Felotenz retarde sustained release pills 2.5mg, 30pcs

Composition

1 tablet of prolonged action, film-coated, contains:

Active ingredient:

felodipine 2.5 mg;

excipients:

hypromellose (hydroxypropylmethylcellulose) 52 mg,

calcium hydrophosphate dihydrate 19 mg,

colloidal silicon dioxide 1 mg,

lactose monohydrate 34.8 mg,

magnesium stearate 0.7 mg,

sodium alginate 5 mg,

povidone K-30 5 mg;

film shell composition:

Opadray II yellow 4 mg, including: polyvinyl alcohol 1.6 mg, macrogol (polyethylene glycol) 0.8 mg, talc 0.6 mg, titanium dioxide 0.94 mg, iron oxide yellow dye 0.06 mg

Pharmacological action

Pharmacotherapy group:

blocker of “slow” calcium channels

ATX code:  C08CA02

Pharmacological properties

Pharmacodynamics

Felodipine belongs to the “slow” calcium channel blockers of the dihydropyridine series. It has an antihypertensive, antianginal effect. Lowers blood pressure (BP) by reducing total peripheral vascular resistance, especially in the arterioles. It has a dose-dependent anti-ischemic effect.

Reduces the size of myocardial infarction, protects against reperfusion complications. The conduction and contractility of vascular smooth muscle is suppressed by affecting the calcium channels of cell membranes. Due to its high selectivity for arteriolar smooth muscle, felodipine in therapeutic doses does not have a negative inotropic effect on the cardiac conduction system.

Felodipine relaxes the smooth muscles of the respiratory tract, also has a slight effect on the motility of the gastrointestinal tract. With prolonged use, felodipine does not have a clinically significant effect on the concentration of blood lipids. In patients with type 2 diabetes mellitus, the use of felodipine for 6 months did not have a clinically significant effect on metabolic processes. Felodipine can also be prescribed to patients with reduced left ventricular function, receiving standard therapy, patients with bronchial asthma, diabetes mellitus, gout, or hyperglycemia.

The antihypertensive effect of 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”, “sitting” and “standing” positions, at rest and during exercise. Since felodipine has no effect on venous smooth muscle or adrenergic vasomotor control, orthostatic hypotension does not occur.

At the beginning of treatment, as a result of a decrease in blood pressure against the background of taking felodipine, a temporary reflex increase in heart rate (HR) and cardiac output may occur. The increase in heart rate is prevented by the simultaneous use of beta-blockers with felodipine. The effect of felodipine on blood pressure and total peripheral vascular resistance correlates with the plasma concentration of felodipine. At steady state, the clinical effect is maintained between doses and a decrease in blood pressure for 24 hours.

Treatment with felodipine leads to regression of left ventricular hypertrophy. Felodipine has natriuretic and diuretic effects and does not have a potash 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 increases renal perfusion. Felodipine has no effect on glomerular filtration rate and albumin excretion. For the treatment of arterial hypertension, felodipine can be used alone or in combination with other antihypertensive drugs, such as beta-blockers, diuretics or angiotensin-converting enzyme (ACE) inhibitors.

The anti-ischemic effect of felodipine is due to an improvement in blood supply to the myocardium due to dilation of coronary vessels. Reducing the load on the heart is provided by reducing the total peripheral vascular resistance (reducing the load overcome by the heart muscle), which leads to a decrease in the need for oxygen in the myocardium. Felodipine relieves spasm of the coronary vessels.

Pharmacokinetics

Absorption and distribution

The delayed release of felodipine from coated tablets leads to an elongation of the absorption phase of the drug and ensures a uniform concentration of felodipine in the blood plasma for 24 hours. Felodipine is almost completely absorbed in the gastrointestinal tract. The systemic bioavailability of felodipine is approximately 15% and does not depend on food intake. However, the rate of absorption, but not its degree, may vary depending on food intake, and the maximum concentration in blood plasma, thus, increases by about 65%. The maximum concentration in blood plasma (cmax) is reached in 3-5 hours. The drug binds to plasma proteins by 99%, primarily with albumins. The volume of distribution in the equilibrium state is 10 l/kg.

Felodipine is completely metabolized in the liver, and all its metabolites are inactive. The elimination half-life of felodipine is 25 hours, and the plateau phase is reached within about 5 days. It does not accumulate even with prolonged use. The average total plasma clearance is 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 blood plasma.

Pharmacokinetics in special patient groups

In elderly patients and in cases of impaired liver function, the concentration of felodipine in blood plasma is higher than in young patients. The pharmacokinetic parameters of felodipine do not change in patients with impaired renal function, including during hemodialysis. About 70% of the dose taken is excreted by the kidneys, and the remainder is excreted through the intestines in the form of metabolites. Less than 0.5% of the dose is excreted unchanged by the kidneys. Felodipine penetrates the blood-placental barrier and is excreted in breast milk.

