No

Antiplatelet Agent

Platelet aggregation inhibitor that reduces the risk of thrombotic stroke in patients who have had a stroke or stroke precursors

B

Hypersensitivity to ticlopidine or any component; active pathological bleeding such as PUD or intracranial hemorrhage; severe liver dysfunction; hematopoietic disorders (neutropenia, thrombocytopenia, a past history of TTP)

Use with caution in patients who may be at risk of increased bleeding. Consider discontinuing 10-14 days before elective surgery. Use caution in mixing with other antiplatelet drugs. Use with caution in patients with severe liver disease (experience is limited). Monitor for signs and symptoms of neutropenia including WBC count. Discontinue if the absolute neutrophil count falls to <1200/mm³ or if the platelet count falls to <80,000/mm³.

As with all drugs which may affect hemostasis, bleeding is associated with ticlopidine. Hemorrhage may occur at virtually any site. Risk is dependent on multiple variables, including the use of multiple agents which alter hemostasis and patient susceptibility.

1% to 10%: Central nervous system: Dizziness (1.1%)

Dermatologic: Rash (5.1%), purpura (2.2%), pruritus (1.3%)

Gastrointestinal: Nausea (7%), dyspepsia (7%), gastrointestinal pain (3.7%), vomiting (1.9%), flatulence (1.5%), anorexia (1%)

Hematologic: Neutropenia (2.4%)

Hepatic: Abnormal liver function test (1%)

<1% (Limited to important or life-threatening symptoms): Thrombotic thrombocytopenic purpura (TTP), thrombocytopenia (immune), agranulocytosis, eosinophilia, pancytopenia, thrombocytosis, bone marrow suppression, gastrointestinal bleeding, ecchymosis, epistaxis, hematuria, menorrhagia, conjunctival bleeding, intracranial bleeding (rare), urticaria, exfoliative dermatitis, Stevens-Johnson syndrome, erythema multiforme, maculopapular rash, erythema nodosum, headache, weakness, pain, tinnitus, hemolytic anemia, aplastic anemia, hepatitis, jaundice, hepatic necrosis, peptic ulcer, renal failure, nephrotic syndrome, hyponatremia, vasculitis, sepsis, pneumonitis (allergic), angioedema, positive ANA, systemic lupus erythematosus, peripheral neuropathy, serum sickness, arthropathy, myositis

Case reports: Chronic diarrhea, increase in serum creatinine, bronchiolitis obliterans-organized pneumonia

Symptoms of overdose include ataxia, seizures, vomiting, abdominal pain, hematologic abnormalities; specific treatments are lacking; after decontamination

Treatment is symptomatic and supportive

CYP2C19 inhibitor; CYP1A2 inhibitor

Anticoagulants or other antiplatelet agents may increase the risk of bleeding; use with caution.

Carbamazepine blood levels may be increased by ticlopidine.

Cimetidine increases ticlopidine levels.

Cyclosporine blood levels may be reduced by ticlopidine.

Digoxin blood levels may be decreased by ticlopidine.

Phenytoin blood levels may be increased by ticlopidine.

Theophylline blood levels may be increased by ticlopidine.

Ticlopidine is an inhibitor of platelet function with a mechanism which is different from other antiplatelet drugs. The drug significantly increases bleeding time. This effect may not be solely related to ticlopidine's effect on platelets. The prolongation of the bleeding time caused by ticlopidine is further increased by the addition of aspirin in ex vivo experiments. Although many metabolites of ticlopidine have been found, none have been shown to account for in vivo activity.

Onset of action: Within 6 hours

Peak: Achieved after 3-5 days of oral therapy; serum levels do not correlate with clinical antiplatelet activity

Metabolism: Extensively in the liver and has at least one active metabolite

Half-life, elimination: 24 hours

Adults: Oral: 1 tablet twice daily with food

Should be administered with food to reduce stomach upset; high fat meals increase absorption, antacids decrease absorption

Signs of bleeding; CBC with differential every 2 weeks starting the second week through the third month of treatment; more frequent monitoring is recommended for patients whose absolute neutrophil counts have been consistently declining or are 30% less than baseline values. Liver function tests (alkaline phosphatase and transaminases) should be performed in the first 4 months of therapy if liver dysfunction is suspected.

cholesterol (S), alkaline phosphatase, transaminases (S)

In the setting of acute myocardial infarction, ticlopidine may be considered in aspirin-intolerant patients. Ticlopidine combined with aspirin therapy in low- to high-risk patients undergoing coronary stent insertion has been shown in several studies to improve cardiac events compared to aspirin monotherapy. In the secondary prevention of cerebrovascular disease, ticlopidine is similar or superior to aspirin therapy. Ticlopidine may cause neutropenia and therefore complete blood counts should be evaluated routinely (every 2 weeks) during the first 3 months of therapy.

None reported

May cause neutropenia; use caution with clozapine and carbamazepine

No information available to require special precautions

No effects or complications reported

Take exact dosage prescribed, with food. Do not use aspirin or aspirin-containing medications and OTC medications without consulting prescriber. You may experience easy bleeding or bruising (use soft toothbrush or cotton swabs and frequent mouth care, use electric razor, avoid sharp knives or scissors). Report unusual bleeding or bruising or persistent fever or sore throat; blood in urine, stool, or vomitus; delayed healing of any wounds; skin rash; yellowing of skin or eyes; changes in color of urine of stool; pain or burning on urination; respiratory difficulty; or skin rash. Breast-feeding precautions: Consult prescriber if breast-feeding.

Monitor bleeding times, platelets, CBC, hemoglobin and hematocrit

Tablet, as hydrochloride: 250 mg

Hsu VD, "Criteria for Use of Ticlopidine in Adult Inpatients and Outpatients," Clin Pharm, 1993, 12(1):64-6.

Ito MK, Smith AR, and Lee ML, "Ticlopidine: A New Platelet Aggregation Inhibitor," Clin Pharm, 1992, 11(7):603-17.

Rosen H, el-Hennaway AS, Greenberg S, et al, "Acute Interstitial Nephritis Associated With Ticlopidine," Am J Kidney Dis, 1995, 25(6):934-6.

Saltiel E and Ward A, "Ticlopidine. A Review of Its Pharmacodynamic and Pharmacokinetic Properties, and Therapeutic Efficacy in Platelet-Dependent Disease States," Drugs, 1987, 34(2):222-62.

Schömig A, Neumann, FJ, Kastrati A, et al, "A Randomized Comparison of Antiplatelet and Anticoagulant Therapy After the Placement of Coronary-Artery Stents," N Engl J Med, 1996, 334(17):1084-9.

Shah J, Teitelbaum P, Molony B, et al, "Single and Multiple Dose Pharmacokinetics of Ticlopidine in Young and Elderly Subjects," Br J Clin Pharmacol, 1991, 32:761-4.