Plendil - instructions for use, dose, side effects, contraindications

Excipients: core: giprolose (hydroxypropyl cellulose) 10.0 mg, hypromellose (hydroxypropylmethylcellulose) 100.0 mg, lactose anhydrous 28.0 mg, microcrystalline cellulose 3.0 mg, macrogol glyceryl hydroxy stearate 2.5 mg, propyl gallate 0.06 mg, sodium, aluminosilicate 47.0 mg, sodium stearyl fumarate 3.9 mg;

shell: wax Karnauba ≈0.1 mg, iron oxide oxide yellow 0.15 mg, hypromellose 4.9 mg, macrogol 6000 1.2 mg, titanium dioxide E 171 0.7 mg.

Each 5 mg tablet contains:

active substance: felodipine 5.0 mg;

Excipients: core: giprolose (hydroxypropylcellulose) 10.0 mg, hypromellose (hydroxypropylmethylcellulose) 100.0 mg, anhydrous lactose 28.0 mg, microcrystalline cellulose 3.0 mg, macrogol glyceryl hydroxy stearate 5.0 mg, propyl gallate 0.06 mg, sodium-aluminosilicate 47.0 mg, sodium stearyl fumarate 4.0 mg;

shell: wax Karnauba ≈ 0.1 mg, iron dye oxide reddish brown 0.03 mg, iron oxide oxide yellow 0.01 mg, hypromellose 5.0 mg, macrogol 6000 1.3 mg, titanium dioxide E 171 0.7 mg.

Each 10 mg tablet contains:

active substance: felodipine 10.0 mg;

Excipients: core: giprolose (hydroxypropyl cellulose) 10.0 mg, hypromellose (hydroxypropylmethylcellulose) 100.0 mg, anhydrous lactose 28.0 mg, microcrystalline cellulose 3.0 mg, macrogol glyceryl hydroxy stearate 10.0 mg, propyl gallate 0.06 mg, sodium aluminosilicate 47.0 mg sodium stearyl fumarate 4.2 mg;

shell: wax Karnauba ≈0.1 mg, iron dye oxide reddish brown 0.1 mg, iron dye oxide yellow 0.07 mg, hypromellose 5.3 mg, macrogol 6000 1.3 mg, titanium dioxide E 171 0.6 mg.

Description:

Film-coated tablets with sustained release of "active substance, which is due to the presence of a matrix of hydrophilic gel, providing a gradual release of the active substance.

Tablets 2.5 mg: round biconvex tablets of yellow, color, covered, film membrane; with engraving "A on one side and" 2.5 "- on the other side of FL".

Tablets 5 mg: round biconvex tablets of pink color, covered with film sheath; with engraving "A on one side and" 5 "on the other side Fm ".

Tablets 10 mg: round biconvex tablets of red-brown color, Film-coated shells with engraving "A on one side and" 10 "on other side of FE ".

Pharmacotherapeutic group:blocker of "slow" calcium channels

ATX: & nbsp

C.08.C.A.02 Felodipine

Pharmacodynamics:

Felodipine (Plendil®) - a blocker of "slow" calcium channels, used to treat hypertension and stable angina.

Felodipine, a dihydropyridine derivative, is a racemic mixture. Felodipine reduces blood pressure (BP) by reducing the overall peripheral vascular resistance, especially in arterioles.

Conductivity and contractility of the smooth muscles of blood vessels are suppressed by affecting the calcium channels of cell membranes.

Due to the high selectivity for smooth arteriolar musculature, felodipine in therapeutic doses does not have a negative inotropic effect on contractility or conduction / myocardium. Felodipine relaxes the smooth muscles of the respiratory tract.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 the concentration of lipids in the blood. In patients with type 2 diabetes mellitus, the use of felodipine for 6 months had no clinically significant effect on metabolic processes (glycosylated hemoglobin (HbA1c)).

Felodipine can also be administered to patients with reduced left ventricular function receiving standard therapy, and to patients with bronchial asthma, diabetes, gout, or hyperlipidemia.

Antihypertensive effect: a decrease in blood pressure when taking felodipine is due to a decrease in peripheral vascular resistance.

