Ticlid


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.

ticlopidine

(tye-cloe-pi-deen) ticlopidine,

Ticlid

(trade name)

Classification

Therapeutic: antiplatelet agents
Pharmacologic: platelet aggregation inhibitors
Pregnancy Category: B

Indications

Prevention of stroke in patients who have had a completed thrombotic stroke or precursors to stroke and are unable to tolerate aspirin.Prevention of subacute stent thrombosis in patients receiving intracoronary stents (given with aspirin).

Action

Inhibits platelet aggregation by altering the function of platelet membranes.Prolongs bleeding time.

Therapeutic effects

Decreased incidence of stroke in high-risk patients.Decreased incidence of subacute stent thrombosis.

Pharmacokinetics

Absorption: >80% absorbed after oral administration.Distribution: Unknown.Protein Binding: 98%.Metabolism and Excretion: Extensively metabolized by the liver; minimal excretion of unchanged drug by the kidneys.Half-life: Single dose—12.6 hr; multiple dosing—4–5 days.

Time/action profile (effect on platelet function)

ROUTEONSETPEAKDURATION
POwithin 4 days8–11 days2 wk

Contraindications/Precautions

Contraindicated in: Hypersensitivity; Bleeding disorders; Active bleeding; Severe liver disease.Use Cautiously in: Risk of bleeding (trauma, surgery, history of ulcer disease); Renal or hepatic impairment (dosage adjustments may be necessary); Obstetric / Lactation / Pediatric: Safety not established; Geriatric: Appears on Beers list. Have ↑ sensitivity.

Adverse Reactions/Side Effects

Central nervous system

  • dizziness
  • headache
  • weakness

Ear, Eye, Nose, Throat

  • epistaxis
  • tinnitus

Gastrointestinal

  • diarrhea (most frequent)
  • anorexia
  • GI pain
  • ↑ liver enzymes
  • nausea
  • vomiting

Genitourinary

  • hematuria

Dermatologic

  • rash (most frequent)
  • ecchymoses
  • pruritus
  • urticaria

Hematologic

  • agranulocytosis (life-threatening)
  • aplastic anemia (life-threatening)
  • intracerebral bleeding (life-threatening)
  • neutropenia (life-threatening)
  • bleeding
  • thrombocytopenia

Metabolic

  • hypercholesterolemia
  • hypertriglyceridemia

Interactions

Drug-Drug interaction

Aspirin potentiates the effect of ticlopidine on platelets (concurrent use not recommended).↑ risk of bleeding with heparins, warfarin, tirofiban, eptifibatide, or thrombolytic agents.Cimetidine ↓ metabolism of ticlopidine and may ↑ the risk of toxicity.Ticlopidine ↓ metabolism and ↑ the risk of toxicity of theophylline.Absorption ↑ by taking with food.

Route/Dosage

Oral (Adults) 250 mg twice daily with food.

Availability (generic available)

Tablets: 250 mg

Nursing implications

Nursing assessment

  • Assess patient for symptoms of stroke periodically throughout therapy.
  • Lab Test Considerations: Monitor bleeding time throughout therapy. Prolonged bleeding time (2–5 times the normal limit), which is time- and dose-dependent, is expected.
    • Monitor CBC with differential and platelet count every 2 wk from the 2nd wk to the end of the 3rd mo of therapy; more frequently if absolute neutrophil count (ANC) is declining or <30% of baseline. If neutropenia occurs, ticlopidine should be discontinued. Neutrophil counts usually return to normal within 1–3 wk of discontinuation of therapy. After the first 3 mo of therapy, CBCs need to be obtained only for patients with signs and symptoms of infection.
    • May cause thrombocytopenia, usually within 3–12 wk of initiation of therapy. If platelet count is <80,000/mm3, discontinue ticlopidine.
    • May cause ↑ serum total cholesterol and triglyceride levels. Levels usually increase 8–10% within the first mo and persist at that level.
    • May cause ↑ alkaline phosphatase, bilirubin, AST, and ALT levels during the first 4 mo of therapy.
  • Prolonged bleeding time is normalized within 2 hr after administration of IV methylprednisolone. May also use platelet transfusions to reverse effects of ticlopidine on bleeding time.

Potential Nursing Diagnoses

Risk for injury (Indications, Side Effects)

Implementation

  • Oral: Administer with food or immediately after eating to minimize GI discomfort and increase absorption.

Patient/Family Teaching

  • Instruct patient to take medication as directed. Missed doses should be taken as soon as possible unless almost time for next dose; do not double doses.
  • Advise patient to notify health care professional promptly if fever, chills, sore throat, unusual bleeding or bruising, severe or persistent diarrhea, skin rash, jaundice, dark-colored urine, or light-colored stools occur.
  • Advise patient to notify health care professional of medication regimen before treatment or surgery. Medication may need to be discontinued 10–14 days before surgery.
  • Emphasize the importance of routine lab tests during the first 3 mo of therapy to monitor for side effects.

Evaluation/Desired Outcomes

  • Prevention of stroke.

Ticlid

(tī′klĭd) A trademark for the drug ticlopidine hydrochloride.