Index of drugs

The drug is indicated for use to improve the maximum walking distance without experiencing pain in patients with intermittent claudication who have no resting pain or show signs of peripheral tissue necrosis (type II peripheral arterial disease according to Fontaine). The preparation is a second-line drug for patients in whom lifestyle modifications (including smoking cessation and [supervised] exercise programs) and other appropriate interventions have not sufficiently alleviated symptoms of intermittent claudication.

1 tabl contains 100 mg cilostazol.

An anti-inflammatory medicine, an inhibitor of platelet aggregation. In the treadmill test, cilostazol improves exercise capacity assessed by changing the absolute claudication distance (ACD) and the initial distance of claudication (ICD - distance that the patient is able to pass without experiencing pain). After 24 weeks, cilostazol 100 mg 2 times daily increased the mean ACD value in the range of 60.4 to 129.1 m, while the mean ICD increased from 47.3 to 93.6 m. Animal studies showed that cilostazol dilates blood vessels, as observed in small studies in humans. Cilostazol also inhibitsin vitro smooth muscle cell proliferation in rats and smooth muscle cells in humans, and inhibits the platelet-release and PF-4 release of platelet-derived growth factor in human platelets. Cilostazol causes reversible suppression of platelet aggregation. The inhibition is maintained for up to 12 h and after discontinuation of cilostazol, restoration of aggregation occurs within 48-96 h, without excessive tendency to aggregate "from rebound". After 12 weeks, cilostazol 100 mg twice daily caused a decrease in triglycerides of 0.33 mmol / L (15%) and an increase in HDL cholesterol by 0.10 mmol / L (10%) compared with placebo. Following repeated administration of cilostazol 100 mg 2 times per day to patients with peripheral vascular disease, steady state was achieved within 4 days. Cilostazol binds in 95-98% with proteins, mainly with albumin. The binding of dehydrometabolite and 4'-trans-hydroxymetabolite is 97.4% and 66%, respectively. Apparent T_0,5 in the elimination phase is 10.5 h. The drug has two important metabolites: dehydrocylostazol and 4'-trans-hydroxycyl stasis, and both have similar apparent half lives. The antiplatelet effect of dehydrometabolite is 4-7 times greater than the parent compound, and the 4'-trans-hydroxymetabolite has 1/5 of the cilostazol activity. Cilostazol is eliminated mainly through metabolism and subsequent excretion of metabolites in the urine. The main isoenzymes involved in its metabolism are CYP3A4, to a lesser extent CYP2C19 and even less CYP1A2. Cilostazol is mainly excreted in the urine (74%) and the remainder in the faeces.

Hypersensitivity to the active substance or to any of the excipients. Severe renal dysfunction: creatinine clearance ≤ 25 ml / min. Moderate or severe liver problems. Congestive heart failure. Pregnancy. Bleeding predisposition (eg active peptic ulcers, recent (within 6 months) hemorrhagic stroke, proliferative diabetic retinopathy, insufficiently controlled hypertension). Ventricular tachycardia, ventricular fibrillation or a multifocal ventral extrasystole (regardless of whether they are / were adequately treated) and prolonged QTc interval. Severe tachyarrhythmia in an interview. Concomitant use of 2 or more additional antiplatelet or anticoagulant agents (ie Acetylsalicylic acid, Clopidogrel, Heparin, Warfarin, acenocoumarol, dabigatran, rivaroxaban or apixaban). Unstable angina, myocardial infarction in the last 6 months or coronary intervention in the last 6 months.

