid, a substance present in many medicines 

used to relieve pain and lower fever. An occasional use of acetylsalicylic acid (no more than 1,000 mg 

in any 24 hour period) should generally not cause a problem, but prolonged use in other circumstances 

should be discussed with your doctor. 

 

Pregnancy and breast-feeding 

It is preferable not to take this medicine during pregnancy. 

 

If you are pregnant or suspect that you are pregnant, you should tell your doctor or your pharmacist 

before taking Clopidogrel Mylan. If you become pregnant while taking Clopidogrel Mylan, consult 

your doctor immediately as it is recommended not to take clopidogrel while you are pregnant. 

 

You should not breast-feed while taking this medicine. 

If you are breast-feeding or planning to breast-feed, talk to your doctor before taking this medicine. 

 

Ask your doctor or pharmacist for advice before taking any medicine. 

 

Driving and using machines 

Clopidogrel Mylan is unlikely to affect your ability to drive or to use machines. 

 

Clopidogrel Mylan contains hydrogenated castor oil 

This may cause stomach upset or diarrhoea. 

 

 

3. How to take Clopidogrel Mylan  

 

Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor 

or pharmacist if you are not sure. 

 

The recommended dose, including for patients with a condition called ‘atrial fibrillation’ (an irregular 

heartbeat), is one 75 mg tablet of Clopidogrel Mylan per day to be taken orally with or without food, 

and at the same time each day. 

 

If you have experienced severe chest pain (unstable angina or heart attack), your doctor may give you 

300 mg of Clopidogrel Mylan (4 tablets of 75 mg) once at the start of treatment. Then, the 

recommended dose is one 75 mg tablet of Clopidogrel Mylan per day as described above. 

 

You should take Clopidogrel Mylan for as long as your doctor continues to prescribe it. 

 

If you take more Clopidogrel Mylan than you should 

Contact your doctor or the nearest hospital emergency department because of the increased risk of 

bleeding. 

 

If you forget to take Clopidogrel Mylan  

If you forget to take a dose of Clopidogrel Mylan, but remember within 12 hours of your usual time, 

take your tablet straightaway and then take your next tablet at the usual time. 



 

33 

 

If you forget for more than 12 hours, simply take the next single dose at the usual time. Do not take a 

double dose to make up for a forgotten tablet. 

 

For the 7, 14, 28, 56, 84 tablets (calendar blister) pack sizes, you can check the day on which you last 

took a tablet of Clopidogrel Mylan by referring to the calendar printed on the blister 

 

If you stop taking Clopidogrel Mylan  

Do not stop the treatment unless your doctor tells you so. Contact your doctor or pharmacist before 

stopping. 

 

If you have any further questions on the use of this medicine, ask your doctor or pharmacist. 

 

 

4. Possible side effects 

 

Like all medicines, this medicine can cause side effects, although not everybody gets them. 

 

Contact your doctor immediately if you experience: 

- fever, signs of infection or extreme tiredness. These may be due to rare decrease of some blood 

cells. 

- signs of liver problems such as yellowing of the skin and/or the eyes (jaundice), whether or not 

associated with bleeding which appears under the skin as red pinpoint dots and/or confusion 

(see section 2 ‘Warnings and precautions’). 

- swelling in the mouth or skin disorders such as rashes and itching, blisters of the skin. These 

may be the signs of an allergic reaction. 

 

The most common side effect reported with Clopidogrel Mylan is bleeding. 

Bleeding may occur as bleeding in the stomach or bowels, bruising, haematoma (unusual bleeding or 

bruising under the skin), nose bleed, blood in the urine. In a small number of cases, bleeding in the 

eye, inside the head, the lung or the joints has also been reported. 

 

If you experience prolonged bleeding when taking Clopidogrel Mylan 

If you cut or injure yourself, it may take longer than usual for bleeding to stop. This is linked to the 

way your medicine works as it prevents the ability of blood clots to form. For minor cuts and injuries 

e.g., cutting yourself, shaving, this is usually of no concern. However, if you are concerned by your 

bleeding, you should contact your doctor straightaway (see section 2 ‘Warnings and precautions’). 

 

Other side effects include: 

 

Common side effects (may affect up to 1 in 10 people): 

Diarrhoea, abdominal pain, indigestion or heartburn. 

 

Uncommon side effects (may affect up to 1 in 100 people): 

Headache, stomach ulcer, vomiting, nausea, constipation, excessive gas in stomach or intestines, 

rashes, itching, dizziness, sensation of tingling and numbness. 

 

Rare side effect (may affect up to 1 in 1000 people): 

Vertigo, enlarged breasts in males.  

 

Very rare side effects (may affect up to 1 in 10,000 people): 

Jaundice; severe abdominal pain with or without back pain; fever, breathing difficulties sometimes 

associated with cough; generalised allergic reactions (for example, overall sensation of heat with 

sudden general discomfort until fainting); swelling in the mouth; blisters of the skin; skin allergy; sore 

mouth (stomatitis); decrease in blood pressure; confusion; hallucinations; joint pain; muscular pain; 

changes in taste or loss of taste of food. 

 



 

34 

Side effects with frequency not known (frequency cannot be estimated from the available data): 

Hypersensitivity reactions with chest or abdominal pain, persistent low blood sugar symptoms. 

 

In addition, your doctor may identify changes in your blood or urine test results. 

