Usage
- Ticlopidine is prescribed to reduce the risk of stroke in patients who have experienced a previous stroke or transient ischemic attack (TIA) and in those with certain medical conditions that may increase stroke risk, particularly in individuals intolerant or unresponsive to aspirin. It is also utilized to prevent blood clots after coronary artery stent placement.
- Pharmacological Classification: Antiplatelet agent.
- Mechanism of Action: Ticlopidine irreversibly inhibits platelet aggregation by interfering with the ADP-induced binding of fibrinogen to platelet receptors (glycoprotein IIb/IIIa), thus preventing platelet-platelet interaction and subsequent thrombus formation.
Alternate Names
- International Nonproprietary Name (INN): Ticlopidine hydrochloride
- Brand Name: Ticlid (discontinued in several countries including the US)
How It Works
- Pharmacodynamics: Ticlopidine primarily affects platelet function. It prolongs bleeding time and reduces platelet reactivity to agonists like ADP. It does not significantly affect prostacyclin/thromboxane pathways or platelet cAMP levels.
- Pharmacokinetics:
- Absorption: Rapidly absorbed after oral administration, with peak plasma levels occurring around 2 hours post-dose. Food increases absorption by about 20%.
- Metabolism: Extensively metabolized in the liver, with numerous metabolites identified. Unchanged ticlopidine is a minor component in plasma after a single dose but becomes the major component at steady state.
- Elimination: Primarily eliminated via the urine (60%) and to a lesser extent in feces (23%). The terminal elimination half-life is prolonged with repeated dosing, reaching 4-5 days. Clearance is reduced in elderly patients.
Dosage
Standard Dosage
Adults:
250 mg orally twice daily, taken with food. For coronary artery stenting, it’s often administered with aspirin for up to 30 days. A loading dose of 500 mg may be used in some stent placement protocols.
Children:
Ticlopidine use is not generally recommended for children as safety and efficacy have not been established. If deemed necessary, dosing must be determined by a physician on a case-by-case basis.
Special Cases:
- Elderly Patients: Due to decreased clearance, elderly patients may experience higher plasma concentrations. Monitoring is essential.
- Patients with Renal Impairment: Limited data suggest dosage adjustments are generally unnecessary in mild to moderate renal impairment. Careful monitoring is required, and dose reduction or discontinuation may be needed if hematological complications arise.
- Patients with Hepatic Dysfunction: Contraindicated in severe hepatic disease due to increased bleeding risk. Caution and dose adjustment are necessary in milder hepatic impairment.
- Patients with Comorbid Conditions: Use with caution in patients with a history of bleeding disorders or other conditions predisposing to bleeding.
- Intubation, Surgical Procedures, Mechanical Ventilation, Intensive Care Unit (ICU) Use, Emergency Situations: Ticlopidine is not typically indicated in these settings. Its antiplatelet effects can increase bleeding risk, making it unsuitable for acute or perioperative use.
Dosage Adjustments
Modifications may be necessary in patients with renal or hepatic impairment and those exhibiting hematological side effects. Close monitoring of complete blood counts and liver function tests is crucial, especially during the first few months of therapy.
Side Effects
Common Side Effects
Diarrhea, rash, nausea, vomiting, gastrointestinal pain, neutropenia, dyspepsia, purpura, flatulence, pruritus, dizziness, anorexia, abnormal liver function tests.
Rare but Serious Side Effects
Thrombocytopenia, agranulocytosis, thrombotic thrombocytopenic purpura (TTP), aplastic anemia, severe or persistent diarrhea, cholestatic jaundice, intracranial hemorrhage, Stevens-Johnson syndrome, hepatic necrosis.
Long-Term Effects
Increased serum cholesterol and triglycerides.
Adverse Drug Reactions (ADR)
Neutropenia/agranulocytosis, TTP, aplastic anemia, cholestatic jaundice, severe bleeding.
Contraindications
- Active pathological bleeding (e.g., peptic ulcer, intracranial hemorrhage)
- History of or current haematopoietic disorders (e.g., neutropenia, thrombocytopenia, agranulocytosis, TTP, aplastic anemia)
- Severe hepatic impairment
- Hypersensitivity to ticlopidine or thienopyridines
Drug Interactions
- Anticoagulants, Antiplatelet Agents: Increased bleeding risk.
- CYP2D6 Inhibitors: Elevated ticlopidine levels.
- CYP2C19 Inhibitors: Increased ticlopidine levels.
- Theophylline: Reduced theophylline clearance, necessitating dose adjustment.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: B (animal studies show no fetal harm, but adequate human studies are lacking). Ticlopidine should be used during pregnancy only if clearly needed.
- Breastfeeding: Excretion in human milk is unknown. Due to the potential for serious adverse reactions in infants, a decision should be made whether to discontinue breastfeeding or the drug.
Drug Profile Summary
- Mechanism of Action: Irreversibly inhibits ADP-induced platelet aggregation.
- Side Effects: Diarrhea, rash, neutropenia, bleeding, TTP.
- Contraindications: Active bleeding, hematopoietic disorders, severe hepatic impairment.
- Drug Interactions: Anticoagulants, antiplatelet agents, CYP2C19 and 2D6 inhibitors.
- Pregnancy & Breastfeeding: Category B; use with caution. Consider discontinuing breastfeeding.
- Dosage: 250 mg BID with food.
- Monitoring Parameters: CBC with differential, including platelet count, every 2 weeks for the first 3 months; liver function tests for the first 4 months.
Popular Combinations
Aspirin (for a limited period following coronary stent placement). However, this combination increases bleeding risk.
Precautions
- Monitor blood counts and liver function.
- Assess for bleeding risk.
- Caution in renal/hepatic impairment.
- Avoid in pregnancy unless absolutely necessary.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Ticlopidine?
A: 250 mg orally twice daily, taken with food.
Q2: What are the most serious side effects of ticlopidine?
A: Neutropenia, agranulocytosis, thrombotic thrombocytopenic purpura (TTP), and aplastic anemia.
Q3: How does ticlopidine differ from clopidogrel?
A: Both are antiplatelet agents, but clopidogrel is generally considered safer due to a lower incidence of hematological side effects like neutropenia.
Q4: Can ticlopidine be used during pregnancy?
A: It’s a pregnancy category B drug. Use only if the potential benefits outweigh the risks. No adequate and well-controlled studies in pregnant women exist.
Q5: What should be monitored in patients taking ticlopidine?
A: Complete blood counts, including platelet counts, should be checked every two weeks for the first three months of treatment. Liver function tests should also be monitored regularly.
Q6: What are the contraindications to ticlopidine use?
A: Active bleeding, history of hematopoietic disorders (e.g., neutropenia, TTP), severe hepatic impairment, and hypersensitivity to ticlopidine or other thienopyridines.
Q7: Does ticlopidine interact with other medications?
A: Yes. It can interact with anticoagulants, other antiplatelet agents, and drugs metabolized by CYP2C19 and CYP2D6.
Q8: What patient education is important for ticlopidine?
A: Patients should be informed about the risk of bleeding and hematological side effects and instructed to report any unusual symptoms promptly. Advise patients to take the medication with food and to adhere to the prescribed dosing schedule. Explain the importance of regular blood test monitoring.
Q9: Can ticlopidine be used in patients with renal impairment?
A: It can be used cautiously in mild to moderate renal impairment. Close monitoring is required, and dose adjustments may be necessary. It is contraindicated in severe renal disease.
