Verapamil

General characteristics. Structure:

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

Excipients: potato starch, lactose (sugar milk), povidone (polyvinylpirrolidone), calcium stearate, talc.

Structure of a cover: gipromelloz (gidroksipropilmetiltsellyuloz), macrogoal (polyethyleneglycol 6000), глицерол (glycerin), talc, titanium dioxide, lactose (sugar milk), tropeolin O.

Pharmacological properties:

Pharmacodynamics. Verapamil - a blocker of "slow" calcium channels (brakes transmembrane transport of calcium ions to sokratitelny fibers of smooth muscle cells), derivative a difenilalkilamina. Possesses anti-anginal, antiarrhytmic and hypotensive action. The anti-anginal effect is connected both with direct action on a myocardium, and with influence on a peripheral hemodynamics (reduces a tone of peripheral arteries, the general peripheric vascular resistance).

Blockade of receipt of calcium ions in a cell leads to reduction of the transformation concluded in energy ATP energy-rich bonds in mechanical work, to decrease in contractility of a myocardium. Reduces the need of a myocardium for oxygen, renders vazodilatiruyushchy, negative other and chronotropic actions. Significantly reduces atrioventricular (AV) conductivity, extends the period of a refrakternost and suppresses automatism of a sinus node.

Increases the period of diastolic relaxation of a left ventricle, reduces a myocardium wall tone (is supportive application for treatment of a hypertrophic subaortic stenosis).

Suppresses metabolism with P450 cytochrome participation.

The beginning of effect at intake - in 1-2 h, the maximum effect develops in 30-90 min. (usually during 24-48 h), effect duration - 8-10 h. The anti-anginal effect has dozozavisimy character, tolerance does not arise.

Pharmacokinetics. At intake it is quickly soaked up in a small intestine, absorption - 90-92%, bioavailability after a single dose - 24-35% owing to intensive metabolism at "the first passing" through a liver and increases by 1,5-2 times at prolonged use. At prolonged use in the increasing doses bioavailability can increase.
Time of achievement of the maximum concentration of drug in a blood plasma - 1-2 h at intake. The maximum concentration of drug in a blood plasma (Cmax) - 80-400 ng/ml. Communication with proteins of a blood plasma - 90%. Gets through a blood-brain barrier, 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, CYP3A7 participate in metabolism of drug.

Drug elimination half-life - 3-7 h at a single dose, 4-12 h - at prolonged use (in connection with saturation of fermental systems of a liver and increase in plasma concentration the period of semi-removal of drug increases almost twice). At a liver failure bioavailability increases and the drug elimination half-life increases. 70% by kidneys (3-5% in not changed look), 16-25% - with bile are removed. It is not removed at a hemodialysis.

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:

To take a pill, not rassasyvy and without chewing, washing down with a small amount of liquid, it is preferable before meal or right after food. On 40-80 mg 3 times a day - at stenocardia and supraventricular tachycardia in 3 receptions, at arterial hypertension - in 2 receptions, a daily dose at arterial hypertension - to 480 mg. Maximum daily dose of 480 mg.

For patients with a heavy liver failure the daily dose should not exceed 120 mg.

Features of use:

Heart failure needs to be compensated previously. At treatment control of functions of cardiovascular system, respiratory system, content of glucose and electrolytes in blood, the 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: 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).

From the central 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 an alkaline phosphatase.

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

Others: increase in body weight, is very rare - an agranulocytosis, a gynecomastia, a giperprolaktinemiya, a galactorrhoea, arthritis, a fluid lungs, thrombocytopenia asymptomatic, peripheral hypostases.

Interaction with other medicines:

Increases the area under a curve "concentration - time" (AUC) of carbamazepine at patients with steady partial epilepsy (risk of development of side effects, such as a diplopia, a headache, an ataxy, dizziness).

Raises AUC, equilibrium concentration (Css) and the maximum concentration (Cmax) of cyclosporine in a blood plasma.

Increases concentration of theophylline (owing to decrease in clearance), ethanol (and extends its effect), concentration of quinidine (risk of the expressed decrease in the ABP, especially at patients with IGSS).

Can increase concentration of an atorvastatin and lovastatin at simultaneous use. Significantly raises 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 a r-glycoprotein). Significantly raises AUC and Cmax of doxorubicine. Slightly raises AUC of Imipraminum, does not influence concentration of an active metabolite of desipramine. Raises Cmax of Prazozinum and a terazozin and AUC of a terazozin.

CYP3A4 inhibitors (including erythromycin, ритонавир and other antiviral HIV drugs), телитромицин increase plasma concentration of verapamil. Grapefruit juice raises AUC and Cmax R-and S-isomers 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-isomers 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 AV of 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 (APF inhibitors, vazodilatator, diuretics, beta adrenoblockers) strengthen hypotensive effect.

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 a lethal outcome).

Increases risk of emergence of neurotoxic effect of drugs of lithium.

Strengthens action of peripheral muscle relaxants (can demand change of the mode of dosing).

At simultaneous use with acetylsalicylic acid a little bigger increase in a bleeding time was noted, than at use only of acetylsalicylic acid.

Contraindications:

Hypersensitivity to verapamil and other components of drug, the expressed dysfunction of a left ventricle, the expressed arterial hypotension (systolic arterial pressure (ABP) less than 90 mm hg) or cardiogenic shock, the expressed bradycardia, an atrioventricular block of the II-III degree, a sick sinus syndrome (except patients with a pacemaker), trembling and fibrillation of auricles and a WPW-syndrome (WPW) or a syndrome of Launa-Ganonga-Levina (except patients with a pacemaker), pregnancy, the lactation period, age up to 18 years (efficiency and safety are not established), a concomitant use of colchicine.

With care. Sinuatrial blockade, atrioventricular block of the I degree, bradycardia, idiopathic hypertrophic subaortal stenosis (IHSS), chronic heart failure, liver and/or renal failure, neuromuscular transmission delay, advanced age.

Overdose:

Symptoms: bradycardia, an atrioventricular block, the expressed decrease in the ABP, heart failure, shock, an asystolia, sinuatrial blockade.

Treatment: at early identification - a gastric lavage, absorbent carbon; at disturbance of a rhythm and conductivity - in/in изопреналин, Norepinephrinum, atropine, 10-20 ml of 10% of solution of calcium of a gluconate, an artificial pacemaker; in/in infusion of plasma substituting solutions. For increase in the ABP 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:

List B. In the dry, protected from light place, at a temperature not above 25 °C. To store in the place, unavailable to children. Not to use drug after a period of validity. A period of validity - 3 years.

Issue conditions:

According to the recipe

Packaging:

Tablets, film coated, 40 mg and 80 mg. On 10 or 20 tablets in a blister strip packaging. 2 or 5 blister strip packagings on 10 tablets or 1 or 2 blister strip packagings on 20 tablets together with the application instruction in a pack from a cardboard.