Felodipine, 5 mg 30 pcs

Pharmacotherapeutic group

Slow calcium channel blocker

ATX code

C08CA02

Pharmacodynamics:

Felodipine is a slow calcium channel blocker (SCB) used to treat arterial hypertension and stable angina.

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

The conductivity and contractility of vascular smooth muscle is inhibited by acting on calcium channels of cell membranes.

Felodipine at therapeutic doses has no adverse inotropic effect on cardiac contractility or conduction due to its high selectivity for arteriolar smooth muscle.

Felodipine relaxes the smooth muscles of the airways.

Felodipine has been shown to have little effect on gastrointestinal motility.

Felodipine has no clinically significant effect on blood lipid concentrations with long-term use.

In patients with type 2 diabetes mellitus when using felodipine for 6 months there were no clinically significant effects on metabolic processes.

Felodipine may also be indicated in patients with reduced left ventricular function receiving standard therapy and in patients with bronchial asthma, diabetes, gout, or hyperlipidemia.

Antihypertensive effect: Decrease in BP when taking felodipine is due to decrease in peripheral vascular resistance. Felodipine effectively decreases BP in patients with arterial hypertension when lying down as well as when sitting and standing at rest and during physical activity. Since felodipine has no effect on venous smooth muscle or adrenergic vasomotor control, there is no development of orthostatic hypotension.

At the beginning of treatment, a temporary reflex increase in heart rate (HR) and cardiac output may be observed as a result of BP reduction with felodipine administration. Concurrent use of beta-adrenoblockers with felodipine prevents HR increase.

The effects of felodipine on BP and peripheral vascular resistance correlate with the plasma concentration of felodipine. At equilibrium, the clinical effect is maintained between doses and the BP reduction persists for 24 h.

Felodipine treatment results in regression of left ventricular hypertrophy.

Felodipine has a natriuretic and diuretic effect and no potassium effect. Taking felodipine reduces tubular reabsorption of sodium and water, 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.

The use of felodipine in combination with angiotensin-converting enzyme inhibitors (ACE) beta-adrenoblockers and, if necessary, with diuretics reduces diastolic BP below 90 mmHg in 93% of patients.

The use of dihydropyridine derivative DMARDs as initial therapy followed by the addition of beta-adreno-blockers if necessary has no effect on cardiovascular mortality compared to standard therapy with beta-adreno-blockers and/or diuretics.

Felodipine may be used in monotherapy or in combination with other hypotensive medications such as beta-adrenoblockers diuretics or ACE inhibitors to treat arterial hypertension.

Anti-ischemic effect: use of felodipine leads to improvement of myocardial blood supply due to dilatation of coronary vessels. Decrease of cardiac load is provided due to decrease of peripheral vascular resistance (decrease of load overcome by heart muscle) which leads to decrease of myocardial oxygen demand.

Felodipine reduces coronary vasospasm and improves contractility and reduces the frequency of angina attacks in patients with stable angina pectoris. At the beginning of therapy, a temporary increase in HR may be observed, which is stopped by prescription of beta-adrenoblockers. The effect occurs after 2 hours and lasts for 24 hours. For treatment of stable angina pectoris felodipine may be used in combination with beta-adrenoblockers or in monotherapy.

Pharmacokinetics:

The systemic bioavailability of felodipine is approximately 15% and is independent of the time of ingestion. However, the rate of absorption but not its degree may vary depending on the time of ingestion and the maximum plasma concentration is thus increased by approximately 65%.

The maximum plasma concentration is reached after 3-5 hours. The drug is 99% bound to plasma proteins. Volume of distribution in equilibrium state is 10 l/kg.

The elimination half-life is about 25 h the plateau phase is reached within about 5 days. It does not cumulate even with prolonged administration. Total plasma clearance averages 1200 ml/min.

Decreased clearance in elderly patients and in patients with decreased liver function leads to increased plasma concentrations of felodipine. However, age-related features only partially explain individual changes in plasma felodipine concentrations.

