Clopidogrel Teva Pharma B.V.

ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 
 

1 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



1. NAME OF THE MEDICINAL PRODUCT 
 
Clopidogrel Teva Pharma B.V. 75 mg film-coated tablets 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each film-coated tablet contains 75 mg of clopidogrel (as hydrobromide).  
 
Excipients with known effect: 
Each tablet contains 62.16 mg lactose monohydrate and 10 mg hydrogenated castor oil.  
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Film-coated tablet. 
Light pink to pink, capsule-shaped film-coated tablets debossed with “C75” on one side and plain on 
the other side. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
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 older people 
 
 Clopidogrel should be given as a single daily dose of 75 mg. 
 

2 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



 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 (seesection 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 2 or 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 

3 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



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). 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). 
 
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 

4 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



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 
Clopidogrel Teva Pharma B.V. contains lactose. Patients with rare hereditary problems of galactose 
intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this 
medicinal product. 
 
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 
 
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. 

5 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



 
Other concomitant therapy: 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 inhibit CYP2C19 include omeprazole and esomeprazole, fluvoxamine, 
fluoxetine, moclobemide, voriconazole, fluconazole, ticlopidine, ciprofloxacin, cimetidine, 
carbamazepine, oxcarbazepine and chloramphenicol. 
 
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 esomeprozole 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 
(except cimetidine which is a CYP2C19 inhibitor) or antacids interfere with antiplatelet activity of 
clopidogrel. 
 
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. 
 
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. 
 

6 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



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 Teva Pharma B.V. 
 
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 

7 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



+ 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 drug 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  

Immune system 
disorders  

      Serum sickness, 
anaphylactoid 
reactions, 
cross-reactive drug 
hypersensitivity 
among 
thienopyridines 
(such as ticlopidine, 
prasugrel) (see 
section 4.4)*  

Psychiatric 
disorders  

      Hallucinations, 
confusion  

Nervous system 
disorders  

  Intracranial 
bleeding (some 
cases were reported 
with fatal outcome), 
headache, 
paraesthesia, 
dizziness  

  Taste disturbances  

Eye disorders    Eye bleeding 
(conjunctival, 
ocular, retinal)  

    

8 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



System Organ 
Class  

Common  Uncommon  Rare  Very rare, not 
known* 

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  

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), 
angioedema, 
drug-induced 
hypersensitivity 
syndrome, drug 
rash with 
eosinophilia and 
systemic symptoms 
(DRESS), rash 
erythematous or 
exfoliative, 
urticaria, eczema, 
lichen planus   

9 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



System Organ 
Class  

Common  Uncommon  Rare  Very rare, not 
known* 

Musculoskeletal, 
connective tissue 
and bone 
disorders  

      Musculo-skeletal 
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 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: platelet aggregation inhibitors excl. heparin, ATC Code: B01AC-04. 
 
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. 

10 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



 
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 

11 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



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 

12 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



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. 
 
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.  
 

13 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



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 

14 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



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. In vitro, this metabolic pathway is mediated by 
CYP3A4, CYP2C19, CYP1A2 and CYP2B6. 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 

15 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



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. 
 

16 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



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 
Lactose monohydrate 
Cellulose, microcrystalline 
Hydroxypropylcellulose (E463) 
Crospovidone (type A) 
Hydrogenated castor oil 
Sodium laurilsulfate 
 
Film-coating 
Lactose monohydrate 
Hypromellose (E464) 
Titanium dioxide (E171) 
Macrogol 4000 
Iron oxide red (E172) 
Iron oxide yellow (E172) 
Indigo carmine aluminium lake (E132) 
 
 
6.2 Incompatibilities 
 
Not applicable. 
 
6.3 Shelf life 
 
24 months 
 
For the HDPE bottle presentation chemical and physical in-use stability have been demonstrated for: 
• 30 tablets bottle: 30 days 
• 100 tablets bottle: 100 days 
Any remaining tablets should be discarded at the end of this period. 
 
6.4 Special precautions for storage 
 
Do not store above 25ºC.  
Store in the original package to protect from light. 
 
