Verapamil gidrokhlorid-Darnitsa

General characteristics. Structure:

Active ingredient: verapamile; 1 ml of solution contains hydrochloride verapamil in terms of 100% dry matter – 2,5 mg;

excipients: sodium chloride; citric acid, monohydrate; sodium hydroxide; Acidum hydrochloricum, 1 M solution; water for injections.

Pharmacological properties:

Pharmacodynamics. Verapamil is an antagonist of calcium (a blocker of slow calcium channels) and belongs to antiarrhytmic means of the IV class. Verapamil is derivative a fenilalkilamina.

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 elimination of a coronary spasm improves perfusion of a myocardium and delivery of oxygen to heart. As a result of expansion of peripheral arteries the general peripheric vascular resistance (GPVR), system the ABP and resistance of emission of a left ventricle decreases (afterload) that in general reduces tension of walls of heart and the need of a myocardium for oxygen. By decrease in intracellular concentration of calcium ions 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 that slows down AV conductivity. Verapamil can extend PQ interval on an ECG that, generally correlates with concentration of verapamil in a blood plasma (especially in an initiation of treatment). Verapamil practically does not exert impact on duration of intervals of QRS or QT.

Pharmacokinetics. At intravenous administration the maximum concentration in a blood plasma (Cmax) – 80–400 ng/ml are reached in 2–5 minutes. In 10 minutes after introduction the amount of the circulating drug in blood makes 5% of the entered dose. Communication with proteins of plasma – 90%. Gets through a blood-brain barrier (GEB), a placental barrier (20–92% of concentration in a blood plasma of mother) and into breast milk (in low concentration). It is quickly metabolized in a liver by N-dealkylation and O-demethylation, with formation of several metabolites (at the person indentifitsirovano 12). Accumulation of drug and its metabolites in an organism explains strengthening of action at course treatment. Pharmacological the active metabolite – norverapamit the main (20% of hypotensive activity of verapamil). Isoenzymes of CYP3A4, CYP3A5 and CYP3A7 participate in metabolism of drug. An elimination half-life (T1/2) at intravenous administration – two-phase: about 4 min. – early and 2–5 h – final. At a liver failure bioavailability increases and T1/2 increases. 70% by kidneys (3–5% in not changed look), 16–25% – with bile are removed. It is not removed at a hemodialysis.

Pharmaceutical characteristics.

main physical and chemical properties: transparent colourless liquid.

Incompatibility. Drug is incompatible with albumine, Amphotericinum In, a gidralazina a hydrochloride, sulfamethoxazole and Trimethoprimum for injections. In any solution with рН higher than 6,0 drug can drop out in a deposit.

Indications to use:

Unstable stenocardia. Paroxysms of supraventricular arrhythmias. Hypertensive crisis.

Route of administration and doses:

Apply intravenously in the form of a slow injection or infusion. Infusion solution prepare at the rate of 5 mg of verapamil on 150 ml 0,9% of solution of sodium of chloride. The initial dose for adults and children is more senior than 14 years makes 5 mg which is entered struyno for 2–5 minutes under electrocardiographic control and monitoring of arterial pressure. In the absence of effect administration of drug needs to be repeated in 5–10 minutes. The maintenance dose is entered in the form of infusion on 5–10 mg for an hour. The daily dose should not exceed 100 mg.

Verapamil dose for babies: 0,75–2 mg, for children of 1-5 years – 2–3 mg, for children of 6-  14 years – 2,5–5 mg.

Features of use:

Verapamil-Darnitsa can cause a symptomless atrioventricular block of the I degree and tranzitorny bradycardia which are sometimes combined with a vyskalzuyushchy nodal rhythm. Lengthening of an interval of PQ on the electrocardiogram is associated with increase in concentration of verapamil in a blood plasma, especially at the beginning of therapy. At patients with a hypertrophic cardiomyopathy tendency to adverse cardial effects is shown. Frequency of side cardial effects is also increased at patients who at the same time accept beta adrenoblockers. At elderly people the elimination half-life of verapamil is extended. At certain patients the simultaneous use with verapamil of alcohol (ethanol) can slow down removal of alcohol from an organism. Blockers of calcium channels can reduce fertility at men what it is necessary to remember if the obscure infertility which is completely reversible after drug withdrawal is diagnosed for the man who accepts blockers of calcium channels. With extra care it is necessary to appoint Verapamil-Darnitsa to newborns and children of the first year of life because they are more sensitive to the disturbances of a heart rhythm induced by verapamil. The dose of Verapamila-Darnitsa is reduced for patients with liver diseases. At insufficiency of adrenal glands patients have to be under medical control in spite of the fact that, generally to change doses there is no requirement. Therapy by verapamil is carried out also during dialysis. Verapamil-Darnitsa it has to be appointed with care to patients with heart failure of moderate severity. By the beginning of therapy with use of verapamil it is necessary to carry out treatment of heart failure using cardiac glycosides and/or diuretics. Sometimes there is a need to reduce doses of Verapamila-Darnitsa to patients with reduced neuromuscular conductivity (for example, with muscular dystrophy of Dyushen, at use of muscle relaxants during an anesthesia). At heart failure or disturbances of cordial conductivity during treatment by verapamil the dose of drug either is reduced, or stop its use and/or begin the corresponding therapy. During treatment by verapamil through certain intervals it is necessary to control function of a liver. Solution for injections of Verapamil-Darnitsa at the beginning of therapy has to be used only in a hospital where there is a possibility of holding resuscitation actions. A condition of patients which enter intravenously verapamil it has to be controlled by electrocardiographic and hemodynamic monitoring.

