Verapamil hydrochloride

General characteristics. Structure:

International and chemical names: Verapamil, [(3,4-dimetoksifenit) (2RS)-2-5-[[2-(3,4-dimetoksifenit) ethyl] (methyl) of amine]-2-(1 methylethyl) a pentannitrile a hydrochloride]; main physical and chemical properties: round tablets, coated, white color, with a biconvex surface. On cross section two layers of different structure are visible; structure: 1 tablet contains 80 mg of verapamil of a hydrochloride in terms of 100% dry matter; excipients: starch corn, lactoses monohydrate, коповидон, magnesium stearate, film-forming covering 39G28601 Opadry II White.

Pharmacological properties:

Pharmacodynamics. Verapamil the hydrochloride is the selection blocker of calcium channels of the L type I of a class, possesses anti-anginal and hypotensive actions. Blocks potentsialzavisimy calcium channels and breaks penetration of calcium ions in cells, especially cardiomyocytes and cells of smooth muscles of vessels, concentration of calcium in blood at the same time does not change.
Anti-anginal effect of drug is implemented thanks to decrease in a tone of coronary and peripheral arterial vessels, improvement of blood supply of a cardiac muscle, including in ischemic sites; reduces the need of a myocardium for oxygen, reducing contractility of a myocardium and increasing a coronary blood stream. The anti-anginal effect is caused by also vazodilatiruyushchy peripheral action which reduces an afterload and the need of a myocardium for oxygen.
Verapamil the hydrochloride belongs to antiarrhytmic drugs IV of a class. The antiarrhytmic effect is caused by blockade of calcium channels in cells of the carrying-out system of heart (sinuatrial and atrioventricular nodes) that leads to delay of automatism of R-cells of a sinus node, the ectopic centers in auricles and speed of carrying out excitement through an atrioventricular node. Thereof the effective refractory period in sinus lasts and atrioventricular nodes, the sinoatrial rate is slowed down, heart rate decreases.
Anti-hypertensive effect of Verapamil of a hydrochloride is caused by relaxation of smooth muscles of vessels, decrease in the general peripheric vascular resistance, arterial pressure, as a rule, without development of postural hypotension and reflex tachycardia; bradycardia (frequency of cordial reductions less than 50 in a minute) develops seldom.

Pharmacokinetics. After oral administration more than 90% of the entered hydrochloride Verapamil dose are soaked up. Drug is metabolized preferential in a liver, owing to intensive metabolism at the first passing through portal system of a liver, bioavailability of drug makes 20–35%. The maximum concentration of Verapamil of a hydrochloride in a blood plasma is observed in 1–2 hours after administration of drug.
Extent of pressure decrease of blood does not depend on concentration of Verapamil of a hydrochloride in a blood plasma.
About 90% of drug contact blood proteins.
Verapamil the hydrochloride gets through a placenta and is excreted in breast milk. The average elimination half-life makes 2,8–7,4 hours after the first reception and 4,5–12 hours against the background of long reception. At patients of the senior age group the elimination half-life can increase.
At patients with a liver failure the elimination half-life increases till 14-16 o'clock, the volume of distribution increases, the plazmovy clearance makes about 30% of norm. Therefore the dose for such patients is reduced to 1/3 usual daily doses. Drug is removed preferential by kidneys (70%), partially – intestines.

Indications to use:

• Arterial hypertension.
• Coronary heart disease: stable stenocardia.
• Alternative stenocardia (Printsmetal's stenocardia).
• Supraventricular arrhythmias (atrial fibrillations, atrial flutters,
supraventricular premature ventricular contraction); Bouveret's supraventricular disease.

Route of administration and doses:

Doses are selected individually for each patient.
Arterial hypertension: the usual initial dose makes 80 mg of Verapamil of a hydrochloride three strike in days (only 240 mg).
The anti-hypertensive effect develops for a week from the date of the beginning of therapy.
The initial dose is gradually increased depending on a condition of the patient and the clinical answer which is estimated after administration of drug.
The maximum daily dose of drug – 480 mg.
Swallow of tablets whole, without chewing, they cannot be split up, divided into parts. Tablets are washed down with water.
Stenocardia: the usual dose makes 80 – 120 mg three times a day (only 240 - 360 mg).
To patients with the expected raised clinical answer and to persons of advanced age the initial dose can be reduced to 40 mg three strike in days (only 120 mg).
The initial dose is gradually increased depending on a condition of the patient and the clinical answer. The dose can be increased every day or every week before achievement of the optimum clinical answer (the maximum daily dose of drug – 480 mg).
Hypertrophic cardiomyopathy: the same doses are recommended, as well as at stenocardia.
Arrhythmias: the usual dose for patients with chronic fibrillation of the auricles accepting foxglove drugs makes 240 – 320 mg a day divided into 3 receptions.
The usual dose for prevention of Bouveret's supraventricular disease at the patients who are not accepting foxglove drugs makes 240 – 320 mg a day divided into 3 - 4 receptions.
The maximum effect develops , as a rule, for 48 hours after an initiation of treatment.
To children drug in this dosage form is not appointed.

