Verapamil

General characteristics. Structure:

Active agent: verapamil hydrochloride of 80 mg; 40 mg.

Pharmacological properties:

The selection blocker of calcium channels of the I class, derivative difenilalkilamina. Has anti-anginal, antiarrhytmic and anti-hypertensive effect.
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, OPSS). Blockade of intake of calcium 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 effect.
Verapamil significantly reduces 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). Has antiarrhytmic effect at supraventricular arrhythmias.

Pharmacokinetics. At intake more than 90% of a dose are absorbed. Linkng with proteins - 90%. Is exposed to metabolism at "the first passing" through a liver. The main metabolite is norverapamit, having less expressed hypotensive activity, than not changed verapamil.
T1/2 at reception of a single dose makes 2.8-7.4 h, at reception of repeated doses - 4.5-12 h (in connection with saturation of fermental systems of a liver and increase in concentration of verapamil in a blood plasma). Later in/in introductions initial T1/2 - about 4 min., final - 2-5 h.

Also 9-16% through intestines are removed preferential by kidneys.

Indications to use:

Stenocardia (tension, stable without vasomotor spasm, stable vasospastic), supraventricular tachycardia (including paroxysmal, at a WPW syndrome, a syndrome of Launa-Ganonga-Levina), sinus tachycardia, a ciliary tachyarrhythmia, an atrial flutter, atrial premature ventricular contraction, arterial hypertension, hypertensive crisis (in/in introduction), a hypertrophic subaortic stenosis, primary hypertensia in a small circle of blood circulation.

Route of administration and doses:

Individual. Inside the adult - in an initial dose of 40-80 mg of 3 times/days. For dosage forms of the prolonged action the single dose should be increased, and to reduce the frequency of reception. To children at the age of 6-14 years - 80-360 mg/days, up to 6 years - 40-60 mg/days; reception frequency - 3-4 times/days.
If necessary verapamil can be entered in/in struyno (slowly, under control of the ABP, ChSS and ECG). The single dose for adults makes 5-10 mg, in the absence of effect in 20 min. perhaps repeated introduction in the same dose. The single dose for children at the age of 6-14 years makes 2.5-3.5 mg, 1-5 years - 2-3 mg, till 1 year - 0.75-2 mg. For patients with the expressed abnormal liver functions the daily dose of verapamil should not exceed 120 mg.
The maximum daily dose for adults at intake makes 480 mg.

Features of use:

With care it is necessary to apply at AV blockade of the I degree, bradycardia, a heavy stenosis of the mouth of an aorta, chronic heart failure, at slight or moderate arterial hypotension, a myocardial infarction with a left ventricular failure, a liver and/or renal failure, at patients of advanced age, at children and teenagers aged up to 18 years (efficiency and safety of use are not investigated).

If necessary the combination therapy of stenocardia and arterial hypertension verapamil and beta adrenoblockers is possible. However it is necessary to avoid in/in administrations of beta adrenoblockers against the background of verapamil use.

Influence on ability to driving of motor transport and to control of mechanisms

After reception of verapamil individual reactions (drowsiness, dizzinesses) influencing ability of the patient to perform the work demanding high concentration of attention and speed of psychomotor reactions are possible.

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); at bystry in introduction - AV blockade of the III degree, an asystolia, a collapse.
- From TsNS and a 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).
- 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 Cmax, a fluid lungs, thrombocytopenia asymptomatic, peripheral hypostases.

Interaction with other medicines:

At simultaneous use to anti-hypertensive drugs (vazodilatator, thiazide diuretics, APF inhibitors) there is mutual strengthening of anti-hypertensive action.

At simultaneous use with beta adrenoblockers, antiarrhytmic means, means for an inhalation anesthesia the risk of development of bradycardia, the AV blockade expressed to arterial hypotension, heart failure in connection with mutual strengthening of the oppressing influence on automatism of a sinuatrial node and AV conductivity, contractility and conductivity of a myocardium increases.

At parenteral administration of verapamil to the patients who were recently receiving beta adrenoblockers there is a risk of development of arterial hypotension and an asystolia.

At simultaneous use with nitrates anti-anginal effect of verapamil amplifies.

At simultaneous use with Amiodaronum negative inotropic effect, bradycardia, conductivity disturbance, AV blockade amplifies.

As verapamil inhibits an isoenzyme of CYP3A4 which participates in metabolism of an atorvastatin, a lovastatina and a simvastatina, the manifestations of medicinal interaction caused by increase in concentration of statines in a blood plasma are theoretically possible. Cases of development of a rabdomioliz are described.

