Hematological Adverse Reactions
NEUTROPENIA
Neutropenia may occur suddenly. Bone-marrow examination typically shows a reduction in white blood cell precursors. After withdrawal of ticlopidine, the neutrophil count usually rises to > 1200/mm3 within 1 to 3 weeks.
THROMBOCYTOPENIA
Rarely, thrombocytopenia may occur in isolation or together with neutropenia.
THROMBOTIC THROMBOCYTOPENIC PURPURA (TTP)
TTP is characterized by thrombocytopenia, microangiopathic hemolytic anemia (schistocytes [fragmented RBCs] seen on peripheral smear), neurological findings, renal dysfunction, and fever. The signs and symptoms can occur in any order; in particular, clinical symptoms may precede laboratory findings by hours or days. With prompt treatment (often including plasmapheresis), 70% to 80% of patients will survive with minimal or no sequelae. Because platelet transfusions may accelerate thrombosis in patients with TTP on ticlopidine, they should, if possible, be avoided.
APLASTIC ANEMIA
Aplastic anemia is characterized by anemia, thrombocytopenia and neutropenia together with a bone marrow examination that shows decreases in the precursor cells for red blood cells, white blood cells, and platelets. Patients may present with signs or symptoms suggestive of infection, in association with low white blood cell and platelet counts. Prompt treatment, which may include the use of drugs to stimulate the bone marrow, can minimize the mortality associated with aplastic anemia.
MONITORING FOR HEMATOLOGIC ADVERSE REACTIONS
Starting just before initiating treatment and continuing through the third month of therapy, patients receiving ticlopidine hydrochloride must be monitored every 2 weeks. Because of ticlopidine’s long plasma half-life, patients who discontinue ticlopidine during this 3-month period should continue to be monitored for 2 weeks after discontinuation. More frequent monitoring, and monitoring after the first 3 months of therapy, is necessary only in patients with clinical signs (e.g., signs or symptoms suggestive of infection) or laboratory signs (e.g., neutrophil count less than 70% of the baseline count, decrease in hematocrit or platelet count) that suggest incipient hematological adverse reactions.
Clinically, fever might suggest neutropenia, TTP or aplastic anemia; TTP might also be suggested by weakness, pallor, petechiae or purpura, dark urine (due to blood, bile pigments, or hemoglobin) or jaundice, or neurological changes. Patients should be told to discontinue ticlopidine hydrochloride and to contact the physician immediately upon the occurrence of any of these findings. Laboratory monitoring should include a complete blood count, with special attention to the absolute neutrophil count (WBC x % neutrophils), platelet count, and the appearance of the peripheral smear. Ticlopidine is occasionally associated with thrombocytopenia unrelated to TTP or aplastic anemia. Any acute, unexplained reduction in hemoglobin or platelet count should prompt further investigation for a diagnosis of TTP, and the appearance of schistocytes (fragmented RBCs) on the smear should be treated as presumptive evidence of TTP. A simultaneous decrease in platelet count and WBC count should prompt further investigation for a diagnosis of aplastic anemia. If there are laboratory signs of TTP or aplastic anemia, or if the neutrophil count is confirmed to be < 1200/mm3, then ticlopidine hydrochloride should be discontinued immediately.
Other Hematological Effects
Rare cases of agranulocytosis, pancytopenia or leukemia have been reported in postmarketing experience, some of which have been fatal. All forms of hematological adverse reactions are potentially fatal.
Cholesterol Elevation
Ticlopidine hydrochloride therapy causes increased serum cholesterol and triglycerides. Serum total cholesterol levels are increased 8% to 10% within 1 month of therapy and persist at that level. The ratios of the lipoprotein subfractions are unchanged.
Anticoagulant Drugs
The tolerance and safety of coadministration of ticlopidine hydrochloride with heparin, oral anticoagulants, or fibrinolytic agents have not been established. If a patient is switched from an anticoagulant or fibrinolytic drug to ticlopidine hydrochloride, the former drug should be discontinued prior to ticlopidine hydrochloride administration.
There is currently no manufacturer warning information available for this drug.
Ticlopidine hydrochloride tablets are indicated:
Ticlopidine hydrochloride is a platelet aggregation inhibitor. Chemically it is 5-[(2-chlorophenyl)methyl]-4,5,6,7-tetrahydrothieno [3,2-c] pyridine hydrochloride. The structural formula is:
Ticlopidine hydrochloride is a white crystalline solid. It is freely soluble in water and self buffers to a pH of 3.6. It also dissolves freely in methanol, is sparingly soluble in methylene chloride and ethanol, slightly soluble in acetone, and insoluble in a buffer solution of pH 6.3. It has a molecular weight of 300.25.
Each tablet, for oral administration, contains 250 mg of ticlopidine hydrochloride. In addition, each tablet contains the following inactive ingredients: ammonium chloride, magnesium stearate, microcrystalline cellulose, povidone, starch (corn), and stearic acid. The white film coating contains hydroxypropylmethyl cellulose, lactose monohydrate, titanium dioxide and triacetin.