Features of use:

It is necessary to adhere to extreme care in case of purpose of drug to patients with heart failure.
Verapamil the hydrochloride can cause an asymptomatic atrioventricular block of the first degree or the passing bradycardia. In case of development of an atrioventricular block it is necessary to reduce a dose of Verapamil of a hydrochloride or to stop administration of drug.
With care appoint Verapamil a hydrochloride to patients with a hypertrophic cardiomyopathy, and also to patients with the hypertrophic cardiomyopathy complicated by obstruction of a left ventricle, high pressure of jamming in pulmonary capillaries, dysfunction of a sinus and atrial node.
At patients with muscular dystrophy of Dyushenn Verapamil the hydrochloride reduces neuromuscular conductivity and increases recovery period duration after the neuromuscular blockade caused vekuroniy. Such patients require reduction of a dose of Verapamil of a hydrochloride.
With care it is necessary to appoint Verapamil the hydrochloride to patients with an abnormal liver function, in this case is recommended to lower a dose to 30% of usual daily. It is necessary to control PQ-interval duration on an ECG, and also other signs of possible overdose of Verapamil of a hydrochloride at patients (regular control of the ABP, ChSS, etc.).
With care patients should appoint Verapamil a hydrochloride with a renal failure, to carefully control the PQ-interval duration, and also other signs of possible overdose of Verapamil of a hydrochloride.
Patients of advanced age can have hypersensitivity to effect of drug, even at a usual dosage.
With care appoint drug at operative measures in connection with potentiation of the oppressing influence on a myocardium of the general anesthetics and on skeletal muscles – muscle relaxants.
Use during pregnancy and a lactation. There are no proofs of teratogenic effect of Verapamil of a hydrochloride, however its use during pregnancy it is necessary to avoid as drug gets through a placenta and appears in an umbilical vein at the time of delivery, it is unknown whether the hydrochloride influences Verapamil at once or possesses the remote side effect on a fruit and also whether it influences duration of childbirth.
Verapamil the hydrochloride gets into breast milk. Due to a possibility of negative influence on the child, during Verapamil treatment by a hydrochloride breastfeeding needs to be stopped.
Verapamil the hydrochloride can negatively influence ability to drive the car or other equipment.
At simultaneous use of grapefruit juice bioavailability of Verapamil of a hydrochloride increases by 30%.

Side effects:

Side below-mentioned effects are possible:
from cardiovascular system: sometimes – stenocardia, arterial hypotension, sinuatrial and atrioventricular blockade, bradycardia, provoking of strengthening of displays of heart failure, pain behind a breast, a myocardial infarction, a heart consciousness, a purpura, a syncope, an asystolia, tachycardia;
from a digestive tract: a lock, dryness in a mouth, gastrointestinal frustration, a hyperplasia of gums, pains, nausea, vomiting, an intestines atony;
from a nervous system: disturbances of cerebral circulation, confusion of consciousness, balance disturbance, sleeplessness, muscular spasms, paresthesia, psychoses, drowsiness, headache;
from urinogenital system: gynecomastia, impotence, frequent urinations, disturbances of a menstrual cycle.
Other manifestations:  an enanthesis, the strengthened hair loss, a hyperkeratosis, pigmentation disturbances, Stephens-Johnson's syndrome, a multiformny erythema, bruises, an illegibility of sight and a sonitus.
At treatment increase in level of transaminases, an alkaline phosphatase and bilirubin can be observed by Verapamil of a hydrochloride. In certain cases these changes independently take place at therapy continuation.
Injuries of a liver with clinical manifestations (feeling sick, fervescence and/or pain in right hypochondrium) and increase in the ALT, nuclear Heating Plant level and an alkaline phosphatase are possible. In this regard it is reasonable to control periodically function of a liver at patients who accept Verapamil a hydrochloride.