Indications

-arterial hypertension (in monotherapy or in combination with other antihypertensive agents, such as beta-blockers, diuretics and ACE inhibitors);

-stable angina pectoris (in monotherapy and in combination with beta-blockers).

Contraindications

– hypersensitivity to felodipine and other derivatives digidropiridinovmi number;

– unstable angina;

acute myocardial infarction and within one month after myocardial infarction;

– cardiogenic shock;

– hemodynamically significant aortic and mitral stenosis;

hypertrophic obstructive cardiomyopathy;

– pregnancy and lactation;

– chronic heart failure in the stage of decompensation;

– severe hypotension;

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

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

With caution

Impaired liver function, severe renal insufficiency (creatinine clearance less than 30 ml / min), aortic and mitral stenosis, lability of blood pressure and heart failure after myocardial infarction, elderly age.

Side effects

As with other “slow” calcium channel blockers, the drug can cause redness of the face, headache, palpitation, dizziness and increased fatigue. These reactions are reversible and most often occur at the beginning of treatment or with an increase in the dose of the drug. Also, depending on the dose, peripheral edema may appear, which are a consequence of precapillary vasodilation. Patients with gum disease or periodontitis may experience mild swelling of the gums. This can be prevented by careful oral hygiene.

WHO (World Health Organization) classification of the incidence of side effects:

often from ≥1/100 to < 1/10 appointments (>1% and <10%);

infrequently – from ≥1/1000 to <1/100 appointments (>0.1% and <1%);

rare – from ≥1/10000 to <1/1000 appointments (>0.01% and <Is 0.1%);

very rarely – <1/10000 appointments (<0,01%).

From the cardiovascular system

often – “hot flashes” of blood to the skin of the face, accompanied by facial hyperemia, swelling of the ankles;

infrequently – tachycardia, palpitation, pronounced decrease in blood pressure, accompanied by reflex tachycardia and worsening of angina;

very rarely – extrasystole, leukocytoclastic vasculitis.

From the nervous system

often – headache;

infrequently-paresthesia, dizziness;

rarely-fainting.

From the digestive system

infrequently – nausea, abdominal pain;

rarely-vomiting;

very rarely-increased activity of “liver” transaminases, gum hyperplasia, tongue mucosa, gingivitis.

From the musculoskeletal

system rarely-arthralgia, myalgia.

Allergic reactions

infrequently-skin rash, pruritus;

rarely-urticaria;

very rarely-angioedema of the lips or tongue, photosensitization reaction.

From the urinary system

very rarely – frequent urination.

Other services:

infrequently-increased fatigue;

rarely-impotence/sexual dysfunction;

very rarely-fever, hyperglycemia.

No causal relationship has been established: chest pain, facial edema, flu-like syndrome, marked decrease in blood pressure, myocardial infarction, syncope, angina pectoris, arrhythmia, extrasystole, diarrhea, dry oral mucosa, flatulence, gynecomastia, anemia, arthralgia, back pain, myalgia, pain in the upper and lower extremities, depression, insomnia, anxiety, nervousness, drowsiness, irritability, pharyngitis, shortness of breath bronchitis, flu, sinusitis, nosebleeds, erythema, bruising, leukocytoclastic vasculitis, visual impairment, polyuria, dysuria.

Composition

Digoxin Interaction: felodipine increases the concentration of digoxin in the blood plasma, but changes in the dose of felodipine are not required.

Inhibitors of the CYP3A4 isoenzyme (cimetidine, erythromycin, itraconazole, ketoconazole) slow down the metabolism of felodipine in the liver, increasing the concentration of the drug in the blood plasma.

Inducers of the CYP3A4 isoenzyme (phenytoin, carbamazepine, rifampicin, barbiturates, phenobarbital, St. John’s wort preparations) reduce the AUC (area under the pharmacokinetic curve “concentration-time”) of felodipine by 93% and Cmax by 82%. Co-assignment should be avoided.

Nonsteroidal anti-inflammatory drugs do not weaken the antihypertensive effect of felodipine.

Warfarin: the high degree of protein binding of felodipine does not affect the binding of the free fraction of warfarin.

Beta-blockers, verapamil, tricyclic antidepressants and diuretics enhance the antihypertensive effect of felodipine.

Azole antimicrobials (ketoconazole, itraconazole) when co-administered, the AUC of felodipine increases by 8 times, Cmax-by 6 times.

Macrolide antibiotics (erythromycin): when co-administered, the AUC and Cmax of felodipine increases 2.5 times.

HIV protease inhibitors also increase the concentration of felodipine in the blood.

Grapefruit juice increases the AUC and Cmax of felodipine by 2 times, so felodipine should not be used simultaneously with grapefruit juice.

Tacrolimus: felodipine increases the concentration of tacrolimus in the blood plasma when used together (it is recommended to monitor the concentration of tacrolimus in the blood plasma and possible dose adjustment).

