cilostazol

6 ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of the labeling: Patients with Heart Failure [see Boxed Warning] Tachycardia [see Warnings and Precautions ( 5.1 )] Left Ventricular Outflow Tract Obstruction [see Warnings and Precautions ( 5.2 )] Hematologic Adverse Reactions [see Warnings and Precautions ( 5.3 )] Hemostatic Disorders or Active Pathologic Bleeding [see Warnings and Precautions ( 5.4 )] Most common adverse reactions greater than or equal to 2% and at least twice that for placebo in patients on 100 mg twice daily are headache, diarrhea, abnormal stools, and palpitation ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Apotex Corp. at 1-800-706-5575 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Adverse reactions were assessed in eight placebo-controlled clinical trials involving patients exposed to either 50 or 100 mg twice daily cilostazol tablets (n=1301) or placebo (n=973), with a median treatment duration of 127 days for patients on cilostazol tablets and 134 days for patients on placebo. The most frequent adverse reaction resulting in discontinuation of therapy in more than 3% of patients treated with cilostazol tablets was headache [50 mg twice daily (1.3%), 100 mg twice daily (3.5%) and placebo (0.3%)]. Other frequent causes of discontinuation included palpitation and diarrhea, both 1.1% for cilostazol tablets (all doses) versus 0.1% for placebo. The most common adverse reactions, occurring in at least 2% of patients treated with cilostazol tablets 50 or 100 mg twice daily, are shown in Table 1. Table 1: Most Common Adverse Reactions in Patients on cilostazol tablets 50 or 100 mg Twice Daily (Incidence at least 2% and Occurring More Frequently (≥ 2%) in the 100 mg Twice Daily Group than on Placebo) Adverse Reactions Placebo (N=973) Cilostazol tablets 50 mg twice daily (N=303) Cilostazol tablets 100 mg twice daily (N=998) Headache 14% 27% 34% Diarrhea 7% 12% 19% Abnormal stools 4% 12% 15% Palpitation 1% 5% 10% Dizziness 6% 9% 10% Pharyngitis 7% 7% 10% Infection 8% 14% 10% Peripheral edema 4% 9% 7% Rhinitis 5% 12% 7% Dyspepsia 4% 6% 6% Abdominal pain 3% 4% 5% Tachycardia 1% 4% 4% Less frequent clinical significant adverse reactions (less than 2%) that were experienced by patients treated with cilostazol 50 mg twice daily or 100 mg twice daily in the eight controlled clinical trials and that occurred at a frequency in the 100 mg twice daily group greater than in the placebo group are listed below. Body as a whole: fever, generalized edema, malaise Cardiovascular: atrial fibrillation, heart failure, myocardial infarction, nodal arrhythmia, supraventricular tachycardia, ventricular extrasystoles, ventricular tachycardia Digestive: anorexia, melena Hematologic and Lymphatic: anemia Metabolic and Nutritional: increased creatinine, hyperuricemia Nervous: insomnia Respiratory: epistaxis Skin and Appendages: urticaria Special Senses: conjunctivitis, retinal hemorrhage, tinnitus Urogenital: urinary frequency 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of cilostazol tablets. Because these reactions are reported voluntarily from a population of an unknown size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Blood and lymphatic system disorders: Aplastic anemia, granulocytopenia, pancytopenia, bleeding tendency Cardiac disorders: Torsade de pointes and QTc prolongation in patients with cardiac disorders (e.g. complete atrioventricular block, heart failure; and bradyarrythmia), angina pectoris. Gastrointestinal disorders: Gastrointestinal hemorrhage, vomiting, flatulence, nausea General disorders and administration site conditions: Pain, chest pain, hot flushes Hepatobiliary disorders: Hepatic dysfunction/abnormal liver function tests, jaundice Immune system disorders: Anaphylaxis, angioedema, and hypersensitivity Investigations: Blood glucose increased, blood uric acid increased, increase in BUN (blood urea increased), blood pressure increase Nervous system disorders: Intracranial hemorrhage, cerebral hemorrhage, cerebrovascular accident, extradural hematoma and subdural hematoma Renal and urinary disorders: Hematuria Respiratory, thoracic and mediastinal disorders: Pulmonary hemorrhage, interstitial pneumonia Skin and subcutaneous tissue disorders: Hemorrhage subcutaneous, pruritus, skin eruptions including Stevens-Johnson syndrome, skin drug eruption (dermatitis medicamentosa), rash Vascular disorders: Subacute stent thrombosis, hypertension.