Felodipine is metabolized in the liver under the action of CYP3A4 isoenzyme all identified metabolites have no vasodilatory effect (hemodynamic activity).

About 70% of the administered dose is excreted as metabolites with the kidneys and the rest is excreted through the intestine. Less than 05% is excreted unchanged by the kidneys.

In impaired renal function the plasma concentration of felodipine does not change, but there is a cumulation of inactive metabolites.

Felodipine is not excreted by hemodialysis.

Indications

– Arterial hypertension (in monotherapy or in combination with other hypotensive agents such as beta-adrenoblockers diuretics or ACE inhibitors).

– Stable angina pectoris (in monotherapy or in combination with beta-adrenoblockers).

Active ingredient

Felodipine

Composition

Active ingredient: felodipine – 5.00 mg.

Excipients: lactose monohydrate (milk sugar) – 93.00 mg; hypromellose – 84.00 mg; macrochlor stearate – 4.00 mg; colloidal silica – 3.0 mg; magnesium stearate – 1.00 mg.

Shell composition: hypromellose, 2.90 mg; macrogol 4000, 0.70 mg; titanium dioxide, 1.33 mg; iron oxide yellow dye, 0.07 mg.

How to take, the dosage

Take it orally in the morning with water. The tablet should not be crushed or chewed. The tablets can be taken on an empty stomach or with a small amount of food low in fat and carbohydrates.

Hypertension

The dose must be adjusted individually.

The starting dose is 5 mg once daily.

The usual maintenance dose is 5 mg once daily.

If necessary, the dose may be increased or another hypotensive drug (e.g., a beta-adrenoblocker diuretic or ACE inhibitor) may be added to therapy with Felodipine. The drug is rarely prescribed more than 10 mg per day.

The maximum daily dose is 10 mg/day.

Stable angina pectoris

The dose must be adjusted individually.

The treatment should be started with a dose of 5 mg once daily, increasing the dose to 10 mg once daily if necessary.

May be combined with beta-adrenoblockers.

The use in elderly patients

In elderly patients, the recommended starting dose is 25 mg.

Renal dysfunction

Renal dysfunction does not affect plasma concentrations of the drug. There is no need to adjust the regimen in patients with impaired renal function; however, caution should be exercised when prescribing the drug in patients with severe renal impairment (see “Caution” and “Cautions”).

Hepatic impairment

Patients with hepatic impairment may have elevated plasma concentrations of felodipine; therefore a dose of 25 mg is usually sufficient (see section “Pharmacokinetics”).

Children

The experience with felodipine in children under 18 years of age is limited.

Interaction

Felodipine is a substrate for CYP3A4 isoenzyme. Drugs that induce or inhibit CYP3A4 isoenzyme have a significant effect on the plasma concentration of felodipine.

The drugs inducing cytochrome P450 isoenzyme system: phenytoin carbamazepine phenobarbital and rifampicin and preparations of St. John’s Wort increase felodipine metabolism through induction of cytochrome P450 isoenzyme system.

The co-administration of phenytoin carbamazepine phenobarbital and rifampicin decreases the area under the curve “concentration-time” (AUC) by 93% and maximum concentration (Cmax) of felodipine by 82%. Co-administration with CYP3A4 isoenzyme inducers should be avoided.

Drugs that inhibit the cytochrome P450 isoenzyme system: azole antifungal drugs (itraconazole ketoconazole) macrolide antibiotics (such as erythromycin) and HIV protease inhibitors are CYP3A4 inhibitors.

The co-administration of itraconazole increases Cmax of felodipine by 8 times AUC by 6 times.

When erythromycin is coadministered, the Cmax and AUC of felodipine is increased approximately 25-fold.

The co-administration of felodipine and CYP3A4 isoenzyme inhibitors should be avoided.

Grapefruit juice inhibits the CYP3A4 isoenzyme. Use of felodipine with grapefruit juice increases Cmax and AUC of felodipine by approximately 2-fold. Simultaneous use should be avoided.

