OVERVIEW

CASE REPORTS

PRODUCT INFORMATION

REPRESENTATIVE TRADE NAMES

Ticlopidine – Generic, Ticlid®

DRUG CLASS

Antithrombotic Agents

COMPLETE LABELING

Product labeling at DailyMed, National Library of Medicine, NIH

CHEMICAL FORMULA AND STRUCTURE

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DRUG	CAS REGISTRY NUMBER	MOLECULAR FORMULA	STRUCTURE
Ticlopidine	55142-85-3	C14-H14-Cl-N-S

CITED REFERENCES

1.

Skurnik YD, Tcherniak A, Edlan K, Sthoeger Z. Ticlopidine-induced cholestatic hepatitis. Ann Pharmacother. 2003;37:371–5. [PubMed: 12639165]

2.

Chen LK, Hsieh BH, Chen WC, Tsai ST, Hou MC. Ticlopidine-induced hepatitis. Zhonghua Yi Xue Za Zhi (Taipei). 2001;64:59–63. [PubMed: 11310373]

3.

Nurhussein MA. Ticlopidine-induced prolonged cholestasis. J Am Geriatr Soc. 1993;41:1371–2. [PubMed: 8227923]

ANNOTATED BIBLIOGRAPHY

References updated: 25 September 2020

• Zimmerman HJ. Platelet aggregation inhibitors. Drugs used in cardiovascular disease. In, Zimmerman HJ. Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver. 2nd ed. Philadelphia: Lippincott, 1999, pp. 641-3.

  (Textbook of hepatotoxicity published in 1999; ticlopidine is said to have been implicated in at least 32 cases of cholestatic and 2 of hepatocellular liver injury, usually with onset within 6 weeks of starting).
• De Marzio DH, Navarro VJ. Hepatotoxicity of cardiovascular and antidiabetic drugs. In, Kaplowitz N, DeLeve LD, eds. Drug-induced liver disease. 3rd ed. Amsterdam: Elsevier, 2013, pp. 520-40.

  (Review of hepatotoxicity of antiplatelet drugs including ticlopidine which has been linked to more than 30 cases of acute liver injury).
• Hogg K, Weitz JI. Blood coagulation and anticoagulant, fibrinolytic, and antiplatelet drugs. In, Brunton LL, Hilal-Dandan R, Knollman BC, eds. Goodman & Gilman's the pharmacological basis of therapeutics. 13th ed. New York: McGraw-Hill, 2018, pp. 849-76.

  (Textbook of pharmacology and therapeutics).
• Biour M, Toussaint P, Duhamel G, Canuel C, Krulick M, Calmus Y. Therapie. 1982;37:222–4. [Ticlopidine: blood and liver involvement?] French. [PubMed: 7112492]

  (5 cases of severe side effects due to ticlopidine, one liver-related: 48 year old man developed jaundice and pruritus 3 months after starting ticlopidine [bilirubin 26.3 mg/dL, ALT 80 U/L, Alk P 1000 U/L], resolving over next 7 months).
• Deschamps JP, Lassègue A, Ottignon Y, Vuitton D, Allemand H, Carayon P, Miguet JP. Gastroenterol Clin Biol. 1982;6:595–6. [Cholestatic jaundice associated with ingestion of ticlopidine: apropos of the first 2 cases] French. [PubMed: 7117772]

  (2 cases: 45 year old woman developed rash followed by pruritus and jaundice 24 days after starting ticlopidine [bilirubin 5.8 mg/dL, ALT 405 U/L, Alk P 500 U/L], jaundice resolving 1 month and Alk P elevations 10 months after stopping; 82 year old woman developed jaundice 20 days after starting ticlopidine [bilirubin 12.9 mg/dL, ALT 180 U/L, Alk P 550 U/L], jaundice resolving in 3 and Alk P elevations 10 months after stopping).
• Saint-Marc Girardin MF, Cordonnier C. Gastroenterol Clin Biol. 1982;6:716–7. [Cholestatic icterus and agranulocytosis due to ticlopidine] French. [PubMed: 7129024]

  (86 year old woman developed jaundice and agranulocytosis 4 weeks after starting ticlopidine [bilirubin 7.1 rising to 15.8 mg/dL, ALT 42 U/L, Alk P 180 U/L, white count 1000/µL], with progressive pancytopenia, sepsis and death 2 weeks after presentation).
• Eugene C, Lefebvre JF, Gury B, Quevauvilliers J. Sem Hop. 1983;59:2923–4. [Cholestatic hepatitis. Presumptive role of ticlopidine] French. [PubMed: 6318329]

  (71 year old woman developed jaundice within 10 days of starting ticlopidine [bilirubin 5.3 mg/dL, ALT 6 times ULN, Alk P 4 times ULN], resolving within 1 month of stopping).
• 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. 1989;321:501–7. [PubMed: 2761587]

  (Among 3069 patients with high risk from stoke treated with ticlopidine or aspirin for 2 to 6 years, side effects of ticlopidine included diarrhea [20.4% vs 9.8%], rash [11.9% vs 5.2%], and severe but reversible neutropenia [0.9% vs none] usually within first 3 months; no mention of liver injury or ALT elevations).
• Gent M, Blakely JA, Easton JD, Ellis DJ, Hachinski VC, Harbison JW, Panak E, et al. The Canadian American Ticlopidine Study (CATS) in thromboembolic stroke. Lancet. 1989;1:1215–20. [PubMed: 2566778]

