"Nov. 19, 2012 -- Unemployment and a history of job loss may raise the risk for heart attack, a new study suggests.
The risk of heart attack may be highest during the first year of unemployment. And the more jobs a person loses, the hi"...
- Patient Information:
Details with Side Effects
Mechanism of Action: When taken orally, ticlopidine hydrochloride causes a time- and dose-dependent inhibition of both platelet aggregation and release of platelet granule constituents, as well as a prolongation of bleeding time. The intact drug has no significant in vitro activity at the concentrations attained in vivo; and, although analysis of urine and plasma indicates at least 20 metabolites, no metabolite which accounts for the activity of ticlopidine has been isolated.
Ticlopidine hydrochloride, after oral ingestion, interferes with platelet membrane function by inhibiting ADP-induced platelet-fibrinogen binding and subsequent platelet-platelet interactions. The effect on platelet function is irreversible for the life of the platelet, as shown both by persistent inhibition of fibrinogen binding after washing platelets ex vivo and by inhibition of platelet aggregation after resuspension of platelets in buffered medium.
Pharmacokinetics and Metabolism: After oral administration of a single 250-mg dose, ticlopidine hydrochloride is rapidly absorbed with peak plasma levels occurring at approximately 2 hours after dosing and is extensively metabolized. Absorption is greater than 80%. Administration after meals results in a 20% increase in the AUC of ticlopidine.
Ticlopidine hydrochloride displays nonlinear pharmacokinetics and clearance decreases markedly on repeated dosing. In older volunteers the apparent half-life of ticlopidine after a single 250-mg dose is about 12.6 hours; with repeat dosing at 250 mg bid, the terminal elimination half-life rises to 4 to 5 days and steady-state levels of ticlopidine hydrochloride in plasma are obtained after approximately 14 to 21 days.
Ticlopidine hydrochloride binds reversibly (98%) to plasma proteins, mainly to serum albumin and lipoproteins. The binding to albumin and lipoproteins is nonsaturable over a wide concentration range. Ticlopidine also binds to alpha-1 acid glycoprotein. At concentrations attained with the recommended dose, only 15% or less ticlopidine in plasma is bound to this protein.
Ticlopidine hydrochloride is metabolized extensively by the liver; only trace amounts of intact drug are detected in the urine. Following an oral dose of radioactive ticlopidine hydrochloride administered in solution, 60% of the radioactivity is recovered in the urine and 23% in the feces. Approximately 1/3 of the dose excreted in the feces is intact ticlopidine hydrochloride, possibly excreted in the bile. Ticlopidine hydrochloride is a minor component in plasma (5%) after a single dose, but at steady-state is the major component (15%). Approximately 40% to 50% of the radioactive metabolites circulating in plasma are covalently bound to plasma proteins, probably by acylation.
Clearance of ticlopidine decreases with age. Steady-state trough values in elderly patients (mean age 70 years) are about twice those in younger volunteer populations.
Hepatically Impaired Patients: The effect of decreased hepatic function on the pharmacokinetics of TICLID (ticlopidine hcl) was studied in 17 patients with advanced cirrhosis. The average plasma concentration of ticlopidine in these subjects was slightly higher than that seen in older subjects in a separate trial (see CONTRAINDICATIONS).
Renally Impaired Patients: Patients with mildly (Ccr 50 to 80 mL/min) or moderately (Ccr 20 to 50 mL/min) impaired renal function were compared to normal subjects (Ccr 80 to 150 mL/min) in a study of the pharmacokinetic and platelet pharmacodynamic effects of TICLID (ticlopidine hcl) (250 mg bid) for 11 days. Concentrations of unchanged TICLID (ticlopidine hcl) were measured after a single 250-mg dose and after the final 250-mg dose on Day 11.
AUC values of ticlopidine increased by 28% and 60% in mild and moderately impaired patients, respectively, and plasma clearance decreased by 37% and 52%, respectively, but there were no statistically significant differences in ADP-induced platelet aggregation. In this small study (26 patients), bleeding times showed significant prolongation only in the moderately impaired patients.
Pharmacodynamics: In healthy volunteers over the age of 50, substantial inhibition (over 50%) of ADP-induced platelet aggregation is detected within 4 days after administration of ticlopidine hydrochloride 250 mg bid, and maximum platelet aggregation inhibition (60% to 70%) is achieved after 8 to 11 days. Lower doses cause less, and more delayed, platelet aggregation inhibition, while doses above 250 mg bid give little additional effect on platelet aggregation but an increased rate of adverse effects. The dose of 250 mg bid is the only dose that has been evaluated in controlled clinical trials.