Felodipine effectively reduces blood pressure in patients with arterial hypertension both in the "lying" position, and in the "sitting" and "standing" positions, at rest and at physical activity. Because the felodipine has no effect on the smooth musculature of veins or adrenergic vasomotor control, then the development of orthostatic hypotension does not occur. At the beginning of treatment, as a result of a decrease in blood pressure on the background of admission felodipine, a temporary reflex increased heart rate (heart rate) and cardiac output. Increase Heart rate is prevented by the simultaneous application of f-adrenoblockers with felodipine. The effect of felodipine on AD and peripheral vascular resistance correlates with the plasma concentration of felodipine. At an equilibrium state, the clinical effect persists between taking doses and reducing blood pressure is maintained for 24 hours.

Treatment with felodipine leads to regression of left ventricular hypertrophy. Felodipine has natriuretic and diuretic effect and has no potassium-uretic effect. When taking felodipine, the tubular reabsorption of sodium and water decreases, which explains the absence of salt and fluid retention in the body. Felodipine reduces vascular resistance in the kidneys and enhances renal perfusion. Felodipine does not affect the rate of glomerular filtration and albumin excretion.

The use of Plendil® in combination with angiotensin-converting enzyme (ACE) inhibitors, beta-blockers and / or need diuretics, reduces diastolic blood pressure less than 90 mm Hg. in 93% of patients.

The frequency of cardiovascular complications in patients with type 2 diabetes mellitus (n= 1.501) is significantly lower (50%) in the group of patients who managed to achieve a diastolic BP reduction to a level of ≤ 80 mm Hg (11.9 / 100 patient-years) compared to the group where the diastolic blood pressure was <90 mm Hg, (24.4 / 1000 patient-years).

The use of dihydropyridine blockers of "slow" calcium channels as initial therapy with the subsequent addition of beta-blockers, if necessary, does not affect the death rate from cardiovascular diseases in comparison with standard therapy beta-blockers and / or diuretics.

For the treatment of arterial hypertension, Plendil® can be used as a 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 improved blood supply to the myocardium due to dilatation of the coronary vessels. Reducing the load on the heart is provided by reducing the peripheral vascular resistance (reducing the load overcome by the heart muscle), which leads to a decrease in myocardial oxygen demand. Felodipine eliminates the spasm of the coronary vessels.

Felodipine improves contractility and reduces the frequency of angina attacks in patients with stable angina pectoris. At the beginning of therapy, there may be a temporary increase in heart rate, stopped by the appointment of beta-blockers. The effect occurs after 2 hours and persists for 24 hours. For the treatment of stable angina pectoris felodipine, can be used in combination with beta-blockers or in the form of monotherapy.

Pharmacokinetics:

Systemic bioavailability of felodipine is approximately 15% and does not depend on food intake. However, the rate of absorption, but not its degree, can vary with food intake, and the maximum plasma concentration is thus increased by about 65%. The maximum concentration in the blood plasma is achieved in 3-5 hours. The drug binds to plasma proteins by 99%. The volume of distribution in the equilibrium state is 10 l / kg. The half-life is approximately 25 hours, the plateau phase is reached approximately for 5 days. Do not cumulate even with prolonged admission.

The total plasma clearance is 1200 ml / min on average. 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.However, the age sign is only partially explains the individual changes in the plasma concentration of felodipine.

Felodipine is metabolized in the liver by isoenzyme CYP3A4, all identified metabolites do not have a vasodilating effect (haemodynamic activity). About 70% of the accepted dose in the form of metabolites is excreted by the kidneys, the rest is excreted through the intestine. Less than 0.5% is excreted by the kidneys unchanged. If the renal function is impaired, the plasma concentration of felodipine does not change, but cumulation of inactive metabolites is observed. Felodipine not excreted by hemodialysis.

Indications:

- Arterial hypertension (in monotherapy or in combination with other antihypertensive drugs, such as beta-blockers, diuretics or ACE inhibitors).

- Stable angina (in monotherapy or in combination with beta-blockers).

Contraindications:

- Hypersensitivity to felodipine or other components that make up the drug.

