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Ticlid (Ticlopidine Hydrochloride) - Drug Interactions, Contraindications, Overdosage, etc

 
 



DRUG INTERACTIONS

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 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).

OVERDOSAGE:

One case of deliberate overdosage with TICLID has been reported by a foreign postmarketing surveillance program. A 38-year-old male took a single 6000-mg dose of TICLID (equivalent to 24 standard 250-mg tablets). The only abnormalities reported were increased bleeding time and increased SGPT. No special therapy was instituted and the patient recovered without sequelae.

Single oral doses of ticlopidine at 1600 mg/kg and 500 mg/kg were lethal to rats and mice, respectively. Symptoms of acute toxicity were GI hemorrhage, convulsions, hypothermia, dyspnea, loss of equilibrium and abnormal gait.

CONTRAINDICATIONS:

The use of TICLID is contraindicated in the following conditions:

  • Hypersensitivity to the drug
  • Presence of hematopoietic disorders such as neutropenia and thrombocytopenia or a past history of either TTP or aplastic anemia
  • Presence of a hemostatic disorder or active pathological bleeding (such as bleeding peptic ulcer or intracranial bleeding)
  • Patients with severe liver impairment

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