Финоптин®

General characteristics. Structure:

Active ingredient: 40,0 mg or 80,0 mg of verapamil of a hydrochloride.

Excipients: lactoses monohydrate, cellulose microcrystallic, gelatin, silicon colloid anhydrous, magnesium stearate, gipromeloza of 5-6 cPs, sucrose, titanium dioxide, polysorbate 80, глицерол 85%.

Verapamil has antiarrhytmic, anti-anginal and hypotensive activity. Causes expansion of coronary arteries, increase in a coronary blood-groove. Verapamil reduces the need of a myocardium for oxygen due to reduction of the heart rate (HR) and decrease in contractility of a myocardium, practically without exerting impact on the minute volume of heart.

Pharmacological properties:

Pharmacodynamics. Verapamil (verapamil a hydrochloride) is an antagonist of calcium or a blocker of slow calcium channels, belongs to antiarrhytmic drugs IV of a class. Pharmacological effect of verapamil is based generally on regulation of receipt of calcium ions through cellular membranes of walls of blood vessels and cells of a myocardium.

Verapamil the hydrochloride is a derivative of a fenilalkilamin. Tablets of verapamil contain the ratsemizirovanny mix L-and D-forms; as the blocker of calcium channels L-isomer is at 10-18 times stronger, than D-isomer.

The main physiological effect of verapamil is oppression of receipt of calcium ions through cellular membranes of cells of a myocardium and smooth muscle cells of walls of blood vessels, without decrease in concentration of calcium in blood serum. At vasospastic stenocardia relaxation of coronary arteries and oppression of development of a coronary spasm improves myocardial perfusion and delivery of oxygen to heart. Expansion of peripheral arteries reduces the general peripheric resistance, system arterial pressure and resistance to emission of a left ventricle (afterload) that in general reduces tension of myocardial walls and reduces oxygen requirements of a myocardium. By decrease in intracellular concentration of calcium in myocardium cells verapamil reduces contractility of a myocardium (a negative inotropic effect), and also expands coronary and peripheral arteries. Verapamil extends the refractory period which slows down atrioventricular conductivity. The antegrade refractory period of additional ways of carrying out can decrease. Verapamil can extend PQ interval on the electrocardiogram that, generally correlates with concentration of verapamil in plasma (especially in an initiation of treatment). Verapamil practically does not exert impact on duration of intervals of QRS or QT.

Pharmacokinetics. After reception of a single dose of the tableted form about 90% of verapamil of a hydrochloride quickly are soaked up in digestive tract. As result of extensive metabolism (by means of CYP3A4 enzyme) at the first passing through a liver, nevertheless system bioavailability is low - 10-20% of a single dose. At prolonged use relative bioavailability increases to 20-35%. Dysfunction of a liver can increase considerably bioavailability of verapamil at oral administration. The peak of concentration in a blood plasma generally is registered in 1-2 hours (a tablet of verapamil of 80 mg). Interindividual concentration in a blood plasma considerably vary.

Verapamil is widely distributed in various parts of an organism; the average volume of distribution makes 4-7 l/kg. Verapamil comes to cerebrospinal fluid and breast milk, and also gets through a placenta. At people of 90% of verapamil it is connected with proteins of plasma.

Verapamil is actively metabolized by a liver (by means of CYP3A4 enzyme), generally through N-dealkylation and O-demethylation. The main metabolite is norverapamit, the having concentration level in plasma exceeding concentration of verapamil. After administration of drug for 5 days of 70% of verapamil it is allocated from mochy and 16% with excrements. Less than 4% are excreted in not changed look. The elimination half-life fluctuates from 2 to 8 hours after oral administration of a single dose. After repeated reception the elimination half-life is extended till 4,5-12 o'clock.

Action of tablets of verapamil averages 8-10 hours.

The verapamil Bodostupnost at women is higher, than at men.

At diseases of a liver there is an increase in bioavailability of peroral verapamil, volume of distribution and an elimination half-life, decrease in level of hepatic transaminases and clearance.

Patients with diseases of kidneys have changes of kinetics, generally are absent. The hemodialysis, haemo filtering and peritoneal dialysis do not influence verapamil elimination therefore there is no need to increase a verapamil dose in day of the procedure.

Indications to use:

Prevention of attacks of stenocardia (tension, unstable, vasospastic – Printsmetal's stenocardia, alternative stenocardia).

Prevention and therapy of the supraventricular tachycardias including blinking and fibrillation of auricles.

Arterial hypertension.

Secondary prevention of stenocardia after the postponed acute myocardial infarction.

