Skip to Content

Ticlopidine Side Effects

In Summary

Commonly reported side effects of ticlopidine include: diarrhea. Other side effects include: dyspepsia, nausea, skin rash, and increased serum alkaline phosphatase. See below for a comprehensive list of adverse effects.

For the Consumer

Applies to ticlopidine: oral tablet

As well as its needed effects, ticlopidine may cause unwanted side effects that require medical attention.

Major Side Effects

If any of the following side effects occur while taking ticlopidine, check with your doctor immediately:

Less common or rare:
  • Abdominal or stomach pain (severe) or swelling
  • back pain
  • blistering, peeling, or loosening of the skin or lips or mucous membranes (moist lining of many body cavities, including the mouth, lips, inside of nose, anus, and vagina)
  • blood in eyes
  • bloody or black tarry stools
  • bruising or purple areas on skin
  • change in mental status
  • convulsions (seizures)
  • coughing up blood
  • dark or bloody urine
  • decreased alertness
  • dizziness
  • fever, chills, or sore throat
  • headache (severe or continuing)
  • joint pain or swelling
  • nosebleeds
  • pale color of skin
  • paralysis or problems with coordination
  • pinpoint red spots on skin
  • red lesions on the skin, often with a purple center
  • red, thickened, or scaly skin
  • sores, ulcers, or white spots in mouth
  • stammering or other difficulty in speaking
  • unusually heavy bleeding or oozing from cuts or wounds
  • unusual tiredness
  • unusually heavy or unexpected menstrual bleeding
  • vomiting of blood or material that looks like coffee grounds
  • weakness
  • yellow eyes or skin

Severity: Moderate

If any of the following side effects occur while taking ticlopidine, check with your doctor or nurse as soon as possible:

More common:
  • Skin rash
Less common or rare:
  • General feeling of discomfort or illness
  • hives or itching of skin
  • ringing or buzzing in ears

Minor Side Effects

Some ticlopidine side effects may not need any medical attention. As your body gets used to the medicine these side effects may disappear. Your health care professional may be able to help you prevent or reduce these side effects, but do check with them if any of the following side effects continue, or if you are concerned about them:

More common:
  • Abdominal or stomach pain (mild)
  • diarrhea
  • indigestion
  • nausea
Less common:
  • Bloating or gas
  • dizziness
  • vomiting

For Healthcare Professionals

Applies to ticlopidine: oral tablet

Hematologic

The majority of cases of neutropenia, agranulocytosis, aplastic anemia, and thrombotic thrombocytopenic purpura occur during the first three months of treatment. US physicians reported 100 cases of TTP between 1992 and 1997. Delayed onset of neutropenia, after discontinuation of ticlopidine, has been reported. Hematologic parameters should be monitored every other week for the first three months of therapy and ticlopidine should be discontinued if laboratory values are altered or if symptoms of infection or bleeding are noted. Thereafter, the patient should be monitored for signs of infection. Patients should be counseled concerning signs and symptoms of TTP (weakness, pallor, petechiae, purpura, dark urine, jaundice or mental status changes) and instructed to discontinue ticlopidine and immediately report any of these findings. Platelet infusions may accelerate thrombosis and should be avoided if possible.

Ecchymosis, epistaxis, hematuria, conjunctival hemorrhage, and gastrointestinal bleeding have been associated with ticlopidine therapy. Intracerebral bleeding occurred in approximately 0.5% of patients in clinical trials.

Postsurgical bleeding may also occur. To minimize the effects of postsurgical bleeding, it is generally recommended that ticlopidine be discontinued 2 weeks before any surgical or dental interventions.[Ref]

Hematologic dyscrasias have been the most serious adverse effects associated with ticlopidine therapy. Reversible neutropenia (severe in 0.9%) occurred in 2.4% of patients. Thrombocytopenia, agranulocytosis, pancytopenia, hemolytic anemia with reticulocytosis, and aplastic anemia have been reported.

