Composition:

Each film coated tablet contains 250mg Ticlopidine Hydrochloride.

Mechanism of action:

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. Ticlopidine hydrochloride, after oral ingestion, interferes with platelet membrane function by inhibiting ADP-induced platelet-fibrinogen binding and subsequent platelet-platelet interactions.

Pharmacokinetics:

Ticlopidine hydrochloride is rapidly absorbed with peak plasma levels occurring at approximately 2 hours (Absorption is greater than 80%). Administration after meals results in a 20% increase in the AUC of ticlopidine. It binds reversibly (98%) to plasma proteins mainly to serum albumin and lipoproteins. It is metabolizes extensively by the liver. It is excreted in urine and feces. Possibly excreted in the bile.

Indications:

Ticlopidin Domina tablets is indicated for

• To reduce the risk of thrombotic stroke in patients who have experienced

stroke precursors, and in patients who have had a completed thrombotic stroke.

• As adjunctive therapy with aspirin to reduce the incidence of subacute stent thrombosis in patients undergoing successful coronary stent implantation.

Dosage:

Stroke: The recommended dose is 250mg bid taken with food.

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

- Ticlopidine hydrochloride should be taken with food or just after eating in order to minimize gastrointestinal discomfort.

Overdose:

Symptoms of acute toxicity were GI hemorrhage, convulsions, hypothermia, dyspnea, loss of equilibrium and abnormal gait. No special therapy was instituted

Side effects:

Common side effects include: diarrhea, rash, nausea, vomiting, GI pain and neutropenia, dyspepsia, purpura, flatulence, pruritus, dizziness, anorexia, abnormal liver function test.

Contraindications:

Hypersensitivity to the active material, presence of hematopoietic disorders (neutropenia, thrombocytopenia), past history of either TTP or aplastic anemia, presence of a hemostatic disorder or active pathological bleeding, (such as bleeding peptic ulcer orintracranial bleeding) severe liver impairment.

Drug interactions:

• Ticlopidine potentiates the effect of aspirin or other NSAIDs on 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.
• Antacids decrease plasma levels of ticlopidine.
• Chronic administration of cimetidine reduced the clearance of of ticlopidine.
• Coadministration of ticlopidine with digoxin resulted in a slight decrease  in digoxin plasma levels but little or no change in therapeutic efficacy of  digoxin.
• Concomitant administration of ticlopidine resulted in a significant increase in the theophylline elimination half-life and a comparable reduction in total plasma clearance of theophylline.
• Caution should be exercised in coadministering phenytoin or propanol with ticlopidine, and it may be useful to remeasure phenytoin blood concentrations.
• Ticlopidine was used concomitantly with beta blockers, calcium channel blockers, diuretics and phenobarbital without evidence of clinically significant adverse interactions.

Precautions:

1. It cause a plastic aneamia which characterized by decrease in the number of white blood cells (neutropenia) or platelets (thrombocytopenia) can occur with ticlopidine, especially during the first 3 months of treatment and that neutropenia, if it is severe, can result in an increased risk of infection. It is critically important to obtain the scheduled blood tests to detect neutropenia or thrombocytopenia. Patients should be reminded to contact their physicians if they experience any indication of infection such as fever, chills, or sore throat, any of which might be a consequence of neutropenia.
2. Thrombocytopenia may be part of a syndrome called Thrombotic Thrombocytopenic Purpura (TTP). Symptoms and signs of TTP, such as fever, weakness, difficulty speaking, seizures, yellowing of skin or eyes, dark or bloody urine, pallor or petechiae (pinpoint hemorrhagic spots on the skin), should be reported immediately.
3. All patients should be told that it may take them longer than usual to stop bleeding when they take ticlopidine and that they should report any unusual bleeding to their physician. Patients should tell physicians and dentists that they are taking ticlopidine before any surgery is scheduled and before any new drug is prescribed.
4. Patients should be told to promptly report side effects of ticlopidine such as severe or persistent diarrhea, skin rashes or subcutaneous bleeding or any signs of cholestasis, such as yellow skin or sclera, dark urine, or light-colored stools.
5. Liver function testing, including ALT, AST, and GGT, should be considered whenever liver dysfunction is suspected, particularly during the first 4 months of treatment.
6. Ticlopidine therapy causes increased serum cholesterol and triglycerides.
7. If a patient is switched from an anticoagulant or fibrinolytic drug to ticlopidine, the former drug should be discontinued prior to ticlopidine administration.
8. For renally impaired patients, it may be necessary to reduce the dosage of ticlopidine or discontinue it if hematopoietic problems are encountered.
9. Your doctor will arrange for you to have your blood tested before you start taking ticlopidine hydrochloride tablets and then every 2 weeks for the first 3 months you are on ticlopidine hydrochloride tablets.

Use in pregnancy or lactation:

- Pregnancy category: B. This drug should be used during pregnancy only if clearly needed.

- 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.