The validity of cilostazol treatment should be carefully considered in comparison with other treatments such as revascularization. Cilostazol can cause tachycardia, palpitations, tachyarrhythmia and / or hypotension. Acceleration of the heart rhythm during treatment with cilostazol is approx.5-7 strokes / min, which in patients at risk can cause angina. During the treatment with cilostazol, patients should be closely monitored for the increased risk of serious cardiac adverse events caused by accelerated cardiac rhythm, eg stable ischemic heart disease. Caution should be exercised when prescribing cilostazol to patients with additional atrial or ventricular contractions and patients with atrial fibrillation or atrial flutter. Patients should be advised to report any bleeding episode or easy bruising during treatment. If retinal bleeding occurs, cilostazol should be discontinued. Because cilostazol inhibits platelet aggregation, it is possible to increase the risk of bleeding during surgery (including minor invasive procedures such as tooth extraction). If the patient is to undergo a planned surgical procedure and antiplatelet effect is not necessary, cilostazol should be discontinued 5 days before the procedure. Because of the risk of hematologic abnormalities, patients should be advised to report any other symptoms immediately, which could also indicate an early stage of blood abnormalities such as fever and sore throat. In case of suspected infection or the presence of any other clinical evidence of blood abnormalities, complete blood counts should be performed. If clinical or laboratory evidence of haematological abnormalities is found, cilostazol should be discontinued immediately. The safety and efficacy of cilostazol in children has not been established.

Cilostazol must not be used during pregnancy. It is not known whether cilostazol is excreted in human milk. Due to the possibility of harmful effects on the newborn, it is not recommended to use during breastfeeding.

Very common: headache, diarrhea, abnormal stools. Common: ecchymosis, edema (peripheral, face), anorexia, dizziness, palpitations, tachycardia, angina, cardiac arrhythmia, additional ventricular contractions, rhinitis, pharyngitis, nausea and vomiting, indigestion, bloating, abdominal pain , rash, pruritus, chest pain, asthenia. Uncommon: anemia, allergic reaction, hyperglycemia, diabetes, anxiety, insomnia, nightmares, myocardial infarction, atrial fibrillation, congestive heart failure, supraventricular tachycardia, ventricular tachycardia, syncope, ocular haemorrhage, epistaxis, gastrointestinal haemorrhage , indefinite hemorrhage, orthostatic hypotension, shortness of breath, pneumonia, cough, gastritis, muscle pain, chills, malaise. Rare: prolonged bleeding time, thrombocytosis, renal failure, renal dysfunction. Not known: bleeding tendencies, thrombocytopenia, agranulocytosis, leukopenia, pancytopenia, aplastic anemia, paresis, hypoesthesia, conjunctivitis, tinnitus, hot flushes, hypertension, hypotension, cerebral haemorrhage, pulmonary haemorrhage, muscle haemorrhage, haemorrhage in the respiratory system, subcutaneous hemorrhage, interstitial pneumonitis, hepatitis, liver dysfunction, jaundice, eczema, eruptions, Stevens-Johnson syndrome toxic necrotic decay of the epidermis, urticaria, presence of blood in the urine, pollakiuria, fever, pain, increase in concentration uric acid, increased urea in the blood, increased blood creatinine. Increased frequency of palpitations and peripheral edema has been observed with the simultaneous use of cilostazol and other vasodilators that trigger reflex tachycardia, e.g. Calcium channel blockers, i.e. dihydropyridine derivatives. Cilostazol may increase the risk of bleeding, and this risk may increase if co-administered with another medicine with this effect. The risk of intraocular hemorrhage may be greater in patients with diabetes. In patients over 70 years of age, there was an increase in the incidence of diarrhea and palpitations.

Orally. Adults: the recommended dose of cilostazol is 100 mg twice daily. The drug should be taken 30 minutes before breakfast and dinner. Taking cilostazol with a meal increases C_maxcilostazol, which may cause a greater frequency of side effects.Treatment with cicostazol should be started by a doctor who has experience in the treatment of intermittent claudication. The physician should re-assess the patient's condition after 3 months of treatment, in case of ineffective therapy or lack of alleviation of symptoms, discontinue cilostazol. Patients receiving cilostazol should continue to modify their lifestyle (discontinuation of smoking and exercise) and pharmacological treatment (ie lipid-lowering and antiplatelet therapy) to reduce the risk of cardiovascular events. Cilostazol is not a substitute for such therapeutic methods. In patients receiving strong CYP3A4 inhibitors, eg some macrolide antibiotics, azole antifungals, protease inhibitors or strong CYP2C19 inhibitors (eg omeprazole), a dose reduction to 50 mg twice daily is recommended. There are no special dosing requirements for elderly people. In patients with impaired renal function with a creatinine clearance> 25 ml / min and in patients with mild liver disease, no dose adjustment is necessary.