Generic Name: Ticlopidine Hydrochloride
Class: 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
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 Ticlid
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Ticlopidine for this use largely has been replaced by other antiplatelet agents.994 1010 ACCP and other experts currently recommend dual-drug antiplatelet therapy with other P2Y12-receptor antagonists (e.g.,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
Acute Coronary Syndromes
Has been used as an alternative to aspirin in patients with unstable angina or non-ST-segment-elevation MI† 991 (i.e., non-ST-segment-elevation acute coronary syndrome) when aspirin therapy has failed, cannot be tolerated, or is contraindicated; however, clopidogrel generally is preferred in these situations.37 991
May be used as an alternative to aspirin therapy in patients with ST-segment-elevation MI† (i.e., ST-segment elevation acute coronary syndrome) who have true aspirin allergy (hives, nasal polyps, bronchospasm, or anaphylaxis); however, clopidogrel generally is preferred in such patients.57
Ticlid 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 Ticlid
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 Ticlid
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, 2004-2016, Selected Revisions November 13, 2015. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.
1. Roche Laboratories, Inc. Ticlid (ticlopidine hydrochloride) tablets prescribing information. Nutley, NJ; 2001 Mar.
2. Saltiel E, Ward A. Ticlopidine: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in platelet-dependent disease states. Drugs. 1987; 34:222-62. [IDIS 236503] [PubMed 3304967]
3. Gent M, Blakely JA, Easton JD et al. The Canadian American Ticlopidine Study (CATS) in thromboembolic stroke. Lancet. 1989; 1:1215-20. [IDIS 255568] [PubMed 2566778]
4. Hass WK, Easton JD, Adams HP Jr et al for the Ticlopidine Aspirin Stroke Group. A randomized trial comparing ticlopidine hydrochloride with aspirin for the prevention of stroke in high-risk patients. N Engl J Med. 1989; 321:501-7. [IDIS 257956] [PubMed 2761587]
5. Balsano F, Rizzon P, Violi F et al. Antiplatelet treatment with ticlopidine in unstable angina. A controlled multicenter clinical trial. Circulation. 1990; 82:17-26. [IDIS 271140] [PubMed 2194694]
6. Desager J-P. Clinical pharmacokinetics of ticlopidine. Clin Pharmacokinet. 1994; 26:347-55. [PubMed 8055680]
7. Anon. Ticlopidine for prevention of stroke. Med Lett Drugs Ther. 1992; 34:65-6. [PubMed 1614367]
8. Haynes RB, Sandler RS, Larson EB et al. A critical appraisal of ticlopidine, a new antiplatelet agent. Effectiveness and clinical indications for prophylaxis of atherosclerotic events. Arch Intern Med. 1992; 152:1376-80. [IDIS 298947] [PubMed 1627017]
9. Ito MK, Smith AR, Lee ML. Ticlopidine: a new platelet aggregation inhibitor. Clin Pharm. 1992; 11:603-17. [IDIS 298182] [PubMed 1617911]
10. McTavish D, Faulds D, Goa KL. Ticlopidine. An updated review of its pharmacology and therapeutic use in platelet-dependent disorders. Drugs. 1990; 40:238-59. [PubMed 2226215]
11. Syntex Laboratories, Inc. Ticlid (ticlopidine hydrochloride) product monograph. 1991 Nov.
12. Ruiz-Valverde P, Zafon C, Segarra A et al. Ticlopidine-induced granulomatous hepatitis. Ann Pharmacother. 1995; 29:633-4. [IDIS 349739] [PubMed 7663041]
13. Yoder JD, Algozzine GJ, Hill GW. More ticlopidine-induced cholestatic jaundice. Am J Hosp Pharm. 1994; 51:1821-2. [IDIS 332667] [PubMed 7942916]
14. Carlson JA, Maesner JE. Fatal neutropenia and thrombocytopenia associated with ticlopidine. Ann Pharmacother. 1994; 28:1236-8. [IDIS 339198] [PubMed 7849334]
15. Greaney JJ Jr, Hess DA, Mahoney CD. Ticlopidine-induced cholestatic jaundice. Clin Pharm. 1993; 12:398-9. [IDIS 314323] [PubMed 8403812]
16. Rodriguez JN, Fernandez-Jurado A, Dieguez JC et al. Ticlopidine and severe aplastic anemia. Am J Hematol. 1994; 47:332. [PubMed 7977309]
