Pletaal Special Precautions

This drug should be administered with caution in the following patients: Patients on anticoagulants (e.g., warfarin), antiplatelet drugs (e.g., aspirin and ticlopidine), thrombolytic drugs (e.g., urokinase and alteplase), prostaglandin E, or its derivatives (e.g., alprostadil and limaprost alfadex).
Patients during menstruation (There is a risk of menorrhagia).
Patients with complication of coronary artery stenosis (Increased pulse rate possibly resulting from treatment with cilostazol could induce angina pectoris).
Patients with severe renal failure (Creatinine clearance: 25 ml/min) (The blood concentration of cilostazol metabolite may be increased). (See 'Other Precautions' as follows.)
Patients with moderate or severe hepatic failure. (The blood concentration of cilostazol may be increased.) (See 'Other Precautions' as follows.)
Patients with diabetes mellitus or abnormal glucose tolerance. (Hemorrhagic adverse events may occur.)
Patients of hypertension with consistently high blood pressure (e.g., malignant hypertension).
Patients with ventricular transposition, atrial transposition, atrial fibrillation, atrial flutter, ventricular tachycardia, ventricular fibrillation, multifocal ventricular ectopics and prolongation of the QTc interval.
Patients with or having a risk of sigmoid shaped interventricular septum (especially elderly): Left ventricular outflow tract obstruction has been reported in patients with sigmoid shaped interventricular septum. Monitor patients for the development of a new systolic murmur or cardiac symptoms after starting cilostazol.
Important Precautions: Cilostazol should not be administered to patients with cerebral infarction until their condition has stabilized.
Attention should be paid to cerebral infarction patients who are receiving other anti-platelet agents, or to hypertension patients, whose blood pressure should be well-controlled during treatment.
If an excessive increase in pulse rate is observed in patients with coronary artery stenosis during treatment with cilostazol, the dosage should be reduced or the drug discontinued and appropriate corrective measures taken, since the increased pulse rate could induce angina pectoris.
Patients should be warned to report any other signs which might also suggest the early development of blood dyscrasia such as bleeding or easy bruising, pyrexia and sore throat whilst on therapy. A full blood count should be performed if infection is suspected or there is any other clinical evidence of blood dyscrasia. Cilostazol should be discontinued promptly if there is clinical or laboratory evidence of hematological abnormalities.
Cilostazol may cause dizziness and patients should be warned to exercise caution before they drive or operate machinery.
Other Precautions: Cilostazol is a drug with PDE III inhibitory activity. Foreign long-term comparative studies conducted of cardiotonic agents with PDE III inhibitory activity in patients with congestive heart failure (NYHA class III to IV) demonstrated lower survival rates in patients receiving such cardiotonic agents compared with patients receiving placebo. In addition, prognosis following long-term treatment with PDE3 inhibitors, including cilostazol, has not yet been determined in patients without congestive heart failure.
Endocardial thickening and coronary arterial lesions were observed at high doses in 13- and 52-week oral repeated-dose toxicity studies of cilostazol in beagle dogs. The non-toxic doses were 30 and 12 mg/kg/day, respectively. These cardiac changes were not observed in either rats or monkeys. In 1-week intravenous repeated-dose cardiotoxicity studies, changes in the left ventricular endocardium, right atrial epicardium, and coronary arteries were observed in dogs and mild hemorrhagic changes in the left ventricular endocardium were observed in monkeys. Cardiac changes have also been reported in studies of other PDE inhibitors and vasodilators, and dogs are considered to be highly sensitive in showing such changes.
The mean survival time of stroke-prone spontaneously hypertensive rats (SHR-SP, Stroke-Prone Spontaneously Hypertensive Rats) given 0.3% cilostazol in the diet was shorter than that of control animals (40.2 weeks versus 43.5 weeks).
In a clinical study to evaluate cilostazol's efficacy in the prevention of recurrence of cerebral infarction, diabetes mellitus occurred or was worsened in more patients in the cilostazol group (11/520 patients) than in the placebo group (1/523 patients).
Coadministration of a single dose of a HMG-CoA reductase inhibitor, lovastatin 80 mg with a single dose of cilostazol 100 mg increased lovastatin AUC by 64% compared with administration of lovastatin alone.
The effects of cilostazol on cerebral infarction have not been studied in patients with asymptomatic cerebral infarction.
Taking a single dose of cilostazol with food has been shown to increase the maximum plasma concentrations (Cmax) of cilostazol by 90%, which may be associated with an increased incidence of adverse effects.
Ketoconazole, Erythromycin, and Omeprazole: Coadministration of ketoconazole 400 mg increased cilostazol Cmax by 94% and AUC by 117%. Coadministration of erythromycin 500 mg increased cilostazol Cmax by 47% and AUC by 72%. Coadministration of a CYP2C19 inhibitor, Omeprazole increased the systemic exposure to a metabolite, 3,4-dehydro-cilostazol by 68%.
Pharmacokinetics in Patients with renal dysfunction: After 8-day administration of 100 mg/day in patients with severe renal impairment, Cmax and AUC were 29% and 39% lower respectively than in subjects with normal renal function. The Cmax and AUC of an active metabolite were 173% and 209% greater in patients with severe renal impairment. There is no significant difference between in subjects with mild and moderate renal impairment and in normal subjects.
Pharmacokinetics in Patients with hepatic dysfunction: There is no significant difference in patient with mild hepatic dysfunction and in normal subjects after single administration of 100 mg (7% decrease in Cmax, 8% increase in AUC).
Use in Children: The safe use of cilostazol in premature babies, newborns, suckling infants, infants, and children has not been established. (Clinical experience in these populations is insufficient.)
Use in the Elderly: In clinical studies, no overall differences in safety or effectiveness were observed between elderly subjects (>65 years old) and younger subjects, but greater sensitivity of some older individuals cannot be ruled out.