Ticlopidine drug interactions
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ahmed Zaghw, M.D. [2]
Drug Interactions
Therapeutic doses of ticlopidine caused a 30% increase in the plasma half-life of antipyrine and may cause analogous effects on similarly metabolized drugs. Therefore, the dose of drugs metabolized by hepatic microsomal enzymes with low therapeutic ratios or being given to patients with hepatic impairment may require adjustment to maintain optimal therapeutic blood levels when starting or stopping concomitant therapy with ticlopidine. Studies of specific drug interactions yielded the following results:
Aspirin and Other NSAIDs
Ticlopidine potentiates the effect of aspirin or other NSAIDs on platelet aggregation. The safety of concomitant use of ticlopidine and NSAIDs has not been established. The safety of concomitant use of ticlopidine and aspirin beyond 30 days has not been established (see CLINICAL TRIALS: Stent Patients). Aspirin did not modify the ticlopidine-mediated inhibition of ADP-induced platelet aggregation, but ticlopidine potentiated the effect of aspirin on collagen-induced platelet aggregation. Caution should be exercised in patients who have lesions with a propensity to bleed, such as ulcers. Long-term concomitant use of aspirin and ticlopidine is not recommended (see PRECAUTIONS: GI Bleeding).
Antacids
Administration of ticlopidine after antacids resulted in an 18% decrease in plasma levels of ticlopidine.
Cimetidine
Chronic administration of cimetidine reduced the clearance of a single dose of ticlopidine hydrochloride by 50%.
Digoxin
Coadministration of ticlopidine with digoxin resulted in a slight decrease (approximately 15%) in digoxin plasma levels. Little or no change in therapeutic efficacy of digoxin would be expected.
Theophylline
In normal volunteers, concomitant administration of ticlopidine resulted in a significant increase in the theophylline elimination half-life from 8.6 to 12.2 hours and a comparable reduction in total plasma clearance of theophylline.
Phenobarbital
In 6 normal volunteers, the inhibitory effects of ticlopidine on platelet aggregation were not altered by chronic administration of phenobarbital.
Phenytoin
In vitro studies demonstrated that ticlopidine does not alter the plasma protein binding of phenytoin. However, the protein binding interactions of ticlopidine and its metabolites have not been studiedin vivo. Several cases of elevated phenytoin plasma levels with associated somnolence and lethargy have been reported following coadministration with ticlopidine. Caution should be exercised in coadministering this drug with Ticlopidine Tablets, and it may be useful to remeasure phenytoin blood concentrations.
Propranolol
In vitro studies demonstrated that ticlopidine does not alter the plasma protein binding of propranolol. However, the protein binding interactions of ticlopidine and its metabolites have not been studied in vivo. Caution should be exercised in coadministering this drug with Ticlopidine Tablets. Other Concomitant Therapy: Although specific interaction studies were not performed, in clinical studies ticlopidine was used concomitantly with beta blockers, calcium channel blockers and diuretics without evidence of clinically significant adverse interactions (see PRECAUTIONS).
Food Interaction
The oral bioavailability of ticlopidine is increased by 20% when taken after a meal. Administration of Ticlopidine Tablets with food is recommended to maximize gastrointestinal tolerance. In controlled trials in stroke patients, ticlopidine was taken with meals.[1]
References
Adapted from the FDA Package Insert.