TICLID (ticlopidine hydrochloride) is a platelet aggregation inhibitor. Chemically it is 5-[(2-chlorophenyl)methyl]-4,5,6,7-tetrahydrothieno [3,2-c] pyridine hydrochloride. The structural formula is:
Ticlopidine hydrochloride is a white crystalline solid. It is freely soluble in water and self-buffers to a pH of 3.6. It also dissolves freely in methanol, is sparingly soluble in methylene chloride and ethanol, slightly soluble in acetone and insoluble in a buffer solution of pH 6.3. It has a molecular weight of 300.25.
TICLID tablets for oral administration are provided as white, oval, film-coated, blue-imprinted tablets containing 250 mg of ticlopidine hydrochloride. Each tablet also contains citric acid, magnesium stearate, microcrystalline cellulose, povidone, starch and stearic acid as inactive ingredients. The white film-coating contains hydroxypropylmethyl cellulose, polyethylene glycol and titanium dioxide. Each tablet is printed with blue ink, which includes FD&C Blue #1 aluminum lake as the colorant. The tablets are identified with Ticlid on one side and 250 on the reverse side.
Therapeutic doses of TICLID 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 concomitantuse 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 TICLID 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 TICLID by 50%.
Digoxin: Coadministration of TICLID 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 TICLID 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 TICLID 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 studied in vivo. Several cases of elevated phenytoin plasma levels with associated somnolence and lethargy have been reported following coadministration with TICLID. Caution should be exercised in coadministering this drug with TICLID, 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 TICLID.
Other Concomitant Therapy: Although specific interaction studies were not performed, in clinical studies TICLID 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 TICLID with food is recommended to maximize gastrointestinal tolerance. In controlled trials in stroke patients, TICLID was taken with meals.