Felodipine-SZ - instructions for use, dose, side effects, contraindications

auxiliary substances (core): lactose monohydrate (lactopress) (sugar milk) 127.9 mg; kollidone SR (polyvinyl acetate 80%, povidone 19%, sodium lauryl sulfate 0.8%, silicon dioxide 0.2%) 76.5 mg; silicon dioxide colloid (aerosil) 1.05 mg; sodium stearyl fumarate 1.05 mg;

auxiliary substances (shell): Opadrai II (polyvinyl alcohol, partially hydrolyzed 2.4 mg, macrogol (polyethylene glycol) 3350 1.212 mg, talc 0.888 mg, titanium dioxide E 171 1.35996 mg, iron oxide oxide yellow E 172 0.1355 mg, iron dye oxide red E 172 0.00192 mg, iron dye oxide black E 172 0.00162 mg);

dosage of 5 mg:

active substance: felodipine 5 mg;

auxiliary substances (core): lactose monohydrate (lactopress) (sugar milk) 125.9 mg; kollidone SR (polyvinyl acetate 80%, povidone 19%, sodium lauryl sulfate 0.8%, silicon dioxide 0.2%) 76.0 mg; silicon dioxide colloid (aerosil) 1.05 mg; sodium stearyl fumarate 1.05 mg;

auxiliary substances (shell): Opadrai II (polyvinyl alcohol, partially hydrolyzed 2.64 mg, macrogol (polyethylene glycol) 3350 0.741 mg, talc 1.2 mg, titanium dioxide E 171 1.1502 mg, soy lecithin E 322 0.21 mg, aluminum dye based on the dye indigo carmine 0.0036 mg, aluminum varnish based on the dye azorubin 0.0306 mg, aluminum lacquer based on the dye crimson [Ponso 4R0.0246 mg);

dosage of 10 mg:

active substance: felodipine 10 mg;

auxiliary substances (core): lactose monohydrate (lactopress) (sugar milk) 124.9 mg; kollidone SR (polyvinyl acetate 80%, povidone 19%, sodium lauryl sulfate 0.8%, silicon dioxide 0.2%) 72.0 mg; silicon dioxide colloid (aerosil) 1.05 mg; sodium stearyl fumarate 1.05 mg;

auxiliary substances (shell): Opadrai II (polyvinyl alcohol, partially hydrolyzed 2.4 mg, macrogol (polyethylene glycol) 3350 1.212 mg, talc 0.888 mg, titanium dioxide E 171 1.3122 mg, aluminum lacquer based on indigo carmine dye 0.0012 mg, iron dye oxide yellow E 172 0.0018 mg, aluminum lacquer based on dye quinoline yellow 0.1806 mg, aluminum dye-based lacquer sunset yellow 0.0042 mg).

Description:

The tablets covered with a film cover from beige-yellow to beige color, round, biconcave. On the cross section, the core of the tablet is white or almost white (dosage of 2.5 mg).

The tablets covered with a film cover of pink color, round, biconcave. On the cross section, the core of the tablet is white or almost white (dosage of 5 mg).

The tablets covered with a film cover of yellow color, round, biconcave. On the cross section, the core of the tablet is white or almost white (dosage of 10 mg).

Pharmacotherapeutic group:blocker of "slow" calcium channels

ATX: & nbsp

C.08.C.A.02 Felodipine

Pharmacodynamics:

Felodipine-SZ - a blocker of "slow" calcium channels, used to treat hypertension and stable angina.

Felodipine is a dihydropyridine derivative.

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 the contractility or conduction of the heart. 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 patients with type 2 diabetes mellitus when using felodipine for 6 months, there is no clinically significant effect on the metabolic processes of glycosylated hemoglobin (HbAlc). 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.

Hypotensive effect: a decrease in blood pressure when taking felodipine is due to a decrease in total 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 under physical exertion. Because the felodipine has no effect on smooth veins musculature or adrenergic vasomotor control, then orthostatic hypotension does not develop.At the beginning of treatment, as a result of lowering blood pressure on the background of taking felodipine, there may be a temporary reflex increase in the heart rate (heart rate) and cardiac output. The increase in heart rate is prevented by the simultaneous application of β-blockers with felodipine. The effect of felodipine on AD and peripheral vascular resistance correlates with the plasma concentration of felodipine. The therapeutic effect of the drug continues for 24 hours.

Treatment with felodipine leads to regression of left ventricular hypertrophy.

Felodipine has a natriuretic and diuretic effect and does not have a 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 has no effect on glomerular filtration and albumin excretion.

For the treatment of arterial hypertension, Felodipine-SZ can be used in monotherapy or in combination with other antihypertensive drugs, such as β-blockers, diuretics or angiotensin-converting enzyme (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 overall peripheral vascular resistance, 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 angina pectoris.

