Felodipine

Pharmacological properties

felodip is a vasoselective calcium channel blocker with a predominant effect on blood vessels similar to dihydropyridine, which reduces hell by lowering peripheral vascular resistance. in therapeutic doses, felodipine selectively affects the smooth muscles of arterioles, does not directly affect myocardial contractility and the cardiac conduction system. the drug does not affect smooth muscle veins and adrenergic vasomotor mechanisms, and, accordingly, taking felodipine does not cause symptoms of orthostatic hypotension. felodip has a slight natriuretic and diuretic effect, and accordingly, there is no fluid retention in the body.

Felodip is effective in various degrees of hypertension. It can be used as monotherapy or in combination with other antihypertensive drugs, for example: β-adrenergic receptor blockers, diuretics or ACE inhibitors to increase the antihypertensive effect. Felodip reduces systolic and diastolic blood pressure and can be prescribed in case of isolated systolic hypertension. Felodip retains its antihypertensive efficacy also in combination with NSAIDs.

Felodip has an antianginal and anti-ischemic effect due to the effect on the balance between consumption and oxygen saturation of the myocardium. Felodip reduces vascular resistance of coronary vessels. Blood flow through the coronary vessels and oxygen saturation of the myocardium increases due to the dilatation of the epicardial arteries and arterioles. Felodip effectively prevents the formation and development of coronary spasm. Decreased systemic blood pressure reduces afterload on the left ventricle and myocardial oxygen demand.

Felodip improves exercise tolerance and reduces the incidence of seizures in patients with stable exertional angina. Felodip reduces the frequency of symptomatic and latent forms of coronary heart disease in patients with a vasospastic form of angina pectoris.

Felodip is an effective drug that is well tolerated by adult patients, regardless of age, race, as well as by persons with concomitant diseases such as congestive heart failure, AD and other obstructive pulmonary diseases, renal failure, diabetes mellitus, gout, hyperlipidemia, Raynauds phenomenon, as well as patients after kidney transplantation. Felodip does not affect glycemia and lipid profile.

Mechanism of action. The main pharmacodynamic feature of felodipine is high vascular selectivity. Myogenically active smooth muscles of resistant arterioles are especially sensitive to the action of felodipine. Felodipine inhibits the electrical and contractile activity of vascular smooth muscle by acting on calcium channels in the cell membrane.

Hemodynamic effects. The primary hemodynamic effect of felodipine is to lower the OPSS, which leads to a decrease in blood pressure. This effect is dose dependent. In general, a decrease in blood pressure is observed 2 hours after a single dose and lasts at least 24 hours, and the T / P ratio (trough / peak - the ratio of the final and peak effect) reaches values ​​significantly higher than 50%. There is a positive correlation between the concentration of the drug in plasma, the level of decrease in peripheral vascular resistance and a decrease in blood pressure.

Effect on heart function. In therapeutic doses, felodipine does not affect cardiac contractility, AV conduction, and the refractory period of the AV node. Felodipine positively affects the function of the left ventricle, as evidenced by measurements of the ejection fraction and systolic volume in patients with heart failure. Reception of felodipine is not associated with neurohumoral activation. Felodipine probably does not affect patients lifespan.In patients with hypertension or angina pectoris, felodipine may be used in case of left ventricular dysfunction. Antihypertensive therapy with felodipine is associated with significant regression of existing left ventricular hypertrophy.

Effect on renal function. Felodipine has a slight natriuretic and diuretic effect, since it reduces tubular reabsorption of sodium. The delay of sodium and fluid in the body is noted in the case of taking other vasoconstrictor drugs. Felodipine does not affect the daily excretion of potassium or albumin. Renal vascular resistance decreases after taking felodipine. The normal glomerular filtration rate (GFR) does not change. In patients with impaired renal function, GFR may increase during treatment with felodipine.

In patients taking cyclosporine after kidney transplantation, felodipine lowers blood pressure, improves blood flow in the kidneys and GFR. Felodipine may improve transplant function in the early stages after transplantation.

An effective reduction in blood pressure is especially beneficial for patients with diabetes mellitus.

Pharmacokinetics Suction and distribution. Felodip is completely absorbed in the digestive tract after oral administration of the modified-release tablet. Bioavailability is about 15% in humans and does not depend on the dose taken during the entire therapeutic interval. 99% of felodipine binds to plasma proteins, mainly with albumin. Due to the characteristics of the dosage form, the modified release of felodipine prolongs the absorption phase and ensures its uniform concentration in the blood plasma for 24 hours.

Metabolism and excretion. Felodip is mainly metabolized in the liver, all of its metabolites are inactive. T_½ felodipine is 24 hours. With prolonged use, the accumulation of the active substance does not occur.

In elderly patients and patients with impaired liver function, the concentration of felodipine in blood plasma is higher than in patients of a young age. The pharmacokinetics of felodipine does not change in patients with impaired renal function, including those on hemodialysis. About 70% of the dose is excreted in the urine, and 30% with feces in the form of metabolites. In unchanged form, less than 0.5% of the dose is excreted in the urine.

Indications

Essential Ag. preventive treatment of chronic stable angina pectoris.

Application

Ag adults (including elderly patients): the dosage regimen is determined individually.

Therapy begins with a dose of 5 mg once a day. If necessary, the dose can be reduced to 2.5 mg or increased, or add another antihypertensive drug. As a rule, the maintenance dose is 5–10 mg once a day.

Angina pectoris. The dosage regimen is always determined individually.

Therapy begins with a dose of 5 mg 1 time per day. If necessary, this dose can be increased to 10 mg once a day. The maximum dose is 20 mg / day.

