Drug Information for CILOSTAZOL TABLETS (Apotex Corp.): ADVERSE REACTIONS

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  • Adverse events were assessed in eight placebo-controlled clinical trials involving 2274 patients exposed to either 50 or 100 mg b.i.d. cilostazol (n=1301) or placebo (n=973), with a median treatment duration of 127 days for patients on cilostazol and 134 days for patients on placebo.

    The only adverse event resulting in discontinuation of therapy in ≥ 3% of patients treated with cilostazol 50 or 100 mg b.i.d. was headache, which occurred with an incidence of 1.3%, 3.5%, and 0.3% in patients treated with cilostazol 50 mg b.i.d., 100 mg b.i.d, or placebo, respectively. Other frequent causes of discontinuation included palpitation and diarrhea, both 1.1% for cilostazol (all doses) versus 0.1% for placebo.

    The most commonly reported adverse events, occurring in ≥ 2% of patients treated with cilostazol 50 or 100 mg b.i.d., are shown in the table (below).

    Other events seen with an incidence of ≥ 2%, but occurring in the placebo group at least as frequently as in the 100 mg b.i.d. group were: asthenia, hypertension, vomiting, leg cramps, hyperesthesia, paresthesia, dyspnea, rash, hematuria, urinary tract infection, flu syndrome, angina pectoris, arthritis, and bronchitis.

    Most Commonly Reported AEs (Incidence ≥2%) in Patients on Cilostazol50 mg b.i.d. or 100 mg b.i.d. and Occurring at a Rate in the 100 mg b.i.d. Group Higher Than in Patients on Placebo
    Adverse Events (AEs) by Body SystemCilostazol 50 mg b.i.d.(N=303)%Cilostazol 100 mg b.i.d.(N=998)%Placebo(N=973)%
    BODY AS A WHOLE
    Abdominal pain453
    Back pain676
    Headache273414
    Infection 14108
    CARDIOVASCULAR
    Palpitation5101
    Tachycardia441
    DIGESTIVE
    Abnormal stools 12154
    Diarrhea12197
    Dyspepsia664
    Flatulence232
    Nausea676
    METABOLIC & NUTRITIONAL
    Peripheral edema974
    MUSCULO-SKELETAL
    Myalgia232
    NERVOUS
    Dizziness9106
    Vertigo311
    RESPIRATORY
    Cough increased343
    Pharyngitis7107
    Rhinitis1275

    Less frequent adverse events (<2%) that were experienced by patients exposed to cilostazol 50 mg b.i.d. or 100 mg b.i.d. in the eight controlled clinical trials and that occurred at a frequency in the 100 mg b.i.d. group greater than in the placebo group, regardless of suspected drug relationship, are listed below.

    Body as a whole: Chills, face edema, fever, generalized edema, malaise, neck rigidity, pelvic pain, retroperitoneal hemorrhage.

    Cardiovascular: Atrial fibrillation, atrial flutter, cerebral infarct, cerebral ischemia, congestive heart failure, heart arrest, hemorrhage, hypotension, myocardial infarction, myocardial ischemia, nodal arrhythmia, postural hypotension, supraventricular tachycardia, syncope, varicose vein, vasodilation, ventricular extrasystoles, ventricular tachycardia.

    Digestive: Anorexia, cholelithiasis, colitis, duodenal ulcer, duodenitis, esophageal hemorrhage, esophagitis, increased GGT, gastritis, gastroenteritis, gum hemorrhage, hematemesis, melena, peptic ulcer, periodontal abscess, rectal hemorrhage, stomach ulcer, tongue edema.

    Endocrine: Diabetes mellitus.

    Hemic and Lymphatic: Anemia, ecchymosis, iron deficiency anemia, polycythemia, purpura.

    Metabolic and Nutritional: Increased creatinine, gout, hyperlipemia, hyperuricemia.

    Musculoskeletal: Arthralgia, bone pain, bursitis.

    Nervous: Anxiety, insomnia, neuralgia.

    Respiratory: Asthma, epistaxis, hemoptysis, pneumonia, sinusitis.

    Skin and Appendages: Dry skin, furunculosis, skin hypertrophy, urticaria.

    Special Senses: Amblyopia, blindness, conjunctivitis, diplopia, ear pain, eye hemorrhage, retinal hemorrhage, tinnitus.

    Urogenital: Albuminuria, cystitis, urinary frequency, vaginal hemorrhage, vaginitis.

  • Post-Marketing Experience

  • The following events have been reported spontaneously from worldwide post-marketing experience since the launch of cilostazol in the US.

    • Blood and lymphatic system disorders:
      • - agranulocytosis, granulocytopenia, thrombocytopenia, leukopenia, bleeding tendency
    • Cardiac disorders:
      • - Torsades de pointes, QTc prolongation (Torsades de pointes and QTc prolongation occurred in patients with cardiac disorders, e.g. complete atrioventricular block, cardiac failure and bradyarrythmia, when treated with cilostazol. Cilostazol was used “off label” due to its positive chronotropic action.)
    • Gastrointestinal disorders:
      • - gastrointestinal hemorrhage
    • General disorders and administration site conditions:
      • - pain, chest pain, hot flushes
    • Hepatobiliary disorders:
      • - hepatic dysfunction/abnormal liver function tests, jaundice
    • Injury, poisoning and procedural complications:
      • - extradural haematoma and subdural haematoma
    • Investigations:
      • - blood glucose increased, blood uric acid increased, platelet count decreased, white blood cell count decreased, increase in BUN (blood urea increased)
    • Nervous system disorders:
      • - intracranial hemorrhage, cerebral hemorrhage, cerebrovascular accident
    • 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)
    • Vascular disorders:
      • - subacute thrombosis (These cases of subacute thrombosis occurred in patients treated with aspirin and “off label” use of cilostazol for prevention of thrombotic complication after coronary stenting.)
  • Drug Information Provided by National Library of Medicine (NLM).
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