Elderly people need to enter a dose of drug slowly, it is more than two minutes, for minimization of risk of side effects. At a liver failure the single dose is not reduced as in this case duration of effect of verapamil can increase. Dose adjustment at a renal failure most often is not carried out, nevertheless careful observation of a clinical situation is necessary for overdose avoidance.

Ability to influence the speed of reactions at control of motor transport or other mechanisms. Drug can influence the speed of reactions at control of motor transport and during the work with difficult mechanisms.

Side effects:

From cardiovascular system: bradycardia ( less than 50 beats/min), the expressed lowering of arterial pressure, development or aggravation of heart failure, tachycardia; seldom – stenocardia, up to development of a myocardial infarction (especially at patients with a stenosis of coronary arteries), arrhythmias (including blinking and trembling of ventricles); at bystry intravenous administration – AV blockade the III Art., an asystolia, a collapse.

From a 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), at prolonged use a hyperplasia of gums (bleeding, morbidity, puffiness), increase in appetite, increase in activity of "hepatic" transaminases and an alkaline phosphatase.

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

Others: increase in body weight, very seldom an agranulocytosis, a gynecomastia, a giperprolaktinemiya, a galactorrhoea, arthritis, tranzitorny loss of sight against the background of the maximum concentration of drug in a blood plasma, a fluid lungs, asymptomatic thrombocytopenia, peripheral hypostases.

Interaction with other medicines:

Increases concentration in blood of digoxin, theophylline, Prazozinum, cyclosporine, carbamazepine, muscle relaxants, quinidine, valproic acid owing to suppression of metabolism with P450 cytochrome participation. Cimetidinum increases bioavailability of verapamil almost by 40–50% (due to decrease in hepatic metabolism) in this connection there can be a need of reduction of a dose of the last. Drugs of calcium reduce efficiency of use of verapamil. Rifampicin, barbiturates, nicotine, accelerating metabolism in a liver, lead to decrease in concentration of verapamil in blood, reduce expressiveness of anti-anginal, hypotensive and antiarrhytmic effects. At simultaneous use with inhalation anesthetics the risk of development of bradycardia, AV blockade, heart failure increases. Procaineamide, quinidine and others medicinal the means causing lengthening of an interval of QT increase risk of its considerable lengthening. The combination with beta adrenoblockers can lead to strengthening of a negative inotropic effect, increase in risk of development of disturbances of AV conductivity, bradycardia (administration of verapamil and beta adrenoblockers needs to be carried out at an interval of several hours). Prazozinum and other alpha adrenoblockers strengthen hypotensive effect. Non-steroidal anti-inflammatory drugs reduce hypotensive effect owing to suppression of synthesis of prostaglandins, delays of sodium and liquid in an organism. Increases 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 during 48 h to or 24 h 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, non-steroidal anti-inflammatory drugs, quinine, salicylates, Sulfinpyrazonum). The medicines reducing arterial pressure strengthen hypotensive effect of verapamil. Increases risk of emergence of neurotoxic effect of drugs of lithium. Increases activity of peripheral muscle relaxants (can demand change of the mode of dosing).

Contraindications:

Hypersensitivity to drug components. Atrioventricular blockade of the II-III degree. Arterial hypotension. A sick sinus syndrome (except patients with a pacemaker). Wolff-Parkinson-Whyte's syndrome or a syndrome of Launa-Genonta-Levina in combination with trembling or fibrillation of auricles. Heavy stenosis of the mouth of an aorta. A myocardial infarction with a left ventricular failure. Tachycardia with the wide QRS complex. Heavy functional hepatic unsufficiency and/or kidneys. Ischemic or hemorrhagic stroke.

Use during pregnancy or feeding by a breast. Drug is contraindicated during the periods of pregnancy and feeding by a breast.

Children. At children use of drug from chest age is possible.

Overdose:

Symptoms: bradycardia, SA blockade, AV blockade, the expressed lowering of arterial pressure, heart failure, shock, an asystolia.

Treatment: at disturbance of a rhythm and conductivity – intravenously изопреналин, Norepinephrinum, atropine, 10–20 ml of 10% of solution of calcium of a gluconate, an artificial pacemaker, intravenous infusion of plasma substituting solutions. For increase in arterial pressure at patients with a hypertrophic subaortic stenosis appoint alpha адреностимуляторы (Phenylephrinum); it is not necessary to apply изопреналин and Norepinephrinum. The hemodialysis is inefficient.

Storage conditions:

To store in protected from light and the place, unavailable to children, at a temperature from 8 °C to 25 °C. A period of validity - 3 years.

Issue conditions:

According to the recipe

Packaging:

In ampoules on 2 ml, on 10 ampoules in cardboard packaging.