Rhea Cilostazol Special Precautions

Careful Administration (This drug should be administered with caution in the following patients.): Patients on anticoagulants (e.g., warfarin), antiplatelet drugs (e.g., aspirin or ticlopidine), thrombolytic drugs (e.g., urokinase or alteplase), or prostaglandin E1 or its derivative (e.g., alprostadil). (See Interactions.)
Patients during menstruation. (There is a risk of menorrhagia.)
Patients with bleeding tendency or predisposition to bleeding. (If bleeding occurs, bleeding tendency may be increased.)
Patients with coronary artery stenosis. (Increased pulse rate possibly resulting from treatment with RHEA cilostazol could induce angina pectoris.) (See Warnings, Important Precautions as follows, Adverse Reactions and Pharmacology: Clinical Studies under Actions.)
Patients with diabetes mellitus or abnormal glucose tolerance. (Hemorrhagic adverse events may occur.)
Patients with severe hepatic impairment. (Blood concentration of cilostazol may be increased.) (See Pharmacology: Pharmacokinetics under Actions.)
Patients with severe renal impairment. (Blood concentration of cilostazol and its metabolites may be increased.) (See Pharmacology: Pharmacokinetics under Actions.)
Patients of severe hypertension with consistently high blood pressure e.g., malignant hypertension. (See Other Precautions as follows.)
Important Precautions: RHEA Cilostazol should not be administered to patients with cerebral infraction until their condition has stabilized.
When RHEA cilostazol is administered to patients with cerebral infarction, administration should be performed with caution for possible interaction with other drugs, such as antiplatelet drugs. In cerebral infarction patients with high blood pressure, the blood pressure should be sufficiently controlled during RHEA cilostazol treatment. (See Careful Administration as previously mentioned and Interactions.)
If an excessive increase in pulse rate is observed in patients with coronary artery stenosis during treatment with RHEA cilostazol the dosage should be reduced or the drug discontinued and appropriate corrective measures should be taken, since the increased pulse rate could induce angina pectoris. (See Warnings, Careful Administration as previously mentioned, Adverse Reactions and Pharmacology: Clinical Studies under Actions.)
RHEA Cilostazol is a drug with the PDE3 inhibitory activity. Long-term comparative studies of cardiotonic agents with PDE3 inhibitory activity (milrinone and vesnarinone) in patients with congestive heart failure (NYHA class III to IV) conducted outside Japan 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 RHEA cilostazol, has not yet been determined in patients without congestive heart failure.
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.
Other Precautions: 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) 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 the efficacy of RHEA cilostazol in the prevention of recurrence of cerebral infarction, diabetes mellitus occurred or was worsened in more patients in the RHEA cilostazol group (11/520 patients) than in the placebo group (1/523 patients).
Coadministration of a single dose of lovastatin 80 mg with a single dose of RHEA cilostazol 100 mg increased the lovastatin AUC by 64% compared with administration of lovastatin alone.
Use in Children: The safe use of RHEA 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: Elderly patients may be physiologically more sensitive to RHEA cilostazol than younger patients. It may be necessary to use a reduced dosage when prescribing this drug for elderly patients.