Route of administration and doses:

Stenocardia or arterial hypertension. The initial dose for adults makes 40-80 mg 3 or 4 times a day. The dose can be increased weekly (at unstable stenocardia – daily) before achievement of desirable clinical effect. Usually day maintenance dose for adults fluctuates between 240 mg and 480 mg in 3-4 receptions (stenocardia) or for 2-3 receptions (arterial hypertension).

Arrhythmias. At preventive treatment of returnable Bouveret's supraventricular disease usually initial dose for adults and teenagers makes 240-480 mg a day for 3-4 receptions. For control of frequency of reductions of ventricles at chronic trembling or atrial fibrillation usually day dose for adults makes 240-320 mg for 3-4 receptions. The maximum antiarrhytmic action is usually observed within 48 hours from the beginning of therapy in the given dosages.

Secondary prevention of a myocardial infarction. Treatment has to be begun as soon as possible, in 7-14 days after a heart attack. The usual dose for adults makes 120 mg 3 times a day.

At long reception of verapamil its bioavailability, as a rule, increases. Therefore, correction of a dosage after 2-3 weeks of therapy by verapamil can be necessary.

Children. The usual day dose for children till 1 year makes 4-10 mg/kg of body weight, given in 2 or 3 receptions. For children from 1 to 14 years the usual day dose makes body weight mg/kg ZB in 2 or 3 receptions.

Elderly people. Elderly people can be more sensitive to effect of verapamil at reception of a usual adult dose. Therefore, there can be necessary a reduction of a dosage. This phenomenon is expressed to a thicket at women, than at men.

Renal failure. Dose adjustment generally is not necessary at a renal failure.

Liver failure. At a liver failure the dosage has to be reduced; at the expressed insufficiency - to 1/5 from a usual adult dose.

Features of use:

Verapamil can cause a symptomless atrioventricular block of 1 degree and tranzitorny bradycardia which are sometimes combined with the escaping nodal rhythm.

Patients with a hypertrophic cardiomyopathy are subject to high risk of adverse cardial effects.

The risk of side cardial effects increases at the patients who are at the same time accepting beta-blockers.

In case of heart failure or disturbances of conductivity during treatment by verapamil the dose of drug needs to be reduced or to stop its reception, if necessary it is necessary to begin the corresponding therapy.

Special attention has to be paid to use of verapamil at treatment of newborns and children of the first year of life because they can be more sensitive to the disturbances of a rhythm induced by verapamil.

At elderly people elimination of verapamil is slowed down and the elimination half-life is extended.

The dose of verapamil has to decrease for patients with liver diseases. During treatment by verapamil with certain intervals function of a liver has to be controlled.

Patients with a renal failure have to be observed carefully in spite of the fact that generally change of a dose for them is not necessary. Therapy by verapamil continues during dialysis.

There can be necessary a reduction of a dose of verapamil for patients with reduced neuromuscular conductivity (for example with Myasthenia gravis, with Lambert-Eaton's syndrome, with muscular dystrophy of Dyushen, when using muscle relaxants during an anesthesia).

Blockers of calcium channels can reduce fertility at men that has to be taken into account if infertility is diagnosed for the man accepting blockers of calcium channels inexplicable by other reasons. This action is completely reversible after cancellation of drugs.

At certain patients at alcohol intake (ethanol) during treatment by verapamil removal of alcohol from an organism can decrease.

The patients receiving therapy by verapamil have to abstain from the use of grapefruit juice.

Verapamil gets through a placenta and can be found in blood of an umbilical vein after the delivery. Verapamil was used at prevention of premature births, however was not reported neither about a prolonigirovaniye of childbirth, nor about increase in need for obstetric interventions. Nevertheless there are no comparative researches concerning safety of use of verapamil during pregnancy and childbirth therefore veralamit has to be used only in some cases when the expected advantages of therapy exceed potential harm for a fruit; with extra care – in the I trimester of pregnancy.

Verapamil is excreted with breast milk, concentration can make 60% in relation to contents in a blood plasma of mother. Exposure of the child – is less than 0,01% of a maternal dose, and the probability of development of side effects is improbable. It was reported about cases of the hypersensitivity reactions caused by verapamil in breast milk.

Influence on reaction when driving motor transport and control of cars. Depending on individual sensitivity verapamil can worsen ability to drive автомобіль and to manage mechanisms, especially in an initiation of treatment. During therapy by verapamil the alcohol kontsetration in blood can be higher, than usually, and influence of a drunkenness – long.

Side effects:

The majority adverse effects of verapamil occur owing to its vazodilatiruyushchy and negative chronotropic effects.