6.5 Nature and contents of container 
 
Aluminium-aluminium peelable perforated unit-dose blisters, aluminium-aluminium perforated unit 
dose blisters and HDPE bottles with polypropylene closures or child resistant polypropylene closures 
and silica gel desiccant. 
 
- Peelable perforated blisters contain 14x1, 28x1, 30x1, 50x1, 84x1, 90x1 or 100x1 film-coated tablet. 

17 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



- Perforated blisters contain 14x1, 28x1, 30x1, 50x1, 84x1, 90x1 or 100x1 film-coated tablet. 
- Bottles contain 30 or 100 film-coated tablets. 
 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Teva Pharma B.V. 
Computerweg 10 
3542 DR Utrecht 
The Netherlands 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/10/649/001-016 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
16.06.2011 
 
 
10. DATE OF REVISION OF THE TEXT 
 
<DD month YYYY> 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency: http://www.ema.europa.eu/. 
 

18 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d

http://www.emea.europa.eu/


 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 

A. MANUFACTURER 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 
 

19 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 
 
Name and address of the manufacturer(s) responsible for batch release 
 
Teva Pharmaceutical Works Private Limited Company 
Pallagi út 13 
HU-4042 Debrecen 
Hungary 
 
TEVA UK Ltd 
Brampton Road, Hampden Park  
Eastbourne  
BN22 9AG East Sussex 
United Kingdom 
 
Pharmachemie B.V. 
Swensweg 5  
2031 GA Haarlem 
The Netherlands 
 
TEVA Santé SA 
Rue Bellocier  
89107 Sens 
France 
 
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. 
 

20 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 

21 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 

22 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
OUTER CARTON of peelable blisters (14x1, 28x1, 30x1, 50x1, 84x1, 90x1 or 100x1 film-coated 
tablet) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Clopidogrel Teva Pharma B.V. 75 mg film-coated tablets 
clopidogrel 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each film-coated tablet contains 75 mg clopidogrel (as hydrobromide)  
 
 
3. LIST OF EXCIPIENTS 
 
It also contains lactose and hydrogenated castor oil. See leaflet for further information 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
14x1 film-coated tablet 
28x1 film-coated tablet 
30x1 film-coated tablet 
50x1 film-coated tablet 
84x1 film-coated tablet 
90x1 film-coated tablet 
100x1 film-coated tablet 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Oral use.  
Read the package leaflet before use. 

 
 
 
 
 
 

Separate one individual blister cell from the rest of the strip by gently tearing along the perforations 
around it. 
Carefully peel off the backing 
Push the tablet out 
Put the tablet in your mouth and swallow with water or another liquid. 
 
 
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. 

23 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP  
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Do not store above 25°C. 
Store in the original package to protect from 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 
 
Teva Pharma B.V. 
Computerweg 10 
3542 DR Utrecht 
The Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Clopidogrel Teva Pharma B.V. 75 mg 

24 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



 
MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
BLISTER (14x1, 28x1, 30x1, 50x1, 84x1, 90x1 or 100x1 film-coated tablets) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Clopidogrel Teva Pharma B.V. 75 mg film-coated tablets 
clopidogrel 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Teva Pharma B.V. 
 
 
3. EXPIRY DATE 
 
EXP  
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 

25 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
OUTER CARTON of blisters (14x1, 28x1, 30x1, 50x1, 84x1, 90x1 or 100x1 film-coated tablet) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Clopidogrel Teva Pharma B.V. 75 mg film-coated tablets 
clopidogrel 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each film-coated tablet contains 75 mg clopidogrel (as hydrobromide)  
 
 
3. LIST OF EXCIPIENTS 
 
It also contains lactose and hydrogenated castor oil. See leaflet for further information 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
14x1 film-coated tablet 
28x1 film-coated tablet 
30x1 film-coated tablet 
50x1 film-coated tablet 
84x1 film-coated tablet 
90x1 film-coated tablet 
100x1 film-coated tablet 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Oral use.  
Read the package leaflet before 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  
 
 

26 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



9. SPECIAL STORAGE CONDITIONS 
 
Do not store above 25°C. 
Store in the original package to protect from 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 
 
Teva Pharma B.V. 
Computerweg 10 
3542 DR Utrecht 
The Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Clopidogrel Teva Pharma B.V. 75 mg 

27 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



 
MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
BLISTER (14x1, 28x1, 30x1, 50x1, 84x1, 90x1 or 100x1 film-coated tablet) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Clopidogrel Teva Pharma B.V. 75 mg film-coated tablets 
clopidogrel 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Teva Pharma B.V. 
 