17. Elias M, Reichman N, Flatau E. Bone marrow aplasia associated with ticlopidine therapy. Am J Hematol. 1993; 44:289-90. [PubMed 8238004]
18. Grimm IS, Litynski JJ. Severe cholestasis associated with ticlopidine. Am J Gastroenterol. 1994; 89:279-80. [IDIS 325602] [PubMed 8304320]
19. Rosen H, El-Hennawy AS, Greenberg S et al. Acute interstitial nephritis associated with ticlopidine. Am J Kidney Dis. 1995; 25:934-6. [IDIS 347912] [PubMed 7771492]
20. Lesesve J-F, Callat M-P, Lenormand B et al. Hematological toxicity of ticlopidine. Am J Hematol. 1994; 47:149-50. [PubMed 8092140]
21. Farver DK, Hansen LA. Delayed neutropenia with ticlopidine. Ann Pharmacother. 1994; 28:1344-6. [IDIS 340451] [PubMed 7696722]
22. Mallet L, Mallet J. Ticlopidine and fatal aplastic anemia in an elderly woman. Ann Pharmacother. 1994; 28:1169-71. [IDIS 337074] [PubMed 7841572]
23. Kovacs MJ, Soong PY, Chin-Yee IH. Thrombotic thrombocytopenic purpura associated with ticlopidine. Ann Pharmacother. 1993; 27:1060-1. [IDIS 320299] [PubMed 8219438]
24. Mataix R, Ojeda E, del Carmen Perez M et al. Ticlopidine and severe aplastic anemia. Br J Haematol. 1992; 80:125-6. [PubMed 1531614]
25. Troussard X, Mayo P, Mosquet B et al. Ticlopidine and severe aplastic anaemia. Br J Haematol. 1992; 82:779-80. [PubMed 1482671]
26. Khelif A, Assouline D, Ffrench M et al. Ticlopidine and aplastic anemia. Br J Haematol. 1993; 83:678-9. [PubMed 8518187]
27. Martin-Nu˜nez G, Fdez-Soria RR, Sanchez-Gil F et al. Aplastic anaemia and ticlopidine. Br J Haematol. 1993; 85:633. [PubMed 8136291]
28. Caliendo G, Bradbury K, Mehl B. Ticlopidine, bleeding, and surgery. Mt Sinai J Med. 1994; 61:372-3. [PubMed 7969234]
29. Colivicchi F, Magnanimi S, Sebastiani F et al. Ticlopidine-induced chronic cholestatic hepatitis: a case report. Curr Ther Res. 1994; 55:929-31.
30. Page Y, Tardy B, Zeni F et al. Thrombotic thrombodytopenic purpura related to ticlopidine. Lancet. 1991; 337:774-6. [IDIS 279383] [PubMed 1672401]
31. Nurhussein MA. Ticlopidine-induced prolonged cholestasis. J Am Geriatr Soc. 1993; 41:1371-2. [IDIS 323149] [PubMed 8227923]
32. Ellie E, Durrieu C, Besse P et al. Thrombotic thrombocytopenic purpura associated with ticlopidine. Stroke. 1992; 23:922-3. [PubMed 1595122]
33. Roche Laboratories, Nutley, NJ: Personal communication.
35. Wolf PA, Clagett P, Easton JD et al. Preventing ischemic stroke in patients with prior stroke and transient ischemic attack. A statement for healthcare professionals for the Stroke Council of the American Heart Association. Stroke. 1999; 30:1991-4. [PubMed 10471455]
36. Steinhubl SR, Tan WA, Foody JM et al. Incidence and clinical course of thrombotic thrombocytopenic purpura due to ticlopidine following coronary stenting. JAMA. 1999; 281:806-10. [IDIS 420367] [PubMed 10071001]
37. Ryan TJ, Antman EM, Brooks NH et al. ACC/AHA guidelines for the management of patients with acute myocardial infarction: 1999 update: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Management of Acute Myocardial Infarction). From website.
44. Albers GW, Hart RG, Lutsep HL et al. Addendum to the Supplement to the Guidelines for the Management of Transient Ischemic Attacks. Stroke. 2000; 31:1001. [PubMed 10754016]
45. Weisberg LA. The efficacy and safety of ticlopidine and aspirin in non-whites: analysis of a patient subgroup from the Ticlopidine Aspirin Stroke Study. Neurology. 1993; 43:27-31. [IDIS 308714] [PubMed 8423906]
46. Leon MB, Baim DS, Popma JP et al. A clinical trial comparing three antithrombotic-drug regimens after coronary artery stenting. N Engl J Med. 1998; 339: 1665-71.
52. Schor K. Antiplatelet drugs. A comparative review. Drugs. 1995; 50(1):7-28. [PubMed 7588091]
53. Bristol Myers Squibb/Sanofi Pharmaceutical Partnership. Plavix (clopidogrel bisulfate) Clinical Review. New York, NY; 1998.