Interaction with other medicines:

Simultaneous use of Verapamil of a hydrochloride with beta adrenoblockers increases the mutual oppressing action by automatism of a sinuatrial node, AV-conductivity and contractility of a myocardium owing to what the risk of development of the expressed arterial hypotension, AV-and SA-blockade, bradycardia, heart failure increases, especially when using high doses of beta adrenoblockers or at their intravenous administration.
The special risk group is made by patients with symptoms of the chronic heart failure expressed to a cardiomyopathy or recently had a myocardial infarction. The combination therapy of Verapamil of a hydrochloride with beta adrenoblockers has to be carried out only according to accurate indications and under strict observation of the doctor.
Verapamil the hydrochloride exponentiates effect of other anti-hypertensive drugs (for example vazodilatator, inhibitors of an angiotenzinkonvertaza, diuretics, beta-blockers, alpha blockers, Prazozinum and terazozin).
Tricyclic antidepressants, neuroleptics exponentiate hypotensive effect of Verapamil of a hydrochloride.
At purpose of Verapamil of a hydrochloride patients who accept foxglove drugs need to consider that in the beginning treatments (the 1st week) digoxin level in blood serum increases by 50 – 70% therefore it is necessary to modify a digoxin dose, and periodically to control its level in blood serum, especially in an initiation of treatment.
The hydrochloride Verapamil combination with antiarrhytmic drugs І – the III class is not recommended.
Hydrochloride it is not necessary to use verapamil along with Disopyramidum (Rhytmilenum) which reception needs to be stopped in 48 hours prior to hydrochloride Verapamil use. Reception of Disopyramidum can be resumed not earlier than in 24 hours after the hydrochloride Verapamil reception termination.
At the combined use of Verapamil of a hydrochloride and flekainid the mutual oppressing action on a myocardium significantly changes, contractility of atrioventricular conductivity is exponentiated and repolarization duration increases.
At patients with a hypertrophic cardiomyopathy at simultaneous use of Verapamil of a hydrochloride and quinidine the expressed arterial hypotension therefore it is not necessary to appoint these drugs at the same time can develop.
Owing to high extent of linkng of Verapamil of a hydrochloride with proteins, the patients accepting other drugs, the possessing similar properties (peroral contraceptive drugs, hydantoin, salicylates, streptocides and derivative sulfanylurea) should appoint it with care.
At simultaneous use of Verapamil of a hydrochloride with salts of calcium and vitamin D pharmacological effect of Verapamil of a hydrochloride obviously decreases.
Verapamil the hydrochloride can reduce clearance of propranolol, a metoprolol; rifampicin, phenobarbital as inductors of microsomal enzymes can reduce efficiency of drug.
Under the influence of hydrochloride Verapamil concentration of the lithium salts accepted along with it in blood serum can change therefore the patients who are at the same time accepting both of these drugs have to be under careful observation. Similar interaction is noted at a concomitant use of Verapamil of a hydrochloride and theophylline.
Verapamil the hydrochloride causes increase in level of cyclosporine, carbamazepine and theophylline in blood serum at their simultaneous use.
At simultaneous use of Verapamil of a hydrochloride with inhalation anesthetics or blockers of neuromuscular transfer, dose of drugs it is necessary to modify to avoid the oppressing action on cordial activity. Drug exponentiates action of muscle relaxants.
Beta adrenoblockers, antiaritmik І the Class A, cardiac glycosides, X-ray contrast means can exponentiate the oppressing effect of Verapamil of a hydrochloride on automatism of a sinuatrial node, AV-conductivity and contractility of a myocardium.

Contraindications:

• Heart failure.
• Arterial hypotension (systolic pressure of blood is lower than 90 mm of mercury.).
• Cardiogenic shock.
• Bradycardia (<50 beats/min).
• Sinuatrial (SA) blockade.
• A sick sinus syndrome (except for patients with an artificial ritmovoditel).
• Atrioventricular (AV) blockade of the II-III degree (except for patients with an artificial ritmovoditel).
• Atrial fibrillation or an atrial flutter (against the background of syndromes of WPW and LGL).
• Hypersensitivity to Verapamil to a hydrochloride or to other components of drug.
• Pregnancy and period of feeding by a breast.

Overdose:

The specific antidote is absent.
The main symptoms of overdose of Verapamil of a hydrochloride is arterial hypotension, heart failure, an asystolia and an atrioventricular block of different degree.
At overdose it is necessary to provide careful medical control of a condition of the patient in chamber of intensive therapy (arterial pressure, breath, an ECG).
To the patient appoint a gastric lavage, purgatives and absorbent carbon.
In case of development of the expressed arterial hypotension or a total atrioventricular block intravenously appoint Isoproterenolum, noradrenaline, метараминолтартрат, atropine (in usual doses), a calcium gluconate (10% solution); in extremely serious conditions use pacemakers.
At tachycardia, a bystry ventricular rhythm at patients with trembling and fibrillation of auricles, with syndromes of WPW and LGL use electric cardioversion, intravenous administration of procaineamide (novokainamid) or lidocaine.
If the used means were insufficiently effective, use of inotropic drugs (dopamine or Dobutaminum) is possible.
The hemodialysis is inefficient for bystry removal of Verapamil of a hydrochloride.

Storage conditions:

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

Period of validity - 3 years.

Issue conditions:

According to the recipe

Packaging:

On 10 tablets in a blister strip packaging; or on 10 tablets in a blister strip packaging, on 5 planimetric packagings in a pack.