- Heart failure in the stage of decompensation.

- Acute myocardial infarction.

- Unstable angina.

- Hemodynamically significant stenosis of the heart valves.

- Dynamic stenosis of the cardiac output tract.

- Age to 18 years (effectiveness and safety not established).

- Pregnancy.

- Lactose intolerance, lactase deficiency or glucose-galactose malabsorption (the preparation contains lactose).

- It is not recommended to prescribe Plendil® to women during lactation (due to lack of experience).

Carefully:Aortic stenosis, lability of arterial pressure, impaired liver function, severe renal failure (creatinine clearance less than 30 ml / min), heart failure after acute myocardial infarction, elderly age.

Arterial hypotension, which in predisposed patients can cause myocardial ischemia.

Pregnancy and lactation:

Pregnancy

Currently, there is insufficient data on the use of Plendil® pregnant women. Based on animal data on impaired development of the fetus, Plendil® should not be given during pregnancy. The blockers of the "slow" calcium channels can inhibit uterine contractions in premature birth, but at the same time there is insufficient data confirming the increase in the duration of physiological labor.

There is a risk of fetal hypoxia in the presence of arterial hypotension in the mother and a decrease in perfusion in the uterus due to redistribution of blood flow and peripheral vasodilation.

Lactation

Felodipine penetrates into breast milk. When taking a nursing mother Felodipine in therapeutic doses, only a small amount of the drug is ingested with breast milk to a child. Inadequate experience with the use of felodipine in women during lactation does not exclude the risk of exposure to children who are breastfeeding, and therefore it is not recommended to prescribe Plendil® to women during lactation. If continuation of therapy is necessary to achieve a clinical effect, consideration should be given to stopping breastfeeding.

Dosing and Administration:

Inside, take in the morning, wash down with water. Do not divide the tablet, do not crush or chew. Tablets can be used on an empty stomach or with a small amount of food with a low content of fats and carbohydrates.

Arterial hypertension

The dose should be selected individually. The initial dose is 5 mg once a day. The usual maintenance dose is 5 mg once a day.If necessary, the dose may be increased or another antihypertensive agent (beta-blocker, diuretic or ACE inhibitor) may be added to the Plendil® therapy. Rarely prescribed drug more than 10 mg per day. The recommended maximum dose is 10 mg per day.

Stable angina

The dose should be selected 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. Can be prescribed together with beta-blockers.

Elderly patients

For elderly patients, the recommended initial dose is 2.5 mg, usually this dose is sufficient.

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, but caution should be exercised when administering the drug to patients with severe renal failure (see "With caution" and "Special instructions").

Impaired liver function

In patients with impaired hepatic function, an increase in the concentration of felodipine in the blood plasma can be observed, therefore, a dose of 2.5 mg is usually sufficient (see Fig.section "Pharmacokinetics").

Children

Experience with the use of felodipine in children is limited.

Side effects:

The most frequent adverse reactions with Plendil® include a dose-dependent effect: mild to moderate ankle edema due to the vasodilating properties of felodipine, for this reason approximately 2% of patients refuse to take the drug.

At the beginning of therapy or with an increase in the dose, reddening of the face accompanied by "hot flashes", headache, palpitation, dizziness and weakness can be noted. Usually these reactions are temporary and pass on their own.

There are some reports of sleep disturbances, but there is no connection with the use of felodipine.

Reported cases of hyperplasia of the mucous tongue and gums after the administration of felodipine in patients with severe gingivitis / periodontitis. To avoid this side effect or reduce its manifestation, it is recommended to conduct a thorough oral hygiene.

It is believed that hyperglycemia occurs against the background of taking a group of blockers of "slow" calcium channels, but with felodipine, hyperglycemia was noted only in isolated cases.The following are side effects noted during clinical trials and in post-marketing applications.

Adverse reactions are classified according to the frequency of development and the class of organ system. The incidence of adverse reactions is indicated using the following symbols: very often (≥1 / 10), often (≥1 / 100, <1/10), infrequently (≥1 / 1000, <1/100), rarely (≥1 / 10000, <1/1000), very rarely (<1/10000).