Cyclosporine increases the Cmax of felodipine by 150%, AUC by 60% (the effect of felodipine on the pharmacokinetic parameters of cyclosporine is minimal).

Cimetidine increases the Cmax and AUC of felodipine by 55%.

How to take, course of use and dosage

Inside, preferably washed down with water, on an empty stomach, or with a small amount of food low in fat and carbohydrates.

Do not divide, crush or chew the tablet.

Arterial hypertension

The dose is always determined individually. Therapy begins with a dose of 5 mg once a day. If necessary, the dose can be increased. Usually, the maintenance dose is 5-10 mg once a day. To determine the individual dose, it is best to use tablets containing 2.5 mg of felodipine.

In elderly patients or patients with impaired liver function, the recommended starting dose is 2.5 mg once a day. The maximum daily dose is 10 mg.

Stable angina pectoris

The dose is always determined individually. Treatment begins with a dose of 5 mg once a day, if necessary, you can increase the dose to 10 mg once a day.

Gelotenz ® retard can be used in combination with beta-blockers, ACE inhibitors or diuretics. Combination therapy usually enhances the antihypertensive effect of the drug. It is necessary to avoid the development of arterial hypotension. In patients with impaired renal function, the pharmacokinetics of the drug does not change significantly. Caution should be exercised in patients with impaired renal function (creatinine clearance less than 30 ml/min).

Overdose

Symptoms: In case of overdose, symptoms of intoxication appear 12-16 hours after taking the drug, sometimes symptoms may occur several days after taking the drug. The following symptoms may occur: marked decrease in blood pressure, bradycardia, AV (atrioventricular) block I-III degree, ventricular extrasystole, atrioventricular dissociation, asystole, ventricular fibrillation; headache, dizziness, impaired consciousness (or coma), convulsions; shortness of breath, pulmonary edema (non-cardiac) and apnea; adults may develop respiratory distress syndrome; acidosis, hypokalemia, hyperglycemia, hypocalcemia; redness of the face, hypothermia; nausea, vomiting.

Treatment: Gastric lavage, the appointment of activated charcoal, in some cases is effective even at a late stage of intoxication. A specific antidote is calcium supplements. With a marked decrease in blood pressure, the patient should be given a horizontal position, raise his legs. With the development of bradycardia, intravenous use of atropine at a dose of 0.25-0.5 mg is indicated, which should be prescribed before gastric lavage, due to the risk of vagus nerve stimulation. ECG monitoring. If necessary, ensure airway patency and adequate ventilation of the lungs. Correction of the acid-base state and blood serum electrolytes is shown. In the case of bradycardia and AV block, atropine 0.5-1.0 mg IV is prescribed, if necessary, repeated use, or isoprenaline 0.05-0.1 mcg/kg/min is initially administered. In case of acute intoxication at an early stage, it may be necessary to install an artificial pacemaker. Decrease in blood pressure is corrected by intravenous use of a liquid (dextrose solution,0.9% sodium chloride solution, dextran), adults are given an intravenous solution of calcium gluconate 20-30 ml for 5 minutes, if necessary, repeat the use at the same dose. If necessary, an infusion of norepinephrine (epinephrine) or dopamine is administered. In acute intoxication, glucagon may be prescribed. For convulsions, diazepam is prescribed.

Special instructions

Felotenz retard should be used with caution in patients with a tendency to tachycardia and severe left ventricular dysfunction. As with other vasodilators, in rare cases felodipine can cause significant hypotension, which in some predisposed patients can lead to the development of myocardial ischemia. Currently, there are no data on the feasibility of using the drug as a secondary prevention of myocardial infarction.

Felodipine is effective and well tolerated by patients regardless of gender and age, as well as patients with concomitant diseases such as bronchial asthma and other lung diseases, impaired renal function, diabetes mellitus, gout, hyperlipidemia, Raynaud’s syndrome, as well as after lung transplantation.

Phelotens® retard has no effect on blood glucose concentration and lipid profile. Hyperglycemia is observed only in some cases.

Impaired renal function does not affect the concentration of the drug in the blood plasma, so dose adjustment in patients with impaired renal function is not required. However, caution should be exercised when prescribing the drug to patients with renal insufficiency.

It is necessary to observe careful oral hygiene, in connection with the possible development of gum hyperplasia and gingivitis.

Influence on the ability to drive vehicles and mechanisms Patients who experience weakness or dizziness during treatment with Felotenz ® retard should refrain from driving vehicles and work that requires increased concentration of attention and speed of psychomotor reactions.

Form of production

Tablets, film-coated from light yellow to yellow in color, round, biconvex. Two layers are visible on the fracture: the shell is light yellow to yellow in color, and the core is white in color.

Active ingredient

Felodipine

Conditions of release from pharmacies

By prescription

Dosage form

long-acting tablets