Verapamil

General characteristics. Structure:

One tablet of 40 mg, film coated, contains Active agent of verapamil of a hydrochloride 40 mg.

Excipients: a kernel — sugar milk (lactose) — 41,3 mg, potato starch — 5 mg, povidone (коллидон 25) — 2,5 mg, microcrystallic cellulose — 10 mg, calcium stearate — 0,6 mg, talc — 0,6 mg; a cover — a gipromelloz (gidroksipropilmetiltsellyuloz) — 1,8 mg, polysorbate (twin-80) — 0,35 mg, titanium dioxide — 0,8 mg, talc — 0,05 mg.

One tablet of 80 mg, film coated, contains Active agent of verapamil of a hydrochloride 80 mg.

Excipients: a kernel — sugar milk (lactose) — 82,6 mg, potato starch — 10 mg, povidone (коллидон 25) — 5 mg, microcrystallic cellulose — 20 mg, calcium stearate — 1,2 mg, talc — 1,2 mg; a cover — a gipromelloz (gidroksipropilmetiltsellyuloz) — 3,6 mg, polysorbate (twin-80) — 0,7 mg, titanium dioxide — 1,6 mg, quinolinic yellow — 0,1 mg.

Pharmacological properties:

Pharmacodynamics. Verapamil is one of the main drugs of group of blockers of "slow" calcium channels. It has antiarrhytmic, anti-anginal and anti-hypertensive activity. Drug reduces the need of a myocardium for oxygen due to decrease in contractility of a myocardium and reduction of heart rate. Causes expansion of coronary vessels of heart and increases a coronary blood stream; reduces a tone of smooth muscles of peripheral arteries and the general peripheric vascular resistance. Verapamil significantly slows down atrioventricular conductivity, automatism of a sinus node oppresses that allows to use drug for treatment of supraventricular arrhythmias. Verapamil is choice drug for treatment of stenocardia of vasospastic genesis (Printsmetal's stenocardia). Renders effect at an angina of exertion.

Pharmacokinetics. At intake more than 90% of the accepted dose are soaked up. Bioavailability — 10-20%. Maksikmalny concentration of drug in a blood plasma is reached in 1-2 hours after intake (80-400 ng/ml). Verapamil gets through hematoencephalic and placental barriers. Is exposed to metabolism at "the first passing" through a liver. The main metabolites are norverapamit, N-dealkilnorverapamil. Accumulation of drug and its metabolites in an organism explains strengthening of action at course treatment. Communication with proteins of a blood plasma — 90%. The elimination half-life at reception of a single dose makes 2,8-7,4 hours; at reception of repeated doses — 4,5-12 hours. Other part — in the form of metabolites (70%) by kidneys, about 25% — with bile is removed in a small amount in not changed look (3-4%). Secretion with breast milk low.

Indications to use:

1. Treatment and prevention of disturbances of a cordial rhythm:
— Bouveret's supraventricular disease;
— tremblings and atrial fibrillations (takhiaritmichesky option);
— supraventricular premature ventricular contraction;
2. Treatment and prevention
— chronic stable stenocardia (angina of exertion);
— unstable stenocardia;
— vasospastic stenocardia (Printsmetal's stenocardia, alternative stenocardia);
3. Treatment of arterial hypertension.

Route of administration and doses:

Verapamil is accepted inside in time or after food, washing down with a small amount of water. The mode of dosing and duration of treatment are established individually depending on a condition of the patient, severity, features of a course of a disease and efficiency of therapy.
For prevention of attacks of stenocardia, arrhythmia and at treatment of arterial hypertension drug is appointed by the adult in an initial dose on 40-80 mg by 3-4 times a day. If necessary increase a single dose to 120-160 mg the Maximum daily dose of drug makes 480 mg At patients with the expressed abnormal liver functions removal of Verapamil from an organism in a slowed-up way therefore it is reasonable to begin treatment with the minimum doses. The daily dose of drug should not exceed 120 mg.

Features of use:

At increase in arterial pressure at patients with a hypertrophic cardiomyopathy appoint alfaadrenostimulyator (Phenylephrinum); it is not necessary to apply изопреналин.
Before therapy at heart failure it is necessary to reach a condition of compensation. At treatment control of function of cardiovascular and respiratory systems, behind the content of glucose and electrolytes of blood, volume of the circulating blood and amount of the emitted urine is necessary.
It is not recommended to stop treatment suddenly.

Side effects:

At use of Verapamil are possible:
- From cardiovascular system: face reddening, the expressed bradycardia, an atrioventricular block, the expressed lowering of arterial pressure, development or aggravation of heart failure, tachycardia is possible; seldom — stenocardia, up to development of a myocardial infarction (especially at patients with crushing obstructive defeat of coronary arteries), arrhythmias (including blinking and trembling of ventricles).
- From digestive tract: nausea, vomiting, a lock (it is rare — diarrhea), a hyperplasia of gums, increase in appetite; in some cases — tranzitorny increase in "hepatic" transaminases and an alkaline phosphatase in a blood plasma;
- From the central nervous system: dizziness, headache, faint, uneasiness, block, increased fatigue, adynamy, drowsiness, depression, extrapyramidal disturbances.
- Allergic reactions: skin itch, skin rash, dermahemia of the person, multiformny exudative erythema (including Stephens-Johnson's syndrome).
- Other: increase in body weight, is very rare — an agranulocytosis, a gynecomastia, a giperprolaktinemiya, a galactorrhoea, arthritis, tranzitorny loss of sight against the background of Sglakh, a fluid lungs, thrombocytopenia asymptomatic, peripheral hypostases.

