ticlopidine hydrochloride
Ticlid

Available forms
Available by prescription only
Tablets (film-coated): 250 mg

Indications and dosages
 Reduction of risk of thrombotic CVA in patients with history of CVA, those who have experienced CVA precursors, or those who are intolerant to aspirin therapy. Adults: 250 mg P.O. b.i.d. with meals.

Pharmacodynamics
Antithrombotic action: Ticlopidine blocks adenosine diphosphate-induced platelet-fibrinogen and platelet-platelet binding.

Pharmacokinetics
Absorption: Rapidly and extensively (more than 80%) absorbed after oral administration. Absorption is enhanced by food.
Distribution: 98% bound to serum proteins and lipoproteins.
Metabolism: Extensively metabolized by the liver. It’s unknown whether parent drug or active metabolites are responsible for pharmacologic activity.
Excretion: About 60% is excreted in urine and 23% in feces; only trace amounts of intact drug are found in urine. After one dose, half-life is 12 1/2 hours; with repeat dosing, half-life increases to 4 to 5 days.

Contraindications and precautions
Contraindicated in patients hypersensitive to drug; in patients with hematopoietic disorders, such as neutropenia, thrombocytopenia, or disorders of hemostasis; in patients with active pathologic bleeding from peptic ulceration or active intracranial bleeding; and in patients with severe liver dysfunction.

Interactions
Drug-drug. Antacids: Decreases ticlopidine levels. Separate administration times by at least 2 hours.
Aspirin: Potentiates effects of aspirin on platelets. Avoid use together.
Cimetidine: Decreases ticlopidine clearance; increases risk of toxicity. Don’t use together.
Digoxin: Causes slightly decreased serum digoxin levels. Monitor serum digoxin levels.
Phenytoin: Increases phenytoin levels. Use together cautiously. Monitor phenytoin levels.
Theophylline: Increases risk of theophylline toxicity. Monitor patient closely; adjust theophylline dose as needed.
Drug-herb. Dong quai, feverfew, garlic, ginger, horse chestnut, red clover: Increases risk of bleeding. Discourage use together.

Adverse reactions
CNS: dizziness, intracerebral bleeding,peripheral neuropathy.
CV: vasculitis, postoperative bleeding.
EENT: epistaxis, conjunctival hemorrhage.
GI: diarrhea, nausea, dyspepsia, abdominal pain, anorexia, vomiting, flatulence, GI bleeding, light-colored stools.
GU: hematuria, nephrotic syndrome, dark-colored urine.
Hematologic: neutropenia, pancytopenia, agranulocytosis, immune thrombocytopenia.
Hepatic: hepatitis, cholestatic jaundice.
Metabolic: hyponatremia.
Musculoskeletal: arthropathy, myositis.
Respiratory: allergic pneumonitis.
Skin: rash, pruritus, maculopapular rash, urticaria, thrombocytopenic purpura, ecchymoses.
Other: hypersensitivity reactions, systemic lupus erythematosus, serum sickness.

Effects on lab test results
• May increase ALT, AST, and alkaline phosphatase levels.
• May prolong bleeding time. May decrease neutrophil, WBC, RBC, platelet, and granulocyte counts.

Overdose and treatment
Limited information available. Toxicity may increase bleeding time and ALT levels.
 Provide supportive therapy.

Special considerations
• If drug is being substituted for a fibrinolytic or anticoagulant, stop previous drug before starting ticlopidine.
• Perform baseline liver function tests and repeat whenever liver dysfunction is suspected. Monitor patient closely, especially during the first 4 months of treatment.
 ALERT Patients who receive ticlopidine may develop aplastic anemia. Development of the disorder seems to peak after about 4 to 8 weeks of treatment; only a few of the reported cases developed after 3 months of treatment.
• If needed, methylprednisolone 20 mg I.V. has been shown to normalize the bleeding time within 2 hours. Platelet transfusions also may be needed.
• Drug has been used investigationally for many conditions, including intermittent claudication, chronic arterial occlusion, subarachnoid hemorrhage, primary glomerulonephritis, sickle cell disease, and uremic patients with AV shunts. When used preoperatively, it may decrease risk of graft occlusion in patients receiving coronary artery bypass grafts and reduce the severity of decreased platelet count in patients receiving extracorporeal hemoperfusion during open heart surgery.
 ALERT Monitor CBC, including neutrophil count, platelet count, and peripheral smear, every 2 weeks for the first 3 months of therapy. Patients with a simultaneous decrease in platelets and WBCs should be evaluated for aplastic anemia. Stop drug immediately if laboratory findings suggest aplastic anemia.
Pregnant patients
• Use drug during pregnancy only when clearly needed.
Breast-feeding patients
• It isn’t known whether drug appears in breast milk. Breast-feeding isn’t recommended.
Pediatric patients
• Safety and efficacy in children younger than age 18 haven’t been established.

Patient education
• Tell patient to take drug with meals because food substantially increases bioavailability and improves GI tolerance.
• Emphasize that drug prolongs bleeding time. Tell patient to report unusual bleeding and to inform dentists and other health care providers that he’s taking ticlopidine.
• Make sure patient understands the need to report for regular blood tests. Neutropenia can result in an increased risk of infection. Tell patient to immediately report signs and symptoms of infection, such as fever, chills, or sore throat.
• Warn patient to avoid aspirin and aspirin-containing products, which may prolong bleeding. Instruct him to call before taking OTC medications because many contain aspirin.
• Tell patient to report yellow skin or sclera, severe or persistent diarrhea, rash, S.C. bleeding, light-colored stools, or dark urine.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use