Thrombotic thrombocytopenic purpura (TTP), not noted during clinical trials, has occurred at an estimated incidence of 1 case per 2000 to 4000 exposures. Symptoms include thrombocytopenia, microangiopathic hemolytic anemia (fragmented RBCs on a peripheral smear), renal dysfunction, fever, and neurological changes.[Ref]

Gastrointestinal

Gastrointestinal disturbances have been noted in up to 40% of patients. Dyspepsia, nausea, diarrhea, vomiting, flatulence, and gastric pain have occurred. Some gastrointestinal symptoms lessen with continued therapy and administration with food may decrease gastrointestinal intolerance. Cases of ticlopidine-induced chronic diarrhea have been reported.[Ref]

Dermatologic

Two case reports of patients developing maculopapular pruritic rashes following administration of clopidogrel have been reported. The rash recurred in both patients after switching to ticlopidine. In one patient, rechallenge resulted in recurrence of the rash. These two cases illustrate the possibility of cross-sensitivity between thienopyridines.[Ref]

Dermatologic adverse effects have occurred frequently. Rash, generally maculopapular or urticarial, has been experienced in up to 15% of treated patients. At least one case of multiple fixed-drug eruptions, consisting of rash and generalized patches of hyperpigmentation, has been reported.[Ref]

Hepatic

Hepatic side effects typically have been mild and have included reversible elevations in liver function tests (up to 4%). The incidence of cholestatic jaundice has increased. Postmarketing side effects have included hepatitis and hepatic necrosis.[Ref]

Cholestatic jaundice has developed within 1 to 4 months of initiating therapy. Resolution of jaundice and normalization of hepatic enzymes concentrations occurred upon discontinuation of therapy.

Numerous cases of ticlopidine-induced cholestatic hepatitis have been reported. Time to the onset of hepatotoxicity is variable and ranges from 1 week to 6 months after initiating ticlopidine, 2 to 12 weeks in most patients. In one patient, hepatotoxicity appeared 1 month after discontinuing ticlopidine because of rash. Symptoms and liver abnormalities resolved following discontinuation of ticlopidine, typically within 1 to 3 months; however, recovery time may be protracted (i.e. more than 12 months). Cases of irreversible hepatic damage have not been reported.[Ref]

Metabolic

Metabolic disturbances have included persistent elevation of total serum cholesterol.[Ref]

Renal

Reversible renal failure has been reported in patients receiving ticlopidine after stent implantation. Other postmarketing reports have included incidences of nephrotic syndrome.[Ref]

General

Side effects have occurred in up to 50% of patients. Generally, side effects have been mild and most frequently involved the gastrointestinal tract (30% to 40%). Diarrhea, rash, nausea, vomiting, gastric pain, and neutropenia were the primary cause of a 21% discontinuation rate. Asthenia and generalized pain have been reported.[Ref]

Nervous system

Nervous system side effects of dizziness, anorexia, and headache have been reported. Postmarketing reports of peripheral neuropathy have been noted.[Ref]

Hypersensitivity

Postmarketing hypersensitivity reactions have included allergic pneumonitis, angioedema, vasculitis, and serum sickness. Several cases of ticlopidine-induced systemic and cutaneous lupus erythematosus (positive ANA) have been reported. Clinical improvement occurred in all patients following withdrawal of ticlopidine.[Ref]

Musculoskeletal

Postmarketing musculoskeletal side effects have included arthropathy and myositis. At least one case of ticlopidine-associated arthritis has been reported.[Ref]

References

1. Saltiel E, Ward A "Ticlopidine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in platelet-dependent disease states." Drugs 34 (1987): 222-62

2. Mataix R, Ojeda E, Perez MC, Jimenez S "Ticlopidine and severe aplastic anaemia." Br J Haematol 80 (1992): 125-6

3. Quinn MW, Dillard TA "Delayed traumatic hemothorax on ticlopidine and aspirin for coronary stent." Chest 116 (1999): 257-60

4. McTavish D, Faulds D, Goa KL "Ticlopidine. An updated review of its pharmacology and therapeutic use in platelet-dependent disorders [published erratum appears in Drugs 1990 Oct;40(4):following Table of Contents]." Drugs 40 (1990): 238-59

5. "Ticlopidine for prevention of stroke." Med Lett Drugs Ther 34 (1992): 65-6

6. Mallet L, Mallet J "Ticlopidine and fatal anemia in an elderly woman." Ann Pharmacother 28 (1994): 1169-71

7. Janzon L, Bergqvist D, Boberg J, Boberg M, Eriksson I, Lindgarde F, Persson G, Almgren B, Fagher B, Kjellstrom T, et al "Prevention of myocardial infarction and stroke in patients with intermittent claudication; effects of ticlopidine. Results from STIMS, the Swedish Ticlopidine Multicentre Study [published erratum appears in J Intern Med 1990 Dec;228(6):659]." J Intern Med 227 (1990): 301-8

