Pletax

2024 Author: Rachel Wainwright | [email protected]. Last modified: 2023-12-15 07:39

Pletax: instructions for use and reviews

1. Release form and composition
2. Pharmacological properties
3. Indications for use
4. Contraindications
5. Method of application and dosage
6. Side effects
7. Overdose
8. Special instructions
9. Application during pregnancy and lactation
10. Use in childhood
11. In case of impaired renal function
12. For violations of liver function
13. Use in the elderly
14. Drug interactions
15. Analogs
16. Terms and conditions of storage
17. Terms of dispensing from pharmacies
18. Reviews
19. Price in pharmacies

Latin name: Pletaks

ATX code: B01AC23

Active ingredient: Cilostazol (Cilostazolum)

Manufacturer: Novalek Pharmaceuticals Pvt. Ltd. (Novalek Pharmaceuticals Pvt. Ltd.) (India)

Description and photo update: 2019-27-11

Prices in pharmacies: from 959 rubles.

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Pletax is an antiplatelet drug.

Release form and composition

Dosage form - tablets: white or almost white, biconvex, round, smooth on one side, scored on the other (in a cardboard box 3, 4 or 6 blisters containing 10 or 14 tablets each, and instructions for use of Pletax).

Composition of 1 tablet of 50/100 mg, respectively:

active substance: cilostazol - 50/100 mg;
auxiliary components: hypromellose - 19 / 26.5 mg; magnesium stearate - 1.7 / 2.3 mg; carmellose calcium - 1.5 / 2.2 mg; microcrystalline cellulose - 26/35 mg; pregelatinized potato starch - 81.8 / 84 mg.

Pharmacological properties

Pharmacodynamics

Inhibition of phosphodiesterase type 3 is the main mechanism of the pharmacological action of the drug, due to which it increases the intracellular content of cyclic adenosine monophosphate in tissues and organs.

In the course of experimental and small clinical studies, it was found that cilostazol has a vasodilating effect. Mostly it dilates the femoral arteries, to a lesser extent - the superior mesenteric, carotid and vertebral arteries. The renal arteries are insensitive to the effects of Pletax.

Under in vitro conditions, the substance has an inhibitory effect on the proliferation of rat and human smooth muscle cells.

In clinical and experimental studies ex vivo and in vivo, it was found that the drug increases the content of cyclic adenosine monophosphate in platelets and causes a reversible antiplatelet effect.

Cilostazol reversibly inhibits platelet aggregation, the development of which is provoked by various stimuli, including adrenaline, arachidonic acid, collagen, adenosine diphosphate, thrombin and mechanical action (hemodynamic shock). In addition, the substance blocks the release of platelet factor 4 (PF-4) and platelet growth factor by human platelets.

Also, in the course of experimental and clinical studies, additional potentially beneficial effects of the drug were found - an increase in cholesterol in high-density lipoproteins and a decrease in serum triglycerides.

In a clinical study, taking cilostazol at a dose of 100 mg 2 times a day for 84 days, compared with the placebo group, lowered the concentration of triglycerides in the blood by an average of 15% (0.33 mmol per 1 L) and increased the concentration of high lipoprotein cholesterol in the blood. density by an average of 10% (0.1 mmol per 1 liter).

Pletax has a positive inotropic effect. In experimental studies in dogs, it had a species-specific damaging effect on the cardiovascular system (this effect was not observed in monkeys and rats). The drug does not increase the duration of the QT interval in monkeys and dogs.

Nine placebo-controlled clinical studies have confirmed the efficacy of cilostazol in patients with intermittent claudication. It was found that the use of the substance in a dose of 100 mg 2 times a day for 168 days approximately doubles the maximum distance traveled (from 60.4 m to 129.1 m; on average, the absolute increase in the maximum distance traveled is 42 m) and the distance passable before the onset of pain (from 47.3 m ² to 93.6 m ²).

The effectiveness of Pletax in patients with diabetes mellitus was lower than in patients without a violation of carbohydrate metabolism.

According to a prospective double-blind clinical study, cilostazol does not increase mortality in patients with intermittent claudication.

Pharmacokinetics

After oral administration, cilostazol is easily absorbed. In comparison with taking the drug on an empty stomach, its maximum concentration in blood plasma is 16% higher when taken 30 minutes after eating and 93% higher when taken 2 hours after eating.

