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

The only adverse event resulting in discontinuation of therapy in ≥ 3% of patients treated with PLETAL 50 or 100 mg twice daily was headache, which occurred with an incidence of 1.3%, 3.5%, and 0.3% in patients treated with PLETAL 50 mg twice daily, 100 mg twice daily, 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 PLETAL 50 or 100 mg twice daily, and with a frequency higher than placebo, 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 twice daily group were: asthenia, hypertension, vomiting, leg cramps, hypesthesia, paresthesia, dyspnea, rash, hematuria, urinary tract infection, flu syndrome, angina pectoris, arthritis, and bronchitis.

Most Commonly Reported AEs (Incidence ≥ 2%) in Patients on PLETAL (PLT) 50 mg twice daily or 100 mg twice daily and Occurring at a Rate in the 100 mg twice daily Group Higher Than in Patients on Placebo

Adverse Events (AEs) by Body System PLT 50 mg twice daily
(N=303) %
PLT 100 mg twice daily
(N=998) %
(N=973) %
Abdominal pain 4 5 3
Back pain 6 7 6
Headache 27 34 14
Infection 14 10 8
Palpitation 5 10 1
Tachycardia 4 4 1
Abnormal stools 12 15 4
Diarrhea 12 19 7
Dyspepsia 6 6 4
Flatulence 2 3 2
Nausea 6 7 6
Peripheral edema 9 7 4
Myalgia 2 3 2
Dizziness 9 10 6
Vertigo 3 1 1
Cough increased 3 4 3
Pharyngitis 7 10 7
Rhinitis 12 7 5

Less frequent adverse events ( < 2%) that were experienced by patients exposed to PLETAL 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, regardless of suspected drug relationship, are listed below.

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

Cardiovascular: Atrial fibrillation, atrial flutter, cerebral infarct, cerebral ischemia, congestive heart failure, heart arrest, haemorrhage, 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 haemorrhage, esophagitis, increased GGT, gastritis, gastroenteritis, gum haemorrhage, hematemesis, melena, peptic ulcer, periodontal abscess, rectal haemorrhage, 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 haemorrhage, retinal haemorrhage, tinnitus.

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

Post-Marketing Experience

The following adverse drug reactions (ADRs) to PLETAL have been reported worldwide since the launch of PLETAL in the US.

  • Blood and lymphatic system disorders:
    • Agranulocytosis, aplastic anemia, granulocytopenia, pancytopenia, 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 haemorrhage
  • 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), blood pressure increase
  • Nervous system disorders
    • Intracranial haemorrhage, cerebral haemorrhage, cerebrovascular accident
  • Respiratory, thoracic and mediastinal disorders
    • Pulmonary haemorrhage, interstitial pneumonia
  • Skin and subcutaneous tissue disorders
    • Haemorrhage 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)