After discontinuation of ticlopidine hydrochloride, bleeding time and other platelet function tests return to normal within 2 weeks, in the majority of patients.
At the recommended therapeutic dose (250 mg bid), ticlopidine hydrochloride has no known significant pharmacological actions in man other than inhibition of platelet function and prolongation of the bleeding time.
1. Study in Patients Experiencing Stroke Precursors: In a trial comparing ticlopidine and aspirin (The Ticlopidine Aspirin Stroke Study or TASS), 3069 patients (1987 men, 1082 women) who had experienced such stroke precursors as transient ischemic attack (TIA), transient monocular blindness (amaurosis fugax), reversible ischemic neurological deficit or minor stroke, were randomized to ticlopidine 250 mg bid or aspirin 650 mg bid. The study was designed to follow patients for at least 2 years and up to 5 years.
Over the duration of the study, TICLID (ticlopidine hcl) significantly reduced the risk of fatal and nonfatal stroke by 24% (p = .011) from 18.1 to 13.8 per 100 patients followed for 5 years, compared to aspirin. During the first year, when the risk of stroke is greatest, the reduction in risk of stroke (fatal and nonfatal) compared to aspirin was 48%; the reduction was similar in men and women.
2. Study in Patients Who Had a Completed Atherothrombotic Stroke: In a trial comparing ticlopidine with placebo (The Canadian American Ticlopidine Study or CATS) 1073 patients who had experienced a previous atherothrombotic stroke were treated with TICLID (ticlopidine hcl) 250 mg bid or placebo for up to 3 years.
TICLID (ticlopidine hcl) significantly reduced the overall risk of stroke by 24% (p = .017) from 24.6 to 18.6 per 100 patients followed for 3 years, compared to placebo. During the first year the reduction in risk of fatal and nonfatal stroke over placebo was 33%.
Stent Patients: The ability of TICLID (ticlopidine hcl) to reduce the rate of thrombotic events after the placement of coronary artery stents has been studied in five randomized trials, one of substantial size (Stent Anticoagulation Restenosis Study or STARS) described below, and four smaller studies. In these trials, ticlopidine 250 mg bid with ASA (dose range from 100 mg bid to 325 mg qd) was compared to aspirin alone or to anticoagulant therapy plus aspirin. The trials enrolled patients undergoing both planned (elective) and unplanned coronary stent placement. The types of stents used, the use of intravascular ultrasound, and the use of high-pressure stent deployment varied among the trials, although all patients in STARS received a Palmaz-Schatz stent. The primary efficacy endpoints of the trials were similar, and included death, myocardial infarction and the need for repeat coronary angioplasty or CABG. All trials followed patients for at least 30 days.
In STARS, patients were randomized to receive one of three regimens for 4 weeks: aspirin alone, aspirin plus coumadin, or aspirin plus ticlopidine. Therapy was initiated following successful coronary stent placement. The primary endpoint was the incidence of stent thrombosis, defined as death, Q-Wave MI, or angiographic thrombus within the stented vessel demonstrated at the time of documented ischemia requiring emergent revascularization. The incidence rates for the primary endpoint and its components at 30 days are shown in the table below.
|STARS||TICLID + Aspirin
|Q-Wave MI (Recurrent and Procedure Related)||1
|Angiographically Evident Thrombosis||3
|* Comparison of TICLID plus aspirin to aspirin alone.|
The use of ticlopidine plus aspirin did not affect the rate of non-Q-wave MIs when compared with aspirin alone or aspirin plus anticoagulants in STARS.
The use of ticlopidine plus aspirin was associated with a lower rate of recurrent cardiovascular events when compared with aspirin alone or aspirin plus anticoagulants in the other four randomized trials.
The rate of serious bleeding complications and neutropenia in STARS are shown in the table below. There were no cases of thrombotic thrombocytopenic purpura (TTP) or aplastic anemia reported in 1346 patients who received ticlopidine plus aspirin in the five randomized trials.
|STARS||TICLID + Aspirin
|Coumadin + Aspirin
|Hemorrhagic Complications||30 (5.5%)||10 (1.8%)||34 (6.2%)|
|Cerebrovascular Accident||0 (0%)||2 (0.4%)||1 (0.2%)|
|Neutropenia ( ≤ 1200/mm³)||3 (0.5%)||0 (0%)||1 (0.2%)|
Last reviewed on RxList: 6/10/2008
This monograph has been modified to include the generic and brand name in many instances.
Additional Ticlid Information
Ticlid - User Reviews
Ticlid User Reviews
Now you can gain knowledge and insight about a drug treatment with Patient Discussions.
Report Problems to the Food and Drug Administration
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
Get the latest treatment options.