From the nervous system:

Often - a headache; infrequently - dizziness, paresthesia.

From the heart:

Infrequent - tachycardia, a feeling of palpitations.

From the side of the vessels:

Often - redness of the face, "hot flashes"; infrequent - a marked decrease in blood pressure, accompanied by tachycardia, which in sensitive patients can cause the occurrence or frequency of angina attacks; rarely - faint; very rarely - extrasystole.

From the endocrine system:

Very rarely - hyperglycemia.

From the gastrointestinal tract:

Infrequently - nausea, abdominal pain; rarely vomiting; very rarely - hyperplasia of the mucous membrane of the tongue and gums, gingivitis.

From the liver and bile ducts:

Very rarely - increased activity of "liver" enzymes in the blood serum.

From the skin and subcutaneous tissues:

Infrequently - exanthema, itchy skin; rarely - hives; very rarely - increased photosensitivity, leukocytoclastic vasculitis.

From the side of the musculoskeletal and connective tissue:

Rarely - arthralgia, myalgia.

From the side of the kidneys and urinary tract:

Very rarely - frequent urination.

From the genitals and the breast:

Rarely, impotence / sexual dysfunction.

General disorders:

Very often - peripheral edema; infrequently - fatigue; very rarely - reactions of increased sensitivity, for example, angioedema, edema in the form of edema of the lips or tongue, fever.

There is no causal relationship of the following side effects with taking the drug: common disorders: chest pain, face swelling, flu-like syndrome; from the side of the heart and blood vessels: myocardial infarction, arterial hypotension, syncope, stenocardia, arrhythmia, extrasystole; from the gastrointestinal tract: diarrhea, dry mouth, flatulence; from the endocrine system: gynecomastia; on the part of the blood: anemia; from the musculoskeletal and connective tissue: arthralgia, back pain, muscle pain, myalgia, pain in the upper and lower extremities; from the nervous system: depression, insomnia, anxiety disorders, nervousness, drowsiness, irritability; from the respiratory system: pharyngitis, dyspnea, bronchitis, influenza, sinusitis, nosebleeds; from the skin and subcutaneous tissues: erythema, bruising, leukocytoclastic vasculitis; from the side of the organ of vision: visual disorders; from the kidneys and urinary tract: polyuria, dysuria.

Overdose:

Toxicity: 10 mg of felodipine in a 2-year-old child caused minor intoxication. 150-200 mg of felodipine in a 17-year-old patient and 250 mg in an adult caused intoxication from mild to moderate. Probably, felodipine has a more significant effect on the peripheral circulation than on the heart compared with other drugs of this therapeutic group.

In case of an overdose, the symptoms of intoxication appear 12-16 hours after taking the drug, severe symptoms can occur even after a few days after taking. There may be the following symptoms: bradycardia (sometimes tachycardia), marked decrease in blood pressure,AV blockade of I-III degree, ventricular extrasystole, atrial-ventricular dissociation, asystole, ventricular fibrillation; headache, dizziness, impaired consciousness (or coma), seizures; shortness of breath, swelling, lungs (not cardiac), and apnea; in adults, it is possible to develop respiratory distress syndrome; acidosis, hypokalemia, hyperglycemia, possibly hypocalcemia; reddening of the face, accompanied by "hot flashes", hypothermia; nausea and vomiting.

In case of an overdose, the greatest risk is presented by symptoms from the cardiovascular system.

Treatment: the purpose of activated carbon, if necessary, gastric lavage, in some cases is effective even at a late stage of intoxication.

IMPORTANT! Atropine (0.25-0.5 mg IV for adults, 10-20 μg / kg for children) should be prescribed before gastric lavage (because of the risk of stimulating vagus nerve). ECG monitoring, correction of the acid-base state and electrolytes of blood serum should be performed, if necessary, ensure airway patency and adequate ventilation of the lungs.

In the case of bradycardia and AV blockade, appoint atropine 0,5-1 mg in / in adults and 20-50 μg / kg for children (if necessary, repeat the introduction), or inject isoprenaline 0.05-0.1 μg / kg / min. In acute intoxication at an early stage you may need to install an artificial pacemaker. The pronounced decrease in blood pressure should be corrected by intravenous infusion, adult I / O is given 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), with the need to repeat the administration in the same dose. If necessary, infusion is administered epinephrine (epinephrine) or dopamine. When acute intoxication can be prescribed glucagon.