  (Among 1072 patients treated with ticlopidine or placebo after thromboembolic stroke, side effects included severe neutropenia [1% vs 0.1%], rash [15% vs 8%], diarrhea [22% vs 10%], and abnormal liver function [4.4% vs 1.5%] which was severe in 2 patients on ticlopidine).
• Janzon L, Bergqvist D, Boberg J, Boberg M, Eriksson I, Lindgärde F, Persson G, et al. Prevention of myocardial infarction and stroke in patients with intermittent claudication; effects of ticlopidine. Results from STIMS, the Swedish Ticlopidine Multicentre Study. J Intern Med. 1990;227:301–8. [PubMed: 2187948]

  (Among 687 patients with intermittent claudication treated with ticlopidine or placebo for up to 5 years, side effects included diarrhea [22% vs 9%], rash [3.5 vs 1.8%], cytopenia [1.8% vs none], and hepatic symptoms [1.7% vs 1.8%]).
• Balsano F, Rizzon P, Violi F, Scrutinio D, Cimminiello C, Aguglia F, Pasotti C, et al. Antiplatelet treatment with ticlopidine in unstable angina. A controlled multicenter clinical trial. The Studio della Ticlopidina nell'Angina Instabile Group. Circulation. 1990;82:17–26. [PubMed: 2194694]

  (Among 652 patients with unstable angina treated with ticlopidine or placebo for 6 months, side effects requiring discontinuation included diarrhea, nausea, abdominal pain and rash, but no mention of liver injury or ALT elevations).
• Mammarella A, Paoletti V, Moroni C, Cassone R. Clin Ter. 1991;138:45–6. [Ticlopidine-induced cholestatic jaundice] Italian. [PubMed: 1834400]

  (67 year old man developed jaundice 2 weeks after starting ticlopidine [bilirubin 26.9 mg/dL, ALT 122 U/L, Alk P 1156 U/L], resolving within 3 months of stopping).
• Miyahara K, Kasahara N, Kondo Y, Imai Y, Matuzaki F. Changes in plasma lipids and abnormal lipoproteins in a patient with drug-induced cholestatic hepatitis. Jpn J Med. 1991;30:354–9. [PubMed: 1942649]

  (65 year old woman developed rash and abdominal pain 2 weeks after starting ticlopidine and jaundice 2 weeks later despite stopping therapy [bilirubin 22.3 mg/dL, ALT 395 U/L, GGT 3,326 U/L], with resolution in 2 months but persistence of GGT elevations [796 U/L 6 months later]).
• Greany JJ Jr, Hess DA, Mahoney CD. Ticlopidine-induced cholestatic jaundice. Clin Pharm. 1993;12:398–9. [PubMed: 8403812]

  (78 year old woman developed jaundice 6 weeks after starting ticlopidine [bilirubin 6.3 mg/dL, ALT 550 U/L, Alk P 330 U/L], resolving with stopping drug but little follow up available).
• Nurhussein MA. Ticlopidine-induced prolonged cholestasis. J Am Geriatr Soc. 1993;41:1371–2. [PubMed: 8227923]

  (92 year old man developed elevated enzymes [ALT 293 U/L, AST 358 U/L, Alk P 154 U/L] 4 weeks after starting ticlopidine and was found to be jaundiced with a cholestatic hepatitis 3-4 weeks later [bilirubin 5.4 mg/dL, ALT 96 U/L, Alk P 648 U/L], resolving within the next two months: Case 3).
• Sondag D, Bader R, Claude P, Schreiber M. Ann Gastroenterol Hepatol (Paris). 1993;29:40–1. [Hepatitis due to ticlopidine: a new case] French. [PubMed: 8442652]

  (60 year old man developed jaundice 6 weeks after starting ticlopidine [bilirubin not given, ALT 458 U/L, Alk P 252 U/L, GGT 920 U/L], resolving rapidly).
• Weber E, Donckier J. Acta Clin Belg. 1994;49:309–10. [Cholestatic jaundice due to ticlopidine: a new case] French. [PubMed: 7871938]

  (63 year old man developed jaundice 6 weeks after starting ticlopidine [bilirubin 4.3 mg/dL, ALT 156 U/L, Alk P 353 U/L], resolving within 1 month of stopping).
• Yoder JD, Algozzine GJ, Hill GW. More ticlopidine-induced cholestatic jaundice. Am J Hosp Pharm. 1994;51:1821–2. [PubMed: 7942916]

  (Two cases; 69 year old woman developed jaundice and nausea 1 week after starting ticlopidine [bilirubin 2.0 mg/dL, ALT 183 U/L, Alk P 442 U/L], resolving rapidly once drug was stopped; 84 year old woman developed jaundice within 3 weeks of starting ticlopidine [bilirubin 8.5 mg/dL, ALT 217 U/L, Alk P 584 U/L], resolving within 2 months of stopping).
• Grimm IS, Litynski JJ. Severe cholestasis associated with ticlopidine. Am J Gastroenterol. 1994;89:279–80. [PubMed: 8304320]

  (92 year old man developed jaundice 3 months after starting ticlopidine [bilirubin 22.1 mg/dL, ALT 140 U/L, Alk P 577 U/L], resolving within 4 months of stopping).
• Colvicchi F, Magnanimi S, Sebastiani F, Silvestri R, Magnanimi R. Ticlopidine-induced chronic cholestatic hepatitis: a case report. Curr Ther Res. 1994;55:929–31.

