ADVERSE REACTIONS
Adverse events were assessed in eight placebo-controlled clinical trials involving 2274 patients exposed to either 50 or 100 mg b.i.d. 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 b.i.d. was headache, which occurred with an incidence of 1.3%, 3.5%, and 0.3% in patients treated with PLETAL 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 PLETAL 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, 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 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 System | PLT 50 mg b.i.d.
(N=303)
% | PLT 100 mg b.i.d.
(N=998)
% | Placebo
(N=973)
% |
| BODY AS A WHOLE |
| Abdominal pain | 4 | 5 | 3 |
| Back pain | 6 | 7 | 6 |
| Headache | 27 | 34 | 14 |
| Infection | 14 | 10 | 8 |
| CARDIOVASCULAR |
| Palpitation | 5 | 10 | 1 |
| Tachycardia | 4 | 4 | 1 |
| DIGESTIVE |
| Abnormal stools | 12 | 15 | 4 |
| Diarrhea | 12 | 19 | 7 |
| Dyspepsia | 6 | 6 | 4 |
| Flatulence | 2 | 3 | 2 |
| Nausea | 6 | 7 | 6 |
| METABOLIC & NUTRITIONAL |
| Peripheral edema | 9 | 7 | 4 |
| MUSCULO-SKELETAL |
| Myalgia | 2 | 3 | 2 |
| NERVOUS |
| Dizziness | 9 | 10 | 6 |
| Vertigo | 3 | 1 | 1 |
| RESPIRATORY |
| 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 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 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 events have been reported spontaneously from worldwide post-marketing experience since 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.)
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REPORTS OF SIDE EFFECTS / ADVERSE REACTIONS RELATED TO PLETAL
Below is a sample of reports where side effects / adverse reactions may be related to Pletal. The information is not vetted and should not be cosidered as verified clinical evidence.
Possible Pletal side effects / adverse reactions in 66 year old male
Reported by a physician from Japan on 2007-01-24
Patient: 66 year old male
Reactions: Hepatic Function Abnormal, Cardiac Operation
Suspect drug(s):
Aspirin
Administration route: Oral
Lipitor
Dosage: daily dose:10mg
Administration route: Oral
Indication: Hypercholesterolaemia
Start date: 2006-07-01
End date: 2006-07-25
Omepral
Dosage: daily dose:20mg
Administration route: Oral
Phenobarbital TAB
Dosage: daily dose:100mg
Administration route: Oral
Pletal
Dosage: daily dose:100mg
Administration route: Oral
Other drugs received by patient: Gaster; Artist; Norvasc
Possible Pletal side effects / adverse reactions in 59 year old male
Reported by a physician from Japan on 2007-02-05
Patient: 59 year old male weighing 78.0 kg (171.6 pounds)
Reactions: Drug Eruption, Neutrophil Count Increased, Biopsy Bone Marrow, Blood Lactate Dehydrogenase Increased, Chills, Eczema, Pyrexia, Idiopathic Thrombocytopenic Purpura, Diarrhoea, Pigmentation Disorder, Platelet Count Decreased, Thrombocytopenia, Enterocolitis, Lymphocyte Count Decreased
Adverse event resulted in: life threatening event, hospitalization
Suspect drug(s):
Common Cold Medicine
Administration route: Oral
Indication: Nasopharyngitis
Start date: 2006-08-18
End date: 2006-08-18
Pletal
Dosage: 200 mg/day
Administration route: Oral
Indication: Cerebral Infarction
Start date: 2006-06-17
End date: 2006-08-21
Tegretol
Dosage: 200 mg/day
Administration route: Oral
Indication: Facial Spasm
Start date: 2006-08-09
End date: 2006-08-21
Other drugs received by patient: SLO-BID; Spiropent; Rivotril; Rivotril
Possible Pletal side effects / adverse reactions in 59 year old male
Reported by a physician from Japan on 2007-02-28
Patient: 59 year old male weighing 78.0 kg (171.6 pounds)
Reactions: Drug Eruption, Neutrophil Count Increased, Biopsy Bone Marrow, Blood Lactate Dehydrogenase Increased, Chills, Eczema, Pyrexia, Idiopathic Thrombocytopenic Purpura, Diarrhoea, Pigmentation Disorder, Platelet Count Decreased, Thrombocytopenia, Enterocolitis, Lymphocyte Count Decreased
Adverse event resulted in: life threatening event, hospitalization
Suspect drug(s):
Common Cold Medicine
Administration route: Oral
Indication: Nasopharyngitis
Start date: 2006-08-18
End date: 2006-08-18
Pletal
Dosage: 200 mg/day
Administration route: Oral
Indication: Cerebral Infarction
Start date: 2006-06-17
End date: 2006-08-21
Tegretol
Dosage: 200 mg/day
Administration route: Oral
Indication: Facial Spasm
Start date: 2006-08-09
End date: 2006-08-21
Other drugs received by patient: SLO-BID; Spiropent; Rivotril; Rivotril
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