Cilostazol (Cilostazol) - Side Effects and Adverse Reactions

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. 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, hypesthesia, paresthesia, dyspnea, rash, hematuria, urinary tract infection, flu syndrome, angina pectoris, arthritis, and bronchitis.

Most Commonly Reported AEs (Incidence ≥ 2%) in Patients on Cilostazol 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	Cilostazol 50 mg b.i.d. (N = 303) %	Cilostazol 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 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 launch of cilostazol in the US.

• Blood and Lymphatic System Disorders: agranulocytosis, granulocytopenia, thrombocytopenia, leucopenia, 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 it's positive chronotropic action.)
• Gastrointestinal Disorders: gastrointestinal hemorrhage
• General Disorders and Administrative Site Conditions: pain, chest pain, hot flushes
• Hepatobiliary Disorders: hepatic dysfunction/abnormal liver function tests, jaundice
• Injury, Poisoning and Procedural Complications: extradural hematoma and subdural hematoma
• 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
• Respritory, 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.)

REPORTS OF SUSPECTED CILOSTAZOL SIDE EFFECTS / ADVERSE REACTIONS

Possible Cilostazol side effects / adverse reactions in 78 year old female

Reported by a individual with unspecified qualification from Spain on 2011-10-04

Patient: 78 year old female

Reactions: Lymphopenia, Drug Interaction, Toxic Epidermal Necrolysis, Acinetobacter Test Positive, Cardio-Respiratory Arrest, Septic Shock, Staphylococcus Test Positive, Leukopenia, Stevens-Johnson Syndrome, Enterobacter Test Positive

Adverse event resulted in: death

Suspect drug(s):
Carbamazepine
    Dosage: 100 mg milligram(s) sep. dosages / interval: 1 in 1 day;

Cilostazol
    Dosage: 100 mg milligram(s) sep. dosages / interval: 1 in 1 day;

Omeprazole
    Dosage: 20 mg milligram(s) sep. dosages / interval: 21 in 1 day

Other drugs received by patient: Hydroxyzine; Methylprednisolone; Deflazacort; Cetirizine HCL; Sulpride

Possible Cilostazol side effects / adverse reactions in 78 year old female

Reported by a health professional (non-physician/pharmacist) from Spain on 2011-10-05

Patient: 78 year old female

Reactions: Enterobacter Infection, Urticaria, Drug Interaction, Toxic Epidermal Necrolysis, Skin Reaction, Nikolsky's Sign, Acinetobacter Infection, Staphylococcal Infection, Metabolic Disorder, Septic Shock, Cardiac Arrest, Culture Positive, Stevens-Johnson Syndrome

Adverse event resulted in: death, hospitalization

Suspect drug(s):
Carbamazepine
    Dosage: 100 mg, daily dose, oral
    Administration route: Oral
    Indication: Restless Legs Syndrome
    Start date: 2009-12-01
    End date: 2010-03-18

Cilostazol
    Dosage: 100 mg, daily dose, oral
    Administration route: Oral
    Start date: 2010-03-01
    End date: 2010-03-18

Omeprazole
    Dosage: 20 mg, oral
    Administration route: Oral

Other drugs received by patient: Hydroxyzine; Sulpiride (Sulpiride); Cetirizine HCL; Deflazacort (Deflazacort)

Possible Cilostazol side effects / adverse reactions in 45 year old female

Reported by a individual with unspecified qualification from Brazil on 2011-10-10

Patient: 45 year old female weighing 82.0 kg (180.4 pounds)

Reactions: Myocardial Infarction, Transient Ischaemic Attack, Erysipelas

Suspect drug(s):
Aspirin
    Dosage: 200 mg, unk

Citalopram
    Dosage: 20 mg, unk

Crestor
    Dosage: 20 mg, unk

Exforge
    Dosage: 160 mg vals and 5 mg amlo
    Indication: Hypertension

Galvus MET
    Dosage: 500 mg metf and 50 mg vild

Metoprolol Succinate
    Dosage: 100 mg, unk

Monocordil
    Dosage: 50 mg/day

Cilostazol
    Dosage: 200 mg/day

Exforge
    Dosage: 320 mg vals and 5 mg amlo

Other drugs received by patient: Rosuvastatin