Therodel Drug Interactions

Warfarin: the concomitant administration of Clopidogrel with warfarin is not recommended since it may increase the intensity of bleedings.
Glycoprotein IIb/IIIa inhibitors: Clopidogrel should be used with caution in patients who may be at risk of increased bleeding from trauma, surgery or other pathological conditions that receive concomitant glycoprotein IIb/IIIa inhibitors.
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. However, Clopidogrel and ASA have been administered together for up to one year.
Heparin: 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.
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 was similar to that observed when thrombolytic agents and heparins are co-administered with ASA. However, the concomitant use of Clopidogrel with thrombolytic agents should be undertaken with caution.
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs): The concomitant administration of Clopidogrel and naproxen increase 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.
Other concomitant therapy: No significant 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 influence by the co-administration of phenobarbital, cimetidine 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.
Carboxylic acid metabolite of Clopidogrel could inhibit the activity of Cytochrome P450 2C9. This could potentially lead to increased plasma level of drugs such as phenytoin and tolbutamide and the NSAIDs, which are metabolised by Cytochrome P450 2C9. Phenytoin and tolbutamide can be safely co-administered with Clopidogrel.
Apart from the specific drug interaction information described previously, interaction studies with Clopidogrel and some drugs commonly administered in patients with atherothrombotic disease have not been performed. However, patients entered into clinical trials with Clopidogrel received a variety of concomitant medications including diuretics, beta blockers, ACEI, calcium antagonist, cholesterol lowering agents, coronary vasodilators, antidiabetic agents (including insulin), antiepileptic agents, hormone replacement therapy and GPIIb/IIIa antagonist without evidence of clinically significant adverse interactions.