The maximum plasma concentration of both cilostazol and its active metabolites increases less than proportionally to the dose increase. In this case, the area under the concentration-time curve (AUC) for the substance and its main metabolites increases approximately in proportion to the dose increase.

Against the background of occlusive pathologies of peripheral arteries, the equilibrium concentration of the drug in the blood with its regular intake at a dose of 100 mg 2 times a day is achieved after 4 days.

The two pharmacologically active metabolites of cilostazol are dehydrocylostazol and 4'-trans-hydroxycylostazol. The first is 4-7 times superior to the substance in its ability to inhibit platelet aggregation. The second has a 5 times less pronounced ability to inhibit platelet aggregation in comparison with unchanged cilostazol. Plasma levels of dehydrocylostazol and 4'-trans-hydroxycylostazol measured by the value of AUC are 41 and 12% of the content of cilostazol, respectively.

The connection of the drug with blood plasma proteins (mostly with albumin) varies from 95 to 98%. The connection with blood plasma proteins of 4'-trans-hydroxycylostazol and dehydrocylostazol is 66 and 97.4%, respectively.

The drug is actively metabolized mainly under the influence of the CYP3A4 isoenzyme, to a lesser extent - the CYP2C19 isoenzyme, and to an even lesser extent - the CYP1A2 isoenzyme. It is not an inducer of hepatic microsomal peroxidation enzymes.

Excretion of cilostazol from the body is mainly carried out in the urine (74%), the rest of it is excreted in the feces. In unchanged form, the drug is practically not detected in the urine. Less than 2% of the taken dose of the substance is excreted in the urine in the form of dehydrocylostazol, about 30% in the form of 4'-trans-hydroxycylostazol, and the remainder in the form of various metabolites, each of which does not exceed 5% of the dose taken.

The observed half-life of the drug is 10.5 hours. Its active metabolites have similar observed half-lives.

Compared to patients with normal renal function, in patients with severe renal insufficiency, the free fraction of the substance is 27% higher, and the maximum plasma concentration and AUC of unchanged cilostazol are 29% and 39% lower, respectively.

Indicators of the maximum concentration in blood plasma and AUC of dehydrocylostazol against the background of severe renal failure, when compared with the indicators in patients with normal renal function, decrease by 41 and 47%, respectively. At the same time, these indicators for 4'-trans-hydroxycylostazol (the main metabolite excreted in the urine) increase by 173 and 209%, respectively, in comparison with those in patients without renal impairment.

The appointment of Pletax is contraindicated in severe renal failure [creatinine clearance (CC) <25 ml per minute].

Compared with healthy individuals, peak plasma concentration and AUC in moderate hepatic impairment increase by 25 and 10%, respectively. In patients with moderate renal insufficiency, these indicators increase by 50 and 16%, respectively, compared with patients without liver dysfunction.

There are no data on the use of the drug against the background of moderate to severe liver failure. Its use is contraindicated in patients with moderate or severe hepatic impairment, since cilostazol is largely metabolized by hepatic microsomal oxidation enzymes.

According to studies in which volunteers aged 50 to 80 years took part, it was found that gender and age do not significantly affect the pharmacokinetics of Pletax.

The drug is prescribed to patients with intermittent claudication, who do not experience pain at rest and there are no manifestations of peripheral tissue necrosis (according to Fontaine's classification - chronic ischemia of the lower extremities of the II degree), in order to increase the maximum distance and distance overcome by the patient without pain.

Pletax is intended for use as a second-line treatment in patients with intermittent claudication for whom lifestyle changes, including cessation of smoking and supervised physical rehabilitation programs, and other appropriate interventions have been insufficient to reduce the manifestations of the disease.

Indications for use

intermittent claudication - for symptomatic therapy;
intermittent claudication in patients who do not have pain at rest and symptoms of necrosis of peripheral tissues (according to Fontaine's classification - chronic ischemia of the lower extremities of the II degree) - to increase the maximum distance and distance traveled without pain;
intermittent claudication in patients with lifestyle changes, including cessation of smoking and undergoing physical rehabilitation programs under the supervision of a specialist, as well as other appropriate interventions, were insufficient to reduce the manifestations of pathology - as a second-line therapy.