  (76 year old man developed jaundice and pruritus 40 days after starting ticlopidine [bilirubin 7.5 mg/dL, ALT 90 U/L, Alk P 910 U/L], symptoms resolving upon stopping, but liver tests still abnormal 1 year later [bilirubin 2.2 mg/dL, ALT 66 U/L, Alk P 760 U/L]).
• Cassidy LJ, Schuster BG, Halparin LS. Probable ticlopidine-induced cholestatic hepatitis. Ann Pharmacother. 1995;29:30–2. [PubMed: 7711343]

  (76 year old man developed jaundice 3 weeks after starting ticlopidine [bilirubin 18.0 mg/dL, AST 266 U/L, Alk P 580 U/L, GGT 769 U/L], resolving within 3 months of stopping).
• Ruiz-Valverde P, Zafon C, Segarra A, Ribera R, Piera L. Ticlopidine-induced granulomatous hepatitis. Ann Pharmacother. 1995;29:633–4. [PubMed: 7663041]

  (75 year old man developed fatigue 4 weeks after starting ticlopidine [bilirubin 0.7 mg/dL, ALT 50 U/L, Alk P 1526 U/L, GGT 886 U/L], resolving upon stopping).
• Miras Parra FJ, Gómez Jiménez FJ, García Contreras T, Valverde Romera M. Rev Esp Enferm Dig. 1995;87:414–5. [Ticlopidine-induced cholestatic hepatitis] Spanish. [PubMed: 7626305]

  (70 year old woman developed jaundice approximately 4 months after starting ticlopidine [bilirubin 10.1 mg/dL, ALT 487 U/L, GGT 286 U/L], resolving within 1 month of stopping).
• Naschitz JE, Khamessi R, Elias N, Yeshurun D. Ticlopidine-induced prolonged cholestasis. J Toxicol Clin Toxicol. 1995;33:379–80. [PubMed: 7629910]

  (78 year old woman developed fatigue and pruritus 2 weeks after starting ticlopidine [bilirubin 1.7 mg/dL, ALT 285 U/L, Alk P 220 U/L, GGT 2085 U/L], resolving within 2 months of stopping).
• López P, Castiella A, Bujanda L, Arenas JI. Rev Esp Enferm Dig. 1995;87:735–7. [Ticlopidine-induced cholestatic hepatitis. A case report] Spanish. [PubMed: 8519541]

  (74 year old man developed jaundice 3 months after starting ticlopidine [bilirubin 4.7 mg/dL, ALT 745 U/L, Alk P 499 U/L], resolving within 3 months of stopping).
• Roy L, Plante M-A, Perreault H, Biron P. Cholestatic hepatitis: ticlopidine suspected. Therapie. 1995;50:593–4. [PubMed: 8745964]

  (72 year old woman developed jaundice 3 weeks after starting ticlopidine [bilirubin 2.2 rising to 7.3 mg/dL, ALT 2661 U/L, Alk P 910 U/L], resolving within 6 weeks of stopping).
• Pistone AM, Podesta F, Raviolo E, Testa D, Grosso B, Toselli P, Nyffeneger G. Recenti Prog Med. 1986;77:188–90. [Cholestatic fatty liver of probably iatrogenic origin] Italian. [PubMed: 3715186]

  (54 year old woman developed jaundice 1 month after starting ticlopidine [bilirubin 12.6 mg/dL, ALT 112 U/L, Alk P 856 U/L], with slow and incomplete recovery after stopping).
• Pascual S, Sarrión JV, Jarque I, Argüello L, Berenguer J. Gastroenterol Hepatol. 1996;19:208–9. [Cholestatic hepatitis and anemia induced by ticlopidine] Spanish. [PubMed: 8665360]

  (65 year old woman developed jaundice 3 months after starting ticlopidine [bilirubin 11 mg/dL, ALT 126 U/L, Alk P 830 U/L, GGT 2296 U/L], resolving within 3 months of stopping).
• Klepser TB, Jogerst GJ. Ticlopidine-induced elevated liver enzymes. Pharmacotherapy. 1997;17:819–21. [PubMed: 9250564]

  (82 year old woman developed fatigue 6 weeks after starting ticlopidine [bilirubin 0.7 mg/dL, ALT 69 U/L, Alk P 649 U/L, GGT 1385 U/L], symptoms resolving rapidly but liver test abnormalities requiring 6 months to resolve).
• Díaz Fuenzalida A, Valdés Socín H, Laudano O, Avagnina A, Findor JA. Gastroenterol Hepatol. 1997;20:128–30. [Cholestasis associated with ticlopidine] Spanish. [PubMed: 9162532]

  (56 year old man developed jaundice 3 months after starting ticlopidine [bilirubin 20.8 mg/dL, ALT 48 U/L, Alk P 1100 U/L], resolving within 4 months of stopping).
• Yim HB, Lieu PK, Choo PW. Ticlopidine induced cholestatic jaundice. Singapore Med J. 1997;38:132–3. [PubMed: 9269384]

  (65 year old woman developed jaundice 2 months after starting ticlopidine [bilirubin 6.9 mg/dL, ALT 251 U/L, Alk P 1158 U/L], with incomplete resolution 3 months later when she died of a stroke).
• Guzzini F, Banfi L, Gomitoni A, Marchegiani C, Novati P, Mesina M, Frigerio B. Recenti Prog Med. 1997;88:124–7. [2 cases of acute cholestasis caused by ticlopidine] Italian. [PubMed: 9173469]

  (29 and 73 year old women developed jaundice 3 and 4 weeks after starting ticlopidine [bilirubin 3.1 and 7.4 mg/dL, ALT 244 and 101 U/L, Alk P 814 and 873 U/L], resolving within 3 months of stopping in one and after a year in the other).
• Flamenbaum M, Zenut M, Castillo D, Costes-Charlet N, Kemeny JL, Lavarenne J, Cassan P. Therapie. 1997;52:610–1. [Granulomatous hepatitis and ticlopidine] French. [PubMed: 9734117]