When cardiac arrest due to an overdose, resuscitation may be necessary for several hours. With cramps appoint diazepam, as well as conduct other symptomatic treatment.

Interaction:

Felodipine is a substrate of the CYP3A4 isoenzyme of the cytochrome P450 system.

Drugs that induce or inhibit the isoenzyme CYP3A4 have a significant effect on the concentration of felodipine in the blood plasma.

Drugs that induce the cytochrome P450 system: phenytoin, carbamazepine, phenobarbital and rifampicin, and also - a tincture of St. John's wort; perforated 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 (C_m_Oh) of felodipine by 82%. It is necessary to avoid the joint assignment, inductors of the isoenzyme CYP3A4.

Drugs that inhibit the cytochrome P450 system: antifungal preparations of triazole and imidazole derivatives (itraconazole, ketoconazole), antibiotics-macrolides (for example erythromycin) and HIV protease inhibitors are inhibitors of the CYP3A4 isoenzyme. When co-administered itraconazole C_m_Oh Felodipine increases 8-fold, AUC 6-fold. With the joint appointment of erythromycin C_m_Oh and AUC of felodipine increases approximately 2.5-fold. Combined use of felidipine and inhibitors of the isoenzyme CYP3A4 should be avoided.

Grapefruit juice inhibits the isoenzyme CYP3A4. The use of felodipine with grapefruit juice increases C_m_Oh and AUC felodipine approximately 2 times. Joint use should be avoided.

Tacrolimus: felodipine can cause an increase in tacrolimus concentration in the blood plasma. When combined, the concentration of tacrolimus in serum is recommended, and a dose adjustment of tacrolimus may be required.

Cyclosporine: when co-administered with cyclosporine and felodipine. FROM_m_OhFelodipine increases by 150%, 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 C_m_Ohand AUC of felodipine by 55%.

Special instructions:

Care must be taken with the following conditions: aosteal stenosis, impairment, liver function, severe renal failure (creatinine clearance less than 30 ml / min), heart failure after acute myocardial infarction, elderly age.

Arterial hypotension, which in predisposed patients, can cause myocardial ischemia.

The combined use of drugs inducing the CYP3A4 isoenzyme of the cytochrome P450 system leads to a significant decrease in the concentration of felodipine in the blood plasma and the insufficient therapeutic effect of the drug administration (see.section Interaction with other medicines and other types of drug interactions). It should be avoided co-administration of such drugs.

Joint use of drugs that inhibit the isoenzyme CYP3A4, leads to a significant increase in the concentration of felodipine in the blood plasma, and therefore, such combinations should be avoided.

Avoid taking the drug with grapefruit juice because of a significant increase in the concentration of felodipine in the blood plasma.

Effect on the ability to drive transp. cf. and fur:

When driving vehicles or other mechanisms that require increased attention, consideration should be given to the possibility of developing dizziness and weakness 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 requiring concentration of attention and speed of psychomotor reactions.

Form release / dosage:Tablets of prolonged action, film-coated, 2.5 mg, 5 mg, 10 mg.

Packaging:

For 30 tablets in a plastic bottle with a screwed plastic lid with a control of the first opening, 1 bottle is placed in a cardboard box with instructions for use.

Storage conditions:

At temperatures not higher than 30 ° C, out of reach of children.

Shelf life:

3 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:P 013870/01

Date of registration:29.12.2011

The owner of the registration certificate:AstraZeneca UK LtdAstraZeneca UK Ltd United Kingdom

Manufacturer: & nbsp

ASTRAZENECA, AB Sweden

ASTRAZENECA Pharmaceutical, Co. Ltd. China

Representation: & nbspAstraZeneca Pharmaceuticals Ltd.AstraZeneca Pharmaceuticals Ltd.

Information update date: & nbsp19.09.2015

Illustrated instructions

Instructions

Plendil® (Plendil®)