Interaction with other medicines:

At a concomitant use of Verapamil with:
— antiarrhytmic means, beta адренобпокато-рами and inhalation anesthetics observe strengthening of cardiotoxic effect (increase in danger of emergence of an atrioventricular block, sharp decrease in heart rate, development of heart failure, sharp falling of arterial pressure);
— anti-hypertensive means and diuretics — strengthening of hypotensive effect of Verapamil is possible;
— digoxin increase in level of concentration of digoxin in a blood plasma in connection with deterioration in its removal by kidneys is possible (therefore it is necessary to carry out control of level of digoxin in a blood plasma for the purpose of identification of its optimum dosage and prevention of intoxication);
— Cimetidinum and ranitidine the level of concentration of verapamil in a blood plasma increases;
— rifampicin, phenobarbital decrease in concentration in a blood plasma and weakening of effect of verapamil is possible;
— theophylline, Prazozinum, cyclosporine increase in concentration of these substances in a blood plasma is possible;
— muscle relaxants strengthening of myorelaxation action is possible;
— acetylsalicylic acid possibility of bleedings amplifies;
— quinidine the level of concentration of quinidine in a blood plasma increases, the threat of a lowering of arterial pressure amplifies, and at patients with a hypertrophic cardiomyopathy developing of the expressed arterial hypotension is possible;
— carbamazepine and lithium danger of emergence of neurotoxic effects increases;
— increases concentration in valproic acid blood owing to suppression of metabolism with participation of a tsi-tokhrom of P450;
— drugs of calcium reduce efficiency of use of verapamil;
— nicotine, accelerating metabolism in a liver, leads to decrease in concentration of verapamil in blood;
— the procaineamide, quinidine and other medicines causing lengthening of an interval of QT increase risk of its considerable lengthening;
— Prazozinum and other alpha adrenoblockers strengthen hypotensive effect;
— non-steroidal anti-inflammatory drugs (NPVP) reduce hypotensive effect owing to suppression of synthesis of prostaglandins, delays of sodium and liquid in an organism;
— increase concentration of cardiac glycosides (demands careful observation and a dose decline of glycosides);
— sympathomimetics reduce hypotensive effect of verapamil;
— and флекаинид it is not necessary to appoint Disopyramidum within 48 hours to or 24 hours after verapamil use (summation of a negative inotropic effect, up to death);
— estrogen reduces hypotensive effect owing to a liquid delay in an organism.
— increase in plasma concentration of the medicines which are characterized by high extent of linkng with proteins is possible (including derivative coumarin and an indandion, NPVP, quinine, salicylates, Sulfinpyrazonum).

Contraindications:

Hypersensitivity to drug components, the expressed bradycardia, chronic cordial, insufficiency of the II B — the III stage, the expressed arterial hypotension, cardiogenic shock (except for caused by arrhythmia), a sinoauricular block, an atrioventricular block of II and III degrees (excepting patients with an artificial pacemaker); an acute myocardial infarction, a sick sinus syndrome, a stenosis of the mouth of an aorta, a WPW-syndrome, Morganyi-Adams-Stokes's syndrome, an acute heart failure, simultaneous use of beta adrenoblockers (intravenously), pregnancy, the lactation period, age up to 18 years.

With CARE it is necessary to appoint drug sick with the atrioventricular block of the I degree, chronic heart failure expressed by abnormal liver functions, a renal failure at advanced age, soft or moderate degree of arterial hypotension, a myocardial infarction with a left ventricular failure, bradycardia.

Overdose:

Symptoms: the sinus bradycardia passing into an atrioventricular block, sometimes an asystolia, the expressed lowering of arterial pressure, heart failure, shock.
Treatment at early identification — a gastric lavage, absorbent carbon; at disturbance of a rhythm and conductivity — intravenous administration of an izoprenalin, Norepinephrinum, atropine, 10-20 ml of 10% of solution of calcium of a gluconate, an artificial pacemaker; in/in infusion of plasma substituting solutions. The hemodialysis is not effective.

Storage conditions:

List B. To store in the dry, protected from light place at a temperature not above 25 °C.
To store in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

Tablets, film coated 40 and 80 mg. On 10, 50 tablets in a blister strip packaging. On 10,20, 30,40, 50 or 100 tablets in a container polymeric for medicines or a bottle from glass melt with the screwed plastic covers. One container (bottle) or 1,2,3,4, 5, 6,8 or 10 blister strip packagings together with the application instruction place in a pack from a cardboard.
On 5,10 or 20 containers (bottles) or on 20,40,60,80 and 100 blister strip packagings together with the corresponding number of application instructions place in a box from a cardboard (for hospitals).