  (65 year old woman developed rash followed by jaundice one month after starting ticlopidine [bilirubin 3 times ULN, ALT 13 times ULN, Alk P 6 times ULN], resolving within 5 months).
• Friedman ND, Sitlington R, Lodge RS. Thrombocytopenia and hepatitis complicating ticlopidine therapy. Aust N Z J Med. 1997;27:599. [PubMed: 9404597]

  (72 year old man developed jaundice, pruritus and rash 1 month after starting ticlopidine [bilirubin 4.9 mg/dL, AST 42 U/L, Alk P 143 U/L, GGT 412 U/L], resolving within 3 months of stopping).
• San Juan Portugal F, Jiménez Saez J, Naya Manchado J, Fuentes Solsona F. An Med Interna. 1997;14:540–1. [Cholestatic hepatitis due to ticlopidine: a report of a new case] Spanish. [PubMed: 9424151]

  (54 year old man developed jaundice 2 months after starting ticlopidine [bilirubin 4.5 mg/dL, ALT 295 U/L, Alk P 689 U/L], resolving within 2 months of stopping).
• Sánchez-Bisonó JR, Gómez-Moli J, Escudero-Cantó M. Probable ticlopidine-induced severe aplastic anemia and cholestatic hepatitis. Haematologica. 1997;82:639. [PubMed: 9407743]

  (67 year old man developed jaundice and pancytopenia 8 weeks after starting ticlopidine [bilirubin 18 mg/dL, ALT 24 U/L, Alk P 512 U/L], resolving within 3 weeks of stopping).
• Artímez ML, Fernández E, Rodríguez M, González M, Rodrigo L. Rev Esp Enferm Dig. 1997;89:796–7. [Toxic hepatitis by ticlopidine. Three new cases] Spanish. [PubMed: 9424112]

  (Three patients, 86, 83 and 72 year olds, 2 men and 1 woman, developed jaundice 1-2 months after starting ticlopidine [bilirubin 3.2, 11.1 and 25.3 mg/dL, ALT 196, 363 and 225 U/L, Alk P 1033, 2130 and 1072 U/L], resolving 1-2 months after stopping).
• Ceylan C, Kirimli O, Akarsu M, Undar B, Güneri S. Early ticlopidine-induced hepatic dysfunction, dermatitis and irreversible aplastic anemia after coronary artery stenting. Am J Hematol. 1998;59:260. [PubMed: 9798669]

  (68 year old woman developed fever and rash 2 weeks after starting ticlopidine [bilirubin 3.7 mg/dL, ALT 423 U/L, Alk P 317 U/L], with aplastic anemia leading rapidly to sepsis and death).
• Sossai P, Corte GD, Marenzi R. Liver injury with the use of ticlopidine. Ann Pharmacother. 1998;32:1370–1. [PubMed: 9876823]

  (51 year old man developed liver test abnormalities 2 weeks after starting ticlopidine [bilirubin 1.0 mg/dL, ALT 200 U/L, Alk P 632 U/L], which resolved within 3 weeks of stopping).
• Martínez Pérez-Balsa A, De Arce A, Castiella A, López P, Ruibal M, Ruiz-Martínez J, López De Munain A, Martí Massó JF. Hepatotoxicity due to ticlopidine. Ann Pharmacother. 1998;32:1250–1. [PubMed: 9825098]

  (51 year old woman developed pruritus and skin rash 6 weeks after starting ticlopidine [bilirubin 0.5 mg/dL, ALT 575 U/L, Alk P 1069 U/L], resolving within 4 months of stopping; skin rash later diagnosed as eczema).
• 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. 1998;43:2223–6. [PubMed: 9790457]

  (3 cases, all women, ages 74-84 years, onset after 2-4 weeks with jaundice [bilirubin 3.8- 32.4 mg/dL, ALT 119-353 U/L, Alk P 326-454 U/L, GGT 263-780 U/L], resolving in 6 to 12 weeks; review of 28 cases in literature).
• Wegmann C, Müaier R, Dormann AJ, Huchzermeyer H. Dtsch Med Wochenschr. 1998;123:146–50. [Ticlopidine-induced acute cholestatic hepatitis] German. [PubMed: 9505953]

  (52 year old man developed pruritus after 4 and jaundice after 6 weeks of ticlopidine [peak bilirubin 26.4 mg/dL, ALT 197 U/L, Alk P 420 U/L], with prolonged jaundice and resolution 10 weeks after stopping).
• Grieco A, Vecchio FM, Greco AV, Gasbarrini G. Cholestatic hepatitis due to ticlopidine: clinical and histological recovery after drug withdrawal. Case report and review of the literature. Eur J Gastroenterol Hepatol. 1998;10:713–5. [PubMed: 9744703]

  (72 year old woman developed jaundice 6 months after starting ticlopidine [bilirubin 4.4 mg/dL, ALT 466 U/L, Alk P 802 U/L, GGT 456 U/L], resolving in 3 months documented by second liver biopsy).
• Carvajal García-Pando A, García Ortega P, Rueda de Castro AM, García del Pozo J. Med Clin (Barc). 1999;112:557–8. [Ticlopidine and hepatic adverse reactions. Data from the Spanish drug surveillance system] Spanish. [PubMed: 10363248]

