Ticlopidine Hydrochloride

When taken orally, Ticlopidine hydrochloride causes a time- and dose-dependent inhibition of both platelet aggregation and release of platelet granule constituents, as well as a prolongation of bleeding time. The intact drug has no significant in vitro activity at the concentrations attained in vivo; and, although analysis of urine and plasma indicates at least 20 metabolites, no metabolite which accounts for the activity of ticlopidine has been isolated.

Ticlopidine hydrochloride, after oral ingestion, interferes with platelet membrane function by inhibiting ADP-induced platelet-fibrinogen binding and subsequent platelet-platelet interactions. The effect on platelet function is irreversible for the life of the platelet, as shown both by persistent inhibition of fibrinogen binding after washing platelets ex vivo and by inhibition of platelet aggregation after resuspension of platelets in buffered medium.

Stroke: The recommended dose of Ticlopidine is 250 mg bid taken with food. Other doses have not been studied in controlled trials for these indications.

Coronary Artery Stenting: The recommended dose of Ticlopidine is 250 mg bid taken with food together with antiplatelet doses of aspirin for up to 30 days of therapy following successful stent implantation.

Reduced clearance with cimetidine; corticosteroid may antagonise effects on bleeding time. Avoid concurrent use with clopidogrel.

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

Diarrhoea, nausea, dyspepsia, bleeding, pupura, skin rash, increase in serum cholesterol concentration, elevation of LFTs, hepatitis, cholestatic jaundice.

Pregnancy Category B. Teratology studies have been conducted in mice (doses up to 200 mg/kg/day), rats (doses up to 400 mg/kg/day) and rabbits (doses up to 200 mg/kg/day). Doses of 400 mg/kg in rats, 200 mg/kg/day in mice and 100 mg/kg in rabbits produced maternal toxicity, as well as fetal toxicity, but there was no evidence of a teratogenic potential of ticlopidine. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of a human response, this drug should be used during pregnancy only if clearly needed.

Nursing Mothers: Studies in rats have shown ticlopidine is excreted in the milk. It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from ticlopidine, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Patients with increased risk of bleeding from trauma, surgery or pathological disorder. Moderate to severe renal impairment. May need to stop therapy 10-14 days before elective surgery. Full blood counts should be performed prior to therapy and every 2 wk during the first 3 mth of treatment. Pregnancy.

Pediatric Use: Safety and effectiveness in pediatric patients have not been established.

Geriatric Use: Clearance of ticlopidine is somewhat lower in elderly patients and trough levels are increased. The major clinical trials with Ticlopidine in stroke patients were conducted in an elderly population with an average age of 64 years. Of the total number of patients in the therapeutic trials, 45% of patients were over 65 years old and 12% were over 75 years old. No overall differences in effectiveness or safety were observed between these patients and younger patients, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

Renal Impairment: Dose reduction or discontinuance if haemorrhagic or haematopoietic complications occur.

Hepatic Impairment: Severe: contraindicated.

Anti-platelet drugs, Fibrinolytics (Thrombolytics)

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 (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.

Store at 15° to 30° C