ticlopidine hydrochloride


ticlopidine hydrochloride

Apo-Ticlopidine, Dom-Ticlopidine, Gen-Ticlopidine, Novo-Ticlopidine, NU-Ticlopidine, PMS-Ticlopidine, Sandoz Ticlopidine, Ticlid

Pharmacologic class: Platelet aggregation inhibitor

Therapeutic class: Antiplatelet agent

Pregnancy risk category B

FDA Box Warning

Drug may cause life-threatening hematologic adverse reactions, including neutropenia, agranulocytosis, thrombotic thrombocytopenic purpura (TTP), and aplastic anemia. Such reactions may arise within several days of starting therapy. TTP incidence peaks after about 3 to 4 weeks; neutropenia, at approximately 4 to 6 weeks; and aplastic anemia, after about 4 to 8 weeks. Thereafter, incidence of hematologic reactions declines.

During first 3 months of therapy, monitor patient hematologically and clinically for evidence of neutropenia or TTP. If it occurs, discontinue drug immediately.

Action

Inhibits release of first and second phases of adenosine diphosphate-induced effects on platelet aggregation, preventing thrombus formation

Availability

Tablets: 250 mg

Indications and dosages

To reduce risk of thrombotic cerebrovascular accident when aspirin is ineffective or intolerable

Adults: 250 mg P.O. b.i.d. with meals

Adjunctive therapy to prevent subacute stent thrombosis in patients with implanted coronary stents

Adults: 250 mg P.O. b.i.d. with meals, given with antiplatelet doses of aspirin for up to 30 days after successful stent implantation

Dosage adjustment

• Renal impairment

Off-label uses

• Chronic arterial occlusion

• Coronary artery bypass graft

• Open-heart surgery

• Intermittent claudication

• Primary glomerulonephritis

• Sickle cell disease

• Subarachnoid hemorrhage

• Uremic patients with atrioventricular shunts or fistulas

Contraindications

• Hypersensitivity to drug

• Hematopoietic disorders

• Hemostatic disorders or active bleeding

• Severe hepatic disease

• History of thrombotic thrombocytopenia purpura (TTP) or aplastic anemia

Precautions

Use cautiously in:

• renal or hepatic impairment

• high risk for bleeding

• elderly patients

• pregnant or breastfeeding patients

• children younger than age 18 (safety not established).

Administration

• Give with meals.

• Don't give within 2 hours of antacids.

Adverse reactions

CNS: dizziness, headache, weakness, intracerebral bleeding

EENT: conjunctival hemorrhage, tinnitus, epistaxis

GI: nausea, vomiting, diarrhea, full sensation, GI pain, dyspepsia, flatulence, anorexia, GI bleeding

GU: hematuria

Hematologic: ecchymosis, eosinophilia, purpura, TTP, thrombocytosis, neutropenia, agranulocytosis, bone marrow depression

Skin: rashes, bruising, pruritus, urticaria

Other: pain, posttraumatic or perioperative bleeding

Interactions

Drug-drug. Antacids: decreased ticlopidine blood level

Aspirin: potentiation of aspirin's effect on platelets

Cimetidine (long-term use): reduced ticlopidine clearance

Digoxin: slightly decreased digoxin blood level

Phenytoin: increased phenytoin blood level, greater risk of toxicity

Theophylline: decreased theophylline clearance, greater risk of toxicity

Vitamin A: altered anticoagulant effects

Drug-diagnostic tests. Alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase: increased levels

Granulocytes, neutrophils, platelets, white blood cells: decreased counts

Liver function tests: abnormal results

Drug-food. Any food: increased ticlopidine absorption

Drug-herbs. Alfalfa, anise, arnica, astragalus, bilberry, black current seed oil, bladderwrack, bogbean, boldo, borage oil, buchu, capsacin, cat's claw, celery, chapparal, cinchona bark, clove oil, coenzyme Q10, dandelion, dong quai, evening primrose oil, fenugreek, feverfew, garlic, ginger, gingko, guggal, papaya extract, red clover, rhubarb, safflower oil, skullcap, St. John's wort, tan shen: altered anticoagulant effects

Patient monitoring

Closely monitor coagulation studies and CBC with white cell differential. Watch for evidence of bleeding tendency and blood dyscrasias.

Assess neurologic status carefully. Stay alert for signs and symptoms of intracranial bleeding.

• Monitor liver function tests.

Patient teaching

• Tell patient to take with meals, but not within 2 hours of antacids.

Instruct patient to immediately report easy bruising or bleeding.

• Advise patient to stop taking drug 10 to 14 days before elective surgery.

• Tell patient to inform all prescribers that he is taking drug.

• Inform patient that aspirin-containing products and many herbs increase risk of bleeding. Urge him to consult prescriber before taking over-the-counter drugs or herbs.

• Caution patient to avoid activities that can cause injury. Tell him to use soft toothbrush and electric razor to avoid gum and skin injury.

• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, foods, and herbs mentioned above.