 
3. EXPIRY DATE 
 
EXP  
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 
 

28 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON of bottles (30 or 100 film-coated tablets) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Clopidogrel Teva Pharma B.V. 75 mg film-coated tablets 
clopidogrel 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each film-coated tablet contains 75 mg clopidogrel (as hydrobromide)  
 
 
3. LIST OF EXCIPIENTS 
 
It also contains lactose and hydrogenated castor oil. See leaflet for further information 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
30 film-coated tablets 
100 film-coated tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Oral use.  
Read the package leaflet before 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 
 
30 tablets HDPE bottle: 
Discard 30 days after first opening 
 
100 tablets HDPE bottle: 
Discard 100 days after first opening 
 
 

29 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



9. SPECIAL STORAGE CONDITIONS 
 
Do not store above 25°C. 
Store in the original package to protect from 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 
 
Teva Pharma B.V. 
Computerweg 10 
3542 DR Utrecht 
The Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Clopidogrel Teva Pharma B.V. 75 mg 
 
 

30 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



 
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING 
 
BOTTLE LABEL (30 or 100 film-coated tablets) 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Clopidogrel Teva Pharma B.V. 75 mg film-coated tablets 
clopidogrel 
oral use 
 
 
2. METHOD OF ADMINISTRATION 
 
Read the package leaflet before use. 
 
 
3. EXPIRY DATE 
 
EXP  
 
30 tablets HDPE bottle: 
Discard 30 days after first opening 
 
100 tablets HDPE bottle: 
Discard 100 days after first opening 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
30 film-coated tablets 
100 film-coated tablets 
 
 
6. OTHER 
 
 
 
 
 
 
 
 
 
 
 
 
 

31 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 
 

32 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



Package leaflet: Information for the user 
 
 

Clopidogrel Teva Pharma B.V. 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 have any side effects, including any side effects not listed in this leaflet, talk your doctor 

or pharmacist. See section 4 
 
What is in this leaflet 
1. What Clopidogrel Teva Pharma B.V. is and what it is used for 
2. What you need to know before you take Clopidogrel Teva Pharma B.V. 
3. How to take Clopidogrel Teva Pharma B.V. 
4. Possible side effects 
5. How to store Clopidogrel Teva Pharma B.V. 
6. Contents of the pack and other information 
 
 
1.  What Clopidogrel Teva Pharma B.V. is and what it is used for 
 
Clopidogrel Teva Pharma B.V contains clopidogrel and belongs to a group of medicines called 
“platelet aggregation inhibitors.” It works by stopping certain particles in your blood (“platelets”) 
from sticking together to form blood clots which can block blood flow to important parts of your body 
including your heart and your brain.  
 
If you suffer from hardening of the arteries (“atherosclerosis”) there is an increased risk of a blood clot 
forming in your blood vessels. In adults Clopidogrel Teva Pharma B.V. reduces the risk of blood clots 
forming which in turn reduces the risk of serious conditions such as heart attack and stroke from 
occurring. 
 
You have been prescribed Clopidogrel Teva Pharma B.V. because:  
 
• You have hardening of the arteries and have recently suffered from a heart attack, a stroke or 

have a condition known as “peripheral arterial disease” (diseases of the blood vessels except 
those in the brain and heart). 

• 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 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 
Teva Pharma B.V. and acetylsalicylic acid for this condition. Your doctor should have 
prescribed Clopidogrel Teva Pharma B.V. plus acetylsalicylic acid if you cannot take ‘oral 
anticoagulants’ and you do not have a risk of major bleeding. 

