Felotens retard, 2,5mg 30 pcs

Indications

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

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

Pharmacological effect

Pharmacotherapeutic group:

blocker of “slow” calcium channels

ATX code: C08CA02

Pharmacological properties

Pharmacodynamics

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

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

Felodipine relaxes the smooth muscles of the respiratory tract and also has a slight effect on gastrointestinal motility. With long-term use, felodipine does not have a clinically significant effect on blood lipid concentrations. In patients with type 2 diabetes mellitus, no clinically significant effect on metabolic processes was observed when using felodipine for 6 months. 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 supine, sitting and standing positions, at rest and during physical activity. 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 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 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 persists between doses and a decrease in blood pressure for 24 hours.

Treatment with felodipine leads to regression of left ventricular myocardial hypertrophy. Felodipine has natriuretic and diuretic effects and does not have a kaliuretic effect. When taking felodipine, 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 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 improved blood supply to the myocardium due to dilatation of coronary vessels. Reducing the load on the heart is ensured by reducing the total peripheral vascular resistance (reducing the load overcome by the heart muscle), which leads to a decrease in the myocardial oxygen demand. Felodipine relieves spasm of coronary vessels.

Pharmacokinetics

Suction and distribution

The slow release of felodipine from film-coated tablets leads to a prolongation of the absorption phase of the drug and ensures a uniform concentration of felodipine in the blood plasma over 24 hours. Felodipine is almost completely absorbed from the gastrointestinal tract. The systemic bioavailability of felodipine is approximately 15% and is independent of food intake. However, the rate of absorption, but not its extent, may vary with food intake, and the maximum plasma concentration is thus increased by approximately 65%. The maximum concentration in blood plasma (Cmax) is achieved after 3-5 hours. The drug binds to blood plasma proteins by 99%, primarily to albumin. The volume of distribution at steady state is 10 l/kg.

Metabolism and excretion

Felodipine is completely metabolized in the liver, and all its metabolites are inactive. The half-life of felodipine is 25 hours, with a plateau phase reached in approximately 5 days. Does not accumulate even with long-term use. The total plasma clearance averages 1200 ml/min. Reduced clearance in elderly patients and in patients with reduced liver function leads to increased plasma concentrations of felodipine.

Pharmacokinetics in special groups of patients

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

Special instructions

Felotenz® retard should be prescribed 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 arterial hypotension, which in some predisposed patients can lead to the development of myocardial ischemia. Currently, there is no data on the advisability of using the drug as secondary prevention of myocardial infarction.

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

The drug ººPhelotens® retard does not affect the concentration of glucose in the blood and the lipid profile. Hyperglycemia is observed only in isolated cases.

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

It is necessary to maintain careful oral hygiene, due to the possible development of gum hyperplasia and gingivitis.

Effect on the ability to drive vehicles and machinery Patients who experience weakness or dizziness during treatment with Felotenz®retard should avoid driving and work that requires increased concentration and speed of psychomotor reactions.

Active ingredient

Felodipin

Composition

1 extended-release film-coated tablet contains:

active substance:

felodipine 2.5 mg;

excipients:

hypromellose (hydroxypropyl methylcellulose) 52 mg,

calcium hydrogen phosphate 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:

Opadry 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 dye yellow oxide 0.06 mg.

Contraindications

– hypersensitivity to felodipine and other dihydropyridine derivatives;

– unstable angina;

– acute myocardial infarction and the period within one month after myocardial infarction;

– cardiogenic shock;

– hemodynamically significant aortic and mitral stenosis;

– hypertrophic obstructive cardiomyopathy;

– pregnancy and lactation period;

– chronic heart failure in the stage of decompensation;

– severe arterial hypotension;

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

– age under 18 years (efficacy and safety have not been established).

With caution

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

Side Effects

As with other slow calcium channel blockers, the drug may cause facial flushing, headache, palpitations, dizziness and fatigue. These reactions are reversible and most often occur at the beginning of treatment or when the dose of the drug is increased. Also, depending on the dose, peripheral edema may appear, which is a consequence of precapillary vasodilation. Patients with gum disease or periodontitis may experience mild swelling of the gums. This can be prevented by practicing good oral hygiene.

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

often – from ≥1/100 to 1% and <10%));

uncommon – from ≥1/1000 to 0.1% and <1%));

rarely – from ≥1/10000 to 0.01% and <0.1%));

very rarely – <1/10,000 prescriptions (<0.01%).

From the cardiovascular system

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

infrequently – tachycardia, palpitations, marked decrease in blood pressure, accompanied by reflex tachycardia and worsening angina;

very rarely – extrasystole, leukocytoclastic vasculitis.

From the nervous system

often – headache;

uncommon – paresthesia, dizziness;

rarely – fainting.

From the digestive system

uncommon – nausea, abdominal pain;

rarely – vomiting;

very rarely – increased activity of “liver” transaminases, hyperplasia of the gums, the mucous membrane of the tongue, gingivitis.

From the musculoskeletal system

rarely – arthralgia, myalgia.

Allergic reactions

uncommon – skin rash, itching;

rarely – urticaria;

very rarely – angioedema of the lips or tongue, photosensitivity reaction.

From the urinary system

very rarely – frequent urination.

Others:

infrequently – increased fatigue;

rarely – impotence/sexual dysfunction;

very rarely – fever, hyperglycemia.

A cause-and-effect relationship has not been established: chest pain, facial swelling, flu-like syndrome, marked decrease in blood pressure, myocardial infarction, fainting, 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, influenza, sinusitis, nosebleeds, erythema, bruising, leukocytoclastic vasculitis, blurred vision, polyuria, dysuria.

Interaction

Digoxin: Felodipine increases plasma concentrations of digoxin, but no dose adjustment of felodipine is 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 concentration-time curve) of felodipine by 93% and Cmax by
82%. Co-administration should be avoided.

Nonsteroidal anti-inflammatory drugs do not reduce 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 with felodipine, increase the AUC by 8 times and the Cmax by 6 times.

Macrolide antibiotics (erythromycin): when administered together, the AUC and Cmax of felodipine increases by 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 (monitoring of the concentration of tacrolimus in the blood plasma and possible dose adjustment is recommended).

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%.

Overdose

Symptoms: In case of overdose, symptoms of intoxication appear 12-16 hours after taking the drug, sometimes symptoms can occur several days after taking the drug. The following symptoms may be observed: marked decrease in blood pressure, bradycardia, AV (atrioventricular) block of 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; in adults, respiratory distress syndrome may develop; acidosis, hypokalemia, hyperglycemia, hypocalcemia; facial flushing, hypothermia; nausea, vomiting.

Treatment: Gastric lavage, administration of activated carbon, in some cases, is effective even at the late stage of intoxication. A specific antidote is calcium preparations. If there is a pronounced decrease in blood pressure, the patient should be placed in a horizontal position with his legs elevated. With the development of bradycardia, intravenous administration 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 stimulation of the vagus nerve. ECG monitoring. If necessary, ensure airway patency and adequate ventilation. Correction of the acid-base status and electrolytes of blood serum is indicated. In case of bradycardia and AV block, atropine 0.5-1.0 mg IV is prescribed, repeated if necessary, 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. The decrease in blood pressure is corrected by intravenous administration of fluid (dextrose solution, 0.9% sodium chloride solution, dextran), adults are given intravenous calcium gluconate solution 20-30 ml for
5 minutes, if necessary, repeat the administration at the same dose. If necessary, norepinephrine (adrenaline) or dopamine is infused. In case of acute intoxication, glucagon may be prescribed. For convulsions, diazepam is prescribed.

Manufacturer

Kanonpharma production CJSC, Russia