  (Between 1990-98, 301 adverse reactions to ticlopidine were reported to a Spanish registry of which 47 [21%] were hepatic [2.15:10,000 person-years]; among 10 "definite" cases, latency ranged from 7-55 days and most were cholestatic, no fatalities).
• Amaro P, Nunes A, Macoas F, Ministro P, Baranda J, Cipriano A, Martins I, et al. Ticlopidine-induced prolonged cholestasis: a case report. Eur J Gastroenterol Hepatol. 1999;11:673–6. [PubMed: 10418941]

  (60 year old man developed jaundice and pruritus 3 months after starting ticlopidine [bilirubin 7.8 rising to 30 mg/dL, ALT 97 U/L, Alk P 193 to 410 U/L] with subsequent protracted course, with jaundice for 5.5 months and persistent but asymptomatic elevations in Alk P [320 U/L] and GGT [450 U/L]).
• Kubin CJ, Sherman O, Hussain KB, Feinman L. Delayed-onset ticlopidine-induced cholestatic jaundice. Pharmacotherapy. 1999;19:1006–10. [PubMed: 10453975]

  (86 year old man developed rash 2 weeks after starting ticlopidine with subsequent jaundice despite promptly stopping [bilirubin 0.8 rising to 24.4 mg/dL, ALT 15 to 353 U/L, Alk P 68 to 445 U/L], resolving over following 3 months).
• Torrano Larrión F. Aten Primaria. 1999;24:115. [Cholestatic hepatitis from ticlopidine] Spanish. [PubMed: 10432757]

  (69 year old woman developed fatigue 5 weeks after starting ticlopidine [bilirubin 0.3 mg/dL, ALT 220 U/L, Alk P 399 U/L, GGT 371 U/L], resolving within 2 weeks of stopping).
• Meyer MI, Kuhn M, Bühler H, Bertschinger P. Schweiz Med Wochenschr. 1999;129:1405–9. [Ticlopidine-induced cholestasis] German. [PubMed: 10542998]

  (82 year old man developed pruritus after 3 and jaundice after 4 weeks of ticlopidine therapy [bilirubin 7.5 mg/dL, ALT 194 U/L, Alk P 923 U/L, GGT 823 U/L], with resolution of symptoms but persistence of Alk P elevations 8 months later).
• Zeolla MM, Carson JJ. Successful use of clopidogrel for cerebrovascular accident in a patient with suspected ticlopidine-induced hepatotoxicity. Ann Pharmacother. 1999;33:939–41. [PubMed: 10492495]

  (79 year old woman developed elevations in serum enzymes 5 weeks after starting ticlopidine [bilirubin 0.3 mg/dL, ALT 1008 U/L, Alk P 648 U/L]) without jaundice or symptoms, and levels fell to near normal within 20 days of switching to clopidogrel and were completely normal 4 months later).
• Remy AJ, Heran B, Galindo G, Tapie C, Khemissa F, Larrey D. Gastroenterol Clin Biol. 1999;23:151–2. [A new drug responsible for microvesicular steatosis: ticlopidine] [PubMed: 10219621]

  (80 year old woman developed jaundice 2 weeks after starting ticlopidine [bilirubin 11.5 mg/dL, ALT 3 times ULN, Alk P 4 times ULN, GGT 40 times ULN], biopsy showing cholestasis and steatosis, resolving within 4 months of stopping).
• Bertrand ME, Rupprecht HJ, Urban P, Gershlick AH. CLASSICS Investigators. Double-blind study of the safety of clopidogrel with and without a loading dose in combination with aspirin compared with ticlopidine in combination with aspirin after coronary stenting: the clopidogrel aspirin stent international cooperative study (CLASSICS). Circulation. 2000;102:624–9. [PubMed: 10931801]

  (Among 1020 patients undergoing coronary artery stenting treated with aspirin and either clopidogrel or ticlopidine, side effects requiring early discontinuation were less with clopidogrel, including rash [0.7% vs 2.6%] and gastrointestinal upset [1.3% vs 2.6%]; no mention of liver injury).
• Tsai MH, Tsai SL, Chen TC, Liaw YF. Ticlopidine-induced cholestatic hepatitis with anti-nuclear antibody in serum. J Formos Med Assoc. 2000;99:866–9. [PubMed: 11155780]

  (57 year old man developed jaundice 3 weeks after starting ticlopidine [bilirubin 29.3 mg/dL, ALT 305 U/L, Alk P 480 U/L, GGT 664 U/L], resolving 6 months after stopping).
• Wu MS, Chan P, Lien GS, Cheng YS, Pan S. Ticlopidine-induced severe cholestatic hepatitis. Zhonghua Yi Xue Za Zhi (Taipei). 2000;63:663–6. [PubMed: 10969455]

  (86 year old woman developed jaundice 6 weeks after starting ticlopidine [bilirubin 15.1 mg/dL, ALT 360 U/L, Alk P 894 U/L, GGT 1641 U/L] and died suddenly 14 days later).
• Berent R, Hinterholzer G, Höng W, Auer J, Haidenthaler A, Knoflach P. Z Gastroenterol. 2000;38:587–91. [Cholestatic hepatitis as a rare side effect of therapy with ticlopidine] German. [PubMed: 10965556]

  (71 year old man developed fatigue followed by pruritus and jaundice 2-3 weeks after starting ticlopidine [bilirubin 12.5 rising to 18.6 mg/dL, ALT 61 U/L, Alk P 305 U/L, GGT 143 U/L], resolving within 2 months of stopping).
• Pizarro AE, Andrade RJ, García-Cortés M, Lucena MI, Pérez-Moreno JM, Puertas M, Sánchez-Martínez H, et al. Rev Neurol. 2001;33:1014–20. [Acute hepatitis due to ticlopidine. A report of 12 cases and review of the literature] Spanish. [PubMed: 11785026]