Contraindications

Absolute:

chronic heart failure;
moderate or severe hepatic impairment;
severe renal failure (CC <25 ml in 1 min);
polytopic ventricular premature beats, ventricular fibrillation or history of ventricular tachycardia (regardless of the presence or absence of adequate antiarrhythmic treatment);
predisposition to bleeding [for example, poorly controlled arterial hypertension, proliferative diabetic retinopathy, recent (within the last 6 months) hemorrhagic stroke, exacerbation of gastric or duodenal ulcer];
a history of severe tachyarrhythmia;
an extended QT interval on an electrocardiogram;
invasive coronary artery intervention, myocardial infarction or unstable angina in the past 6 months;
combination therapy with potent inhibitors of CYP2C19 or CYP3A4 (for example, HIV-1 protease inhibitors, omeprazole, lansoprazole, ketoconazole, erythromycin, diltiazem, cimetidine);
combined treatment with two or more anticoagulant or antiplatelet drugs (for example, apixaban, rivaroxaban, dabigatran, acenocoumarol, warfarin, heparin, clopidogrel, acetylsalicylic acid);
pregnancy;
period of breastfeeding;
age under 18;
individual intolerance to the components of the drug.

Relative (Pletax tablets are used under medical supervision):

mild liver failure;
chronic ischemic heart disease (in particular, stable exertional angina);
flutter and atrial fibrillation;
ventricular or atrial premature beats;
diabetes;
simultaneous therapy with drugs that lower blood pressure;
the combined use of drugs that reduce blood clotting;
the combined appointment of CYP2C19 or CYP3A4 substrates (for example, verapamil, nifedipine, midazolam, cisapride);
elderly age.

Pletax, instructions for use: method and dosage

Pletax tablets are taken orally, half an hour before meals. Taking the drug with food leads to an increase in its maximum concentration in blood plasma, which may be associated with an increased frequency of side effects.

The recommended dose of the drug is 100 mg 2 times a day.

If you miss the next dose of Pletax, the next tablet is taken as usual. Do not take a double dose of the drug.

Treatment with cilostazol should be started under the supervision of a physician experienced in the treatment of intermittent claudication.

After 3 months from the start of treatment, the doctor must re-evaluate the patient's condition. In the absence of an adequate therapeutic effect or a decrease in the severity of the manifestations of intermittent claudication, Pletax should be canceled and other methods of treatment should be considered.

Patients undergoing Pletax therapy should continue to follow the recommendations for changing lifestyle (exercise, quitting smoking) and undergo drug treatment (use of antiplatelet and lipid-lowering drugs) aimed at reducing the likelihood of cardiovascular complications. The drug is not a substitute for the indicated therapy.

There are no special requirements for changing the dosage regimen for elderly patients.

Dosage adjustment for CC> 25 ml per minute is not performed. Pletax is contraindicated in patients with CC <25 ml per minute.

In cases of mild hepatic insufficiency, changes in the dose of the drug are not required.

There is no experience of using Pletax in moderate / severe liver failure. Since the active substance of the drug is largely metabolized by the enzymes of liver microsomal oxidation, its use is contraindicated against the background of moderate / severe liver failure.

When combined treatment with drugs that have a powerful inhibitory effect on CYP3A4 (for example, some macrolides), or drugs that have a powerful inhibitory effect on CYP2C19 (for example, omeprazole), the dose of cilostazol is reduced by 2 times (up to 50 mg 2 times a day).

Side effects

Possible side reactions of Pletax (> 10% - very often;> 1% and 0.1% and 0.01% and <0.1% - rarely; <0.01%, including individual messages, - very rare; in case when the frequency cannot be determined from the available data, the frequency is unknown):

