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Uses

Thrombotic Stroke

Used to reduce the risk of fatal or nonfatal thrombotic stroke in patients who have had either a previous completed thrombotic stroke or stroke precursors (e.g., TIA, transient monocular or partial blindness [amaurosis fugax], reversible ischemic neurologic deficit, minor stroke).

Because of potentially life-threatening adverse effects (see Boxed Warning), reserve for patients who are unable to tolerate or have hypersensitivity to aspirin or those who have failed to respond to aspirin therapy where indicated to prevent stroke.

Clopidogrel preferred by some clinicians as alternative therapy for stroke prevention because of a more favorable adverse effect profile compared with ticlopidine.

Prevention of Coronary Artery Stent Thrombosis

Used as an adjunct to aspirin therapy to reduce the incidence of subacute stent thrombosis in patients undergoing coronary artery stent placement.

Clopidogrel preferred over ticlopidine by some clinicians as adjunctive therapy for prevention of stent thrombosis because of a more favorable adverse effect profile.

Dosage and Administration

General

Prevention of Coronary Artery Stent Thrombosis

• Some clinicians suggest administering a loading dose prior to stent implantation; otherwise, initiate therapy after successful stent implantation.

Administration

Oral Administration

Administer orally with food to maximize GI absorption and tolerance.

Dosage

Available as ticlopidine hydrochloride; dosage expressed in terms of the salt.

Adults

Thrombotic Stroke

Oral

250 mg twice daily.

Prevention of Coronary Artery Stent Thrombosis

Oral

Manufacturer recommends 250 mg twice daily for up to 30 days in conjunction with antiplatelet dosages of aspirin.

Alternatively, some clinicians suggest a ticlopidine loading dose† of 500 mg at least 6 hours prior to stent implantation, followed by 250 mg twice daily for 2 weeks in patients receiving bare-metal stents.

For aspirin-intolerant patients, some clinicians recommend a ticlopidine loading dose† of 500 mg at least 24 hours prior to stent implantation.

Prescribing Limits

Adults

Thrombotic Stroke

Oral

Therapy has been continued for 5.8 years or longer in some patients.

Special Populations

Dosage in Renal Impairment

Reduce dosage or discontinue therapy if hemorrhagic or hematopoietic complications occur.

Cautions

Contraindications

• Known hypersensitivity to ticlopidine.
• Preexisting hematopoietic disorders (e.g., neutropenia, thrombocytopenia, history of TTP or aplastic anemia). (See Hematologic Toxicity under Cautions.)
• Hemostatic disorders or active pathologic bleeding (e.g., bleeding peptic ulcer, intracranial bleeding). (See Conditions Predisposing to Bleeding under Cautions.)
• Severe hepatic impairment.

Warnings/Precautions

Warnings

Concomitant Anticoagulant Therapy

Tolerance and long-term safety of concomitant heparin, oral anticoagulants, or fibrinolytic agents not established; manufacturer recommends discontinuing anticoagulants and fibrinolytic drugs prior to initiating ticlopidine.

Metabolic Effects

Possible increased total serum cholesterol concentrations without changes in lipoprotein subfractions; not associated with liver dysfunction or an increase in vascular ischemic events. Also, possible increases in triglyceride concentrations.

Major Toxicities

Possible life-threatening adverse effects; carefully weigh potential benefit of therapy against possible risks involved. All adverse hematologic effects potentially fatal. Reserve therapy for patients who are unable to tolerate or do not respond adequately to aspirin therapy where indicated to prevent stroke.

Hematologic Toxicity

Possible life-threatening adverse hematologic effects including neutropenia (ANC <1200/mm³) and/or agranulocytosis, thrombocytopenia (platelet count <80,000/mm³), TTP (i.e., fever, weakness, pallor, petechiae or purpura, dark urine, jaundice, neurologic changes, and/or acute, unexplained decreases in hemoglobin or platelet count), and aplastic anemia (i.e., anemia, thrombocytopenia, and neutropenia together with evidence of depression of myeloid precursors on bone marrow examination).

Pancytopenia or leukemia, sometimes fatal, reported rarely during postmarketing experience.

Perform CBCs (including platelet count) and leukocyte differentials prior to initiation of therapy and every 2 weeks to the end of the third month of therapy; continue monitoring for at least two weeks following discontinuance of ticlopidine within the first 3 months of therapy. Monitor more frequently or continue monitoring after the first 3 months of therapy if clinical manifestations (e.g., suggestive of or consistent with infection) or laboratory evidence (e.g., neutrophil count <70% of baseline count, decrease in hematocrit or platelet count) suggest incipient adverse hematologic effects. Discontinue therapy immediately if laboratory testing confirms neutropenia (<1200/mm³), TTP, aplastic anemia, or thrombocytopenia (platelet count <80,000/mm³). Initiate prompt treatment for TTP (e.g., plasmapheresis) and aplastic anemia (i.e., hematopoietic agents).

Use contraindicated in patients with preexisting hematopoietic disorders such as neutropenia and thrombocytopenia or a history of either TTP or aplastic anemia.

General Precautions

Trauma, Surgery, or Other Pathologic Conditions

Use with caution in patients at risk for increased bleeding from trauma, surgery, or other pathologic conditions. Discontinue therapy 10–14 days prior to elective surgery to minimize excessive surgical bleeding. Administer IV methylprednisolone (20 mg) to normalize prolonged bleeding time or platelet transfusions to reverse effect on bleeding. Avoid administering platelets in patients who have had TTP secondary to ticlopidine therapy; such transfusions may accelerate thrombosis.

Conditions Predisposing to Bleeding

Possible prolonged template bleeding time; use with caution in patients who have lesions (e.g., peptic ulcers) with a propensity to bleed. Also, use with caution in patients receiving drugs that may predispose to development of such lesions.

Hepatic Effects

Possible elevations in liver function test results (e.g., serum alkaline phosphatase, transaminases, and, rarely, bilirubin concentrations); monitoring of hepatic function (e.g., ALT, AST, γ-glutamyltransferase concentrations) recommended when hepatic dysfunction is suspected, especially during the first 4 months of therapy.

Conditions Altering Ticlopidine Metabolism

Use with caution in patients with any systemic disease or condition that may alter metabolism of the drug.

Specific Populations

Pregnancy

Category B.

Lactation

Not known whether ticlopidine is distributed into milk; distributed into milk in rats. Discontinue nursing or the drug.

Pediatric Use

Safety and efficacy not established in children <18 years of age.

Geriatric Use

Safety and efficacy appear to be similar to that in younger adults in clinical trials; however, increased sensitivity to ticlopidine cannot be ruled out. Decreased clearance and increased trough plasma concentrations; also, possible increased frequency of adverse GI effects.

Hepatic Impairment

Possible increased plasma ticlopidine concentrations. Possible risk for bleeding diathesis. Use contraindicated in patients with severe hepatic impairment. (See Contraindications under Cautions and see Special Populations under Pharmacokinetics.)

Renal Impairment

Possible decreased plasma clearance, increased AUC values, and prolonged bleeding times; use with caution in patients with moderate to severe renal impairment. Reduce dosage or discontinue therapy if hemorrhagic or hematopoietic complications occur. Unexpected adverse effects not observed in patients with mild renal impairment.

Common Adverse Effects

Diarrhea, nausea, dyspepsia, rash, GI pain, neutropenia, purpura, vomiting, flatulence, pruritus, dizziness, anorexia, abnormal liver function test.