8. Mukamal KJ, Wu B "Ticlopidine-associated thrombotic thrombocytopenic purpura." Ann Intern Med 129 (1998): 837

9. Haynes RB, Sandler RS, Larson EB, Pater JL, Yatsu FM "A critical appraisal of ticlopidine, a new antiplatelet agent. Effectiveness and clinical indications for prophylaxis of atherosclerotic events." Arch Intern Med 152 (1992): 1376-80

10. Ochoa AB, Wolfe M, Lewis P, Lenihan DJ "Ticlopidine-induced neutropenia mimicking sepsis early after intracoronary stent placement." Clin Cardiol 21 (1998): 304-7

11. Farver DK, Hansen LA "Delayed neutropenia with ticlopidine." Ann Pharmacother 28 (1994): 1344-6

12. Steinhubl SR, Tan WA, Foody JM, Topol EJ "Incidence and clinical course of thrombotic thrombocytopenic purpura due to ticlopidine following coronary stenting." JAMA 281 (1999): 806-10

13. Kupfer Y, Tessler S "Ticlopidine and thrombotic thrombocytopenia purpura." N Engl J Med 337 (1997): 1245

14. Martinnunez G, Fdezsoria RR, Sanchezgil F, Benitezcano E "Aplastic anaemia and ticlopidine." Br J Haematol 85 (1993): 633

15. Chen DK, Kim JS, Sutton DMC "Thrombotic thrombocytopenic purpura associated with ticlopidine use - A report of 3 cases and review of the literature." Arch Intern Med 159 (1999): 311-4

16. Page Y, Tardy B, Zeni F, Comtet C, Terrana R, Bertrand JC "Thrombotic thrombocytopenic purpura related to ticlopidine." Lancet 337 (1991): 774-6

17. Garnier G, Taillan B, Pesce A, Chichmanian RM, Dujardin P "Ticlopidine and severe aplastic anaemia." Br J Haematol 81 (1992): 459-60

18. Ceylan C, Kirimli O, Akarsu M, Undar B, Guneri S "Early ticlopidine-induced hepatic dysfunction, dermatitis and irreversible aplastic anemia after coronary artery stenting." Am J Hematol 59 (1998): 260

19. Arribalzaga K, Garciasuarez J, Lopezrubio M, Krsnik I, Calero MA, Delcampo JF "Sustained granulocyte recovery after g-CSF in a patient with ticlopidine-induced severe aplastic anemia." Am J Hematol 50 (1995): 313

20. Ellie E, Durrieu C, Besse P, Julien J, Gbipki-Benissan G "Thrombotic thrombocytopenic purpura associated with ticlopidine ." Stroke 23 (1992): 922-3

21. Dunn P "Aplastic anemia with ticlopidine therapy in two Chinese patients." Ann Pharmacother 30 (1996): 547

22. Muszkat M, Shapira MY, Sviri S, Linton DM, Caraco Y "Ticlopidine-induced thrombotic thrombocytopenic purpura." Pharmacotherapy 18 (1998): 1352-5

23. Ferrer F, DeArriba F, Moraleda JM, Vicente V "Aplastic anaemia induced by ticlopidine after placement of coronary artery stents: Therapeutic role of granulocyte colony-stimulating factor." Clin Drug Invest 15 (1998): 261-2

24. Hass WK, Easton JD, Adams HP, Jr Pryse-Phillips W, Molony BA, Anderson S, Kamm B "A randomized trial comparing ticlopidine hydrochloride with aspirin for the prevention of stroke in high-risk patients. Ticlopidine Aspirin Stroke Study Group." N Engl J Med 321 (1989): 501-7

25. Bennett CL, Davidson CJ, Raisch DW, Weinberg PD, Bennett RH, Feldman MD "Thrombotic thrombocytopenic purpura associated with ticlopidine in the setting of coronary artery stents and stroke prevention." Arch Intern Med 159 (1999): 2524-8

26. Weiner P, Paz R, Zidan F "Severe aplastic anemia due to ticlopidine." Isr J Med Sci 31 (1995): 444-5

27. Desager JP "Clinical pharmacokinetics of ticlopidine." Clin Pharmacokinet 26 (1994): 347-55

28. Ono K, Kurohara K, Yoshihara M, Shimamoto Y, Yamaguchi M "Agranulocytosis caused by ticlopidine and its mechanism." Am J Hematol 37 (1991): 239-42

29. Lesesve JF, Callat MP, Lenormand B, Monconduit M, Noblet C, Moore N, Caron F, Humbert G, Stamatoullas A, Tilly H "Hematological toxicity of ticlopidine." Am J Hematol 47 (1994): 149-50

30. ParadisoHardy FL, Angelo CM, Lanctot KL, Cohen EA "Hematologic dyscrasia associated with ticlopidine therapy: evidence for causality." Can Med Assn J 163 (2000): 1441-8

31. "Product Information. Ticlid (ticlopidine)." Syntex Laboratories Inc, Palo Alto, CA.

