Ticlid

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., neutropenia^{1 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 anemia^{1 7 16 17 20 22 24 25 26 27 71} ).

  
  


• 
  

  Neutropenia occurred in 2.4% of stroke patients in clinical trials;^{1 71} TTP and aplastic anemia reported rarely.^{1 71}

  
  


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  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}

  
  


• 
  

  Risk factors for development of adverse hematologic effects not identified.^{1 71}

  
  


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  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.)

  
  

Introduction

Platelet-aggregation inhibitor;^{1 2} thienopyridine derivative.^{1 2 48 49 50 52 71}

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 40 59 71}

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}

The American College of Chest Physicians (ACCP) does not recommend use of ticlopidine for stroke prevention;⁵⁹ instead, clopidogrel is recommended as alternative therapy to aspirin for stroke prevention because of a more favorable adverse effect profile.⁵⁹

Prevention of Coronary Artery Stent Thrombosis

Used as an adjunct to aspirin therapy to reduce the incidence of subacute stent thrombosis after percutaneous coronary intervention (PCI) with successful coronary artery stent placement.^{1 46 48 49 62 71}

ACCP and other clinicians currently recommend use of a thienopyridine derivative (i.e., clopidogrel, ticlopidine) as an adjunct to aspirin therapy in patients undergoing PCI and intracoronary stenting.^{49 57 69} However, clopidogrel is preferred over ticlopidine because of a more favorable adverse effect profile.^{48 49 57 62 66 69} Some clinicians suggest ticlopidine may be used in clopidogrel-intolerant patients undergoing PCI.⁶⁶ In patients undergoing stent implantation, ACCP suggests use of ticlopidine or clopidogrel over cilostazol in conjunction with aspirin.⁶⁹

Acute Coronary Syndromes

Has been used as an alternative to aspirin in patients with unstable angina or non-ST-segment-elevation MI†^{38 47 50 58 60 62} (i.e., non-ST-segment-elevation acute coronary syndrome) when aspirin therapy has failed, cannot be tolerated, or is contraindicated.^{37 38 41 42 68}

Has also been used prior to PCI† in patients with unstable angina or non-ST-segment-elevation MI† in conjunction with aspirin or as an alternative to aspirin.⁶⁸

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).⁵⁷

Intermittent Claudication

Has been used as an alternative to aspirin in aspirin-intolerant patients with intermittent claudication†; however, clopidogrel is preferred in such patients.^{39 63}

Ticlid Dosage and Administration

General

Prevention of Coronary Artery Stent Thrombosis

• 
  

  ACCP suggests administering a loading dose prior to stent implantation;^{48 62 68} otherwise, initiate therapy after successful stent implantation.^{1 46 71}

  
  

Administration

Oral Administration

Administer orally with food to maximize GI absorption and tolerance.^{1 2 71}

Dosage

Available as ticlopidine hydrochloride; dosage expressed in terms of the salt.^{1 71}

Adults

Prevention of Thrombotic Stroke

Oral

250 mg twice daily.^{1 71} Has been continued for at least up to 5.8 years in some patients.^{1 2 71}

Prevention of Coronary Artery Stent Thrombosis

Oral

Manufacturer recommends 250 mg twice daily, beginning after stent implantation and continuing for up to 30 days in conjunction with antiplatelet dosages of aspirin.^{1 46 71}

ACCP suggests a ticlopidine loading dose of 500 mg† at least 6 hours before planned PCI when given with aspirin.^{48 62 66 68} For patients unable to tolerate aspirin†, ACCP suggests administration of a ticlopidine loading dose at least 24 hours prior to planned PCI.^{62 68}

ACCP suggests 250 mg twice daily for 2 weeks in addition to aspirin when ticlopidine is used instead of clopidogrel following PCI for placement of a bare-metal stent.^{48 62 66}

Some clinicians suggest that a shorter duration of therapy (i.e., 10–14 days) may reduce the incidence of adverse effects while maintaining efficacy in PCI.^{49 68}

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.^{69 70} (See Compliance with Therapy in Patients with Drug-eluting Stents under Cautions.)

Special Populations

Hepatic Impairment

No specific dosage recommendations at this time;^{1 71} contraindicated in patients with severe hepatic impairment.^{1 71} (See Hepatic Impairment under Cautions.)