blood and lymphatic system: often - ecchymosis; infrequently - anemia; rarely - thrombocytosis, increased bleeding time; frequency unknown - aplastic anemia, pancytopenia, leukopenia, agranulocytosis, granulocytopenia, thrombocytopenia, bleeding tendency;
immune system: infrequently - allergic reactions;
metabolism and nutrition: often - anorexia, edema (edema of the face, peripheral edema); infrequently - diabetes mellitus, hyperglycemia;
mental disorders: infrequently - anxiety;
nervous system: very often - headache; often - dizziness; infrequently - intracranial hemorrhage, sleep disturbance (unusual dreams), insomnia; frequency unknown - hypesthesia, paresis;
organ of vision: often - intraocular hemorrhage; frequency unknown - conjunctivitis;
organ of hearing and labyrinthine disorders: frequency unknown - ringing in the ears;
heart: often - ventricular extrasystoles, arrhythmia, angina pectoris, tachycardia, palpitations; infrequently - syncope, ventricular tachycardia, supraventricular tachycardia, chronic heart failure, atrial fibrillation, myocardial infarction;
vessels: often - orthostatic hypotension; infrequently - arterial hypotension, arterial hypertension, hot flashes;
respiratory system, organs of the chest and mediastinum: often - pharyngitis, rhinitis; infrequently - bleeding from the respiratory tract, pulmonary bleeding, cough, pneumonia, dyspnea (shortness of breath); frequency unknown - interstitial pneumonia;
gastrointestinal tract: very often - stool disorders, diarrhea; often - gastrointestinal bleeding, abdominal pain, flatulence, dyspepsia, vomiting, nausea; infrequently - gastritis;
liver and biliary tract: frequency is unknown - jaundice, deviation of liver function from normal values, hepatitis;
skin and subcutaneous tissue: often - skin rash / itching; infrequently - subcutaneous hemorrhage, urticaria, toxic epidermal necrolysis, Stevens-Johnson syndrome, skin rashes, eczema;
connective and musculoskeletal tissue: infrequently - intramuscular hematomas, myalgia;
kidneys and urinary tract: rarely - impaired renal function, renal failure; frequency unknown - pollakiuria, hematuria;
general disorders and disorders at the injection site: often - asthenia, chest pain; infrequently - malaise, chills; frequency unknown - pain, pyrexia;
laboratory and instrumental data: the frequency is unknown - an increase in the concentration of creatinine / urea / uric acid in the blood.

An increase in the incidence of peripheral edema and palpitations was noted while taking a combination of cilostazol with other vasodilators that cause reflex tachycardia (for example, with dihydropyridine blockers of slow calcium channels).

The drug itself increases the likelihood of bleeding, and this likelihood can be further increased by combined treatment with any other drug that has the same potential as Pletax.

Patients with diabetes mellitus may have an increased risk of intraocular hemorrhage.

Patients over the age of 70 have a higher incidence of heart palpitations and diarrhea.

Overdose

Data on acute overdose of cilostazol in humans are limited.

The main expected symptoms are diarrhea, severe headache, heart rhythm disturbances, arterial hypotension, tachycardia.

Therapy is symptomatic. With the development of an overdose, careful examination and observation of the patient is required. The stomach should be emptied by provoking vomiting, or by performing a gastric lavage according to generally accepted recommendations. Peritoneal dialysis and hemodialysis are practically ineffective due to the high degree of communication of cilostazol with blood plasma proteins.

special instructions

Before you start taking Pletax, it is important to evaluate the possibility of using other methods of therapy, such as conservative treatment or surgical revascularization.

Through the mechanism of pharmacological action, cilostazol can cause arterial hypotension, tachyarrhythmia, palpitations and / or tachycardia. When taken, the heart rate can increase by 5-7 beats per minute, which can lead to the development of an angina attack in patients at risk (for example, in persons with stable angina).

With an increased likelihood of severe cardiovascular complications due to an increase in heart rate (for example, stable coronary heart disease), the drug should be used under close supervision.

Pletax is contraindicated in patients with a history of severe tachyarrhythmia, invasive coronary intervention / myocardial infarction / unstable angina pectoris within the last 6 months. With flutter or atrial fibrillation, ventricular or atrial extrasystole, the drug is prescribed with caution.

The patient should be made aware of the need to inform the doctor about any case of subcutaneous hematoma (bruising) or bleeding with a slight bruise. With the development of retinal hemorrhage, therapy is canceled.

Since the drug is an inhibitor of platelet aggregation, during surgical interventions (including minor invasive procedures such as tooth extraction) while taking it, the likelihood of bleeding increases. In cases of planned operations (if the development of antiplatelet action is undesirable), Pletax is canceled 5 days before they are performed.

