Plendil p / o prolonged-release tablets 5mg, No. 30

• Arterial hypertension

• Angina pectoris

Inside, take in the morning with water. Do not split, crush or chew the tablet. The tablets can be taken on an empty stomach or with a small amount of food that is low in fat and carbohydrates.
Arterial hypertension The
dose should be selected individually. The starting dose is 5 mg once a day. The usual maintenance dose is 5 mg once daily. If necessary, the dose may be increased, or another antihypertensive agent may be added to Plendil therapy.
In elderly patients or in patients with impaired liver function, a dose of 2.5 mg is usually sufficient. Rarely, the drug is prescribed more than 10 mg per day.
Angina pectoris
The dose should be adjusted individually. It is necessary to start treatment with a dose of 5 mg once a day, if necessary, increasing the dose to 10 mg once a day. It can be administered in conjunction with beta-blockers.
Impaired renal function
Impaired renal function does not affect the concentration of the drug in the blood plasma. There is no need to adjust the treatment regimen in patients with impaired renal function, however, caution should be exercised when prescribing the drug to patients with severe renal failure (see section 'Special instructions').
Children
Experience with felodipine in children is limited.

one prolonged-release coated tablet contains
active substances: felodipine 2.5 mg, 5 mg and 10 mg, as well as
auxiliary substances: carnauba wax, hyprolose (hydroxypropyl cellulose), hypromellose (hydroxypropyl methylcellulose), lactose, microcrystalline cellulose, macrogol stearate, macrogol, propyl gallate, sodium aluminosilicate, sodium stearyl fumarate, titanium dioxide E171, iron dye yellow oxide E172, iron dye red oxide E172 (for dosages of 5 and 10 mg).

Hypersensitivity to felodipine or other components of the drug
Heart failure in the stage of decompensation
Acute myocardial infarction
Unstable angina
Age up to 18 years (efficacy and safety have not been established)

With care: aortic stenosis, lability of blood pressure, impaired liver function, severe renal failure (creatinine clearance <30 ml / min), heart failure after acute myocardial infarction.

Trade name: PlendilЃ

International non-proprietary name:

Felodipine

Dosage form:

sustained-release film-coated tablets

Composition:

one prolonged-release coated tablet contains
active substances: felodipine 2.5 mg, 5 mg and 10 mg, as well as
auxiliary substances: carnauba wax, hyprolose (hydroxypropyl cellulose), hypromellose (hydroxypropyl methylcellulose), lactose, microcrystalline cellulose, macrogol stearate, macrogol, propyl gallate, sodium aluminosilicate, sodium stearyl fumarate, titanium dioxide E171, iron dye yellow oxide E172, iron dye red oxide E172 (for dosages of 5 and 10 mg).

Description:

Film-coated tablets with a sustained release of the active substance, which is due to the presence of a hydrophilic gel matrix, which provides a gradual release of the active substance.
Plendil 2.5 mg, round, biconvex, yellow film-coated tablets; engraved on one side and 2.5 on the other.
Plendil 5 mg, pink, round biconvex film-coated tablets; engraved on one side and 5 on the other.
Plendil 10 mg, red-brown, round biconvex film-coated tablets; engraved on one side and 10 on the other.

Pharmacological properties.

Pharmacotherapeutic group:

blocker of 'slow' calcium channels.

ATX code: —08—ј02

Pharmacodynamics:

Felodipine (Plendil) is a slow calcium channel blocker used to treat hypertension and stable angina pectoris.
Felodipine, a dihydropyridine derivative, is a racemic mixture. Felodipine lowers blood pressure (BP) by reducing the total peripheral vascular resistance, especially in the arterioles.
The conductivity and contractility of vascular smooth muscles are suppressed by acting on the calcium channels of cell membranes.
Due to its high selectivity for smooth muscles of arterioles, felodipine in therapeutic doses does not have a negative inotropic effect on cardiac contractility or conduction.
Felodipine relaxes the smooth muscles of the airways.
It has been shown that felodipine has an insignificant effect on the motility of the gastrointestinal tract. With prolonged use, felodipine does not have a clinically significant effect on blood lipids. In patients with type 2 diabetes mellitus, when using felodipine for 6 months, there was no clinically significant effect on metabolic processes (HbA1c).
Felodipine can also be administered to patients with reduced left ventricular function receiving standard therapy and to patients with bronchial asthma, diabetes mellitus, gout, or hyperlipidemia.
Antihypertensive effect: a decrease in blood pressure when taking felodipine is due to a decrease in peripheral vascular resistance.
Felodipine effectively lowers blood pressure in patients with hypertension both in the supine position and in the sitting and standing position, at rest and during exercise. Since felodipine has no effect on the smooth muscles of the veins or adrenergic vasomotor control, the development of orthostatic hypotension does not occur. At the beginning of treatment, as a result of a decrease in blood pressure while taking felodipine, a temporary reflex increase in heart rate (HR) and cardiac output may be observed.
An increase in heart rate is prevented by the simultaneous use of felodipine with felodipine (?-blockers. The effect of felodipine on blood pressure and peripheral vascular resistance correlates with the plasma concentration of felodipine. In an equilibrium state, the clinical effect persists between doses and a decrease in blood pressure persists for 24 hours.
Treatment with felodipine leads to regression of hypertrophy the left ventricle.
felodipine has a natriuretic and diuretic effect and has no kaliyureticheskim effect. When receiving felodipine reduced tubular reabsorption of sodium and water, which explains the absence delay of salts and fluids in the body. felodipine reduces vascular resistance in the kidney and increases renal perfusion. felodipine has no effect on glomerular filtration and albumin excretion.
In the Hypertension Optimal Treatment Study (Hypertension Optimal Treatment Study), involving 18,790 patients with mild to moderate arterial hypertension, the use of Plendil in combination with ACE inhibitors, beta-blockers and / or diuretics, if necessary, reduced diastolic blood pressure less than 90 mm Hg in 93% of patients.
In the same study, the incidence of cardiovascular complications in patients with type 2 diabetes mellitus (n = 1.501) was significantly lower (50%) in the group of patients who managed to achieve a decrease in diastolic blood pressure to a level of? 80 mm Hg (11.9 / 100 patient-years), compared with the group where the level of diastolic blood pressure was <90 mm Hg. Art. (24.4 / 1000 patient-years).
In the STOP-2 study, where Plendil was used as one of two slow calcium channel blockers, in 6614 patients aged 70 to 84 years, it was shown that the use of dihydropyridine calcium antagonists as initial therapy followed by the addition of beta adrenergic blockers, if necessary, do not affect the mortality rate from cardiovascular diseases in comparison with traditional therapy with beta-blockers and / or diuretics.
For the treatment of arterial hypertension, Plendil can be used as monotherapy or in combination with other antihypertensive drugs such as beta-blockers, diuretics or ACE inhibitors.
Anti-ischemic effect:The use of Felodipine leads to an improvement in the blood supply to the myocardium due to dilatation of the coronary vessels. A decrease in the load on the heart is provided by a decrease in peripheral vascular resistance (a decrease in the load overcome by the heart muscle), which leads to a decrease in myocardial oxygen demand. Felodipine relieves spasm of the coronary vessels.
felodipine improves contractility and reduces the frequency of angina attacks in patients with stable exertional angina. At the beginning of therapy, there may be a temporary increase in heart rate, which is stopped by the appointment of beta-blockers. The effect occurs in 2 hours and lasts for 24 hours. For the treatment of stable angina pectoris, felodipine can be used in combination with beta-blockers or as monotherapy.

Pharmacokinetics:

The systemic bioavailability of felodipine is approximately 15% and does not depend on food intake. However, the rate of absorption, but not its extent, can vary with food intake, and the maximum plasma concentration is thus increased by about 65%.
The maximum concentration in blood plasma is reached after 3-5 hours.
The drug binds to plasma proteins by 99%. The volume of distribution at equilibrium is 10 l / kg. The half-life is approximately 25 hours, the plateau phase is reached within approximately 5 days. Does not cumulate even with prolonged use.
The total plasma clearance averages 1200 ml / min.
Reduced clearance in elderly patients and in patients with reduced liver function leads to an increase in the concentration of felodipine in the blood plasma. At the same time, the age characteristic only partially explains the individual changes in the plasma concentration of felodipine. Felodipine is metabolized in the liver, all identified metabolites do not have a vasodilatory effect (hemodynamic activity). About 70% of the dose taken is excreted in the form of metabolites in the urine, the rest in the faeces. Less than 0.5% is excreted in the urine unchanged. In case of impaired renal function, the plasma concentration of felodipine does not change, but cumulation of inactive metabolites is observed. Felodipine is not excreted during hemodialysis.

Indications for use:

? Arterial hypertension

? Angina pectoris

Contraindications:

Hypersensitivity to felodipine or other components of the drug
Heart failure in the stage of decompensation
Acute myocardial infarction
Unstable angina
Age up to 18 years (efficacy and safety have not been established)

With care: aortic stenosis, lability of blood pressure, impaired liver function, severe renal failure (creatinine clearance <30 ml / min), heart failure after acute myocardial infarction.