In patients with impaired renal function, changes in pharmacokinetics are insignificant, therefore, dose adjustment is not required.

In patients with hypertension and angina pectoris with severe impaired liver function, the therapeutic dose of felodipine should be reduced (recommended dose is 2.5 mg / day).

For the elderly, an initial dose of 2.5 mg once daily may be sufficient.

Method of application: the drug is taken in the morning, before meals or after a light breakfast. The tablets are not chewed, divided and crushed. The tablets must be swallowed whole and washed down with water.

Contraindications

• An allergic reaction to felodipine and other dihydropyridines (theoretical risk of developing cross-reactivity) or to other components of the drug; decompensated heart failure; unstable angina pectoris; acute myocardial infarction; dynamic obstruction of the outflow tract of the left ventricle. clinically significant aortic stenosis.

Side effects

Like other calcium channel blockers, the drug can cause facial flushing, headache, palpitations, dizziness, and fatigue. these reactions are temporary and often occur at the beginning of treatment and / or with an increase in dose. edema in the ankles, which are the result of precapillary vasodilation, and not a tendency to retain fluid in the body, can also occur, depending on the dose. in patients with gum disease or periodontitis, a gum abscess may occur. this can be avoided by observing oral hygiene. as with the use of other dihydropyridines, in rare cases, there was a deterioration in the manifestations of angina pectoris, mainly at the beginning of treatment.

The following side effects have been reported in clinical trials and in the post-registration period of drug monitoring.

From the side of the immune system: hypersensitivity reactions (urticaria and angioedema).

From the nervous system: headache, sleep disturbance, drowsiness, dizziness, paresthesia, anxiety, irritability, confusion, depression.

From the respiratory system: shortness of breath, nosebleeds.

From the cardiovascular system: increased manifestations of angina pectoris (especially at the beginning of treatment), mainly in patients with symptomatic coronary heart disease, syncope, sensation of increased heart rate, tachycardia, myocardial infarction. Peripheral edema (the degree of edema in the ankles depends on the dose), arterial hypotension, leukocytoclastic vasculitis.

From the reproductive system: sexual dysfunction.

From the urinary system: frequent urination.

From the digestive system: nausea, gingivitis, gingival hyperplasia, abdominal pain, vomiting, periodontitis, diarrhea, constipation, dry mouth.

On the part of the liver and gall bladder function: increased levels of liver enzymes, cholestatic hepatitis.

On the part of the skin and subcutaneous tissue: hyperemia, hot flashes (especially at the beginning of treatment when a high dose is increased or administered), rash, itching, photosensitivity, angioedema, erythema multiforme, erythema nodosum.

From the musculoskeletal system and connective tissue: arthralgia, myalgia, tremor.

Systemic disorders and local reactions: fatigue, fever.

special instructions

As with other vasodilators, the felodip preparation can rarely cause severe hypotension with tachycardia, which in sensitive patients can lead to myocardial ischemia.

The efficacy and safety of felodipine in the treatment of malignant hypertension has not been studied.

Felodipine is used with caution in patients with severe left ventricular dysfunction.

Grapefruit juice increases peak plasma concentrations and the bioavailability of the drug, possibly due to interactions with flavonoids in fruit juice.

The drug contains lactose, therefore, patients with rare hereditary forms of galactose intolerance, lactase deficiency or with malabsorption of glucose-galactose should not use this drug.

During pregnancy and breastfeeding. Felodipine is contraindicated in pregnancy.

Felodipine can pass into breast milk, but it is not known whether it has a negative effect on newborns. However, due to limited safety data on the use of the drug in breast-fed infants, Felodipine should not be used during breast-feeding.

Children. The drug is not prescribed for children.

Interactions

The simultaneous use of substances interacting with the cytochrome p450 3a4 enzyme system can affect plasma felodipine levels.

Enzyme inhibitors, such as cimetidine, ranitidine, erythromycin, itraconazole, ketoconazole, ritonavir, saquinavir and quinidine, increase the concentration of felodipine in blood plasma, so it may be necessary to reduce its dose when used simultaneously with these drugs.

Enzyme inducers, such as phenytoin, carbamazepine, rifampicin, barbiturates, and St. Johns wort (hypericum perforatum), can lower the concentration of felodipine in blood plasma, so you may need to use doses higher than recommended for patients taking this drug.

Felodipine may increase tacrolimus concentration. In the case of the simultaneous use of felodipine and tacrolimus, it is necessary to control the concentration of tacrolimus in the blood plasma and adjust the dose accordingly.

Grapefruit juice increases the level of felodipine in blood plasma, as well as its bioavailability due to the presence of flavonoids in it, so it can not be used simultaneously with felodipine.

Antihypertensive drugs prolong the hypotensive effect of felodipine.

Sympathomimetics reduce the effect of felodipine.

Dose adjustment is not required with the simultaneous use of felodipine with digoxin.

Felodipine does not affect the fraction of free fractions of other drugs that are characterized by significant binding to plasma proteins, such as warfarin.

Overdose

May cause excessive peripheral vasodilation with severe arterial hypotension, which can sometimes be accompanied by bradycardia.

Treatment. In severe arterial hypotension, symptomatic treatment is indicated. The patient should be given a horizontal position with legs raised up. With bradycardia, atropine 0.5–1 mg is administered. If this is not enough, it is necessary to replenish the bcc by infusion, for example, dextrose, 0.9% sodium chloride solution, polyglucin. Sympathomimetics may be prescribed with a predominant effect on α₁-adrenoreceptors.

Storage conditions

At a temperature not exceeding 25 ° c.