There are reports of rare or very rare cases of hematological disorders, including aplastic anemia, pancytopenia, agranulocytosis, leukopenia, or thrombocytopenia. In most cases, after discontinuation of Pletax, these disorders resolved on their own, but in several cases, aplastic anemia and pancytopenia resulted in death.

The patient should be made aware of the need to immediately inform the doctor about any signs that may be early symptoms of hematological complications such as sore throat and pyrexia (high fever). If clinical manifestations of hematological complications appear or an infection is suspected, a detailed blood test should be performed. The drug is immediately discontinued if laboratory signs or clinical symptoms of hematological complications occur.

Combined therapy with Pletax with drugs that inhibit platelet aggregation, reduce blood clotting or blood pressure (the possibility of additive action with the development of reflex tachycardia and arterial hypotension) should be carried out with caution.

Influence on the ability to drive vehicles and complex mechanisms

Since Pletax can cause dizziness, patients during the period of therapy are advised to be careful when driving or conducting potentially hazardous activities, the performance of which requires increased attention and speed of psychomotor reactions.

Application during pregnancy and lactation

Pletax is not prescribed during pregnancy / lactation.

There is no data on the use of cilostazol during pregnancy. According to ongoing experimental studies on animals, it has reproductive toxicity. Also, during these studies, its ability to penetrate into breast milk was not found. It is not known whether the drug passes into human breast milk. The drug had no adverse effect on the fertility of laboratory animals.

Pediatric use

Pletax is not prescribed to patients under 18 years of age, since the safety and efficacy of its use in patients of this age category have not been established.

With impaired renal function

Pletax is contraindicated in severe renal failure (CC <25 ml per minute).

For violations of liver function

the use of Pletax is contraindicated: moderate or severe hepatic impairment;
use requires caution: mild hepatic impairment.

Use in the elderly

Elderly patients are prescribed Pletax with caution.

Drug interactions

Possible interactions of Cilostazol with other substances / drugs:

acetylsalicylic acid (ASA): short-term (for less than 4 days) combined use of drugs leads to an increase in ADP-induced platelet aggregation in ex vivo conditions by 23-25% compared with ASA monotherapy. Since the use of the combination increases the likelihood of bleeding, the patient should be closely monitored;
erythromycin (a potent inhibitor of CYP3A4): the AUC of cilostazol / dehydrocylostazol / 4'-trans-hydroxycylostazol increase by 72/6/119%, respectively. Taking into account the change in these indicators, it was found that the total pharmacological activity of Cilostazol in combination with erythromycin increases by 34%. It is recommended to reduce the dose of the first to 50 mg 2 times a day in combination with erythromycin and other drugs of this group (for example, clarithromycin);
ketoconazole (a potent inhibitor of CYP3A4): the AUC of cilostazol / 4'-trans-hydroxycylostazol increases by 117/87%, respectively, the AUC of dehydrocylostazol decreases by 15%. Taking into account the change in these indicators, it was found that the total pharmacological activity of Cilostazol in combination with ketoconazole increased by 34%. It is recommended to reduce the dose of the first to 50 mg 2 times a day in combination with ketoconazole and other drugs of this group (for example, itraconazole);
diltiazem (a weak inhibitor of CYP3A4): the AUC values of cilostazol / dehydrocylostazol / 4'-trans-hydroxycylostazol increase by 44/4/43%, respectively. Taking into account the change in these indicators, it was found that the total pharmacological activity of Cilostazol in combination with diltiazem increased by 19%. Correction of the dosage regimen is not carried out;
grapefruit juice (intestinal CYP3A4 inhibitor): a single dose of 100 mg of cilostazol with 240 ml of juice does not cause significant changes in the pharmacokinetic parameters of the former and does not require a dose adjustment. However, large amounts of grapefruit juice can affect the pharmacokinetics of cilostazol;
omeprazole (a potent inhibitor of CYP2C19): the AUC of cilostazol / dehydrocylostazol increase by 22/68%, respectively, and the AUC of 4'-trans-hydroxycilostazol is reduced by 36%. Taking into account the change in these indicators, it was found that the total pharmacological activity of Cilostazol in combination with omeprazole increased by 47%. When prescribing a combination, the dose of the drug is reduced to 50 mg 2 times a day;
lovastatin (a CYP3A4 substrate) and its beta-hydroxyl metabolite: their AUC values increase by 70%.