 

33 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



 
2. What you need to know before you take Clopidogrel Teva Pharma B.V. 
 
Do not take Clopidogrel Teva Pharma B.V. 
• If you are allergic (hypersensitive) to clopidogrel or any of the other ingredients of this 

medicine (listed in section 6). 
• If you have severe liver disease. 
• If you are suffering from another condition which is currently causing bleeding such as a 

stomach ulcer or bleeding within the brain. 
• If you think any of these apply to you, or if you are in any doubt at all, consult your doctor 

before taking Clopidogrel Teva Pharma B.V. 
 
Warnings and precautions 
Tell your doctor before you start to take this medicine if: 
• You are at increased risk of bleeding. For example: 

o If you have recently suffered from a serious injury 
o If you have recently undergone surgery or are due to have surgery (including dental 

surgery) 
o If you have any blood disorder which makes internal bleeding (bleeding inside your body) 

more likely 
o If you suffer from any other illness which makes internal bleeding more likely (e.g. stomach 

ulcers or wounds inside the eye) 
• You have had a clot in an artery of your brain (ischaemic stroke) which occurred within the last 

seven days 
• You have liver or kidney disease. 
• You have had an allergy or reaction to any medicine used to treat your disease. 
 
While you are taking Clopidogrel Teva Pharma B.V.: 
• You should tell your doctor if surgery (including dental) is planned 
• You should also tell your doctor immediately if you develop a medical condition (known as 

Thrombotic Thrombocytopenic Purpura) that includes altered behaviour, headaches, coma, 
visual disturbances, seizures (fitting), kidney failure, fever, extreme tiredness, weakness or 
bleeding into the stomach, bowels or skin (including small red spots or large bruised areas) (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 Teva Pharma B.V. 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines, including medicines obtained without a prescription. 
 
Talk to your doctor if you are using or have recently used any of the following medicines:   
 
• Oral anticoagulants (oral medicines used to stop blood clotting) such as warfarin.  Their use 

with Clopidogrel Teva Pharma B.V. is not recommended. 
• Glycoprotein IIb/IIIa inhibitors (medicines used to stop blood clotting).  E.g. abciximab, 

eptifibatide or tirofiban. 
• Heparin (medicine used to prevent blood clotting). 

34 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



• Medicines used to break down blood clots (e.g. alteplase and streptokinase). 
• Non-steroidal anti-inflammatory medicines (used to treat painful inflammatory conditions of the 

joints or muscles).  E.g. ibuprofen, diclofenac and meloxicam. 
• Omeprazole, esomeprazole or cimetidine, medicines to treat upset stomach. 
• Fluconazole, voriconazole, ciprofloxacin, or chloramphenicol, medicines to treat bacterial and 

fungal infections. 
• Carbamazepine, or oxcarbazepine, medicines to treat some forms of epilepsy. 
• Ticlopidine, other antiplatelet agent. 
• a selective serotonin reuptake inhibitor (including but not restricted to fluoxetine or 

fluvoxamine), medicines usually used to treat depression, 
• moclobemide, medicine to treat depression. 

 
 
Taking these medicines in combination with Clopidogrel Teva Pharma B.V. could result in an 
increased risk of bleeding. 
 
If you have experienced severe chest pain (unstable angina or heart attack), you may be prescribed 
clopidogrel in combination with acetylsalicylic acid, a substance 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. 
 
Clopidogrel Teva Pharma B.V. with food and drink 
You can take Clopidogrel Teva Pharma B.V. with or without food. 
 
Pregnancy and breast-feeding 
It is preferable not to use 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 Teva Pharma B.V. If you become pregnant while taking Clopidogrel Teva 
Pharma B.V., consult your doctor immediately as it is recommended not to take clopidogrel while you 
are pregnant. 
 
You should not breastfeed while taking this medicine. 
If you are breastfeeding or planning to breastfeed, talk to your doctor before taking this medicine. 
 
Ask your doctor or pharmacist for advice before taking any medicine. 
 
Driving and using machines 
Clopidogrel Teva Pharma B.V. is unlikely to affect your ability to drive or operate machinery. 
 
Clopidogrel Teva Pharma B.V. contains lactose 
If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor 
before taking this medicinal product. 
 
Clopidogrel Teva Pharma B.V. contains hydrogenated castor oil. This may cause stomach upset 
and diarrhoea. 
 
