Wirkstoffe & Arzneimittelsicherheit

Wechselwirkungen · Clopidogrel Zentiva (previously Clopidogrel Winthrop)

Clopidogrel Zentiva 75 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 8

HOS-209899 · Präparat HOS-154399

The pharmacokinetics of digoxin or theophylline were not modified by the co-administration of clopidogrel. Antacids did not modify the extent of clopidogrel absorption.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): digoxin (HOS-086172) theophylline (HOS-085910)

Wechselwirkungen · Clopidogrel Zentiva (previously Clopidogrel Winthrop)

Clopidogrel Zentiva 75 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 8

HOS-209900 · Präparat HOS-154399

Data from the CAPRIE study indicate that phenytoin and tolbutamide which are metabolised by CYP2C9 can be safely co-administered with clopidogrel.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): phenytoin (HOS-084531) tolbutamide (HOS-086568)

Wechselwirkungen · Clopidogrel Zentiva (previously Clopidogrel Winthrop)

Clopidogrel Zentiva 75 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 8

HOS-209902 · Präparat HOS-154399

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).

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): paclitaxel (HOS-087959) repaglinide (HOS-086935)

Wechselwirkungen · Clopidogrel Zentiva (previously Clopidogrel Winthrop)

Clopidogrel Zentiva 75 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 8

HOS-209903 · Präparat HOS-154399

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.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): calcium (HOS-085615) cholesterol (HOS-087961)

Wechselwirkungen · Clopidogrel Zentiva (previously Clopidogrel Winthrop)

Clopidogrel Zentiva 75 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 8

HOS-209905 · Präparat HOS-154399

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.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): morphine (HOS-086053)

Wechselwirkungen · Clopidogrel Zentiva (previously Clopidogrel Winthrop)

Clopidogrel Zentiva 75 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 8–9

HOS-209907 · Präparat HOS-154399

8 Rosuvastatin Clopidogrel has been shown to increase rosuvastatin exposure in patients by 2-fold (AUC) and 1.3-fold (Cmax) after administration of a 300 mg clopidogrel dose, and by 1.4-fold (AUC) without effect on Cmax after repeated administration of a 75 mg clopidogrel dose.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): rosuvastatin (HOS-086307)

Nebenwirkungen · Clopidogrel Zentiva (previously Clopidogrel Winthrop)

Clopidogrel Zentiva 75 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 9

HOS-209908 · Präparat HOS-154399

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.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Clopidogrel Zentiva (previously Clopidogrel Winthrop)

Clopidogrel Zentiva 75 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 9

HOS-209909 · Präparat HOS-154399

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.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Clopidogrel Zentiva (previously Clopidogrel Winthrop)

Clopidogrel Zentiva 75 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 9

HOS-209910 · Präparat HOS-154399

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.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Clopidogrel Zentiva (previously Clopidogrel Winthrop)

Clopidogrel Zentiva 75 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 9

HOS-209911 · Präparat HOS-154399

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.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Clopidogrel Zentiva (previously Clopidogrel Winthrop)

Clopidogrel Zentiva 75 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 9

HOS-209912 · Präparat HOS-154399

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.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Clopidogrel Zentiva (previously Clopidogrel Winthrop)

Clopidogrel Zentiva 75 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 9

HOS-209913 · Präparat HOS-154399

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

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Clopidogrel Zentiva (previously Clopidogrel Winthrop)

Clopidogrel Zentiva 75 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 9–10

HOS-209914 · Präparat HOS-154399

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 9 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 hemorrhagic stroke (0.8% and 0.6%, respectively) between groups.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Clopidogrel Zentiva (previously Clopidogrel Winthrop)

Clopidogrel Zentiva 75 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 10

HOS-209915 · Präparat HOS-154399

In TARDIS, patients with recent ischemic stroke receiving intensive antiplatelet therapy with three medicinal products (ASA + clopidogrel + dipyridamole) had more bleeding and bleeding of greater severity when compared with either clopidogrel alone or combined ASA and dipyridamole (adjusted common OR 2.54, 95% CI 2.05-3.16, p<0.0001).

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Clopidogrel Zentiva (previously Clopidogrel Winthrop)

Clopidogrel Zentiva 75 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 10

HOS-209916 · Präparat HOS-154399

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.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Clopidogrel Zentiva (previously Clopidogrel Winthrop)

Clopidogrel Zentiva 75 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 10

HOS-209917 · Präparat HOS-154399

System Organ Common Uncommon Rare Very rare, not Class known* Blood and the Thrombocytopenia, Neutropenia, Thrombotic lymphatic leucopenia, including severe thrombocytopenic system disorders eosinophilia neutropenia purpura (TTP) (see section 4.4), aplastic anaemia, pancytopenia, agranulocytosis, severe thrombocytopenia, acquired haemophilia A, granulocytopenia, anaemia Cardiac Kounis syndrome disorders (vasospastic allergic angina / allergic myocardial infarction) in the context of a hypersensitivity reaction due to clopidogrel*

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Clopidogrel Zentiva (previously Clopidogrel Winthrop)

Clopidogrel Zentiva 75 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 10–11

HOS-209918 · Präparat HOS-154399

10  System Organ Common Uncommon Rare Very rare, not Class known* Immune system Serum sickness, disorders 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 Hallucinations, disorders confusion Nervous system Intracranial bleeding Taste disturbances, disorders (some cases were ageusia reported with fatal outcome), headache, paraesthesia, dizziness Eye disorders Eye bleeding (conjunctival, ocular, retinal) Ear and Vertigo labyrinth disorders Vascular Haematoma Serious hemorrhage, disorders hemorrhage of operative wound, vasculitis, hypotension Respiratory, Epistaxis Respiratory tract thoracic and bleeding mediastinal (haemoptysis, disorders pulmonary hemorrhage), bronchospasm, interstitial pneumonitis, eosinophilic pneumonia

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Clopidogrel Zentiva (previously Clopidogrel Winthrop)

Clopidogrel Zentiva 75 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 11–12

HOS-209919 · Präparat HOS-154399

11  System Organ Common Uncommon Rare Very rare, not Class known* Gastrointestinal Gastrointestinal Gastric ulcer and Retroperitoneal Gastrointestinal and disorders hemorrhage, duodenal ulcer, hemorrhage retroperitoneal diarrhoea, abdominal gastritis, vomiting, hemorrhage with pain, dyspepsia nausea, constipation, fatal outcome, flatulence pancreatitis, colitis (including ulcerative or lymphocytic colitis), stomatitis Hepato-biliary Acute liver failure, disorders hepatitis, abnormal liver function test Skin and Bruising Rash, pruritus, skin Bullous dermatitis subcutaneous bleeding (purpura) (toxic epidermal tissue disorders 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 Gynaecomastia systems and breast disorders Musculoskeletal Musculo-skeletal and connective bleeding tissue disorders (haemarthrosis), arthritis, arthralgia, myalgia Renal and Haematuria Glomerulonephritis, urinary disorders blood creatinine increased General Bleeding at puncture Fever disorders and site administration site conditions Investigations Bleeding time prolonged, neutrophil count decreased, platelet count decreased * Information related to clopidogrel with frequency “not known”.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Clopidogrel Zentiva (previously Clopidogrel Winthrop)

Clopidogrel Zentiva 75 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 12–13

HOS-209920 · Präparat HOS-154399

12 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.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.