Locks approximately at 10-35% of the patients receiving tablets are possible. Others (connected with a vazodilatation) side reactions include a headache, an erythema, dizziness, puffiness of shins; the hyperplasia of gums can be observed at prolonged use. Heavier reactions which are often demanding decrease in a therapeutic dose or the termination of therapy include bradycardia, hypotension, chronic heart failure, an atrioventricular block and even an asystolia. These side reactions are in most cases observed at patients with a left ventricular failure, disturbances of atrioventricular conductivity or at a concomitant use of beta-blockers.

From cardiovascular system: bradycardia (less than 50 уд. / mines), the expressed decrease in the ABP, development or aggravation of heart failure, tachycardia; seldom - stenocardia, up to development of a myocardial infarction (especially at patients with crushing obstructive defeat of coronary arteries), arrhythmia (including blinking and trembling of ventricles); at bystry in introduction - AV blockade of the III degree, an asystolia, a collapse.

From TsNS and peripheral nervous system: dizziness, a headache, a faint, uneasiness, block, increased fatigue, an adynamy, drowsiness, a depression, extrapyramidal disturbances (the ataxy, a mask-like face shuffling gait, rigidity of hands or legs, trembling of brushes and fingers of hands, swallowing difficulty).

From the alimentary system: nausea, a lock (it is rare - diarrhea), a hyperplasia of gums (bleeding, morbidity, puffiness), increase in appetite, increase in activity of hepatic transaminases and ShchF.

Allergic reactions: skin itch, skin rash, dermahemia of the person, mnogoformny exudative erythema (including Stephens-Johnson's syndrome).

Others: increase in body weight, is very rare - an agranulocytosis, a gynecomastia, a giperprolaktinemiya, a galactorrhoea, arthritis, tranzitorny loss of sight against the background of the maximum concentration in plasma (at in introduction), a fluid lungs, thrombocytopenia asymptomatic, peripheral hypostases.

Interaction with other medicines:

Verapamil possesses some types of pharmakodinamichesky and pharmacokinetic interactions. Verapamil is metabolized by means of CYP3A4 enzyme which it also inhibits. Verapamil is also P-glycoprotein inhibitor.

Verapamil of a pharmakodinamicheska interacts with antiarrhytmic drugs, such as Amiodaronum, Disopyramidum, дофетилид, квинидин, beta-blockers (see below); with anti-hypertensive drugs, such as a clonidine and Prazozinum; simultaneous use can increase risk of heart failure, disturbance of AV conductivity and the expressed hypotension.

Verapamil inhibits metabolism of a dofetilid and kvenidin, and also can inhibit metabolism of Amiodaronum and Disopyramidum. At combined use with difetilidy increase in an interval of QT was observed. At use of verapamil with quinidine hypotension and a fluid lungs at patients with a hypertrophic subaortic stenosis can develop.

Verapamil decreases clearance of an atenolol at the patients inclined to bradycardia. Levels of a metoprolol and verapamil increase at combined use. A smaller measure verapamil inhibits propranolol metabolism. Additional inspection is shown to the patients using eye drops of Timololum.

To patients who accept verapamil contraindicated purpose of intravenous beta-blockers.

Impact of verapamil on other blockers of calcium ions was not investigated. Verapamil exerts pharmacokinetic impact on drugs which metabolism happens by means of CYP3A4 enzyme (such as diltiazem, амлодипин, фелодипин, нилвадипин, нимодипин, nifedipine, низолдипин, нитрендипин and other representatives of antagonists of calcium).

Verapamil can increase concentration in digoxin plasma (by 70%), therefore, at a concomitant use the dose of digoxin needs to be reduced twice. Also at joint reception bioavailability of a digitoskin (by 25-35%) and QT interval increases.

Salts of calcium suppress pharmakodinamichesky effects of verapamil.

Verapamil can exert toxic impact at joint reception with tseftriaksony and clindamycin. Klaritromitsin and erythromycin can also promote increase in toxicity of verapamil, inhibiting his metabolism. Rifampicin exerts the expressed impact on metabolism of peroral.

Verapamil inhibits carbamazepine metabolism, the neurotoxic effect was also noted at their combined use. Phenobarbital and Phenytoinum increases verapamil metabolism. Increase in toxicity of Phenytoinum when sharing was noted. Verapamil and Phenytoinum can cause a hyperplasia of gums.

Influence of verapamil on concentration in plasma of lithium varies, however simultaneous use can raise a neurotoxicity of drugs of lithium.

Verapamil increases (by 15%) bioavailability of an imipramine. Pharmakodinamichesky interactions of verapamil with fluoxetine (CYP3A4 inhibitor) and other antidepressants (CYP3A4 substrates, nefazodony, sertindoly, sertraline and venlafaksiny) were not investigated, however patients have to be inspected different rather possible development of side reactions.