32. Carlson JA, Maesner JE "Fatal neutropenia and thrombocytopenia associated with ticlopidine." Ann Pharmacother 28 (1994): 1236-8

33. Bennett CL, Weinberg PD, Rozenberg-Ben-Dror K, Yarnold PR, Kwaan HC, Green D "Thrombotic thrombocytopenic purpura associated with ticlopidine." Ann Intern Med 128 (1998): 541-4

34. Quinn MJ, Fitzgerald DJ "Ticlopidine and clopidogrel." Circulation 100 (1999): 1667-72

35. Dunlop H "Serious hematologic reactions associated with ticlopidine - update." Can Med Assn J 161 (1999): 867-8

36. Khelif A, Assouline D, Ffrench M, Chaumentin G, Viala JJ "Ticlopidine and aplastic anaemia." Br J Haematol 83 (1993): 678-9

37. Bennett CL, Davidson CJ, Green D, Weinberg PD, Feldman MD "Ticlopidine and TTP coronary stenting." JAMA 282 (1999): 1717

38. 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 43 (1993): 27-31

39. Rimbrot S, Kundzinsh E, Levy Y "Invasive aspergillosis in a patient with ticlopidine-induced agranulocytosis." Arch Intern Med 160 (2000): 3498-9

40. Troussard X, Mayo P, Mosquet B, Reman O, Leporrier M "Ticlopidine and severe aplastic anaemia ." Br J Haematol 82 (1992): 779-80

41. Elangovan L "Thrombotic thrombocytopenic purpura associated with ticlopidine use." Arch Intern Med 159 (1999): 1624

42. Mansoor GA, Aziz K "Delayed chronic diarrhea and weight loss possibly due to ticlopidine therapy." Ann Pharmacother 31 (1997): 870-2

43. Bequemin JP "Effect of ticlopidine on the long-term patency of saphenous-vein bypass grafts in the legs." N Engl J Med 337 (1997): 1726-31

44. Berger PB, Bell MR, Hasdai D, Grill DE, Melby S, Holmes DR "Safety and efficacy of ticlopidine for only 2 weeks after successful intracoronary stent placement." Circulation 99 (1999): 248-53

45. Fraga M, Garcia B, Agud JL, Marco J, de Juana P, Cervero M "Severe chronic diarrhea induced by ticlopidine." Ann Pharmacother 30 (1996): 1496

46. Berrebi D, Sautet A, Flejou JF, Dauge MC, Peuchmaur M, Potet F "Ticlopidine induced colitis: a histopathological study including apoptosis." J Clin Pathol 51 (1998): 280-3

47. Borras-Blasco J, Navarro-Ruiz A, Gutierrez-Casbas A, Matarredona-Catala J, Gonzalez-Delgado M "Multiple fixed-drug eruption and diarrhea with ticlopidine." Ann Pharmacother 36 (2002): 344-5

48. Wall GC, Heyneman CA "Calcitonin in phantom limb pain." Ann Pharmacother 33 (1999): 499-501

49. Makkar K, Wilensky RL, Julien MB, Herrmann HC, Spinler SA "Rash with both clopidogrel and ticlopidine in two patients following percutaneous coronary intervention with drug-eluting stents." Ann Pharmacother 40 (2006): 1204-7

50. Cannavo SP, Borgia F, Guarneri F, Vaccaro M "Acute generalized exanthematous pustulosis following use of ticlopidine." Br J Dermatol 142 (2000): 577-8

51. Yosipovitch G, Rechavia E, Feinmesser M, David M "Adverse cutaneous reactions to ticlopidine in patients with coronary stents." J Am Acad Dermatol 41 (1999): 473-6

52. Hsi DH, Mock DT, Rocco TA "Toxic erythroderma due to ticlopidine." N Engl J Med 340 (1999): 1212

53. Ruiz-Valverde P, Zafon C, Segarra A, Ribera R, Piera L "Ticlopidine-induced granulomatous hepatitis." Ann Pharmacother 29 (1995): 633-4

