Composition, form of production and packaging
Tablets of prolonged action, covered with a film shell of red-brown color, round, biconcave, with the engraving of the letters "A" over the "FE" on one side and "10" on the other.
felodipine 10 mg
Auxiliary substances: giprolose (hydroxypropylcellulose) - 10 mg, hypromellose (hydroxypropylmethylcellulose) - 100 mg, anhydrous anhydrous - 28 mg, microcrystalline cellulose - 3 mg, macrogol glyceryl hydroxy stearate - 10 mg, propyl gallate - 0.06 mg, sodium aluminosilicate 47 mg, sodium stearyl fumarate 4.2 mg.
The composition of the shell: carnauba wax ~ 0.1 mg, iron dye reddish brown oxide 0.1 mg, iron dye oxide yellow 0.07 mg, hypromellose 5.3 mg, macrogol 6000 1.3 mg, titanium dioxide (E171) 0.6 mg.
30 pcs. - plastic bottles (1) - cardboard boxes.
Long-acting tablets covered with a film coating of yellow color, round, biconcave, with letters "A" engraved on "FL" on one side and "2.5" on the other.
felodipine 2.5 mg
Auxiliary substances: giprolose (hydroxypropylcellulose) - 10 mg, hypromellose (hydroxypropylmethylcellulose) - 100 mg, anhydrous anhydrous - 28 mg, microcrystalline cellulose - 3 mg, macrogol glyceryl hydroxy stearate - 2.5 mg, propyl gallate - 0.06 mg, sodium aluminosilicate 47 mg, sodium stearyl fumarate - 3.9 mg.
The composition of the shell: carnauba wax ~ 0.1 mg, iron oxide oxide yellow 0.15 mg, hypromellose 4.9 mg, macrogol 6000-1.2 mg, titanium dioxide (E171) 0.7 mg.
30 pcs. - plastic bottles (1) - cardboard boxes.
Tablets of prolonged action, covered with a film cover of pink color, round, biconcave, with the engraving of the letters "A" over "Fm" on one side and "5" on the other.
felodipine 5 mg
Auxiliary substances: giprolose (hydroxypropylcellulose) - 10 mg, hypromellose (hydroxypropylmethylcellulose) - 100 mg, anhydrous anhydrous - 28 mg, microcrystalline cellulose - 3 mg, macrogol glycerol hydroxy stearate - 5 mg, propyl gallate - 0.06 mg, sodium aluminosilicate 47 mg, sodium stearyl fumarate - 4 mg.
The composition of the shell: carnauba wax ~ 0.1 mg, iron dye oxide reddish brown - 0.03 mg, iron dye oxide yellow 0.01 mg, hypromellose 5 mg, macrogol 6000 1.3 mg, titanium dioxide (E171) 0.7 mg.
30 pcs. - plastic bottles (1) - cardboard boxes.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2008.
The blocker of slow calcium channels, used to treat hypertension and stable angina.
Felodipine, a dihydropyridine derivative, is a racemic mixture. Felodipine reduces blood pressure 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 muscle arterioles, 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. It has been shown that felodipine exerts an insignificant effect on the gastrointestinal motility. With prolonged use, felodipine does not have a clinically significant effect on lipid content 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 (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 in both the prone position and in the sitting and standing position, at rest and under physical exertion. Since felodipine has no effect on smooth veins musculature or adrenergic vasomotor control, 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 heart rate and cardiac output. An increase in 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. In the equilibrium state, the clinical effect persists between taking doses and reducing blood pressure persists 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.
In a study of the 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, if necessary, diuretics, 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 diastolic BP reduction to <80 mmHg. (11.9 / 100 patient-years), in comparison with the group where the level of diastolic blood pressure was <90 mm Hg. (24.4 / 1000 patient-years). In the STOP-2 trial, where Plendil was used as one of two slow calcium channel blockers, involving 6.614 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- adrenoblockers, if necessary, does not affect the level of mortality from cardiovascular disease compared with traditional therapy with 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 the 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 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, stopped by the appointment of beta-blockers. The effect occurs after 2 hours and lasts for 24 hours. For the treatment of stable angina, felodipine can be used in combination with beta-blockers or in the form of monotherapy.