At the beginning of therapy, there may be a temporary increase in heart rate, dosed by the appointment βadrenoblockers. The effect occurs after 2 hours and lasts for 24 hours.

For the treatment of stable angina pectoris felodipine can be used in combination with β-blockers or in 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 depending on the intake of food, and the maximum concentration in the blood plasma, therefore, increases 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. Felodipine is metabolized in the liver, all identified metabolites do not have a vasodilating effect (hemodynamic activity).

About 70% of the dose is allocated in the form of metabolites by the kidneys, the rest - 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 is not excreted in hemodialysis.

Indications:

- Arterial hypertension (in monotherapy or in combination with other antihypertensive drugs);

- ischemic heart disease: stable angina (in monotherapy or in combination with β-blockers).

Contraindications:

- Hypersensitivity to felodipine or other components included in the formulation, as well as to other dihydropyridine derivatives;

- chronic heart failure in the stage of decompensation;

- acute myocardial infarction;

- unstable angina;

- cardiogenic shock;

- hemodynamically significant aortic and mitral stenosis;

- hypertrophic obstructive cardiomyopathy;

- severe violations of liver function;

- lactose intolerance, lactase deficiency, glucose-galactose malabsorption;

- age to 18 years (efficacy and safety not established).

Carefully:

Aortic and mitral stenosis, lability of arterial pressure, impaired liver function, severe renal failure (creatinine clearance <30 ml / min), heart failure after acute myocardial infarction.

Pregnancy and lactation:

Pregnancy

Currently, there is insufficient data on the use of the drug Felodipine-SZ in pregnant women. Based on the data obtained in pre-clinical studies in animals on impaired development of the fetus, the preparation of Felodipine-SZ should not be administered 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 to confirm an 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.

Breast-feeding

Felodipine penetrates into breast milk. When taking felodipine in a nursing mother at therapeutic doses, only a small amount of felodipine is ingested with breast milk to the baby. Inadequate experience with the use of felodipine in women during breastfeeding does not exclude the risk of exposure to children who are breastfeeding, and therefore it is not recommended to prescribe the preparation of Felodipine-SZ to women during breastfeeding. 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 may be added to the therapy with Felodipine-SZ. The maximum daily dose of the drug is 10 mg.

Ischemic heart disease: stable angina (in monotherapy or in combination with βadrenoblockers)

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 administered together with β-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, but caution should be exercised in prescribing patients with severe renal insufficiency (see section "Special instructions").

Impaired liver function

Patients with a dysfunction of the liver usually have a dose of 2.5 mg. In severe hepatic insufficiency, the use of the drug is not recommended (see section "Contraindications").

Elderly patients

Elderly patients usually have a dose of 2.5 mg.

Children

Experience with the use of felodipine in children is limited.

Side effects:

Classification of the incidence of adverse events (WHO): very often more than 1/10, often more than 1/100 and less than 1/10, infrequently more than 1/1000 and less than 1/100, rarely more than 1 / 10,000 and less than 1 / 1000, very rarely - less than 1/10000.

Frequency/ Organ	Often (1≥10)	Often (≥ 1/100, <1/10)	Infrequently (≥1/1 000, <1/100)	Rarely (≥1/10 000, <1/1 000)	Rarely (<1/10 000)
Are common violations			increased fatigue		fever
Violations from the heart, blood vessels	peripheral edema	"tides" of blood to the skin of the face	tachycardia, palpitations, marked decrease in arterial pressure, exacerbation of the course of angina, leukocytoclastic vasculitis		extrasystole
Disorders from the endocrine system					hyperglycemia
Disorders from the gastrointestinal tract			nausea, abdominal pain	vomiting	gingival hyperplasia, gingivitis
Disturbances from the skin and subcutaneous tissues			skin rash, itching	hives	increased photosensitivity angioedema in the form of edema of the lips or tongue
Immune system disorders					hypersensitivity reactions
Disturbances from the liver and bile ducts					increased activity of "hepatic" transaminases in serum
Disturbances from musculoskeletal and connective tissue				arthralgia, myalgia
Disturbances from the nervous system		head pain	paresthesia dizziness	fainting
Disorders from the kidneys and urinary tract					rapidity urination
Disorders from the reproductive system			impotence/ sexual dysfunction

There is no causal relationship of the following side effects with taking the drug:

common violations: pain in the chest, swelling of the face, flu-like syndrome;

from the side of the heart, vessels: myocardial infarction, arterial hypotension, syncope, stenocardia, arrhythmia, extrasystole;

from the gastrointestinal tract: diarrhea, dryness of the oral mucosa, flatulence;

from the endocrine system: gynecomastia;

on the part of the blood and lymphatic system: anemia;

from the musculoskeletal and connective tissue: arthralgia, back pain, muscle pain, myalgia, pain in the upper and lower limbs;

from the nervous system: depression, insomnia, anxiety disorders, nervousness, drowsiness, irritability;

on the part of the respiratory system, the organs of the thorax and the mediastinum: pharyngitis, shortness of breath, bronchitis, sinusitis, nosebleeds;

from the skin and subcutaneous tissues: erythema, bruising, leukocytoclastic vasculitis;

with side of the organ of vision: visual disorders;

from the kidneys and urinary tract: polyuria, dysuria.