Tacrolimus: Felodipine may cause increased plasma concentrations of tacrolimus. Concomitant use recommends monitoring serum tacrolimus concentrations may require tacrolimus dose adjustment.

Cyclosporine: When co-administration of cyclosporine and felodipine the Cmax of felodipine is increased by 150% AUC is increased by 60%. However, the effect of felodipine on the pharmacokinetic parameters of cyclosporine is minimal.

Cimetidine: co-administration of cimetidine and felodipine results in a 55% increase in Cmax and AUC of felodipine.

Special Instructions

Particular caution is required in the following conditions: aortic stenosis hepatic impairment severe renal failure (creatinine clearance less than 30 ml/min) heart failure after acute myocardial infarction arterial hypotension which may cause myocardial ischemia in predisposed patients.

The efficacy and safety of felodipine in the treatment of hypertensive crises have not been well studied.

Felodipine may cause a significant decrease in blood pressure with subsequent development of tachycardia. This may lead to myocardial ischemia in predisposed patients.

The co-administration of drugs inducing CYP3A4 isoenzyme leads to a significant decrease in plasma concentrations of felodipine and insufficient therapeutic effect of the drug (see section “Interaction with other medicinal products”). Co-prescribing of these drugs should be avoided.

The concomitant use of CYP3A4 inhibitors leads to a significant increase in plasma concentrations of felodipine, and therefore such combinations should be avoided. Administration of the drug with grapefruit juice should be avoided because of a significant increase in plasma concentrations of felodipine.

Felodipine is metabolized in the liver; therefore, in patients with impaired liver function, increased plasma concentrations of felodipine may be observed. Therefore, felodipine should be used with caution in patients with hepatic impairment.

Influence on driving and operating ability:

When driving vehicles or operating other mechanisms requiring increased attention, the possibility of dizziness and weakness with the drug should be taken into account. At the beginning of therapy or during the period of increasing the dose patients should refrain from potentially hazardous activities requiring concentration and quick psychomotor reactions.

Contraindications

– Hypersensitivity to felodipine or other components of the drug.

– Heart failure in decompensation stage.

– Acute myocardial infarction.

– Unstable angina pectoris.

– Hemodynamically significant stenosis of heart valves.

– Hypertrophic obstructive cardiomyopathy.

– Age less than 18 years (efficacy and safety not established).

– Lactose intolerance lactase deficiency glucose-galactose malabsorption.

– Pregnancy Breast-feeding period (see section “Use in pregnancy and breast-feeding”).

With caution:

Aortic stenosis mitral stenosis blood pressure lability hepatic function impairment severe renal failure (creatinine clearance less than 30 ml/min) heart failure after acute myocardial infarction elderly age arterial hypotension (in predisposed patients may cause myocardial ischemia) simultaneous use with inhibitors or inducers of CYP3A4 isoenzyme.

Side effects

The most common adverse effects of felodipine include a dose-dependent effect: mild to moderate ankle edema due to the vasodilatory properties of felodipine, for which reason approximately 2% of patients refuse to take the drug.

In the beginning of therapy or when increasing the dose, reddening of the face with “hot flashes” headache, palpitations, dizziness and weakness may occur. These reactions are usually temporary and go away on their own.

There have been isolated reports of sleep disturbances; however, the association with felodipine intake has not been established. There have been reported cases of mucosal hyperplasia of the tongue and gums after felodipine administration in patients with severe gingivitis/parodontitis. Careful oral hygiene is recommended to avoid this side effect or to reduce its manifestation.

Hyperglycemia is thought to occur with the DMARD group, but with felodipine only in isolated cases.

The undesired effects are listed below according to organ and system damage and frequency of occurrence.

The frequency of occurrence is defined as follows: frequently (≥1/100); infrequently (≥1/1000 <1/100); rarely (≥1/10000 <1/1000); very rarely (<1/10000).