Systemic bioavailability of felodipia 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 C max in the plasma, therefore, increases by about 65%. C max in blood plasma is achieved after 3-5 hours. The drug binds to plasma proteins by 99%. V d in the equilibrium state is 10 l / kg.
T 1/2 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 only partially explains the individual changes in the plasma concentration of felodipine.
Felodipine is metabolized in the liver, all the metabolites identified do not have a vasodilator effect (haemodynamic activity). About 70% of the dose is allocated in the form of metabolites with urine, the rest - with feces. Less than 0.5% is excreted in the urine 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.
- arterial hypertension;
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.
The dose should be selected individually. The initial dose is 5 mg / day. The usual maintenance dose is 5 mg / day. 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 prescribed drug more than 10 mg / day.
The dose should be selected individually. It is necessary to start treatment with a dose of 5 mg / day, if necessary, increasing the dose to 10 mg / day. May be administered in conjunction with beta-blockers.
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 prescribing patients with severe renal insufficiency.
Experience with the use of felodipine in children is limited.
The most frequent adverse reactions associated with Plendil include a dose-dependent effect: mild to moderate ankle edema due to 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, palpitations, 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.
Frequently (? 1/100) Less often (? 1/1000, <1/100) Rarely (? 1/10 000, <1/1000) Very rarely (<1 / 10,000)
General Fatigue Fever
Blood circulation reddening of the face, accompanied by "hot flashes", swelling of the ankles tachycardia, heart beat extrasystole, lowering blood pressure, accompanied by tachycardia, which in sensitive patients can cause exacerbation of angina, leukocytoclastic vasculitis
Endocrine system hyperglycemia
Gastrointestinal tract nausea, abdominal pain vomiting hyperplasia of the mucous tongue and gums, gingivitis
Skin of exanthema, itching of urticaria increased photosensitivity, angioedema in the form of edema of the lips or tongue
The hypersensitivity immune system
Liver increased hepatic enzyme activity in blood serum
Musculoskeletal system arthralgia, myalgia
CNS headache paresthesia, dizziness, impotence / sexual dysfunction syncope
Urinary system frequent urination
There is no causal relationship of the following side effects with taking the drug:
Common: chest pain, face swelling, flu-like syndrome.
Cardiovascular: myocardial infarction, arterial hypotension, syncope, angina pectoris, arrhythmia, extrasystole.
From the gastrointestinal tract: diarrhea, dry mouth, flatulence.
On the part of the endocrine system: gynecomastia.
From the side of the circulatory system: anemia.
From the musculoskeletal system: arthralgia, back pain, muscle pain, myalgia, pain in the upper and lower extremities.
From the side of the central nervous system: depression, insomnia, anxiety disorders, nervousness, drowsiness, irritability.
On the part of the respiratory tract: pharyngitis, dyspnea, bronchitis, influenza, sinusitis, nosebleeds.
From the skin: erythema, bruising, leukocytoclastic vasculitis.
From the senses: visual disorders.
From the side of the urinary system: polyuria, dysuria.
- heart failure in the stage of decompensation;
acute myocardial infarction;
- unstable angina;
- age under 18 years (effectiveness and safety not established);
- hypersensitivity to felodipine or other components that make up the drug.
With caution: aortic stenosis, lability of blood pressure, impaired liver function, severe renal failure (CK <30 ml / min), heart failure after acute myocardial infarction.
PREGNANCY AND LACTATION
At present, there is insufficient data on the use of felodipine in pregnant women. Based on the data obtained in animals on the development of the fetus, felodipine 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.
Felodipine penetrates into breast milk. When taking felodipine in a nursing mother at therapeutic doses, only a small amount of the drug falls into the baby with breast milk. 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 appoint felodipine to women during lactation. If continuation of therapy is necessary to achieve a clinical effect, consideration should be given to stopping breastfeeding.
APPLICATION FOR FUNCTIONS OF THE LIVER
With caution: severe renal failure (CK <30 mL / min).
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
With caution: a violation of the liver.
APPLICATION FOR CHILDREN
Contraindication: age under 18 years (efficacy and safety not established).