 
3.  How to take Clopidogrel Teva Pharma B.V. 
 
Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor 
or pharmacist if you are not sure.  
 

35 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



The recommended dose is one 75 mg tablet per day which should be swallowed with water or another 
liquid.  You should take your medicine regularly at the same time each day. You can take it with or 
without food. 
 
If you have experienced severe chest pain (unstable angina or heart attack), your doctor may give you 
300 mg of Clopidogrel Teva Pharma B.V. once at the start of treatment. Then, the usual dose is one 
75-mg tablet of Clopidogrel Teva Pharma B.V. per day 
 
You should continue taking Clopidogrel Teva Pharma B.V. for as long as your doctor has told you to 
take it. 
 
If you take more Clopidogrel Teva Pharma B.V. than you should 
If you (or someone else) swallow a lot of the tablets all together, or if you think a child has swallowed 
any of the tablets, contact your nearest hospital casualty department or your doctor immediately. An 
overdose is likely to cause an increased risk of bleeding. Please take this leaflet, any remaining tablets 
and the container with you to the hospital or doctor so that they know which tablets were consumed.  
 
If you forget to take Clopidogrel Teva Pharma B.V. 
If you forget to take a dose of Clopidogrel Teva Pharma B.V., but remember within 12 hours of the 
missed dose, take your tablet straight away and then take your next tablet at the usual time.   
 
If you forget to take a dose of Clopidogrel Teva Pharma B.V., but don’t remember within 12 hours of 
the missed dose, skip the missed dose and take the next tablet at the usual time. Do not take a double 
dose to make up for a forgotten tablet. 
 
If you stop taking Clopidogrel Teva Pharma B.V. 
Do not stop taking Clopidogrel Teva Pharma B.V. without discussing it with your doctor first. 
 
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. 
 
Some of the side effects may be serious.  If you suffer from any of the following symptoms you should 
contact your doctor immediately: 
 
• Fever, signs of infection (e.g. sore throat), pale skin or extreme tiredness. These may be due to a 

decrease of some blood cells 
• Altered behaviour, headaches, coma, visual disturbances, seizures (fitting), kidney failure, fever, 

extreme tiredness, weakness or bleeding into the stomach, bowels or skin (including small red 
spots or large bruised areas). This could indicate that you are suffering from a serious condition 
called thrombotic thrombocytic purpura (rare disorder of the blood clotting system which causes 
multiple blood clots to form around the body) 

• Signs of liver problems such as yellowing of the skin and whites of 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, itching and blistering of the skin. These 
may be the signs of an allergic reaction. 

 
Bleeding 
The most common side effect (affects 1 to 10 users in 100) reported for medicines containing 
clopidogrel is bleeding. Bleeding may occur as bleeding in the stomach or bowels, bruising, 
haematoma (unusual bleeding or bruising under the skin), nose bleeds or blood in the urine. In a small 

36 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



number of cases, bleeding in the eye, inside the head, the abdomen, the lung and the joints have also 
been reported. 
 
If you cut or injure yourself, it may take slightly longer than usual for bleeding to stop.  This is linked 
to the way that your medicine works.  For minor cuts and injuries (e.g. shaving cuts) you should not 
worry.  However, if you are in any doubt, bleeding becomes serious or you experience unexpected 
bleeding from unusual parts of your body you should contact your doctor straight away (see section 2 
‘Warnings and precautions’). 
 
The following side effects have been reported.   
Common side effects (may affect up to 1 in 10 people): 
• Bruising, haematoma (unusual bleeding under the skin), nose bleeds, bleeding in the stomach or 

bowels, increased bleeding at the site of a puncture wound 
• Diarrhoea, abdominal pain, indigestion or heartburn 
 
Uncommon side effects (may affect up to 1 in 100 people): 
Headache and dizziness 
Prolonged bleeding, bleeding inside the head, bleeding in the eye, blood in the urine and/or purpura 
(red spots on the skin caused by bleeding underneath the skin) 
Rashes, itching, abnormal touch sensation 
Ulcers in the stomach and small intestine, nausea, vomiting, constipation, flatulence (wind) and 
inflammation of the stomach leading to sickness, loss of appetite and discomfort after eating 
Reduction in blood platelets which makes bleeding or bruising more likely 
Blood disorders including a reduction in the number of white blood cells which makes infections more 
likely. 
 