Overdose:

Symptoms:

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, pulmonary edema (not cardiogenic), and apnea; in adults, it is possible to develop respiratory distress syndrome; acidosis, hypokalemia,hyperglycemia, possibly hypocalcemia; "tides" of blood to the skin of the face, hypothermia; nausea and vomiting.

Treatment:

The appointment of activated charcoal, if necessary, gastric lavage, in some cases is effective even at a late stage of an overdose. Specific antidote - calcium preparations.

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 the vagus nerve). ECG monitoring. If necessary, provide airway patency and adequate ventilation of the lungs. The correction of acid-base state and electrolytes of blood serum is shown. In the case of bradycardia and AV blockades are appointed atropine 0,5-1 mg in / in adults (20-50 μg / kg children), if necessary, repeat the introduction, or initially injected isoprenaline 0.05-0.1 μg / kg / min. In acute intoxication at an early stage, it may be necessary to install an artificial pacemaker. A pronounced decrease in blood pressure is corrected by intravenous infusion, adult I / O is given a solution of calcium gluconate (9 mg calcium / ml) 20-30 ml for 5 minutes or as an infusion (3-5 mg calcium / kg for children), if necessary repeat the administration in the same dose. If necessary, infusion is administered norepinephrine (norepinephrine) or dopamine. In acute intoxication may be prescribed glucagon.

When cardiac arrest due to an overdose, resuscitation may be necessary for several hours. When convulsions are prescribed diazepam. Other symptomatic treatment is performed.

Interaction:

Felodipine is a substrate for isoenzyme CYP3A4. Preparations 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, as well as preparations of St. John's wort 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_mOh) of felodipine by 82%. It should avoid joint assignment with isoenzyme inducers CYP3A4.

Drugs that inhibit the cytochrome P450 system: antifungal agents of azole series (itraconazole, ketoconazole), macrolide antibiotics (for example, erythromycin) and HIV protease inhibitors are inhibitors of the isoenzyme CYP3A4. With co-administration of itraconazole C_mOh Felodipine increases 8 times, AUC in 6 times. With the joint appointment of erythromycin C_mOh and AUC Felodipine increases approximately 2.5 times. It should avoid joint use of felodipine and isoenzyme inhibitors CYP3A4.

Grapefruit juice inhibits isoenzyme CYP3A4. The use of felodipine with grapefruit juice increases C_mOh 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, it is recommended that the concentration of tacrolimus in the blood serum be monitored, and tacrolimus dosage adjustment may be required.

Cyclosporine: when co-administered with cyclosporine and felodipine C_mOh Felodipine increases by 150%, AUC increases by 60%. However, the effect of felodipine on the pharmacokinetic parameters of cyclosporine is minimal.

Cimetidine: combined use of cimetidine and felodipine leads to an increase in Stach and AUC felodipine by 55%.

Digoxin: felodipine increases the concentration of digoxin in the blood plasma, however, correction of the dose of felodipine is not required.

Special instructions:

At the beginning of therapy or with increasing doses, there may be "tides" of blood to the skin of the face, headache, palpitations, dizziness and weakness. Usually these reactions are temporary and pass on their own.

Special care must be taken with the following conditions: aortic and mitral stenosis, impaired 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.

Joint use of isozyme inducing drugs CYP3A4, leads to a significant decrease in the concentration of felodipine in the blood plasma and the insufficient therapeutic effect of taking the drug (see section "Interaction with other drugs"). It should be avoided co-administration of such drugs.

Joint use of isozyme inhibitory drugs 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. It is necessary to carefully observe the hygiene of the oral cavity (see section "Side effect").

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 and 10 mg.

Packaging:

For 10 or 30 tablets in a contour cell package.

For 30, 60 or 90 tablets in a jar of polymeric or a bottle of polymer.

Each can or bottle, 3, 6 contour packs of 10 tablets or 1, 2 contour packs of 30 tablets together with the instructions for use are placed in a cardboard box.

Storage conditions:

In a dry, the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-002374

Date of registration:14.02.2014

The owner of the registration certificate:NORTH STAR, CJSC NORTH STAR, CJSC Russia

Manufacturer: & nbsp

NORTH STAR, CJSC Russia

Representation: & nbspNORTH STAR CJSC NORTH STAR CJSC Russia

Information update date: & nbsp18.09.2015

Illustrated instructions

Instructions

Felodipine-SZ (Felodipine-SZ)