Valdorin Drug Interactions

Clopidogrel: Study of specific drug interactions yielded the following results: Aspirin: Aspirin did not modify the clopidogrel-mediated inhibition of ADP-induced platelet aggregation. Concomitant administration of 500 mg of aspirin twice a day for 1 day did not significantly increase the prolongation of bleeding time induced by Clopidogrel. Clopidogrel potentiated the effect of aspirin on collagen-induced platelet aggregation. Clopidogrel and aspirin have been administered together for up to one year.
Heparin: In a study in healthy volunteers, Clopidogrel did not necessitate modification of the heparin dose or alter the effect of heparin on coagulation. Coadministration of heparin had no effect on inhibition of platelet aggregation induced by Clopidogrel.
Nonsteroidal Anti-Inflammatory Drugs (NSAIDs): In healthy volunteers receiving naproxen, concomitant administration of Clopidogrel was associated with increased occult gastrointestinal blood loss. NSAIDS and Clopidogrel should be coadministered with caution.
Warfarin: Because of the increased risk of bleeding, the concomitant administration of warfarin with Clopidogrel should be undertaken with caution.
Other Concomitant Therapy: No clinically significant pharmacodynamic interactions were observed when Clopidogrel was coadministered with atenolol, nifedipine, or both atenolol and nifedipine. The pharmacodynamic activity of Clopidogrel was also not significantly influenced by the coadministration of phenobarbital, cimetidine or estrogen. The pharmacokinetics of digoxin or theophylline were not modified by the coadministration of Clopidogrel (clopidogrel bisulfate).
At high concentrations in vitro, clopidogrel inhibits P450 (2C9). Accordingly, Clopidogrel may interfere with the metabolism of phenytoin, tamoxifen, tolbutamide, warfarin, torsemide, fluvastatin, and many non-steroidal anti-inflammatory agents, but there are no data with which to predict the magnitude of these interactions. Caution should be used when any of these drugs is coadministered with Clopidogrel.
In addition to the above specific interaction studies, patients entered into clinical trials with Clopidogrel received a variety of concomitant medications including diuretics, beta-blocking agents, angiotensin converting enzyme inhibitors, calcium antagonists, cholesterol lowering agents, coronary vasodilators, antidiabetic agents (including insulin), thrombolytics, heparins (unfractionated and LMWH), GPIIb/IIIa antagonists, antiepileptic agents and hormone replacement therapy without evidence of clinically significant adverse interactions.
There are no data on the concomitant use of oral anticoagulants, non study oral antiplatelet drugs and chronic NSAIDs with clopidogrel.
Drug/Laboratory Test Interactions: None known.
Aspirin: Anticoagulants: Aspirin may potentiate the effect of heparin and increases the risk of bleeding with oral anticoagulants, antiplatelet agents and fibrinolytics. Concomitant use is not recommended.
Other non-steroidal anti-inflammatory drugs (NSAIDs): Concurrent administration can increase side effects. Use of two or more NSAIDs increases risk of gastrointestinal haemorrhage. Experimental data suggest that ibuprofen may inhibit the effect of low dose aspirin on platelet aggregation when they are dosed concomitantly. However, the limitations of these data and the uncertainties regarding extrapolation of ex vivo data to the clinical situation imply that no firm conclusions can be made for regular ibuprofen use, and no clinically relevant effect is considered to be likely for occasional ibuprofen use.
Corticosteroids: The risk of gastrointestinal bleeding and ulceration is increased. Corticosteroids reduce the plasma salicylate concentration and salicylate toxicity may occur following withdrawal of corticosteroids.
Carbonic anhydrase inhibitors: Reduced excretion of acetazolamide; salicylate intoxication has occurred in patients on high dose salicylate regimes and carbonic anhydrase inhibitors. Concurrent administration of carbonic anhydrase inhibitors such as acetazolamide and salicylates may result in severe acidosis and increased central nervous system toxicity.
Antacids and adsorbents: The excretion of aspirin is increased in alkaline urine; kaolin possibly reduces absorption. Patients should be advised against ingesting antacids simultaneously to avoid premature drug release.
Mifepristone: The manufacturer of mifepristone recommends that aspirin should be avoided until eight to twelve days after mifepristone has been discontinued.
Antimetabolites: The activity of methotrexate may be markedly enhanced and its toxicity increased.
Antibacterials: The toxicity of sulfonamides may be increased.
Alcohol: Some of the effects of aspirin on the gastrointestinal tract are enhanced by alcohol.
Antiemetics: Metoclopramide enhances the effects of aspirin by increasing the rate of absorption.
ACE inhibitors: Aspirin may reduce the antihypertensive effect of ACE inhibitors.
Anti-epileptics: May enhance the effects of phenytoin and sodium valproate.
Diuretics: Antagonism of the diuretic effect of spironolactone.
Hypoglycaemic agents: Aspirin may enhance the effects of insulin and oral hypoglycaemic agents.
Leukotriene antagonists: The plasma concentration of zafirlukast is increased.
Uricosurics: Effect of probenecid and sulfinpyrazone may be reduced.
Thyroid function tests: Aspirin may interfere with thyroid function tests.