Ticlopidine

263.79

263.79

259-498-5

OM90ZUW7M1

DTXSID5023669

C61972

B01AC05|B - Blood and blood forming organs

2934999090

31.5

3.6

Solid

1.3±0.1 g/cm3

210-212 °C

117-120 °C @ Press: 0.5 Torr

175.9±26.5 °C

1.638

H2O: Freely soluble

UN 3261 8/PG 3

3

R34:Causes burns.

S26-S27-S36/37/39-S45

C,Xi

Single oral doses of ticlopidine at 1600 mg/kg and 500 mg/kg were lethal to rats and mice, respectively. Symptoms of acute toxicity were GI hemorrhage, convulsions, hypothermia, dyspnea, loss of equilibrium and abnormal gait. The FDA label includes a black-box warning of neutropenia, aplastic anemia, thrombotic thrombocytopenia purpura, and agranulocytosis, so it is necessary to monitor patients' WBC and platelets when they are taking ticlopidine.

Ticlopidine has been associated with serum enzyme elevations in approximately 4% of patients during therapy. These elevations are usually mild, asymptomatic and rarely require dose modification or stopping. Ticlopidine has also been associated with clinically apparent, acute liver injury. While these reactions are rare, more than 50 instances have been reported in the literature and some have been severe. The onset of symptoms is typically within 6 weeks (range 1 to 24 weeks) and marked by onset with fatigue, jaundice and itching. The usual pattern of liver enzyme elevations is cholestatic (~75%), but cases with mixed or hepatocellular enzyme elevations have also been described. Immunoallergic features such as fever, rash and eosinophilia can occur but are not common and, if present, are usually mild. Autoantibody formation is rare. Liver biopsy usually shows cholestatic hepatitis with mixed cellular infiltrates. Most cases are self-limited with recovery within 1 to 3 months, but isolated cases of prolonged jaundice or liver test abnormalities have been described, including at least one case of probable vanishing bile duct syndrome that eventually required liver transplantation. Ticlopidine therapy has also been associated with aplastic anemia and thrombotic thrombocytopenic purpura (TTP) that can be severe and lead to death; these patients may also have accompanying cholestatic liver injury.

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 (about 15% or less).

Used in patients, who have had a stroke or stroke precursors and who cannot take aspirin or aspirin has not worked, to try to prevent another thrombotic stroke.|FDA Label

Ticlopidine is an inhibitor of platelet aggregation that is used to decrease the risk of stroke in patients known to have atherosclerosis. Ticlopidine is associated with a low rate of serum enzyme elevations during treatment and has been linked to rare instances of idiosyncratic, clinically apparent acute liver injury.

Antithrombotic Agents

Ticlopidine is a known transformation product of Clopidogrel carboxylic acid.

Ticlopidine is a prodrug that is metabolised to an as yet undetermined metabolite that acts as a platelet aggregation inhibitor. Inhibition of platelet aggregation causes a prolongation of bleeding time. In its prodrug form, ticlopidine has no significant in vitro activity at the concentrations attained in vivo.

Compounds that bind to and block the stimulation of PURINERGIC P2Y RECEPTORS. Included under this heading are antagonists for specific P2Y receptor subtypes. (See all compounds classified as Purinergic P2Y Receptor Antagonists.)|Drugs and compounds which inhibit or antagonize the biosynthesis or actions of CYTOCHROME P-450 CYP2C19. (See all compounds classified as Cytochrome P-450 CYP2C19 Inhibitors.)|Drugs or agents which antagonize or impair any mechanism leading to blood platelet aggregation, whether during the phases of activation and shape change or following the dense-granule release reaction and stimulation of the prostaglandin-thromboxane system. (See all compounds classified as Platelet Aggregation Inhibitors.)|Fibrinolysin or agents that convert plasminogen to FIBRINOLYSIN. (See all compounds classified as Fibrinolytic Agents.)

Absorption is greater than 80%. Food increases absorption by approximately 20%.|Ticlopidine is eliminated mostly in the urine (60%) and somewhat in the feces (23%).|The volume of distribution was not quantified.|Ticlopidine clearance was not quantified, but clearance decreases with age.

Ticlopidine is metabolized extensively by the liver with only trace amounts of intact drug detected. At least 20 metabolites have been identified.|Ticlopidine has known human metabolites that include Thienodihydropyridinium and Ticlopidine S-oxide.

Half-life following a single 250-mg dose is approximately 7.9 hours in subjects 20 to 43 years of age and 12.6 hours in subjects 65 to 76 years of age. With repeated dosing (250 mg twice a day), half-life is about 4 days in subjects 20 to 43 years of age and about 5 days in subjects 65 to 76 years of age.

The active metabolite of ticlopidine prevents binding of adenosine diphosphate (ADP) to its platelet receptor, impairing the ADP-mediated activation of the glycoprotein GPIIb/IIIa complex. It is proposed that the inhibition involves a defect in the mobilization from the storage sites of the platelet granules to the outer membrane. No direct interference occurs with the GPIIb/IIIa receptor. As the glycoprotein GPIIb/IIIa complex is the major receptor for fibrinogen, its impaired activation prevents fibrinogen binding to platelets and inhibits platelet aggregation. By blocking the amplification of platelet activation by released ADP, platelet aggregation induced by agonists other than ADP is also inhibited by the active metabolite of ticlopidine.

53 32C

Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients|Pharmaceuticals -> Blood and blood forming organs -> Anticoagulants