Care must be taken with the following conditions: aortic stenosis, impaired liver function, severe renal failure (QC <30 ml / min), heart failure after acute myocardial infarction. Arterial hypotension, which in predisposed patients can cause myocardial ischemia. The combined use of drugs inducing the enzyme system CYP 3A4, leads to a significant decrease in the concentration of felodipine in the blood plasma and the insufficient therapeutic effect of taking the drug. It should be avoided co-administration of such drugs.
The combined use of drugs that inhibit the CYP 3A4 enzyme system 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.
Influence on the ability to drive and other mechanisms .
When driving a car 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.
Toxicity: 10 mg of felodipine in a 2-year-old child caused minor intoxication. 150-200 mg of felodipia in a 17-year-old patient and 250 mg in an adult caused intoxication from mild to moderate. Probably, felodiin has a more significant effect on the peripheral blood circulation than on the heart compared to other drugs of this therapeutic group.
Symptoms: overdose symptoms of intoxication occur 12-16 hours after taking the drug, severe symptoms can occur and a few days after admission. 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 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. The greatest risk is the effect of overdose on circulation.
Treatment: The appointment of activated charcoal, if necessary, gastric lavage, in some cases is effective even at a late stage of intoxication. Specific antidote - calcium preparations.
Important! Atropine (0.25-0.5 mg / in adults, 10-20 mg / kg for children) should be assigned to gastric lavage (due to the risk of stimulation of the vagus nerve). ECG monitoring. When required to ensure an open airway and adequate ventilation. It shows the correction of acid-base status and serum electrolytes. In the case of bradycardia and AV -blokady atropine administered at 0.5-1 mg / per adult (20-50 mg / kg for children), repeated administration or administered initially isoprenaline 0.05-0.1 ug / kg / min if necessary. In acute toxicity at an early stage may need to install an artificial pacemaker. Reduction of blood pressure is corrected in / introducing fluids into adult / injected calcium gluconate solution (9 mg Ca / ml) was 20-30 ml for 5 minutes or as an infusion (3-5 mg Ca / kg for children), repeated if necessary administration of the same dose.If desired infusion administered norepinephrine (adrenaline) or dopamine. In acute toxicity can be administered glucagon.
In cardiac arrest due to an overdose may require resuscitation measures for several hours. In convulsions diazepam prescribed. Pursue other symptomatic treatment.
Felodipine is a substrate for CYP 3A4. Drugs that induce or inhibit CYP 3A4, have a significant effect on the concentration of felodipine in plasma.
Drugs that induce cytochrome P450 system: phenytoin, carbamazepine, phenobarbital and rifampin, and St. John's wort tincture increase of felodipine metabolism by induction of cytochrome P 450. The combined use fenitoiia, carbamazepine, phenobarbital and rifampin leads to a decrease in AUC values of 93% and C maxfelodipine 82%. Avoid concomitant administration with inducers of CYP 3A4.
Drugs that inhibit the cytochrome P450 system:azole antifungals (itraconazole, ketoconazole), macrolide antibiotics (e.g. erythromycin) and HIV protease inhibitors are inhibitors of the enzyme system CYP 3A4. When coadministered itraconazole C max felodipine is increased 8 times, AUC 6 times. When coadministered erythromycin C max and AUC felodipine increased approximately 2.5 times. Avoid joint destination felidipina and CYP 3A4 inhibitors.
Grapefruit juice inhibits CYP 3A4 enzyme system. Application of felodipine with grapefruit juice increased C max and AUC felodipine about 2 times. Avoid joint use.
tacrolimus:felodipine can cause an increase in the concentration of tacrolimus in the blood plasma. In a joint application it is recommended to monitor the concentration of serum tacrolimus may need a dose adjustment of tacrolimus.
Cyclosporin: when coadministered cyclosporine and felodipine C max felodipine is increased by 150%, AUC increased by 60%. However, the effects of felodipine on the pharmacokinetic parameters of cyclosporine minimum.
Cimetidine: combined use of cimetidine and felodipine leads to an increase in C max and AUC of felodipine at 55%.
TERMS OF RELEASE FROM PHARMACY
TERMS AND CONDITIONS OF STORAGE
List B. Store at 30 В° C, out of reach of children. Shelf life - 3 years.