Ticlopidine Hydrochloride

Pronunciation: (tie-KLOE-pih-DEEN HIGH-droe-KLOR-ide)
Class: Antiplatelet

Trade Names

Ticlid
- Tablets 250 mg

Apo-Ticlopidine (Canada)
Gen-Ticlopidine (Canada)
Nu-Ticlopidine (Canada)
Sandoz Ticlopidine (Canada)

Pharmacology

Produces time- and dose-dependent inhibition of both platelet aggregation and release of platelet granule constituents as well as prolongation of bleeding time; interferes with platelet membrane function by inhibiting platelet-fibrinogen binding and subsequent platelet-platelet interactions.

Pharmacokinetics

Absorption

Ticlopidine is rapidly absorbed with peak levels (T _max ) occurring about 2 after dose. The drug is greater than 80% absorbed. Administration after meals results in a 20% increase in the AUC. Ticlopidine is 98% bound to plasma proteins.

Metabolism

Ticlopidine is metabolized extensively by the liver; only trace amounts are detected in urine.

Elimination

Ticlopidine t _½ is 4 to 5 days.

Special Populations

Hepatic Function Impairment

Average plasma concentration is slightly higher in cirrhosis.

Indications and Usage

Reduction of risk of thrombotic stroke in patients who have experienced stroke precursors and in patients who have had completed thrombotic stroke. Reserved for patients intolerant to aspirin because of greater risk of adverse reactions.

Unlabeled Uses

Improved walking distance in intermittent claudication; vascular improvement in chronic arterial occlusion; reduced incidence of neurologic deficit in subarachnoid hemorrhage; reduced incidence of vascular occlusion in uremic patients with arteriovenous shunts or fistulas; control of platelet count in open heart surgery; decreased graft occlusion in coronary artery bypass grafts; reduced degree of proteinuria and hematuria in primary glomerulonephritis; reduced incidence, duration, and severity of infarctive crises in sickle cell disease.

Contraindications

Presence of hematopoietic disorders (eg, neutropenia, thrombocytopenia); history of thrombotic thrombocytopenic purpura (TTP); presence of hemostatic disorder or active pathologic bleeding (eg, bleeding, peptic ulcer, intracranial bleeding, hemophilia, other coagulation defects); severe liver impairment.

Dosage and Administration

Adults

PO 250 mg twice daily with food.

Storage/Stability

Store at room temperature.

Drug Interactions

Antacids

May reduce ticlopidine absorption.

Aspirin

Increased effect of aspirin on collagen-induced platelet aggregation.

Cimetidine

Elevated ticlopidine levels with possible increase in therapeutic and toxic effects.

Theophylline

Elevated serum theophylline concentrations, increasing risk of toxicity.

Phenytoin

Elevated phenytoin plasma levels with associated somnolence and lethargy have been reported. Exercise caution when administering with ticlopidine.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Vasculitis.

CNS

Headache; peripheral neuropathy; dizziness.

Dermatologic

Maculopapular or urticarial rash; rash; pruritus.

EENT

Tinnitus.

GI

Diarrhea; nausea; fullness; dyspepsia; GI pain; purpura; vomiting; flatulence; anorexia.

Genitourinary

Nephrotic syndrome.

Hematologic

Prolonged bleeding time; bleeding complications (ecchymosis, epistaxis, hematuria, conjunctival hemorrhage, GI bleeding, perioperative bleeding); neutropenia; pancytopenia; hemolytic anemia; serum sickness; immune thrombocytopenia; abnormal LFTs; TTP; agranulocytosis; eosinophilia; bone marrow depression.

Hepatic

Hepatitis; cholestatic jaundice; increased alkaline phosphatase, serum transaminases, and bilirubin.

Metabolic

Increased cholesterol and triglycerides.

Miscellaneous

Weakness; pain; allergic pneumonitis; systemic lupus erythematosus; arthropathy; myositis; hyponatremia; aplastic anemia; hepatic necrosis; peptic ulcer; renal failure; sepsis; angioedema; hepatocellular jaundice.

Precautions

Warnings Hematological Life-threatening events including neutropenia, agranulocytosis, thrombotic thrombocytopenic purpura (TTP), and aplastic anemia. Severe hematological problems may occur within a few days after the start of therapy. Thus, monitor hematologically and clinically. Immediately discontinue therapy at any evidence of neutropenia or TTP. TTP incidence peaks at 3 to 4 wk posttherapy initiation. Neutropenia risk peaks at 4 to 6 wk posttherapy initiation. Aplastic anemia risk peaks at 4 to 8 wk posttherapy initiation. Perform CBC with ANC, platelet count, and appearance of the peripheral smear at baseline and every 2 wk during therapy for the first 3 mo.

Pregnancy

Category B .

Lactation

Undetermined.

Children

Safety and efficacy in children under 18 yr not established.

Elderly

Require dosage reduction.

Hypersensitivity

Reactions range from minor to life-threatening.

Renal Function

Dosage reduction or discontinuation of therapy may be required if hemorrhagic or hematopoietic complications occur.

Hepatic Function

Use not recommended because patient may have preexisting bleeding diathesis.

Cholesterol elevation

May cause increased serum cholesterol and triglycerides.

GI bleeding

Use with caution in patients who have lesions with a propensity to bleed.

Hematologic effects

Fatal reactions (eg, pancytopenia) have occurred.

Increased bleeding risk

Use with caution in patients who may be at risk of increased bleeding from trauma, surgery, or pathological conditions.

Overdosage

Symptoms

Increased bleeding time, increased ALT.

Patient Information

• Instruct patient to take with food.
• Inform patient of increased risk of bleeding and caution patient to take precautionary measures (eg, not to use manual razor, use soft toothbrush, handle knives carefully, always wear shoes when walking).
• Instruct patient to report signs of infection (eg, fever, white overgrowth in mouth, vaginal yeast, nonhealing wounds or wounds that appear red with drainage) to health care provider.
• Advise patient to notify health care provider of signs of blood or changes in stool or urine, unusual bruising, decreased appetite, dark urine, light-colored stools, or yellow skin color.
• Instruct patient to inform health care providers/dentists of drug regimen before undergoing any treatments or surgery or receiving new drugs.
• Suggest that patient carry medical identification (eg, card, bracelet) indicating drug regimen and condition.
• Advise patient to separate administration of ticlopidine and antacids by at least 2.
• Advise patients to immediately report symptoms and signs of TTP (eg, fever, weakness, difficulty speaking, seizures, yellowing of skin or eyes, dark or bloody urine, pallor, or pinpoint hemorrhagic spots on the skin).

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