In a study in healthy volunteers, the use of a combination of cilostazol with clopidogrel had no effect on platelet count, activated partial thromboplastin time, and prothrombin time. Clopidogrel monotherapy, like the combination with cilostazol, in healthy individuals caused an increase in bleeding time. The use of the latter did not lead to an additional significant lengthening of the bleeding time, however, it is recommended to use it with caution in combination with any drug that inhibits platelet aggregation. Regular monitoring of bleeding time is recommended. The appointment of Pletax is contraindicated in patients receiving two or more antiplatelet / anticoagulant drugs at the same time.

In a clinical study, a single dose of the drug did not inhibit the metabolism of warfarin and did not affect blood clotting parameters (platelet count, activated partial thromboplastin time, and prothrombin time). However, it is important to exercise caution when using Cilostazol concomitantly with any anticoagulant agent.

Pletax is contraindicated in patients who are prescribed the use of two or more antiplatelet / anticoagulant drugs.

Cilostazol is mainly metabolized in the liver under the influence of cytochrome P ₄₅₀ enzymes, mostly CYP2C19 and CYP3A4 and to a lesser extent CYP1A2. It is believed that dehydrocylostazol is mainly formed with the participation of CYP3A4, and 4'-trans-hydroxycylostazol is mainly formed by the action of CYP2C19. In this case, the former is 4-7 times superior to cilostazol in its ability to inhibit platelet aggregation, and the latter has a 5 times less pronounced ability to inhibit platelet aggregation.

Accordingly, drugs that inhibit CYP3A4, for example, human immunodeficiency virus protease inhibitors, azole antifungals (itraconazole, ketoconazole), some macrolides (clarithromycin, erythromycin), and CYP2C19, for example, proton pump inhibitors (omeprazole) the general pharmacological activity of cilostazol and may enhance its side effects. In this regard, patients who are prescribed treatment with powerful inhibitors of CYP2C19 or CYP3A4, Cilostazol is prescribed at a dose of 50 mg 2 times a day.

With simultaneous treatment with CYP3A4 substrates, which have a narrow therapeutic range (ergot alkaloids, pimozide, halofantrine, cisapride), care must be taken. It is also important to be careful when using Cilostazol in combination with statins (hydroxymethylglutaryl-CoA reductase inhibitors) metabolized with the participation of CYP3A4 (lovastatin, atorvastatin and simvastatin).

The effect of drugs that increase the activity of CYP2C19 and CYP3A4 (St. John's wort drugs, rifampicin, phenytoin, carbamazepine) on the pharmacokinetics of cilostazol has not been studied. Combination therapy can theoretically reduce its antiplatelet effect, and therefore regular monitoring of bleeding time is important. In ongoing clinical studies, it was found that smoking (a factor that enhances the activity of CYP1A2) reduces the concentration of the substance in the blood plasma by 18%.

With caution, under the supervision of a physician, Pletax should be taken simultaneously with any drugs that lower blood pressure, including phosphodiesterase-5 inhibitors and nitrates. This is due to the fact that an additive effect can develop with the appearance of reflex tachycardia and arterial hypotension.

Analogs

The analogue of Pletax is Aducil.

Terms and conditions of storage

Store in a place protected from light and moisture at temperatures up to 30 ° C. Keep out of the reach of children.

The shelf life is 3 years.

Terms of dispensing from pharmacies

Dispensed by prescription.

Reviews about Pletax

There are few reviews about Pletax, indicating its effectiveness.

Price for Pletax in pharmacies

The approximate price for Pletax is: in a package of 30 tablets of 50 mg each - from 970 to 1045 rubles; in a package of 60 tablets of 100 mg each - from 2041 to 2200 rubles.

Pletax: prices in online pharmacies

Drug name

Price

Pharmacy

Pletax 50 mg tablets 30 pcs.

959 r

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Pletax 100 mg tablets 60 pcs.

1979 RUB

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Anna Kozlova Medical journalist About the author

Education: Rostov State Medical University, specialty "General Medicine".

Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!