Ticlopidine

From Anvita Health Wiki

Contents 1 Introduction 2 Indications 3 Contraindications 4 Dosage 5 Pharmacokinetics 6 Monitor 7 Adverse-effects 8 Drug-interactions 9 Test-interactions 10 Mechanism-of-action 11 More General Terms 12 Internet Database 13 References

Introduction

• Tradename: Ticlid.

Indications

• thromboembolic stroke prophylaxis ( aspirin failure*)
• also has beeb used for:

• intermittent claudication
• AV shunts & fistulas
• cardiac stents
• coronary artery bypass graft ( CABG)
• sickle cell disease

• * No better than aspirin by Beers criteria

Contraindications

• active bleeding disorders
• neutropenia or thrombocytopenia
• severe liver disorder
• hemostatic disorder

• Caution:

• gastric or duodenal ulcers
• patients with underlying hematologic disorders
• patients receiving oral anticoagulants
• concurrent use of NSAIDs including aspirin
• liver disease
• patients undergoing lumbar puncture
• patients udergoing surgical procedures: ticlopidine should be discontinued 14 days prior to surgery
  

• pregnancy category = b
• safety in lactation = ?

Dosage

• 250 mg PO BID

• Tabs: 250 mg.

Pharmacokinetics

• about 80% absorbed from the GI tract
• 98% bound to plasma proteins
• metabolized by the liver
• peak effect after 3-5 days of oral therapy
• trace amounts of drug are found in the urine
• serum levels do NOT correlate with antiplatelet activity
• elimination 1/2life is 4-5 days after repeat dosing
  

• elimination via liver
• protein binding = 98 %
• 1/2life = 4-5 days

Monitor

• complete blood count ( CBC) every 2 weeks for 1st 3 months, then every 6 months
• liver function tests every 6 months

Adverse-effects

• not common (1-10%)

• rash, neutropenia (3%)

• uncommon (< 1%)

• ecchymosis, diarrhea, nausea/vomiting, GI pain, thrombocytopenia, epistaxis, abnormal liver function tests, tinnitus, hematuria

• other

• 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

• 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

• increased cholesterol & triglyceride levels
  
• drug adverse effects of antiplatelet agents

Drug-interactions

• cimetidine decreases clearance of Ticlid by 50%
• antacids (decreased absorption)
• glucocorticoids decrease effect of ticlopidine
• ticlopidine decreases effect of digoxin & cyclosporine
• ticlopidine increases effects/toxicity of

• aspirin, anticoagulants, theophylline, cimetidine, NSAIDs, phenytoin, propranolol
  

• drug interaction(s) of anti-platelet agents with SSRIs
• drug interaction(s) of antiplatelet agents with proton pump inhibitors
• drug interaction(s) of warfarin with antiplatelet agents

Test-interactions

• increased serum cholesterol
• increased serum alkaline phosphatase
• increased serum transaminases

Mechanism-of-action

• platelet aggregation inhibitor
• ADP receptor antagonist
• suppresses platelet-derived growth factor ( PDGF)
• may block von Willebrand factor
• effects irreversible for life of the platelet

More General Terms

• receptor antagonist
• antiplatelet agent

Internet Database

PubChem: 5472
PubChem: 65335

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

ticlopidine (Ticlid)