Class: Platelet-aggregation Inhibitors
- Antithrombotic Agents
- Platelet-aggregation Inhibitors
Chemical Name: 5-[(2-Chlorophenyl)methyl]-4,5,6,7-tetrahydrothieno[3,2-c]pyridine hydrochloride
Molecular Formula: C14H14ClNS•ClH
CAS Number: 53885-35-1
Medically reviewed by Drugs.com. Last updated on Sep 8, 2020.
Possible life-threatening adverse hematologic effects (e.g., neutropenia1 3 4 7 8 9 10 11 14 71 and/or agranulocytosis,1 7 9 10 20 71 thrombotic thrombocytopenic purpura [TTP],1 7 11 23 30 32 71 aplastic anemia1 7 16 17 20 22 24 25 26 27 71 ).
Incidence of neutropenia, TTP, or aplastic anemia peaks about 4–6, 3–4, or 4–8 weeks, respectively, following initiation of therapy and declines thereafter.1 71 Adverse hematologic effects occur infrequently >3 months after initiation of therapy.1 71
Careful clinical and hematologic monitoring required, especially during the first 3 months of therapy.1 4 11 71 Discontinue therapy immediately if adverse hematologic effects occur.1 71 (See Hematologic Toxicity under Cautions.)
Uses for Ticlopidine
Prevention of 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).1 2 71 72 73
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.1 71 72 73
The American College of Chest Physicians (ACCP) states that use of ticlopidine for secondary prevention of stroke has become severely limited because of the risk of serious adverse effects and the availability of safer antiplatelet agents.1009
Prevention of Coronary Artery Stent Thrombosis
Ticlopidine for this use largely has been replaced by other antiplatelet agents.994 1010 ACCP and other experts currently recommend dual-drug antiplatelet therapy with other P2Y12-receptor antagonists (e.g., clopidogrel, prasugrel, ticagrelor) and aspirin in patients undergoing PCI with stent placement.994 1010
Ticlopidine Dosage and Administration
Prevention of Coronary Artery Stent Thrombosis
Prevention of Thrombotic Stroke
Prevention of Coronary Artery Stent Thrombosis
If ticlopidine is used in combination with aspirin following drug-eluting stent (DES) implantation, combined therapy with ticlopidine and aspirin must be continued for ≥12 months to minimize the risk of potentially catastrophic stent thrombosis.70 (See Compliance with Therapy in Patients with Drug-eluting Stents under Cautions.)
Cautions for Ticlopidine
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.1 71
Possible increased total serum cholesterol concentrations without changes in lipoprotein subfractions;1 4 7 9 11 71 not associated with liver dysfunction or an increase in vascular ischemic events.4 Also, possible increases in triglyceride concentrations.1 71
Possible life-threatening adverse effects; carefully weigh potential benefit of therapy against possible risks involved.1 11 71 All adverse hematologic effects potentially fatal.1 71 Reserve therapy for patients who are unable to tolerate or do not respond adequately to aspirin therapy where indicated to prevent stroke.1 11 71
Possible life-threatening adverse hematologic effects including neutropenia (ANC <1200/mm3)1 3 4 7 8 9 10 11 14 71 and/or agranulocytosis,1 7 9 10 20 71 thrombocytopenia (platelet count <80,000/mm3),1 7 10 11 14 71 TTP (i.e., fever, weakness, pallor, petechiae or purpura, dark urine, jaundice, neurologic changes, and/or acute, unexplained decreases in hemoglobin or platelet count),1 7 11 23 30 32 71 and aplastic anemia (i.e., anemia, thrombocytopenia, and neutropenia together with evidence of depression of myeloid precursors on bone marrow examination).1 7 16 17 20 22 24 25 26 27 71
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;1 4 7 8 10 71 continue monitoring for at least two weeks following discontinuance of ticlopidine within the first 3 months of therapy.1 71 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.1 71 Discontinue therapy immediately if laboratory testing confirms neutropenia (<1200/mm3), TTP, aplastic anemia, or thrombocytopenia (platelet count <80,000/mm3).1 8 11 71 Initiate prompt treatment for TTP (e.g., plasmapheresis) and aplastic anemia (i.e., hematopoietic agents).1 71
Compliance with Therapy in Patients with Drug-eluting Stents
Before implantation of a DES, carefully assess patients for likelihood of compliance with prolonged dual-drug antiplatelet therapy.70 81 Consider avoiding use of a DES in patients who are not expected to comply.70 81 (See Advice to Patients.) In patients who are likely to require invasive or surgical procedures ≤12 months after DES implantation, consider implantation of a bare-metal stent or use of balloon angioplasty with provisional stent implantation instead.70