Ketokonazol inhibits metabolism of verapamil and increases its bioavailability. Impact of a flukonazol and itrakonazol on metabolism of verapamil was not investigated, however it is not excluded.

Verapamil increases system exposure of some antineoplastic drugs including adriamycin (doxorubicine) paklitakset, Tamoxifenum, and, perhaps, also cyclophosphamide and торемифен. Verapamil also increases system exposure of cyclosporine. Verapamil with cyclosporine can cause a hyperplasia of gums.

Use of verapamil can strengthen antitrombotichesky effect of acetylsalicylic acid, a tokd as acetylsalicylic acid can reduce hypotensive effect of verapamil.

Verapamil increases bioavailability of midazolam, a triazolam and buspiron and in an essential measure exponentiates their effect. Similar interaction will probably be observed with alprazoly and zolpidemy.

Cimetidinum inhibits verapamil elimination.

The research of influence of verapamil on metabolism of glucocorticoids which metabolism is connected with CYP3A4 enzyme on was conducted, however the possibility of metabolichsky interaction is not excluded.

Influence of verapamil on HIV inhibitors of protease and inhibitors of the return transcriptase of not nucleoside it was not investigated, however the possibility of pharmacokinetic interaction is not excluded.

The negative inotropic and hypotensive effect can be exponentiated when using inhalation anesthetics (such as halothane, потентиат). Simultaneous intravenous use of a dantrolen and verapamil can lead to a hyperpotassemia and serious oppression of circulation.

Verapamil inhibits metabolism of HMG-CoA-inhibitors of reductase ("statines"). At combined use bioavailability of a simvastatin increases by 6,2 times and peak concentration in a blood plasma – by 3,4 times. Similar interaction can be observed at joint reception with atrovastatiny and lovastatiny and it is improbable – with fluvastatiny, rosuvastatiny and pravastatiny.

Combined use of a tsisaprid with verapamil increases QT interval.
Verapamil reduces clearance and increases a theophylline elimination half-life by 20-30%.

Seldenafil has to be appointed with care at therapy by verapamil which can promote development of arrhythmias and hypotonia.

Sulfinpyrazonum strengthens elimination and antithrombocytic effect of verapamil.

Infusion of sodium of a dantrolen at therapy by verapamil can cause hypotension and gastric tachycardia.

Parallel use of alcohol and verapamil mutually exponentiates effect of each other. Verapamil also inhibits alcohol elimination.
Grapefruit juice on 1/3 increases bioavailability of verapamil.

Contraindications:

Hypersensitivity to verapamil to a hydrochloride or any other excipients of drug.

The expressed left ventricular failure (pressure of jamming of a pulmonary artery> of 20 mm hg or fraction of emission of a left ventricle <20-30%).

The expressed hypotension (systolic pressure <90 mm hg). Cardiogenic shock.

Noncompensated heart failure.

The complicated acute myocardial infarction.

Atrioventricular block of II or III degrees (without the functioning pacemaker).

Sick sinus syndrome (if the patient has no functioning artificial pacemaker).

Trembling or atrial fibrillation in combination with the additional carrying-out highway (for example, a WPW-syndrome or a syndrome of Launa-Ganonga-Levine).

Intoxication digitalis derivatives.

Overdose:

The overdose of verapamil is dangerous and can even become menacing for life. The clinical effect is generally observed in 30-60 minutes after oral administration of a dose, at 5-10 times pervyshayushchy therapeutic. Action of overdose of drug on the central nervous system results in instability, confusion of consciousness, spasms; circulator collapse and coma. There can be nausea, vomiting, a metabolic acidosis and a secondary hyperglycemia. The most typical cardiovascular signs are hypotension, bradycardia, an atrioventricular block, the nodal escaping rhythm, the asystolia is possible.

Preventive actions and absorption. At overdose absorbent carbon can be applied. Contents of a stomach need to be evacuated by washing. In case of reception of a large number of tablets of verapamil the enteroclysis (lavage) has to be made.

Specific actions. Treatment of circulator disturbances – symptomatic and supporting; intravenous 10-20 ml of 10% of administration of calcium of a gluconate (2,25-4,5 mmol) at the level of 5 mmol/h can be used. At existence of an atrioventricular block of the II-III degree, bradycardia or an asystolia administration of atropine, an izoprenalin or ortsiprenolin is shown, monitoring of cordial function is also recommended. In case of development of hypotension introduction of a dopamine, Dobutaminum or noradrenaline is possible. At existence of symptoms of heart failure continuation of introduction of a dopamine, Dobutaminum and/or calcium of a gluconate is recommended.

Storage conditions:

To store at the room temperature (15–25 °C) in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

30 or 100 tablets in a bottle, in a cardboard box.