  (12 cases of ticlopidine hepatotoxicity reported to Spanish Pharmacovigilance Registry [5% of total reports]; 10 were men, ages 59-81 [m=68] years, 2/3rds hospitalized, latency of 2 to 13 [m=5.6] weeks, 75% cholestatic, resolving in 7 to 60 weeks, not seemingly dose related).
• Placci A, Melandri G, Cecilioni L, Valgimigli M, Bolondi L, Branzi A. Ital Heart J Suppl. 2001;2:1240–2. [Late-appearing cholestatic icterus after a month of treatment with ticlopidine] Italian. [PubMed: 11775418]

  (65 year old man developed jaundice and pruritus 1 month after starting ticlopidine [bilirubin 11.3 mg/dL, ALT 310 U/L, Alk P 921 U/L], treated with corticosteroids and symptoms resolved rapidly while Alk P fell to normal 6 months after stopping ticlopidine).
• López López M, Martín López A, Moreno Feliu R. Ticlopidina, colestasis y nódulos hepáticos. Med Clin (Barc). 2001;117(12):477. [Ticlopidine, cholestasis and hepatic nodules] Spanish. [PubMed: 11674975]

  (52 year old man developed pruritus and jaundice 4 to 8 weeks after starting ticlopidine [bilirubin 2.3 mg/dL, ALT 408 U/L, Alk P 576 U/L], symptoms resolving in 4 weeks but enzyme elevations requiring 10 months to resolve).
• Blanco JR, Márquez M, Salcedo J, Zabala M. An Med Interna. 2001;18:48–9. [Early hepatopathy induced by ticlopidine] Spanish. [PubMed: 11387849]

  (91 year old man developed worsening fatigue 1 week after starting ticlopidine [bilirubin not given, ALT 70 rising to 129 U/L, Alk P 259 rising to 362 U/L], resolving upon stopping).
• Chen LK, Hsieh BH, Chen WC, Tsai ST, Hou MC. Ticlopidine-induced hepatitis. Zhonghua Yi Xue Za Zhi (Taipei). 2001;64:59–63. [PubMed: 11310373]

  (72 year old man developed jaundice 3 weeks after starting ticlopidine [bilirubin 12.8 mg/dL, ALT 847 U/L, Alk P 487 U/L], resolving within 10 weeks of stopping: Case 2).
• García Ortega P, José Navarro J, Carvajal A, García del Pozo J. Med Clin (Barc). 2001;116:117. [Cholestatic hepatitis by ticlopidin] Spanish. [PubMed: 11181293]

  (52 year old man developed jaundice 2 months after starting ticlopidine [bilirubin 3.0 mg/dL, ALT 479 U/L, Alk P 415 U/L], improving on stopping but recurring on restarting ticlopidine [ALT 105 U/L, Alk P 1067 U/L], with full recovery upon stopping permanently).
• Zapater P, Such J, Pérez-Mateo M, Horga JF. A new Poisson and Bayesian-based method to assign risk and causality in patients with suspected hepatic adverse drug reactions: a report of two new cases of ticlopidine-induced hepatotoxicity. Drug Saf. 2002;25:735–50. [PubMed: 12167069]

  (Use of Bayesian analysis to assign causality using two cases of ticlopidine hepatotoxicity as examples).
• Adams L, Jeffrey GP, Deboer B, Garas G. Ticlopidine-associated cholestatic hepatitis. Intern Med J. 2002;32:359–60. [PubMed: 12088359]

  (60 year old man developed pruritus and jaundice 3 weeks after starting ticlopidine [bilirubin 20.2 rising to 24 mg/dL, ALT 42 U/L, Alk P 776 U/L, GGT 1580 U/L], resolving within 2 months of stopping).
• Rivera Vaquerizo P, Solís García del Pozo J, Villanueva Hernández P. An Med Interna. 2002;19:99–100. [Ticlopidine-induced hepatitis. Report of a new case] Spanish. [PubMed: 11989110]

  (71 year old woman developed jaundice and pruritus 6 weeks after starting ticlopidine [bilirubin 16.3 mg/dL, ALT 576 U/L, Alk P 1488 U/L, GGT 2450 U/L], resolving within 2 months of stopping).
• Ibáñez L, Pérez E, Vidal X, Laporte JR. Grup d'Estudi Multicènteric d'Hepatotoxicitat Aguda de Barcelona (GEMHAB). Prospective surveillance of acute serious liver disease unrelated to infectious, obstructive, or metabolic diseases: epidemiological and clinical features, and exposure to drugs. J Hepatol. 2002;37:592–600. [PubMed: 12399224]

  (Among 107 cases of drug induced liver injury identified in a population-based survey in Spain [1993-1999], ticlopidine was the cause of 8 [7%; ranking 8th], leading to cholestatic injury in 6 and mixed injury in 2).
• Skurnik YD, Tcherniak A, Edlan K, Sthoeger Z. Ticlopidine-induced cholestatic hepatitis. Ann Pharmacother. 2003;37:371–5. [PubMed: 12639165]