Clinicians performing invasive procedures must understand the consequences of premature discontinuance of thienopyridine derivative therapy in patients with DES.70 If issues about a patient’s antiplatelet therapy are unclear (e.g., concern about periprocedural bleeding), such professionals should contact the patient’s cardiologist.70 Defer elective procedures with substantial bleeding risk until completion of dual-drug antiplatelet therapy.70 For non-elective procedures that mandate discontinuance of thienopyridine-derivative therapy, continue aspirin therapy if at all possible.70 Restart thienopyridine therapy as soon as possible after the procedure.70
Trauma, Surgery, or Other Pathologic Conditions
Use with caution in patients at risk for increased bleeding from trauma, surgery, or other pathologic conditions.1 71 Discontinue therapy 10–14 days prior to elective surgery to minimize excessive surgical bleeding.1 28 33 71 Administer IV methylprednisolone (20 mg) to normalize prolonged bleeding time1 10 28 71 or platelet transfusions to reverse effect on bleeding.1 33 71 Avoid administering platelets in patients who have had TTP secondary to ticlopidine therapy; such transfusions may accelerate thrombosis.1 33 71
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.1 71 Also, use with caution in patients receiving drugs that may predispose to development of such lesions.1 71
Possible elevations in liver function test results1 3 11 71 (e.g., serum alkaline phosphatase,1 11 18 71 transaminases, and, rarely, bilirubin concentrations);1 11 71 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.1 71
Conditions Altering Ticlopidine Metabolism
Safety and efficacy appear to be similar to that in younger adults in clinical trials;1 2 71 however, increased sensitivity to ticlopidine cannot be ruled out.1 71 Decreased clearance and increased trough plasma concentrations; also, possible increased frequency of adverse GI effects.1 11 71
Possible increased plasma ticlopidine concentrations.1 71 Possible risk for bleeding diathesis.1 6 9 11 71 Use contraindicated in patients with severe hepatic impairment.1 71 (See Contraindications under Cautions and see Special Populations under Pharmacokinetics.)
Possible decreased plasma clearance, increased AUC values, and prolonged bleeding times; use with caution in patients with moderate to severe renal impairment.1 71 Reduce dosage or discontinue therapy if hemorrhagic or hematopoietic complications occur.1 71 Unexpected adverse effects not observed in patients with mild renal impairment; no experience in patients with more severe degrees of impairment.1 71
Common Adverse Effects
Diarrhea,1 4 11 71 nausea,1 4 11 71 dyspepsia,1 4 11 71 rash,1 4 11 71 GI pain,1 4 11 71 neutropenia,1 71 purpura,1 71 vomiting,1 71 flatulence,1 71 pruritus,1 dizziness,1 anorexia,1 71 abnormal liver function test.1 71
Interactions for Ticlopidine
Drugs Metabolized by Hepatic Microsomal Enzymes
Possible increased plasma half-life of concomitantly administered drugs metabolized by hepatic microsomal enzymes; dosage adjustments may be required when initiating or discontinuing ticlopidine therapy.1 71
Aspirin, other NSAIAs
Plasma Protein Binding
Advice to Patients
Importance of immediately discontinuing therapy and contacting clinician if any manifestations suggestive of aplastic anemia (e.g., fever, weakness, pallor, bruising, bleeding from gums or nose, excessive fatigue) or TTP (e.g., fever, weakness, difficulty speaking, seizures, jaundice, dark or bloody urine, pallor, petechiae) occur.1 71
Before implantation of drug-eluting stent (DES), determine likelihood of patient compliance with ≥12 months of aspirin–ticlopidine combination therapy.70
Importance of informing patients prior to hospital discharge about risks associated with premature discontinuance of such combination therapy.70 Importance of informing patient not to discontinue therapy without consulting their prescribing clinician, even if instructed to do so by another health-care professional (e.g., dentist).70
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Ticlopidine Hydrochloride Tablets
AHFS DI Essentials™. © Copyright 2021, Selected Revisions September 18, 2017. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.
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