Pletaal

Cilostazol.

PLETAAL Tablets 50 mg: Each tablet contains 50 mg of cilostazol.
PLETAAL Tablets 100 mg: Each tablet contains 100 mg of cilostazol.

Treatment of ischemic symptoms including ulceration, pain and coldness of the extremities, in chronic arterial occlusion (Buerger's disease, arteriosclerosis obliterans, diabetic peripheral angiopathy).
Prevention of recurrence of cerebral infarction (excluding cardiogenic cerebral embolism).

The usual adult dose is 100 mg of cilostazol, twice daily, by oral route. The dosage may be adjusted according to the age of patient and the severity of symptoms.

Information on acute overdose in humans is limited. The signs and symptoms can be anticipated to be severe headache, diarrhea, hypotension, tachycardia and possibly cardiac arrhythmias. Patients should be observed and given supportive treatment. Since cilostazol is highly protein-bound, it is unlikely that it can be efficiently removed by hemodialysis or peritoneal dialysis. The stomach should be emptied by induced vomiting or gastric lavage, as appropriate. The oral LOSO of cilostazol is >5.0 g/kg in mice and rats and >2.0 g/kg in dogs.

This drug is contraindicated in the following patients: Patients with hemorrhage (e.g., hemophilia, increased capillary, agility, intracranial hemorrhage, upper gastrointestinal hemorrhage, hemorrhage in the urinary tract, hemoptysis, and hemorrhage in the vitreous body) and with any known predisposition to bleeding (e.g. active peptic ulceration, recent (within six months) haemorrhagic stroke, surgery within the previous three months, proliferative diabetic retinopathy, poorly controlled hypertension) (bleeding tendency may be increased).
Patients with congestive heart failure. (Symptoms may be exacerbated.)
Patients with a history of hypersensitivity to any ingredient of the drug.
Women who are pregnant or may possibly become pregnant or are nursing mothers (see 'Use in Pregnancy & Lactation').

Patients should be closely monitored for any anginal symptoms (e.g., chest pain), since treatment with cilostazol may increase pulse rate, which could induce angina pectoris.
[A significant increase in PRP (pressure rate product) was observed during long-term administration of cilostazol in a clinical study to evaluate the drug's efficacy in the prevention of recurrence of cerebral infarction]. In clinical trials, angina pectoris was reported in patients treated with the drug.

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.

Rat teratogenicity studies of cilostazol showed an increased number of abnormal fetuses, low birth weight and an increased number of stillborn. The drug should not be used in women who are pregnant or may possibly become pregnant.
Rat studies showed that cilostazol is distributed into breast milk in nursing rats. Nursing should be interrupted when the drug is administered to nursing women.

Clinically significant adverse reactions: Congestive heart failure, myocardial infarction, angina pectoris (0.1% to less than 5% for each), and ventricular tachycardia (incidence unknown): Congestive heart failure, myocardial infarction, angina pectoris, and ventricular tachycardia may occur. If any signs of these adverse reactions are observed, the drug should be discontinued, and appropriate measures should be taken.
Hemorrhage: Intracranial hemorrhage, such as cerebral hemorrhage (0.1% to less than 5%): Intracranial hemorrhage, such as cerebral hemorrhage (early symptoms of intracranial hemorrhage include headache, nausea, vomiting, consciousness disturbance, and hemiplegia), may occur. If any such symptoms occur, the drug should be discontinued and appropriate measures should be taken.
Pulmonary hemorrhage (less than 0.1%), hemorrhage in the digestive tract, epistaxis, and bleeding in the ocular fundus (0.1% to less than 5% for each): Pulmonary hemorrhage, hemorrhage in the digestive tract, epistaxis, and bleeding in the ocular fundus may occur. If any such symptoms occur, the drug should be discontinued and appropriate measures should be taken.
Gastric or duodenal ulcers (0.1% to less than 5%): Gastric or duodenal ulcers with hemorrhage may occur. Patients should be closely monitored. If any signs of these adverse reactions are observed, the drug should be discontinued and appropriate measures should be taken.
Pancytopenia, agranulocytosis (both incidence unknown), and thrombocytopenia (0.1% to less than 5%): Pancytopenia, agranulocytosis, and thrombocytopenia may occur. Patients should be closely monitored. If any signs of these adverse reactions are observed, the drug should be discontinued and appropriate measures should be taken.
Interstitial pneumonia (less than 0.1%): Interstitial pneumonia accompanied by fever, cough, dyspnoea, abnormal chest X-rays, and eosinophilia may occur. If any signs of interstitial pneumonia are noted, the drug should be discontinued and appropriate measures should be taken.
Hepatic dysfunction (0.1% to less than 5%) and jaundice (incidence unknown): Hepatic dysfunction, as indicated by elevated AST (GOT), ALT (GPT), ALP, or LDH, and jaundice may occur. Patients should be closely monitored. If signs of hepatic dysfunction are observed, the drug should be discontinued and appropriate measures should be taken.
Acute renal failure (less than 0.1%): Acute renal failure may occur. Patients should be closely monitored, such as by renal function testing. If signs of renal failure are observed, the drug should be discontinued and appropriate measures should be taken.
Other adverse reactions: (See table.)

Click on icon to see table/diagram/image

Cilostazol is extensively metabolized by hepatic cytochrome P450 (CYP) enzymes, mainly CYP3A4 and, to a lesser extent, CYP2D6 and CYP2C19.
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) may cause a tendency to bleed, and frequent monitoring such as a blood coagulation test is required.
Coadministration of CYP3A4 and CYP2C19 inhibitors (cimetidine, diltiazem, erythromycin, ketoconazole, lansoprazole, itraconazole, miconazole, omeprazole, HIV-1 protease inhibitors, etc) may increase the blood concentration and potentiate the effects of cilostazol. Cilostazol should be reduced in dosage or started in a lower dose when coadministered with these drugs. Patients should be cautioned not to drink grapefruit juice when receiving cilostazol.
Caution is needed when co-administering cilostazol with any other agent which has the potential to reduce blood pressure or vasodilators that cause reflex tachycardia (e.g., dihydropyridine calcium channel blockers) due to the possibility that there may be an additive hypotensive effect with a reflex tachycardia.

Keep in room temperature (1-30°C) in well-closed container.
Shelf-Life: 36 months after the date of manufacture.

Anticoagulants, Antiplatelets & Fibrinolytics (Thrombolytics)

POM

Tab 50 mg x 10 x 10's. 100 mg x 10 x 10's.