Impotence/sexual dysfunction

The following side effects have not been found to be causally related to the ingestion of the drug:

Blood and lymphatic system disorders: anemia;

Mental disorders: depression insomnia anxiety disorders nervousness drowsiness irritability;

Visual disturbances: visual disturbances;

Heart disturbances: myocardial infarction angina pectoris arrhythmia;

Vascular disorders: arterial hypotension syncope;

Thoracic and mediastinal respiratory disorders:pharyngitis dyspnea bronchitis flu sinusitis nasal bleeding;

Gastrointestinal disorders: diarrhea dry mouth flatulence;

Skin and subcutaneous tissue disorders: erythema bruising leukocytoclastic vasculitis;

Musculoskeletal and connective tissue disorders: arthralgia back pain muscular pain myalgia pain in the upper and lower extremities;

Renal and urinary tract disorders: polyuria dysuria;

Genital and mammary disorders: gynecomastia;

General disorders and disorders at the site of administration: chest pain facial swelling flu-like syndrome.

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 patient caused mild to moderate intoxication.

Perhaps felodipine has a more significant effect on the peripheral circulation than on the heart compared with other drugs in this therapeutic group.

Symptoms

In overdose, symptoms of intoxication occur 12-16 hours after taking the drug severe symptoms may occur even several days after taking. The following symptoms may be noted: bradycardia (sometimes tachycardia) marked decrease in BP atrioventricular (AV) block of degree I-III ventricular extrasystole atrial-ventricular dissociation asystole ventricular fibrillation; headache dizziness impaired consciousness (or coma) seizures; dyspnea pulmonary edema (not cardiogenic) and apnea; in adults may develop respiratory distress syndrome; acidosis hypokalemia hyperglycemia possibly hypocalcemia; flushed face accompanied by “tides” hypothermia; nausea and vomiting. In case of overdose, the greatest risk is associated with cardiovascular symptoms.

Treatment

The administration of activated charcoal, if necessary, gastric lavage in some cases is effective even in the late stage of intoxication. A specific antidote is calcium preparations.

It is important!

Atropine (025-05 mg w/v for adults 10-20 mcg/kg for children) should be given before gastric lavage (because of the risk of stimulating the vagus nerve).

EKG monitoring.

If necessary, ensure airway patency and adequate ventilation of the lungs.

The correction of acid-base status and serum electrolytes is indicated.

In case of bradycardia and AV blockade, atropine 05-1 mg IV in adults (20-50 mcg/kg in children) is administered repeatedly if necessary, or isoprenaline 005-01 mcg/kg/min is initially administered.

In early acute intoxication, an artificial pacemaker may be necessary.

A marked decrease in BP is corrected by intravenous infusion of fluids adults intravenously administer calcium gluconate solution (9 mg Ca/ml) 20-30 ml for 5 minutes or as an infusion (3-5 mg Ca/kg children) if necessary, repeat the administration in the same dose. If necessary, epinephrine (adrenaline) or dopamine are administered by infusion.

In case of cardiac arrest due to overdose, resuscitation measures may be needed for several hours.

Diazepam is indicated for seizures.

Another symptomatic treatment is given.

Pregnancy use

There are currently insufficient data on the use of felodipine in pregnant women. Based on data obtained in animals on fetal impairment, felodipine should not be prescribed during pregnancy. Slow calcium channel blockers may inhibit uterine contractions in preterm labor, but there is insufficient evidence to increase the duration of physiological labor. There is a possible risk of fetal hypoxia in the presence of maternal arterial hypotension and decreased perfusion in the uterus due to redistribution of blood flow and peripheral vasodilation.

Felodipine penetrates into breast milk. When felodipine is taken by a nursing mother in therapeutic doses, only a small amount of the drug reaches the baby with the breast milk. Insufficient experience of using felodipine in women during lactation does not exclude the risk of the drug affecting breastfed children, therefore, it is not recommended to prescribe felodipine to women during lactation. If continuation of therapy is necessary to achieve a clinical effect, discontinuation of breastfeeding should be considered.

Similarities

Felodipine, Plendil, Felodip