  (Two cases: 66 year old man developed jaundice 6 weeks after starting ticlopidine [bilirubin 5.4 rising to 19.3 mg/dL, ALT 263 U/L, Alk P 99 U/L, eosinophils 9%], resolving in 6 months [Case 1]; 82 year old man developed jaundice 4 weeks after starting ticlopidine [bilirubin 4.0 mg/dL, ALT 440 U/L, Alk P 660 U/L, eosinophils 12%], resolving within 3 months).
• Gandolfi A, Mengoli M, Rota E, Tolomelli S, Zanghieri G, Bernini MV, Lusetti L. Recenti Prog Med. 2004;95:96–9. [Ticlopidine-induced acute cholestatic hepatitis. A case report] Italian. [PubMed: 15072394]

  (72 year old man developed jaundice and pruritus 3 weeks after starting ticlopidine [bilirubin 19.1 mg/dL, ALT 427 U/L, Alk P 1558 U/L, no eosinophilia], resolving within 6 months).
• Björnsson E, Jerlstad P, Bergqvist A, Olsson R. Fulminant drug-induced hepatic failure leading to death or liver transplantation in Sweden. Scand J Gastroenterol. 2005;40:1095–101. [PubMed: 16165719]

  (Among 103 cases of drug induced liver injury resulting in death or liver transplantation reported in Sweden between 1996-2002, ticlopidine was implicated in one).
• Andrade RJ, Lucena MI, Fernández MC, Pelaez G, Pachkoria K, García-Ruiz E, García-Muñoz B, et al. Spanish Group for the Study of Drug-Induced Liver Disease. Drug-induced liver injury: an analysis of 461 incidences submitted to the Spanish registry over a 10-year period. Gastroenterology. 2005;129:512–21. [PubMed: 16083708]

  (Among 446 cases of drug induced liver injury reported to a Spanish registry over a 10-year period, 13 [13%; ranking 6th] were attributed to ticlopidine, including 7 that were hepatocellular, 5 cholestatic and 1 mixed; none fatal).
• Sabaté M, Ibáñez L, Pérez E, Vidal X, Buti M, Xiol X, Mas A, et al. Risk of acute liver injury associated with the use of drugs: a multicentre population survey. Aliment Pharmacol Ther. 2007;25:1401–9. [PubMed: 17539979]

  (Among 126 cases of drug induced liver injury identified between 1993 and 2000 from 12 hospitals in Barcelona, 8 were due to ticlopidine [relative risk=49.3; ranking 7th], all of which were cholestatic).
• Mambelli E, Mancini E, Casanova S, Di Felice A, Santoro A. Severe ticlopidine-induced cholestatic syndrome. Blood Purif. 2007;25:441–5. [PubMed: 18004066]

  (53 year old man with end-stage renal disease developed jaundice within 10 days of starting ticlopidine [bilirubin 16.5 rising to 40 mg/dL, ALT 162 U/L, Alk P 2356 U/L], with progressive jaundice and itching requiring liver transplantation 4 months after initial presentation; no mention of bile duct loss).
• Fukushima K, Kobayashi Y, Okuno T, Nakamura Y, Sakakibara M, Nakayama T, Kuroda N, et al. Incidence of side-effects of ticlopidine after sirolimus-eluting stent implantation. Circ J. 2007;71:617–9. [PubMed: 17384469]

  (Among 440 patients treated with ticlopidine after stent placement, 4.5% had "liver dysfunction" and 1 died of liver failure: 70 year old patient on renal dialysis with onset of jaundice 45 days after starting).
• Kowalski R, Dropiński J, Brzostek T, Szot P, Rzeszutko M, Kasper M, Sawicka A, Szczeklik A. Kardiol Pol. 2008;66:758–60. [Cholestatic hepatitis as a ticlopidine-induced complication of treatment - a case report] Polish. [PubMed: 18690567]

  (Abstract; 68 year old man developed jaundice after starting ticlopidine [bilirubin 5.7 mg/dL, ALT 586 U/L, Alk P 282 U/L], resolving within 6 months of stopping).
• Lee JY, Park EB, Ahn JH, Suh SJ, Jung YK, Kim JH, Shin BK, et al. Korean J Hepatol. 2008;14:102–7. [A case of ticlopidine induced acute cholestatic hepatitis and pure red cell aplasia] Korean. [PubMed: 18367863]

  (Abstract only: patient developed pure red cell aplasia and cholestatic hepatitis while taking ticlopidine).
• Hirata K, Takagi H, Yamamoto M, Matsumoto T, Nishiya T, Mori K, Shimizu S, et al. Ticlopidine-induced hepatotoxicity is associated with specific human leukocyte antigen genomic subtypes in Japanese patients: a preliminary case-control study. Pharmacogenomics J. 2008;8:29–33. [PubMed: 17339877]

  (Analysis of HLA haplotypes in 22 Japanese patients with ticlopidine hepatotoxicity and 85 controls, found association of cholestatic liver injury with five alleles and the extended haplotype A*33:03-B*44:03-Cw*14:03-DRB1*13:02-DQB1*16:04 [71% vs 11%]).
• Chalasani N, Fontana RJ, Bonkovsky HL, Watkins PB, Davern T, Serrano J, Yang H, Rochon J. Drug Induced Liver Injury Network (DILIN). Causes, clinical features, and outcomes from a prospective study of drug-induced liver injury in the United States. Gastroenterology. 2008;135:1924–34. [PMC free article: PMC3654244] [PubMed: 18955056]

  (Among 300 cases of drug induced liver disease in the US collected between 2004 and 2008, none were attributed to ticlopidine or clopidogrel).
• Reuben A, Koch DG, Lee WM., Acute Liver Failure Study Group. Drug-induced acute liver failure: results of a U.S. multicenter, prospective study. Hepatology. 2010;52:2065–76. [PMC free article: PMC3992250] [PubMed: 20949552]

