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

 
 



DRUG INTERACTIONS

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).

OVERDOSAGE

One case of deliberate overdosage with ticlopidine has been reported by a foreign postmarketing surveillance program. A 38-year-old male took a single 6000-mg dose of ticlopidine hydrochloride (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 ticlopidine 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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