Renal Impairment

Reduce dosage or discontinue therapy if hemorrhagic or hematopoietic complications occur.^{1 71}

Geriatric Patients

No specific dosage recommendations at this time.^{1 71}

Cautions for Ticlid

Contraindications

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  Known hypersensitivity to ticlopidine.^{1 9 11 71}

  
  


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  Preexisting hematopoietic disorders (e.g., neutropenia, thrombocytopenia, history of TTP or aplastic anemia).^{1 9 10 11 71} (See Hematologic Toxicity under Cautions.)

  
  


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  Hemostatic disorders or active pathologic bleeding (e.g., bleeding peptic ulcer, intracranial bleeding).^{1 9 10 11 71} (See Conditions Predisposing to Bleeding under Cautions.)

  
  


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  Severe hepatic impairment.^{1 6 9 11 71}

  
  

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.^{1 71}

Metabolic Effects

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}

Major Toxicities

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 59 71}

Hematologic Toxicity

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}

Pancytopenia or leukemia, sometimes fatal, reported rarely during postmarketing experience.^{1 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}

Use contraindicated in patients with preexisting hematopoietic disorders such as neutropenia and thrombocytopenia or a history of either TTP or aplastic anemia.^{1 9 10 11 71}

Compliance with Therapy in Patients with Drug-eluting Stents

Stent thrombosis with potentially fatal sequelae, particularly with DES, associated with premature discontinuance of therapy with a thienopyridine derivative and aspirin.^{70 a b c d e f g}

Before implantation of a DES, carefully assess patients for likelihood of compliance with prolonged dual-drug antiplatelet therapy.^{70 h} Consider avoiding use of a DES in patients who are not expected to comply.^{70 h} (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

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.^{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 time^{1 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}

Hepatic Effects

Possible elevations in liver function test results^{1 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

Use with caution in patients with any systemic disease or condition that may alter metabolism of the drug.^{1 11 71}

Specific Populations

Pregnancy

Category B.^{1 71}

Lactation

Not known whether ticlopidine is distributed into milk;^{1 71} distributed into milk in rats.^{1 11 71} Discontinue nursing or the drug.^{1 9 11 71}

Pediatric Use

Safety and efficacy not established in children <18 years of age.^{1 11 67 71}

Geriatric Use

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}

Hepatic Impairment

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.)

Renal Impairment

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}

Specific Drugs

Drug	Interaction	Comments
Antacids	Decreased plasma ticlopidine concentrations1 71
Anticoagulants	Additive effects1 71	Manufacturer recommends discontinuing anticoagulant therapy prior to initiating ticlopidine1 71
Aspirin, other NSAIAs	Additive effect on platelet aggregation1 71	Use with caution in patients who have lesions with a propensity to bleed (e.g., peptic ulcers)1 71 (see Conditions Predisposing to Bleeding under Cautions) Safety of concomitant use of ticlopidine and aspirin beyond 30 days not established;1 46 71 long-term concomitant use not recommended1
Digoxin	Slight decrease in plasma digoxin concentrations1 71	Little or no change in digoxin efficacy expected1 71
Phenobarbital	No inhibition of platelet aggregation effects of ticlopidine1 71
Phenytoin	Increased plasma phenytoin concentrations with associated somnolence and lethargy reported1 71	Cautious use recommended; monitor plasma phenytoin concentrations1 71
Propranolol	Potential for altered protein binding of propranolol1 71	Cautious use recommended1 71
Theophylline	Decreased elimination half-life and total plasma clearance of theophylline1 71
Thrombolytic agents	Additive effects1 71	Manufacturer recommends discontinuing of thrombolytic agents prior to initiating ticlopidine1 71

Ticlid Pharmacokinetics

Absorption

Bioavailability

Rapidly absorbed (>80%) following oral administration.¹ Peak plasma concentrations at 2 hours.^{1 71}

Food

Increases bioavailability by 20%.^{1 71}

Distribution

Plasma Protein Binding

Binds reversibly (98%), mainly to serum albumin and lipoproteins.^{1 71}

Elimination

Metabolism

Extensively metabolized by the liver.^{1 71}

Elimination Route

Excreted in urine (60%) and feces (23%).^{1 71}

Special Populations

Increased plasma concentrations in patients with advanced cirrhosis.^{1 71} Decreased plasma clearance in patients with mild to moderate renal impairment.^{1 71}

