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ticlopidine (Ticlid)

Tradename: Ticlid. Indications: - prevention of arterial thrombosis - thromboembolic stroke (ischemic stroke) prophylaxis (aspirin failure*) - also has beeb used for: - intermittent claudication - AV shunts & fistulas - cardiac stents - coronary artery bypass graft (CABG) - percutaneous coronary intervention [7] - sickle cell disease * No better than aspirin by Beers criteria Contraindications: 1) active bleeding disorders 2) neutropenia or thrombocytopenia 3) severe liver disorder 4) hemostatic disorder Caution: 1) gastric or duodenal ulcers 2) patients with underlying hematologic disorders 3) patients receiving oral anticoagulants 4) concurrent use of NSAIDs including aspirin 5) liver disease 6) patients undergoing lumbar puncture 7) patients udergoing surgical procedures: ticlopidine should be discontinued 14 days prior to surgery Dosage: 250 mg PO BID Tabs: 250 mg. Pharmacokinetics: 1) about 80% absorbed from the GI tract 2) 98% bound to plasma proteins 3) metabolized by the liver 4) peak effect after 3-5 days of oral therapy 5) trace amounts of drug are found in the urine 6) serum levels do NOT correlate with antiplatelet activity 7) elimination 1/2life is 4-5 days after repeat dosing Monitor: 1) complete blood count (CBC) every 2 weeks for 1st 3 months, then every 6 months 2) liver function tests every 6 months Adverse effects: 1) not common (1-10%) - rash, neutropenia (3%) 2) uncommon (< 1%) - ecchymosis, diarrhea, nausea/vomiting, GI pain, thrombocytopenia, epistaxis, abnormal liver function tests, tinnitus, hematuria 3) other a) neutropenia - most serious adverse effect - generally occurs within 3 weeks to 3 months, but may occur later - monitor CBC every 2 weeks for 1st 3 months - reversible b) thrombocytopenia: - fatal thrombotic thrombocytopenic purpura (TTP) (0.02-0.06%) [6] (more common than with clopidogrel) - discontinue if platelet count drops below 80,000/mm3 c) increased cholesterol & triglyceride levels Drug interactions: 1) cimetidine decreases clearance of Ticlid by 50% 2) antacids (decreased absorption) 3) glucocorticoids decrease effect of ticlopidine 4) ticlopidine decreases effect of digoxin & cyclosporine 5) ticlopidine increases effects/toxicity of - aspirin, anticoagulants, theophylline, cimetidine, NSAIDs, phenytoin, propranolol Test interactions: 1) increased serum cholesterol 2) increased serum alkaline phosphatase 3) increased serum transaminases Mechanism of action: 1) platelet aggregation inhibitor 2) ADP receptor antagonist 3) suppresses platelet-derived growth factor (PDGF) 4) may block von Willebrand factor 5) effects irreversible for life of the platelet

Interactions

drug interactions drug adverse effects (more general classes)

General

antiplatelet agent receptor antagonist

Properties

MISC-INFO: elimination route LIVER pregnancy-category B safety in lactation ? protein-binding 98% 1/2life 4-5 DAYS

Database Correlations

PUBCHEM correlations

References

  1. The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996.
  2. Saunders Manual of Medical Practice, Rakel (ed), WB Saunders, Philadelphia, 1996, pg 1022
  3. Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998 - not on National VA formulary
  4. Kaiser Permanente Northern California Regional Drug Formulary, 1998
  5. Medical Knowledge Self Assessment Program (MKSAP) 11, American College of Physicians, Philadelphia 1998
  6. Ovbiagele B, In: Intensive Course in Geriatric Medicine & Board Review, Marina Del Ray, CA, Sept 29-Oct 2, 2004
  7. Deprecated Reference