54. Cassidy LJ, Schuster BG, Halparin LS "Probable ticlopidine-induced cholestatic hepatitis." Ann Pharmacother 29 (1995): 30-2

55. Iqbal M, Goenka P, Young MF, Thomas E, Borthwick TR "Ticlopidine-induced cholestatic hepatitis: Report of three cases and review of the literature." Dig Dis Sci 43 (1998): 2223-6

56. Yoder JD, Algozzine GJ, Hill GW "More ticlopidine-induced cholestatic jaundice." Am J Hosp Pharm 51 (1994): 1821-2

57. Colivicchi F, Magnanimi S, Sebastiani F, Silvestri R, Magnanimi R "Ticlopidine-induced chronic cholestatic hepatitis: a case report." Curr Ther Res Clin Exp 55 (1994): 929-31

58. Skurnik YD, Tcherniak A, Edlan K, Sthoeger Z "Ticlopidine-induced cholestatic hepatitis." Ann Pharmacother 37 (2003): 371-5

59. Kubin CJ, Sherman O, Hussain KB, Feinman L "Delayed-onset ticlopidine-induced cholestatic jaundice." Pharmacotherapy 19 (1999): 1006-10

60. Wengrower D "Possible ticlopidine-induced cholestatic jaundice." Am Fam Physician 62 (2000): 1258+

61. Greany JJ, Jr Hess DA, Mahoney CD "Ticlopidine-induced cholestatic jaundice." Clin Pharm 12 (1993): 398-9

62. Klepser TB, Jogerst GJ "Ticlopidine-induced elevated liver enzymes." Pharmacotherapy 17 (1997): 819-21

63. Goff JS "Lansoprazole: A cause of secretory diarrhea." Am J Gastroenterol 93 (1998): 2298-9

64. PerezBalsa AM, DeArce A, Castiella A, Lopez P, Ruibal M, RuizMartinez J, DeMunain AL, Masso JFM "Hepatotoxicity due to ticlopidine." Ann Pharmacother 32 (1998): 1250-1

65. Naschitz JE, Khamessi R, Elias N, Yeshurun D "Ticlopidine-induced prolonged cholestasis." J Toxicol Clin Toxicol 33 (1995): 379-80

66. Azar R, Boldron A, Bakhache E, Elazouzi A "Ticlopidine and renal function." Lancet 348 (1996): 1031

67. Zijlstra F, Elsman P "Ticlopidine and renal function - reply." Lancet 348 (1996): 1031

68. Virdee M, Collinson J, Stables RH "Ticlopidine and renal function." Lancet 348 (1996): 1031-2

69. Spiera RF, Berman RS, Werner AJ, Spiera H "Ticlopidine-induced lupus: a report of 4 cases." Arch Intern Med 162 (2002): 2240-3

70. Persoz CF, Cornella F, Kaeser P, Rochat T "Ticlopidine-induced interstitial pulmonary disease - A case report." Chest 119 (2001): 1963-5

71. Persoz CF, Cornella F, Kaeser P, Rochat T "Ticlopidine-induced interstitial pulmonary disease - A case report." Chest 119 (2001): 1963-5

72. Reich A, Bialynicki-Birula R, Szepietowski JC "Drug-induced subacute cutaneous lupus erythematosus resulting from ticlopidine." Int J Dermatol 45 (2006): 1112-4

73. Dakik HA, Salti I, Haidar R, Uthman IW "Ticlopidine associated with acute arthritis." BMJ 324 (2002): 27

It is possible that some side effects of ticlopidine may not have been reported. These can be reported to the FDA here. Always consult a healthcare professional for medical advice.

Disclaimer: Every effort has been made to ensure that the information provided is accurate, up-to-date and complete, but no guarantee is made to that effect. In addition, the drug information contained herein may be time sensitive and should not be utilized as a reference resource beyond the date hereof. This material does not endorse drugs, diagnose patients, or recommend therapy. This information is a reference resource designed as supplement to, and not a substitute for, the expertise, skill , knowledge, and judgement of healthcare practitioners in patient care. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate safety, effectiveness, or appropriateness for any given patient. Drugs.com does not assume any responsibility for any aspect of healthcare administered with the aid of materials provided. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the substances you are taking, check with your doctor, nurse, or pharmacist.

Hide