Stability

Storage

Oral

Tablets

15–30°C¹ or 20–25°C.⁷¹

ActionsActions

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  Structurally and pharmacologically related to clopidogrel.^{1 2 48 49 50 52 71}

  
  


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  Time- and dose-dependent inhibition of platelet aggregation and release of platelet granule constituents; also prolongs bleeding time.^{1 71}

  
  


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  Inhibits ADP-induced platelet-fibrinogen binding and subsequent platelet-platelet interactions.^{1 71}

  
  


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  Platelet effects irreversible for the life of the platelet.^{1 71}

  
  

Advice to Patients

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  Importance of routine laboratory monitoring (e.g., CBCs, leukocyte differential, platelet counts).^{1 3 9 11 33 71}

  
  


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  Importance of informing patients of potential adverse effects and toxicities.^{1 71} Importance of immediately informing clinician of signs or symptoms of these adverse effects.^{1 8 9 11 71}

  
  


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  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}

  
  


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  Before implantation of drug-eluting stent (DES), determine likelihood of patient compliance with ≥12 months of aspirin–ticlopidine combination therapy.⁷⁰

  
  


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  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

  
  


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  Importance of patients informing clinicians and dentists that they are receiving ticlopidine prior to scheduling of any surgery or prescription of any new drug.^{1 9 11 71}

  
  


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  Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.^{1 71}

  
  


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  Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.^{1 71}

  
  


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  Importance of informing patients of other important precautionary information. (See Cautions.)^{1 3 9 11 33 71}

  
  

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Ticlopidine Hydrochloride

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Tablets, film-coated	250 mg	Ticlid (with povidone)	Roche

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 03/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Ticlopidine HCl 250MG Tablets (TEVA PHARMACEUTICALS USA): 100/$179.99 or 300/$509.96

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions February 2011. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

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.

34. Albers GW, Easton JD, Sacco RL et al. Antithrombotic and thrombolytic therapy for ischemic stroke. Chest. 1998; 114:(Suppl 5S):683-98S. [IDIS 416749] [PubMed 9822071]

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 and .

38. Cairns JA, Theroux P, Lewis D et al. Antithrombotic agents in coronary artery disease. Chest. 1998; 114(Suppl.5):611-33S.

39. Jackson MR, Clagett GP. Antithrombotic therapy in peripheral arterial occlusive disease. Chest. 1998; 114(Suppl.5):666-82S. [PubMed 9743145]

40. Albers GW, Hart RG, Lutsep HL et al. Supplement to the guidelines for the management of transient ischemic attacks: a statement from the Ad Hoc Committee on Guidelines for the Management of Transient Ischemic Attacks, American Heart Association. Stroke. 1999; 30:2502-11. [PubMed 10548693]

41. Antman EM, Fox KM et al. Guidelines for the diagnosis and management of unstable angina and non-Q-wave myocardial infarction: proposed revisions. Am Heart J. 2000; 139:461-75. [IDIS 444999] [PubMed 10689261]

42. Salem DN, Levine HJ, Pauker SG et al. Antithrombotic therapy in valvular heart disease. Chest. 1998; 114:(Suppl 5S):590-601S.

43. Popma JJ, Weitz J, Bittl JA et al. Antithrombotic therapy in patients undergoing coronary angioplasty. Chest. 1998; 114:(Suppl 5S):728-741S. [IDIS 416752] [PubMed 9822074]

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.

47. Cairns JA, Theroux P, Lewis HD et al. Antithrombotic agents in coronary artery disease. Chest. 2001; 119:228S-52S. [IDIS 459452] [PubMed 11157652]

48. Popma JJ, Ohman EM, Weitz J et al. Antithrombotic therapy in patients undergoing percutaneous coronary intervention. Chest. 2001; 119(Suppl Jan):321S-36S.

49. Smith SC, Dove JT, Jacobs AK et al. ACC/AHA guidelines for percutaneous coronary intervention: executive summary and recommendations: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1993 Guidelines for Percutaneous Transluminal Coronary Angioplasty). Circulation. 2001; 103:3019-3041. [PubMed 11413094]

50. Braunwald E, Antman EM, Beasley JW et al. ACC/AHA guidelines for the management of