  (Among 1198 patients with acute liver failure enrolled in a US prospective study between 1998 and 2007, 133 were attributed to drug induced liver injury, but none were attributed to ticlopidine or clopidogrel).
• Previtera AM, Pagani R. Agranulocytosis and hepatic toxicity with ticlopidine therapy: a case report. J Med Case Rep. 2010;4:269. [PMC free article: PMC2924862] [PubMed: 20704700]

  (70 year old woman developed agranulocytosis [neutrophils 100/µL] 4 weeks after starting ticlopidine with abnormal liver tests [bilirubin normal, ALT 560 U/L, Alk P 821 U/L, GGT 449 U/L], resolving within 4 weeks of stopping [and switching to dipyridamole and aspirin]).
• Anselmino M, Moretti C, Ravera L, Sheiban I. Clopidogrel treatment in a patient with ticlopidine-induced hepatitis following percutaneous coronary stenting. Minerva Cardioangiol. 2010;58:277–80. [PubMed: 20440256]

  (81 year old woman developed jaundice 45 days after starting ticlopidine [details not given] and recovered after stopping; one year later clopidogrel was started without recurrence of liver injury).
• Petronijevic M, Ilic K, Suzuki A. Drug induced hepatotoxicity: data from the Serbian pharmacovigilance database. Pharmacoepidemiol Drug Saf. 2011;20:416–23. [PubMed: 21370308]

  (Among 1804 adverse events reported to a Serbian pharmacovigilance registry between 1995 and 2008, 70 were hepatic of which 6% were fatal; ticlopidine accounted for 2 cases [3%] with latencies of 18 days and 5 months, one with enzyme elevations alone and one with jaundice; both recovered).
• Motola D, Biagi C, Leone R, Venegoni M, Lapi F, Cutroneo P, Vargiu A, et al. Ticlopidine safety profile: a case/non-case study on the basis of the spontaneous ADRs reporting in Italy. Curr Drug Saf. 2012;7:99–105. [PubMed: 22873494]

  (Analysis of 478 adverse event reports related to ticlopidine from 8 Italian regions from 1990 to 2007 identified 103 as liver related, including one death due to "cholestatic jaundice").
• Kaniwa N, Saito Y. Pharmacogenomics of severe cutaneous adverse reactions and drug-induced liver injury. J Hum Genet. 2013;58:317–26. [PubMed: 23635947]

  (Review of the associations of severe cutaneous adverse reactions with genetic markers; mentions that ticlopidine induced liver injury has been linked to A*33:03 in Japanese populations [Hirata 2008]).
• Hernández N, Bessone F, Sánchez A, di Pace M, Brahm J, Zapata R, A, Chirino R, et al. Profile of idiosyncratic drug induced liver injury in Latin America: an analysis of published reports. Ann Hepatol. 2014;13:231–9. [PubMed: 24552865]

  (Among 176 reports of drug induced liver injury from Latin America published between 1996 and 2012, none were attributed to ticlopidine or clopidogrel).
• Chalasani N, Bonkovsky HL, Fontana R, Lee W, Stolz A, Talwalkar J, Reddy KR, et al. United States Drug Induced Liver Injury Network. Features and outcomes of 899 patients with drug-induced liver injury: The DILIN Prospective Study. Gastroenterology. 2015;148:1340–52.e7. [PMC free article: PMC4446235] [PubMed: 25754159]

  (Among 899 cases of drug induced liver injury enrolled in a US prospective study between 2004 and 2013, none were due to ticlopidine or clopidogrel).
• Nicoletti P, Aithal GP, Bjornsson ES, Andrade RJ, Sawle A, Arrese M, Barnhart HX, et al. International Drug-Induced Liver Injury Consortium. Drug-Induced Liver Injury Network Investigators, and International Serious Adverse Events Consortium. Association of liver injury from specific drugs, or groups of drugs, with polymorphisms in HLA and other genes in a genome-wide association study. Gastroenterology. 2017;152:1078–89. [PMC free article: PMC5367948] [PubMed: 28043905]

  (Genome wide analysis studies done on 862 patients with drug induced liver injury found an association with a single nucleoside polymorphism linked to HLA-A*33:01 that was highly associated with five drugs [allele frequency in controls: 0.01] including ticlopidine (0.40], terbinafine [0.21], methyldopa [0.25] and fenofibrate [0.28]).
• Usui T, Tailor A, Faulkner L, Meng X, Farrell J, Daly AK, Dear GJ, et al. HLA-A*33:03-restricted activation of ticlopidine-specific T-cells from human donors. Chem Res Toxicol. 2018;31:1022–4. [PubMed: 30179004]

  (T cells from 2 of 3 healthy donors with HLA-A*33:03 were activated in vitro by priming with ticlopidine, whereas none of 3 donors without this HLA allele [which is homologous to A*33:01] were activated, and the HLA-specific activation was blocked by antibody suggesting a direct immune reactivity to the drug in subjects with this HLA-type).
• Gabbi C, Bertolotti M. Reduced multidrug resistance-associated protein 2 in ticlopidine-induced cholestatic liver injury. Dig Liver Dis. 2020;52:236–8. [PubMed: 31732442]

  (86 year old woman developed jaundice 2 months after starting ticlopidine [bilirubin 5.7 mg/dL, ALT 262 U/L, Alk P 2009 U/L, liver biopsy showing cholestatic hepatitis and weak staining for MRP2], the injury resolving within 6 weeks of stopping drug).