At simultaneous use with acetylsalicylic acid cases of increase in a bleeding time owing to the additive antiagregantny action are described.

At simultaneous use with buspirony concentration of a buspiron in a blood plasma increases, its therapeutic and side effects amplify.

At simultaneous use cases of increase in concentration of digitoxin in a blood plasma are described.

At simultaneous use with digoxin concentration of digoxin in a blood plasma increases.

At simultaneous use with Disopyramidum heavy arterial hypotension and a collapse, especially at patients with a cardiomyopathy or dekompensirovanny heart failure are possible. The risk of development of heavy manifestations of medicinal interaction is connected, apparently, with strengthening of negative inotropic effect.

At simultaneous use with diclofenac concentration of verapamil in a blood plasma decreases; with doxorubicine - concentration of doxorubicine in a blood plasma increases and its efficiency increases.

At simultaneous use with Imipraminum concentration of Imipraminum in a blood plasma increases and there is a risk of development of undesirable changes on an ECG. Verapamil increases bioavailability of Imipraminum due to reduction of its clearance. Changes on an ECG are caused by increase in concentration of Imipraminum in a blood plasma and the additive oppressing effect of verapamil and Imipraminum on AV conductivity.

At simultaneous use with carbamazepine effect of carbamazepine amplifies and the risk of development of side effects from TsNS owing to inhibition of metabolism of carbamazepine in a liver under the influence of verapamil increases.

At simultaneous use with a clonidine cardiac standstill cases at patients with arterial hypertension are described.

At simultaneous use from lithium a carbonate of manifestation of medicinal interaction are ambiguous and unpredictable. Cases of strengthening of effects of lithium and development of a neurotoxicity, reduction of concentration of lithium in a blood plasma, heavy bradycardia are described.

Vazodilatiruyushchy action of alpha blockers and blockers of calcium channels can be the additive or synergistic. At simultaneous use of a terazozin or Prazozinum and verapamil development of the expressed arterial hypotension is partially caused by pharmacokinetic interaction: increase in Cmax and AUC of a terazozin and Prazozinum.

At simultaneous use rifampicin induces activity of enzymes of a liver, accelerating verapamil metabolism that leads to reduction of its clinical performance.

At simultaneous use concentration of theophylline in a blood plasma increases.

At simultaneous use with Tubocurarini chloridum, a vekuroniya chloride strengthening of myorelaxation action is possible.

At simultaneous use with Phenytoinum, phenobarbital perhaps considerable reduction of concentration of verapamil in a blood plasma.

At simultaneous use with fluoxetine side effects of verapamil owing to delay of his metabolism under the influence of fluoxetine amplify.

At simultaneous use the clearance of quinidine decreases, its concentration in a blood plasma increases and the risk of development of side effects increases. Cases of development of arterial hypotension were observed.

At simultaneous use verapamil inhibits metabolism of cyclosporine in a liver that leads to reduction of its removal and increase in concentration in a blood plasma. It is followed by strengthening of an immunodepressive effect, reduction of manifestations of nephrotoxicity is noted.

At simultaneous use with Cimetidinum effects of verapamil amplify.

At simultaneous use with enflurany anesthesia prolongation is possible.

At simultaneous use with etomidaty anesthesia duration increases.

Contraindications:

Heavy arterial hypotension, AV blockade of II and III degrees, sinuatrial blockade and SSSU (except patients with a pacemaker), a WPW syndrome or a syndrome of Launa-Ganonga-Levina in combination with trembling or fibrillation of auricles (except patients with a pacemaker), pregnancy, the lactation period, hypersensitivity to verapamil.

Use at pregnancy and feeding by a breast
Verapamil is contraindicated at pregnancy and in the period of a lactation.

Use at abnormal liver functions
With care it is necessary to apply at a liver failure.

Use at renal failures
With care it is necessary to apply at a renal failure.

Use for elderly patients
With care it is necessary to apply at patients of advanced age.

Use for children
With care it is necessary to apply at children and teenagers aged up to 18 years (efficiency and safety of use are not investigated).

Overdose:

There are no data.

Storage conditions:

Drug is recommended to be stored in the dry place far from direct sunshine at a temperature from 15 to 25 °C.

Issue conditions:

According to the recipe

Packaging:

Tablets film coated 40, 80 mg (blisters, containers plastic).