Rare side effects (may affect up to 1 in 1000 people): 
Reduced levels of certain white blood cells which increases the risk of infection (neutropenia) 
Vertigo (dizziness accompanied by a whirling sensation) 
Bleeding inside the abdomen 
 
Very rare side effects (may affect up to 1 in 10,000 people): 
A serious condition called thrombotic thrombocytic purpura (rare disorder of the blood clotting system 
which causes multiple blood clots to form around the body).  Symptoms may include altered 
behaviour, headaches, coma, visual disturbances, seizures (fitting), kidney failure, fever, extreme 
tiredness, weakness, or bleeding into the stomach, bowels or skin (including small red spots or large 
bruised areas) 
Severe reduction in certain blood cells leading to increased risk of bleeding or bruising, increased risk 
of infections, pale skin and extreme tiredness 
Generalised allergic reactions (for example, overall sensation of heat with sudden general discomfort 
until fainting); breathing difficulties, swelling or inflammation of the mouth, skin allergy, blisters on 
the skin 
Confusion or hallucinations 
Taste disorders 
Sore mouth (stomatitis) 
Inflammation of the blood vessels, decrease in blood pressure 
Yellowing of the skin and whites of the eyes (jaundice) 
Bleeding in the lungs, throat, stomach or bowels, abdomen or joints 
Bleeding of post-operative wounds or other serious bleeds 
Severe abdominal pain with or without back pain, pain in the joints and muscular pain 
Diarrhoea 
Fever 
Changes in levels of certain substances in your blood or urine.  This may be detectable via blood or 
urine tests. 
 

37 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



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 Teva Pharma B.V. 
 
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 outer carton, bottle or blister after 
EXP. The expiry date refers to the last day of that month.  
 
Do not store above 25°C. Store in the original package to protect from light. 
 
30 tablets HDPE bottles: 
Discard any remaining tablets 30 days after first opening of the bottle. 
 
100 tablets HDPE bottles: 
Discard any remaining tablets 100 days after first opening of the bottle. 
 
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 to protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Clopidogrel Teva Pharma B.V. contains 
The active substance is clopidogrel. Each film-coated tablet contains 75 mg of clopidogrel (as 
hydrobromide). 
The other ingredients in the tablet core are (see section 2 ‘Clopidogrel Teva Pharma B.V. contains 
lactose’ and ‘Clopidogrel Teva Pharma B.V. contains hydrogenated castor oil’) lactose monohydrate, 
microcrystalline cellulose, hydroxypropylcellulose (E463), crospovidone (type A), hydrogenated 
castor oil and sodium laurilsulfate, and in the film-coating are lactose monohydrate, hypromellose 
(E464), titanium dioxide (E171), macrogol 4000, iron oxide red (E172), iron oxide yellow (E172), 
indigo carmine aluminium lake (E132). 
 
What Clopidogrel Teva Pharma B.V. looks like and contents of the pack 
The film-coated tablets are light pink to pink, film coated, capsule shaped tablets. One side of the 
tablet is debossed with “C75”. The other side of the tablet is plain. 
Clopidogrel Teva Pharma B.V. is supplied in peelable perforated blisters of aluminium/ aluminium 
containing 14x1, 28x1, 30x1, 50x1, 84x1, 90x1 or 100x1 tablet; perforated blisters of 
aluminium/ aluminium containing 14x1, 28x1, 30x1, 50x1, 84x1, 90x1 or 100x1 tablet or HDPE 
bottles with polypropylene closures or child resistant polypropylene closures and silica gel desiccant 
containing 30 or 100 tablets.  
 
Not all pack sizes may be marketed. 
 Please note that instructions on how to remove the tablet from the blister strip are given on the outer 
carton of the peelable blisters. 
 