Application during pregnancy and lactation:

Pregnancy
There is currently no sufficient data on the use of felodipine in pregnant women. Based on animal evidence of fetal impairment, felodipine should not be administered during pregnancy. Blockers of 'slow' calcium channels can inhibit uterine contractions in preterm labor, however, there is insufficient data to support an increase in the duration of physiological labor. The risk of developing fetal hypoxia is possible if the mother has arterial hypotension and a decrease in perfusion in the uterus due to redistribution of blood flow and peripheral vasodilation.
Lactation
Felodipine passes into breast milk. When a nursing mother takes felodipine in therapeutic doses, only a small amount of the drug enters the child with breast milk. Insufficient experience in the use of felodipine by women during lactation does not exclude the risk of exposure to the drug on breastfed children, and therefore it is not recommended to prescribe felodipine to women during lactation. If it is necessary to continue therapy to achieve a clinical effect, the question of stopping breastfeeding should be considered.

Method of administration and dosage:

Inside, take in the morning with water. Do not split, crush or chew the tablet. The tablets can be taken on an empty stomach or with a small amount of food that is low in fat and carbohydrates.
Arterial hypertension The
dose should be selected individually. The starting dose is 5 mg once a day. The usual maintenance dose is 5 mg once daily. If necessary, the dose may be increased, or another antihypertensive agent may be added to Plendil therapy.
In elderly patients or in patients with impaired liver function, a dose of 2.5 mg is usually sufficient. Rarely, the drug is prescribed more than 10 mg per day.
Angina pectoris
The dose should be adjusted individually. It is necessary to start treatment with a dose of 5 mg once a day, if necessary, increasing the dose to 10 mg once a day. It can be administered in conjunction with beta-blockers.
Impaired renal function
Impaired renal function does not affect the concentration of the drug in the blood plasma. There is no need to adjust the treatment regimen in patients with impaired renal function, however, caution should be exercised when prescribing the drug to patients with severe renal failure (see section 'Special instructions').
Children
Experience with felodipine in children is limited.

Side effect:

The most common adverse reactions when taking Plendil include a dose-dependent effect: ankle swelling of mild to moderate severity, due to the vasodilating properties of felodipine, for this reason, about 2% of patients refuse to take the drug.
At the beginning of therapy or when the dose is increased, facial flushing accompanied by hot flashes, headache, palpitations, dizziness and weakness may occur. Usually these reactions are temporary and go away on their own.
There are isolated reports of sleep disturbance, but no connection has been established with felodipine.
Cases of hyperplasia of the mucous membrane of the tongue and gums have been reported after taking felodipine in patients with severe gingivitis / periodontitis. Careful oral hygiene is recommended to avoid or reduce this side effect. It is believed that hyperglycemia occurs while taking a group of blockers of 'slow' calcium channels, however, while taking felodipine, hyperglycemia was observed only in isolated cases.

The causal relationship of the following side effects with taking the drug has not been established: general: chest pain, swelling of the face, flu-like syndrome; cardiovascular: myocardial infarction, arterial hypotension, syncope, angina pectoris, arrhythmia, extrasystole; from the gastrointestinal tract: diarrhea, dry mouth, flatulence; from the endocrine system: gynecomastia; from the circulatory system: anemia; from the musculoskeletal system: arthralgia, back pain, muscle pain, myalgia, pain in the upper and lower extremities; from the central nervous system:depression, insomnia, anxiety disorders, nervousness, drowsiness, irritability; from the respiratory tract: pharyngitis, shortness of breath, bronchitis, flu, sinusitis, nosebleeds; on the part of the skin: erythema, bruising, leukocytoclastic vasculitis; from the senses: visual disturbances; from the urinary system: polyuria, dysuria.

Overdose:

Toxicity: 10 mg of felodipine in a 2-year-old child caused mild intoxication. 150-200 mg of felodipine in a 17-year-old patient and 250 mg in an adult caused mild to moderate intoxication. Felodipine probably has a more significant effect on peripheral circulation than on the heart compared to other drugs in this therapeutic group.
Symptoms:In case of an overdose, symptoms of intoxication appear 12-16 hours after taking the drug, severe symptoms can occur several days after taking the drug. The following symptoms may occur: bradycardia (sometimes tachycardia), marked decrease in blood pressure, AV block I-III degree, ventricular premature beats, atrioventricular dissociation, asystole, ventricular fibrillation; headache, dizziness, impaired consciousness (or coma), convulsions; shortness of breath, pulmonary edema (not cardiac) and apnea; in adults, the development of respiratory distress syndrome is possible; acidosis, hypokalemia, hyperglycemia, possibly hypocalcemia; redness of the face, accompanied by 'hot flashes', hypothermia; nausea and vomiting. The greatest risk is the effect of overdose on circulation.
Treatment:The appointment of activated carbon, if necessary, gastric lavage, in some cases, is effective even at a late stage of intoxication. A specific antidote is calcium preparations.
IMPORTANT! Atropine (0.25-0.5 mg IV for adults, 10-20 mcg / kg for children) should be given before gastric lavage (due to the risk of vagus stimulation). ECG monitoring. If necessary, ensure airway patency and adequate ventilation. Correction of acid-base state and serum electrolytes is shown. In the case of bradycardia and AV blockade, atropine 0.5-1 mg IV is prescribed for adults (20-50 ?g / kg for children), if necessary, repeat the administration, or isoprenaline is initially administered 0.05-0.1 ?g / kg / min ... In case of acute intoxication at an early stage, it may be necessary to install an artificial pacemaker. The decrease in blood pressure is corrected by intravenous injection of fluid, adults are injected intravenously with a solution of calcium gluconate (9 mg Ca / ml) 20-30 ml for 5 minutes or as an infusion (3-5 mg Ca / kg for children),if necessary, repeat the introduction at the same dose. If necessary, norepinephrine (epinephrine) or dopamine is given by infusion. In acute intoxication, glucagon may be prescribed.
In case of cardiac arrest due to an overdose, resuscitation may be necessary for several hours. Diazepam is prescribed for convulsions. Other symptomatic treatment is carried out.

Interaction with other medicinal products:

Felodipine is a substrate for CYP3A4. Drugs that induce or inhibit CYP3A4 have a significant effect on the plasma concentration of felodipine.
Drugs that induce the cytochrome P450 system: phenytoin, carbamazepine, phenobarbital and rifampicin, as well as St. John's wort tincture, increase the metabolism of felodipine due to the induction of the cytochrome P450 system. The combined use of phenytoin, carbamazepine, phenobarbital and rifampicin leads to a decrease in the area under the concentration / time curve (AUC) by 93% and the maximum concentration (Cmax) of felodipine by 82%. Co-administration with CYP3A4 inducers should be avoided.
Drugs that inhibit the cytochrome P450 system:azole antifungals (itraconazole, ketoconazole), macrolide antibiotics (eg, erythromycin) and HIV protease inhibitors are inhibitors of the CYP3A4 enzyme system. With the joint appointment of itraconazole, the Cmax of felodipine increases by 8 times, the AUC by 6 times.
With the combined appointment of erythromycin, Cmax and AUC of felodipine increase approximately 2.5 times. Co-administration of felidipine and CYP3A4 inhibitors should be avoided.
Grapefruit juice inhibits the CYP3A4 enzyme system. The use of felodipine with grapefruit juice increases the Cmax and AUC of felodipine approximately 2 times. Joint use should be avoided.
Tanrolimus:felodipine may cause an increase in the concentration of tacrolimus in blood plasma. When used together, it is recommended to control the concentration of tacrolimus in the blood serum; an adjustment of the tacrolimus dose may be required.
Cyclosporine: with the combined appointment of cyclosporine and felodipine, the Cmax of felodipine increases by 150%, the AUC increases by 60%. However, the effect of felodipine on the pharmacokinetic parameters of cyclosporine is minimal.
Cimetidine: the combined use of cimetidine and felodipine leads to an increase in Cmax and AUC of felodipine by 55%.

Special instructions:

Special care is required in the following conditions: aortic stenosis, abnormal liver function, severe renal failure (creatinine clearance <30 ml / min), heart failure after acute myocardial infarction. Arterial hypotension, which in predisposed patients can cause myocardial ischemia.
The combined use of drugs that induce the CYP3A4 enzyme system leads to a significant decrease in the concentration of felodipine in the blood plasma and an insufficient therapeutic effect from taking the drug (see the section УInteractions with other drugs). Co-administration of such drugs should be avoided.
The combined use of drugs that inhibit the CYP3A4 enzyme system leads to a significant increase in the concentration of felodipine in the blood plasma, and therefore, such combinations should be avoided.
You should avoid taking the drug with grapefruit juice due to a significant increase in the concentration of felodipine in the blood plasma.

Influence on the ability to drive a car and other mechanisms:

When driving a car or other mechanisms that require increased attention, one should take into account the possibility of dizziness and weakness developing while taking the drug.
At the beginning of therapy or during the period of increasing the dose, patients should refrain from engaging in hazardous activities that require concentration of attention and speed of psychomotor reactions.

Release form:

Sustained-release film-coated tablets 2.5 mg, 5 mg and 10 mg. 30 tablets in a plastic bottle with a plastic screw cap with first opening control. One bottle is placed in a cardboard box with instructions for use.

Storage conditions:

List B.
At temperatures below 30 ? C, out of the reach of children.

Expiration date:
3 years. Do not use after the expiration date.

Vacation conditions:
By prescription.