54. Anon. Clopidogrel for reduction of athersclerotic event. Med Lett Drugs Ther. 1998; 40:59-60. [IDIS 406769] [PubMed 9629123]
55. Bennett CL, Connors JM, Carwile JM et al. Thrombotic thrombocytopenic purpura associated with clopidogrel. N Engl J Med. 2000; 342:1773-7. [IDIS 447769] [PubMed 10852999]
56. The clopidogrel in unstable angina to prevent recurrent events trial investigators. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med. 2001; 345:494-502. [IDIS 468367] [PubMed 11519503]
57. Antman EM, Anbe DT, Armstrong PW et al. ACC/AHA guidelines for the management of patients with ST-elevation acute myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1999 Guidelines for the Management of Patients with Acute Myocardial Infarction). 2004. From website.
65. Gorelick PB, Richardson D, Kelly M et al. Aspirin and ticlopidine for prevention of recurrent stroke in black patients: a randomized trial. JAMA. 2003; 289:2947-57. [PubMed 12799402]
66. Lansky AJ, Hochman JS, Ward PA et al. Percutaneous coronary intervention and adjunctive pharmacotherapy in women: a statement for healthcare professional from the American Heart Association. Circulation. 2005; 111:940-3. [PubMed 15687113]
70. Grines CL, Bonow RO, Casey DE et al. Prevention of premature discontinuation of dual antiplatelet therapy in patients with coronary artery stenosis. A science advisory from the American Heart Association, American College of Cardiology, Society for Cardiovascular Angiography and Interventions, American College of Surgeons, and American Dental Association, with represntatives from the American College of Physicians. Circulation. 2007; 115:813-8. [PubMed 17224480]
71. Sandoz Inc. Ticlopidine hydrochloride tablets prescribing information. Princeton, NJ; 2008 Nov.
72. Teva Pharmaceuticals. Ticlopidine hydrochloride tablets prescribing information. Sellersville, PA; 2009 July.
73. Sudlow CL, Mason G, Maurice JB et al. Thienopyridine derivatives versus aspirin for preventing stroke and other serious vascular events in high vascular risk patients. Cochrane Database Syst Rev. 2009; :CD001246. [PubMed 19821273]
74. Pfisterer M, Brunner-La Rocca HP, Buser PT et al. Late clinical events after clopidogrel discontinuation may limit the benefit of drug-eluting stents. JACC. 2006; 48:2584-91. [PubMed 17174201]
75. Eisenstein EL, Anstrom KJ, Kong DF et al. Clopidogrel use and long-term clinical outcomes after drug-eluting stent implantation. JAMA. 2007;297:159-168.
76. Kereiakes DJ. Does clopidogrel each day keep stent thrombosis away? JAMA. 2007; 297:209-11. Editorial.
77. Spertus JA, Kettelkamp R, Vance C et al. Prevalence, predictors, and outcomes of premature discontinuation of thienopyridine therapy after drug-eluting stent placement. Results from the PREMIER registry. Circulation. 2006; 113:2803-9. [PubMed 16769908]
78. Jeremias A, Sylvia B, Bridges J et al. Stent thrombosis after successful sirolimus-eluting stent implantation. Circulation. 2004 109:1930-2.
79. Ong ATL, McFadden EP, Regar E et al. Late angiographic stent thrombosis (LAST) events with drug-eluting stents. JACC. 2005; 45:2088-92. [PubMed 15963413]
80. Luscher TF, Steffel J, Eberli FR et al. Drug-eluting stent and coronary thrombosis. Biological mechanisms and clinical implications. Circulation. 2007; 115:1051-8. [PubMed 17325255]
81. Maisel WH. Unanswered questions—drug-eluting stents and the risk of late thrombosis. N Engl J Med. 2007; 356:981-4. Editorial. [PubMed 17296826]
82. Savi P, Herbert JM. Clopidogrel and ticlopidine: P2Y12 adenosine diphosphate-receptor antagonists for the prevention of atherothrombosis. Semin Thromb Hemost. 2005 Apr; 31:174-83.
990. Furie KL, Kasner SE, Adams RJ et al. Guidelines for the prevention of stroke in patients with stroke or transient ischemic attack: a guideline for healthcare professionals from the american heart association/american stroke association. Stroke. 2011; 42:227-76. [PubMed 20966421]
991. Anderson JL, Adams CD, Antman EM et al. 2011 ACCF/AHA Focused Update Incorporated Into the ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2011; 123:e426-579.
994. Levine GN, Bates ER, Blankenship JC et al. 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention. A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions. J Am Coll Cardiol. 2011; 58:e44-122. [PubMed 22070834]
1009. Lansberg MG, O'Donnell MJ, Khatri P et al. Antithrombotic and thrombolytic therapy for ischemic stroke: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012; 141(2 Suppl):e601S-36S. [PubMed 22315273]
1010. Vandvik PO, Lincoff AM, Gore JM et al. Primary and secondary prevention of cardiovascular disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012; 141(2 Suppl):e637S-68S.