Marketing Authorisation Holder and Manufacturer 
 
Marketing Authorisation Holder: 
 
Teva Pharma B.V., 

38 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



Computerweg 10, 
3542 DR Utrecht, 
The Netherlands 
 
Manufacturer: 
 
TEVA Pharmaceutical Works Private Limited Company  
Pallagi út 13,  
4042 Debrecen, 
Hungary 
 
TEVA UK Ltd  
Brampton Road,  
Hampden Park,  
Eastbourne,  
East Sussex,  
BN22 9AG,  
United Kingdom 
 
Pharmachemie B.V.  
Swensweg 5,  
2031 GA Haarlem, 
The Netherlands   
 
TEVA Santé SA, 
Rue Bellocier,  
89107 Sens, 
France 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 

België/Belgique/Belgien  
Teva Pharma Belgium N.V./S.A.  
Tel/Tél: +32 3 820 73 73  

Lietuva 
UAB “Sicor Biotech” 
Tel: +370 5 266 02 03 

 
България  
Тева Фармасютикълс България ЕООД 
Teл: +359 2 489 95 82  

 
Luxembourg/Luxemburg  
ratiopharm GmbH 
Allemagne/Deutschland 
Tél/Tel: +49 731 402 02 

 
Česká republika  
Teva Pharmaceuticals CR, s.r.o.  
Tel: +420 251 007 111  

 
Magyarország  
Teva Gyógyszergyár  Zrt.  
Tel.: +36 1 288 64 00  

 
Danmark  
Teva Denmark A/S  
Tlf: +45 44 98 55 11  

 
Malta  
L-Irlanda 
Teva Pharmaceuticals Ireland 
Tel: +353 51 321740 
 

 
Deutschland 
ratiopharm GmbH 
Tel: +49 731 402 02  

 
Nederland  
Teva Nederland B.V. 
Tel: +31 (0) 800 0228400  

  

39 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d



40 

Eesti 
Teva Eesti esindus UAB Sicor Biotech 
Eesti filiaal 
Tel: +372 661 0801 

Norge 
Teva Norway AS 
Tlf: +47 66 77 55 90 

 
Ελλάδα 
Teva Ελλάς Α.Ε. 
Τηλ: +30 210 72 79 099 

 
Österreich 
ratiopharm Arzneimittel Vertriebs-GmbH 
Tel: +43 1 97007-0 

 
España 
Teva Pharma, S.L.U 
Tél: +(34) 91 387 32 80   

 
Polska 
Teva Pharmaceuticals Polska Sp. z o.o. 
Tel.: +(48) 22 345 93 00 

 
France 
Teva Santé 
Tél: +(33) 1 55 91 7800 

 
Portugal 
Teva Pharma - Produtos Farmacêuticos Lda 
Tel: (351) 21 476 75 50 

 
Hrvatska 
Pliva Hrvatska d.o.o. 
Tel:+ 385 1 37 20 000 

 
România 
Teva Pharmaceuticals S.R.L 
Tel: +4021 230 65 24 

 
Ireland 
Teva Pharmaceuticals Ireland 
Tel: +353 (0)51 321 740 

 
Slovenija 
Pliva Ljubljana d.o.o. 
Tel: +386 1 58 90 390 

 
Ísland 
Finnland 
ratiopharm Oy 
Sími: +358 20 180 5900 

 
Slovenská republika 
Teva Pharmaceuticals Slovakia s.r.o. 
Tel: +(421) 2 5726 7911 

 
Italia 
Teva Italia S.r.l. 
Tel: +(39) 028917981 

 
Suomi/Finland 
ratiopharm Oy 
Puh/Tel: +358 20 180 5900 

 
Κύπρος 
Teva Ελλάς Α.Ε. 
Ελλάδα 
Τηλ: +30 210 72 79 099 

 
Sverige 
Teva Sweden AB 
Tel: +(46) 42 12 11 00 

 
Latvija 
UAB Sicor Biotech filiāle Latvijā  
Tel: +371 67 323 666 

 
United Kingdom 
Teva UK Limited 
Tel: +44 (0) 1977 628500 

 
 
This leaflet was last revised in: <Month YYYY>  
 
Detailed information is available on the European Medicines Agency website: 
http://www.ema.europa.eu. 

Me
dic

ina
l p

rod
uc

t n
o l

on
ge

r a
uth

ori
se

d


	ANNEX ISUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER 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