Verapamil of / x t п / about 40 mg No. 50

General characteristics. Structure:

Active agent: hydrochloride verapamil (in terms of 100% substance) - 40 mg excipients: a kernel - lactose (sugar milk), calcium stearate, potato starch, talc, polysorbate (twin-80), povidone (polyvinylpirrolidone low-molecular); a cover - Onadray II (series 85) (the polyvinyl alcohol which is partially hydrolyzed talc, a macrogoal (полтэтиленгликоль 3350), titanium dioxide, dye ferrous oxide, an aluminum varnish on the basis of yellow quinolinic, an aluminum varnish on the basis of yellow a sunset, an aluminum varnish on the basis of indigo carmine).

Description: tablets, film coated yellow color, round biconvex.

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, and also at treatment of stenocardia with supraventricular disturbances of a rhythm.

Pharmacokinetics. At intake more than 90% of the accepted dose are soaked up. Bioavailability - 10-20%. The maximum concentration (Cmax) 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-dealkilverapamil and N-dealkilnorverapamil. Accumulation of drug and its metabolites in an organism explains strengthening of action at course treatment. Communication with proteins of plasma of blood - 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 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 is slowed down therefore it is reasonable to begin treatment with the minimum doses. The daily dose of drug should not exceed 120 mg for patients with a heavy liver failure.

Features of use:

For increase in arterial pressure at patients with a hypertrophic cardiomyopathy appoint alpha адреностимуляторы (Phenylephrinum); it is not necessary to apply изопреналин. Before therapy at heart failure it is necessary to reach the compensated state. 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:

- from cardiovascular system: face reddening, the expressed bradycardia, an atrioventricular block, the expressed lowering of arterial pressure, emergence of symptoms of heart failure when using drug in high doses, especially at predisposed patients, tachycardia is possible; 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);
- from digestive tract: nausea, vomiting, a lock, it is rare - diarrhea; in some cases - tranzitorny increase in activity of "hepatic" transaminases and an alkaline phosphatase in a blood plasma;
- from the central nervous system: dizziness, a headache, a faint, uneasiness, 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), in rare instances - the increased nervous irritability, block, fatigue;
- allergic reactions: skin rash, itch, dermahemia of the person, multiformny exudative erythema (including Stephens-Johnson's syndrome);
- others: a gynecomastia, a giperprolaktinemiya, a hyperplasia of gums, increase in body weight, it is very rare - an agranulocytosis, a galactorrhoea, arthritis, tranzitorny loss of sight, a fluid lungs, thrombocytopenia asymptomatic, peripheral hypostases.

Interaction with other medicines:

At simultaneous use of verapamil with:
- raises AUC (the area under a curve "concentration - time") carbamazepine at patients with steady partial epilepsy (risk of development of side effects, such as a diplopia, a headache, an ataxy and dizziness).
- raises AUC, Css (clearance) and Cmax (the maximum concentration of drug) of cyclosporine.
- raises AUC and Cmax of Glibenclamidum.
- increases concentration of a sirolimus and takrolimus.
- significantly raises AUC and Cmax of a buspiron and midazolam.
- increases concentration of theophylline (owing to decrease in clearance), ethanol (and extends its effect), concentration of quinidine (risk of the expressed lowering of arterial pressure).
- can increase concentration of an atorvastatin and lovastatin.
- raises significantly AUC and Cmax of a simvastatin.
- raises AUC and Cmax of an almotriptan.
- increases concentration of cardiac glycosides (demands careful observation and a dose decline of glycosides).
- raises AUC and Cmax of a metoprolol and propranolol at patients with stenocardia.
- increases plasma concentration of colchicine (substrate for CYP3A and р-a glycoprotein).
- at intake significantly raises AUC and Cmax of doxorubicine.
- slightly raises AUC of Imipraminum; does not influence concentration of an active metabolite, desipramine.
- raises Cmax of Prazozinum and a terazozin and AUC of a terazozin.
- CYP3A inhibitors (including erythromycin, ритонавир and other antiviral HIV drugs), телитромицин increase plasma concentration of verapamil.
- grapefruit juice raises AUC and Cmax R-and S-of isomer of verapamil.
- 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.
- rifampicin can reduce considerably bioavailability (to 92%) and also AUC and Cmax of verapamil.
- phenobarbital increases clearance of verapamil by 5 times.
- Sulfinpyrazonum increases clearance of verapamil approximately by 3 times and reduces bioavailability (60%).
- drugs of the St. John's Wort which is made a hole reduce AUC R-and S-of isomer of verapamil and according to Cmax.
- at simultaneous use with inhalation anesthetics the risk of development of bradycardia, an atrioventricular block, heart failure increases.
- the combination with beta adrenoblockers can lead to strengthening of a negative inotropic effect, increase in risk of development of disturbances of atrioventricular conductivity, bradycardia (administration of verapamil and beta adrenoblockers needs to be carried out at an interval of several hours)
- Prazozinum and other alpha adrenoblockers, and also other hypotensive medicines (ATP inhibitors, vazodilatator, diuretics, beta adrenoblockers) strengthen hypotensive effect.
- and флекаинид it is not necessary to appoint Disopyramidum within 48 hours or 24 hours after verapamil use (summation of a negative inotropic effect, up to a lethal outcome).
- increases risk of emergence of neurotoxic effect of drugs of lithium.
- strengthens action of peripheral muscle relaxants (change of the mode of dosing can be required).
- at simultaneous use with acetylsalicylic acid (ASK) a little bigger increase in a bleeding time was noted, than at use only of ASK.
- carbamazepine and lithium danger of emergence of neurotoxic effects increases.

Contraindications:

Hypersensitivity to verapamil and other components of drug, the expressed bradycardia, chronic heart failure of the II B - Sh stages, 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, the expressed dysfunction of a left ventricle, trembling and fibrillation of auricles and WPW - a syndrome or a syndrome of Launa-Ganonga-Levina (except patients with a pacemaker), an acute heart failure, simultaneous use of beta adrenoblockers (intravenously), pregnancy, the lactation period, age up to 18 years (efficiency and safety are not established), a concomitant use of colchicine.

With care it is necessary to appoint the patient with the atrioventricular block of the I degree, chronic heart failure of the I-II stage expressed by abnormal liver functions and/or kidneys, arterial hypotension, bradycardia at advanced age, with the slowed-down neuromuscular transmission.

Overdose:

Symptoms - the sinus bradycardia passing into an atrioventricular block, sometimes an asystolia, the expressed lowering of arterial pressure, heart failure, shock, sinuatrial blockade.
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; intravenous infusion of plasma substituting solutions. The hemodialysis is not effective.

Storage conditions:

List B. In the dry, protected from light place, at a temperature not above 25 °C. To store in the place, unavailable to children. Period of validity: 3 years. Not to use after the date specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Tablets, film coated, 40 mg On 10 tablets in a blister strip packaging. On 50 tablets in bank of light-protective glass or bank polymeric, or in a bottle polymeric. Each can or a bottle, 1, 2 or 5 blister strip packagings together with the application instruction are placed in a pack from a cardboard.