 

Reporting of side effects 

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects 

not listed in this leaflet. You can also report side effects directly via the national reporting system 

listed in Appendix V. By reporting side effects you can help provide more information on the safety of 

this medicine. 

 

 

5. How to store Clopidogrel Mylan 

 

Keep this medicine out of the sight and reach of children. 

 

Do not use this medicine after the expiry date which is stated on the carton and blister after EXP. The 

expiry date refers to the last day of that month. 

 

Store in the original package in order to protect from moisture and light. 

 

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 

throw away medicines you no longer use. These measures will help protect the environment. 

 

 

6. Contents of the pack and other information 

 

What Clopidogrel Mylan contains 

The active substance is clopidogrel. Each film-coated tablet contains 75 mg of clopidogrel (as 

hydrochloride). 

The other ingredients are: 

- Tablet core: microcrystalline cellulose, colloidal anhydrous silica, crospovidone (type A), 

macrogol 6000, hydrogenated castor oil (see section 2 ‘Clopidogrel Mylan contains 

hydrogenated castor oil’) 

- Film-coating: polyvinyl alcohol, titanium dioxide (E171), red iron oxide (E172), yellow iron 

oxide (E172), talc and macrogol 3000. 

 

What Clopidogrel Mylan looks like and contents of the pack 

The film-coated tablets are pink, round and biconvex. 

Boxes of 7, 14, 28, 30, 50, 56, 84, 90 and 100 film-coated tablets in blisters are available. 

Boxes of 7, 14, 28, 56, 84 film-coated tablets in calendar blisters are available. 

Boxes of 30x1 and 50x1 film-coated tablets in perforated unit dose blisters are available. 

 

Not all pack sizes may be marketed. 

 

Marketing Authorisation Holder 

Mylan S.A.S, 117 allée des Parcs, 69 800 Saint Priest, France 

 

Manufacturers 

KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia 

TAD Pharma GmbH, Heinz-Lohmann-Straße 5, 27472 Cuxhaven, Germany 

 

For any information about this medicine, please contact the local representative of the Marketing 

Authorisation Holder: 

 

België/Belgique/Belgien 

Mylan bvba/sprl 

Lietuva 

Mylan Healthcare UAB  

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


 

35 

Tél/Tel: + 32 (0)2 658 61 00  

 

Tel: +370 5 205 1288 

България 

Майлан ЕООД 

Тел: +359 2 44 55 400 

 

Luxembourg/Luxemburg 

Mylan bvba/sprl 

/Tel: + 32 (0)2 658 61 00  

(Belgique/Belgien) 

 

Ceská republika 

Mylan Healthcare CZ s.r.o. 

Tel: + 420 222 004 400 

 

Magyarország 

Mylan EPD Kft 

Tel: + 36 1 465 2100 

Danmark 

Mylan Denmark ApS 

Tlf: +45 28 11 69 32 

 

Malta 

V.J. Salomone Pharma Ltd 

Tel: + 356 21 22 01 74 

Deutschland 

Mylan Healthcare GmbH  

Tel: + 49 800 0700 800 

Nederland 

Mylan B.V 

Tel: + 31 (0)20 426 3300 

 

Eesti 

BGP Products Switzerland GmbH Eesti 

filiaal  

Tel: + 372 6363 052 

 

Norge 

Mylan Healthcare Norge AS 

Tel: + 47 66 75 33 00 

Ελλάδα 

Generics Pharma Hellas ΕΠΕ  

Τηλ:  +30 210 993 6410 

 

Österreich 

Arcana Arzneimittel GmbH 

Tel: +43 1 416 24 18 

 

España 

Mylan Pharmaceuticals, S.L 

Tel: + 34 900 102 712 

 

Polska 

Mylan Healthcare Sp.z.o.o 

Tel: +48 22 546 64 00 

 

France 

Mylan SAS 

Tel: +33 4 37 25 75 00 

 

Portugal 

Mylan, Lda. 

Tel: + 351 21 412 72 56 

 

Hrvatska 

Mylan Hrvatska d.o.o.   

Tel: +385 1 23 50 599 

 

România 

BGP Products SRL 

Tel: +40 372 579 000 

 

Ireland 

Mylan Ireland Limited 

Tel:  +353 (0) 87 1694982 

 

Slovenija 

Mylan Healthcare d.o.o. 

Tel: + 386 1 23 63 180 

Ísland 

Icepharma hf  

Tel: +354 540 8000 

 

Slovenská republika 

Mylan s.r.o 

Tel: +421 2 32 199 100 

 

 

Italia 

Mylan Italia S.r.l. 

Tel: + 39 02 612 46921 

 

Suomi/Finland 

Mylan Finland OY 

Puh/Tel: +358 20 720 9555 

Κύπρος 

Varnavas Hadjipanayis Ltd   

Τηλ: + 357 2220 7700  

Sverige 

Mylan AB  

Tel: + 46 855 522 750 



 

36 

  

Latvija 

Mylan Healthcare SIA  

Tel: +371 676 055 80 

United Kingdom 

Generics [UK] Ltd  

Tel: +44 1707 853000 

 

This leaflet was last revised in MM/YYYY. 

 

Detailed information is available on the European Medicines Agency website: 

http://www.ema.europa.eu/ 

 

http://www.ema.europa.eu/

	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET