Verapamil - instructions for use, dose, side effects, contraindications

Excipients: citric acid monohydrate - 18.490 mg; sodium chloride - 8,500 mg; 1M sodium hydroxide solution - 0.175 ml; 0.1 M hydrochloric acid solution - 0.120 ml; water for injection - up to 1 ml.

Description:Pcolorless liquid.

Pharmacotherapeutic group:The blocker of "slow" calcium channels

ATX: & nbsp

C.08.D.A.01 Verapamil

C.08.D.A Phenylalkylamine derivatives

Pharmacodynamics:

Verapamil has antiarrhythmic, anti-anginal and antihypertensive activity. It blocks transmembrannoe intake of calcium ions (and possibly sodium ions) through the "slow" channels into the cells of the conductive system of the myocardium and smooth muscle cells of the myocardium and vessels. The antiarrhythmic effect of verapamil is probably due to its effect on the "slow" channels in the cells of the conduction system of the heart. The electrical activity of the sinoatrial (SA) and the atrioventricular node largely depends on the entry of calcium into the cells through the "slow" channels. Inhibiting calcium intake of verapamil slows the atrioventricular (AV) carrying out and increasing the effective refractory period in AV The site is proportional to the heart rate (heart rate). This effect leads to a decrease in the frequency of ventricular contractions in patients with atrial fibrillation and / or atrial flutter. Terminating the re-entry of excitation in AV node, verapamil can restore the correct sinus rhythm in patients with paroxysmal supraventricular tachycardia, including Wolff-Parkinson-White syndrome (WPW).

Verapamil does not interfere with conduction on additional conductive pathways, does not affect the normal atrial action potential or the time of intraventricular conduction, but decreases the amplitude, rate of depolarization, and conduction in altered atrial fibers. Does not cause spasm of the peripheral arteries and does not change the total content of calcium in the blood serum. Reduces afterload and contractility of the myocardium. In most patients, including patients with organic heart lesions, the negative inotropic effect of verapamil is offset by a decrease in postload, the cardiac index usually does not decrease,but in patients with moderate and severe chronic heart failure (CHF) (pulmonary artery wedge pressure more than 20 mm Hg, LVEF less than 35%) acute CHF decompensation can be observed. The maximum therapeutic effect is noted 3-5 minutes after the bolus intravenous injection of verapamil. Standard therapeutic doses of verapamil 5-10 mg with intravenous administration cause transient, usually asymptomatic, decrease in normal blood pressure (BP), systemic vascular resistance and contractility; the filling pressure of the left ventricle slightly increases.

Pharmacokinetics:

Verapamil is a racemic mixture consisting of the same amount R-enantiomer and Senantiomer.

Distribution

Verapamil is well distributed in the body tissues, the volume of distribution in healthy volunteers is 1.6-1.8 l / kg. The connection with blood plasma proteins is about 90%.

Metabolism

Verapamil undergoes intensive metabolism. Metabolic Research in vitro showed that verapamil is metabolized by isoenzymes CYP3A4, CYP1A2, CYP2C8, CYP2C9 and CYP2C18 cytochrome p450 systems. In healthy volunteers after ingestion verapamil is subject to intensive metabolism in the liver, whileTwelve metabolites were discovered, most of them in trace amounts. The main metabolites were identified as forms N and O-dealkylated derivatives of verapamil. Among the metabolites, only noravapamil has pharmacological activity (about 20% compared to the parent compound), which was revealed during the study on dogs.

Penetrates through the blood-brain and placental barrier and into breast milk (in small amounts).

Excretion

When administered intravenously, the curve of the change in the concentration of verapamil in the blood is bi-exponential with a rapid early distribution phase (half-life (T_1/2) - about 4 minutes) and a slower terminal phase of excretion (T_1/2 - 2-5 hours). Within 24 hours about 50% of the dose of verapamil is excreted by the kidneys, within 5 days - 70%. Up to 16% of the dose of verapamil is excreted through the intestine. Approximately 3-4% of verapamil is excreted by the kidneys unchanged. The total clearance of verapamil roughly coincides with the hepatic blood flow, i.e.about 1 l / h / kg (in the range: 0.7-1.3 l / h / kg).

Special patient groups

Elderly patients

Age can affect the pharmacokinetic parameters of verapamil when it is taken by patients with hypertension. T_1/2can be increased in elderly patients. The relationship between the antihypertensive effect of verapamil and age was not revealed.

Impaired renal function

Impaired renal function does not affect the pharmacokinetic parameters of verapamil, which was found in comparative studies involving patients with terminal renal failure and patients with normal renal function. Verapamil and norverapamil are not excreted by hemodialysis.

Indications:

For the treatment of supraventricular tachyarrhythmias, including:

- restoration of sinus rhythm in paroxysmal supraventricular tachycardia, including conditions associated with the presence of additional pathways in the syndrome of Wolff-Parkinson-White and Launa-Ganong-Levin (LGL).

If there are clinical indications, it is advisable before using the drug Verapamil try to have an effect on the vagus nerve (for example, the Valsalva maneuver).

- temporal control of ventricular frequency during flutter and atrial fibrillation (tachyarrhythmic variant), with the exception of cases when fluttering or atrial fibrillation is associated with the presence of additional pathways (syndromes WPW and LGL).

Contraindications:

- Hypersensitivity to the active substance or auxiliary components of the drug;

- severe arterial hypotension (systolic blood pressure less than 90 mm Hg);

- syndrome of weakness of the sinus node (except for patients with an artificial pacemaker);

- heart failure with a reduced left ventricular ejection fraction of less than 35% and / or a pulmonary artery wedge pressure of more than 20 mm Hg, with the exception of heart failure caused by supraventricular tachycardia to be treated with verapamil;

- atrioventricular blockade of II-III degree (except for patients with an artificial pacemaker);

- cardiogenic shock;

- Atrial fibrillation / flutter in the presence of additional pathways (Wolff-Parkinson-White syndrome, Laun-Ganong-Levin syndrome). These patients are at risk of developing ventricular tachyarrhythmia,including ventricular fibrillation in the case of verapamil;

- ventricular tachycardia with wide complexes QRS (more than 0.12 seconds) (see section "Special instructions");

- pregnancy, the period of breastfeeding;

- simultaneous use with beta-blockers, intravenously. Verapamil and beta-blockers should not be administered simultaneously (for several hours), so both can reduce myocardial contractility and AV conduction (csection "Interaction with other medicinal products");

- use of disopyramide 48 hours before and 24 hours after admission-verapamil:

- simultaneous application with ivabradine (see section "Interaction with other medicinal products");

- age to 18 years (efficacy and safety not established).

Carefully:

Arterial hypotension, atrioventricular blockade of the first degree, bradycardia, asystole, hypertrophic obstructive cardiomyopathy, heart failure, acute myocardial infarction with left ventricular failure, elderly age, severe violations of the liver and / or kidney function, diseases affecting neuromuscular transmission (myasthenia gravis gravis, Lambert-Eaton syndrome, Duchenne muscular dystrophy), simultaneous use with cardiac glycosides, quinidine, flecainide, simvastatin, lovastatin, atorvastatin; ritonavir and other antiviral drugs for the treatment of HIV infection; beta-adrenoblockers for oral administration; agents that bind to blood plasma proteins (see section "Interaction with other medicinal products").

Pregnancy and lactation:

Data on the use of the drug Verapamil in pregnant women there.

Studies in animals have not revealed a direct or indirect toxic effect on the reproductive system. Due to the fact that the results of studies of drugs on animals do not always allow you to predict the response to treatment in humans, the drug Verapamil can be used during pregnancy only if the benefit to the mother exceeds the potential risk to the fetus / child.

Verapamil penetrates the placental barrier and is found in the blood of the umbilical vein during childbirth.

Verapamil and its metabolites are excreted in breast milk. Available limited data on drug intake Verapamil inside show that the dose of verapamil, which is given to infants with mother's milk, is rather small (0.1-1% of the dose of verapamil taken by the mother), and the use of verapamil can be compatible with breastfeeding. However, it is impossible to exclude the risk for the newborn and infants. Given the potential for serious adverse effects in infants, the drug Verapamil in the period of breastfeeding should be used only if the benefit to the mother exceeds the potential risk for the child.

Dosing and Administration:

Enter only intravenously, slowly, for at least 2 minutes, with continuous monitoring of the electrocardiogram, heart rate and blood pressure.

In elderly patients, the administration is carried out for at least 3 minutes to reduce the risk of unwanted effects.

Initial dose is 5-10 mg (0.075-0.15 mg / kg body weight).

Repeated dose is 10 mg (0.15 mg / kg body weight), administered 30 minutes after the first administration with an inadequate response to the first administration.

A drug Verapamil is compatible with the most common solutions for parenteral administration of a large volume and is chemically stable therein for at least 24 hours at 25 ° C in a dark place.

Before use, the dosage form for parenteral administration should be assessed visually for the presence of sediment and discoloration. Do not use if the solution is cloudy. The remaining unused solution should be destroyed immediately after taking a portion of the contents of any volume.

To avoid disturbance of stability, it is not recommended to plant Verapamil solutions of sodium lactate for injection in bags of polyvinyl chloride. Mixing with solutions of albumin, amphotericin B, hydralazine hydrochloride or trimethoprinem and sulfamethoxazole should be avoided.

Verapamil precipitates in any solution with a pH of more than 6.0.

A solution of verapamil is prepared by diluting 2 ml of a 2.5 mg / ml solution in 100-150 ml of a 0.9% solution of sodium chloride.

Side effects:

The frequency of side effects is classified according to the recommendations of the World Health Organization: very often - not less than 10%; often - not less than 1%, but less than 10%; infrequently - not less than 0,1%,but less than 1%; rarely - not less than 0.01%, but less than 0.1%; very rarely - 0,01%; frequency is unknown (can not be calculated from available data).

From the cardiovascular system: often - a bradycardia, "tides" of blood to the skin of the face, a pronounced decrease in blood pressure; infrequently - tachycardia, palpitation; frequency unknown - atrioventricular block I, II, III degrees; development or aggravation of the course of heart failure, stopping the sinus node (sinus arrest), sinus bradycardia, asystole.

From the immune system: frequency is unknown - hypersensitivity.

From the side of metabolism: frequency is unknown - hyperkalemia.

From the central nervous system: often - dizziness, headache; rarely - paresthesia, tremor, drowsiness; frequency unknown - extrapyramidal disorders, paralysis (tetraparesis)¹, convulsive seizures.

From the organ of hearing: rarely - noise in the ears; frequency unknown - vertigo.

From the respiratory system: frequency unknown - bronchospasm, dyspnea.

From the digestive system: often - nausea, constipation; infrequently - abdominal pain; rarely vomiting; frequency is unknown - discomfort in the abdomen, gingival hyperplasia, intestinal obstruction.

From the side of the kidneys and urinary tract: frequency unknown - renal failure.

Laboratory data: the frequency is unknown - increasing the concentration of prolactin, increasing the activity of "hepatic" transaminases.

From the skin: rarely - increased sweating; frequency is unknown - pruritus, rash, angioedema, Stevens-Johnson syndrome, erythema multiforme, alopecia, maculopapular rash, urticaria.

From the side of the musculoskeletal and connective tissue: frequency unknown - arthralgia, muscle weakness, myalgia.

From the genitals and breast: frequency unknown - erectile dysfunction, galactorrhea, gynecomastia.

General disorders: often - peripheral edema; infrequently - increased fatigue.

¹ - during the post-registration application reported a single case of paralysis (tetraparesis) associated with the joint use of verapamil and colchicine, which could be associated with colchicine penetration through the blood brain barrier due to the suppression of isoenzyme activity CYP3A4 and P-glycoprotein under the action of verapamil (see. The section "Interaction with other drugs").

Overdose:

Symptoms: sinus bradycardia, turning into atrioventricular blockade and stopping the sinus node ("sinus arrest"), marked decrease in blood pressure; hyperglycemia, stupor and metabolic acidosis. There are reports of deaths from overdose.

Treatment: symptomatic maintenance therapy.

With clinically pronounced hypotensive reactions or AV blockade should be appointed vasopressors or pacing, respectively. With asystole, it is necessary to use beta-adrenergic stimulation (isoprenaline), other vasopressors or resuscitation. Hemodialysis is ineffective.

Interaction:

In patients with severe cardiomyopathy, CHF, or after a previous myocardial infarction, the simultaneous administration of verapamil and beta-blockers or disopyramide intravenously in rare cases led to the development of serious adverse events.

The simultaneous use of verapamil intravenously with drugs that suppress adrenergic function can lead to an increase in antihypertensive action.

Metabolic Research in vitro evidence that verapamil metabolized by isozymes CYP3A4, CYP1A2, CYP2C8, CYP2C9 and CYP2C18 of the cytochrome P450 system.

Verapamil is an inhibitor of the isoenzyme CYP3A4 and P-glycoprotein. A clinically significant interaction was observed with simultaneous application with isoenzyme inhibitors CYP3A4, with an increase in the concentration of verapamil in blood plasma, while isoenzyme inducers CYP3A4 reduced the concentration of verapamil in blood plasma. With the simultaneous use of such drugs should take into account the possibility of this interaction.

Table 1 presents data on the possible drug interaction due to pharmacokinetic parameters.

Table 1

*Possible types of interactions associated with isoenzymes of the cytochrome P450 system*
A drug	Possible drug interactions	A comment
*Alpha-blockers*
Prazozin	Increase in C_max prazosin (40%), does not affect T_1/2prazosin	Gain antihypertensive action
Terazozin	The increase in AUC terazosin (24%) and C_max(25%)
*Antiarrhythmics*
Flecainide	The minimal effect on the clearance of flecainide in the blood plasma (10%); does not affect the clearance of verapamil in blood plasma	see the section "Interaction with other medicinal products"
Quinidine	Decreased oral clearance of quinidine (35%)	A marked decrease in blood pressure, pulmonary edema can be observed in patients with hypertrophic obstructive cardiomyopathy
*Means for the treatment of bronchial asthma*
Theophylline	Reduction of oral and systemic clearance (20%)	Reduced clearance in smokers (-11%)
*Anticonvulsants / antiepileptics*
Carbamazepine	An increase in carbamazepine AUC (46%) in patients with persistent partial epilepsy	An increase in the concentration of carbamazepine, which can lead to the development of such side effects of carbamazepine as diplopia, headache, ataxia or dizziness
Phenytoin	Reduction of the concentration of verapamil in blood plasma
*Antidepressants*
Imipramine	Increase in AUC of imipramine (15%)	Does not affect the concentration of the active metabolite, desipramine
*Hypoglycemic agents*
Glibenclamide	Increase in C_max Glibenclamide (28%), AUC (26%)
*Anti-gouty agents*
Colchicine	Increase AUC colchicine (2 times) and C_max (1.3 times)	Reduce the dose of colchicine (see instructions for the use of colchicine)
*Antimicrobial medications*
Clarithromycin	It is possible to increase the concentration of verapamil
Erythromycin	It is possible to increase the concentration of verapamil
Rifampicin	The administration of verapamil intravenously does not affect the pharmacokinetic parameters	Antihypertensive effect may decrease
Telithromycin	It is possible to increase the concentration in the blood plasma
*Antineoplastic agents*
Doxorubicin	The administration of verapamil intravenously does not affect the pharmacokinetics of doxorubicin
*Barbiturates*
Phenobarbital	Increase in oral clearance of verapamil (approximately 5 times)
*Benzodiazepines and other tranquilizers*
Buspirone	Increase in AUC and C_maxbuspirone in 3,4 times
Midazolam	Increase AUC (3 times) and C_max(2-fold) of midazolam
*Beta-blockers*
Metoprolol	The increase in AUC (32.5%) and C_max(41%) metoprolol in patients with angina pectoris	see section "Special instructions"
Propranolol	The increase in AUC (65%) and C_max(94%) propranolol in patients with angina pectoris
*Cardiac glycosides*
Digitoxin	A decrease in the total clearance (27%) and extrarenal clearance (29%) of digitoxin
Digoxin	Increase FROM_max (by 44%), C_12h(by 53%), Css (by 44%) and AUC (by 50%) digoxin in healthy volunteers	To reduce the dose of digoxin, see the section "Special instructions"
*H2 receptor antagonists*
Cimetidine	AUC R- (25%) and S- (40%) increase in verapamil with a corresponding decrease in verapamil clearance after R- and S-verapamil	Cimetidine reduces the clearance of intravenous verapamil
*Immunological / immunosuppressive agents*
Cyclosporin	Increase in AUC, Css, С_max (by 45%) cyclosporine
Everolimus	Increase AUC (3.5 times) and C_max(in 2,3 times) Verapamil: increase in concentration of a preparation in a blood plasma directly before reception of the next dose (in 2,3 times)	It may be necessary to determine the concentration and titration of the dose of everolimus
Sirolimus	Increased AUC of sirolimus (2.2 times); increase in AUC S-verapamil (1.5 times)	It may be necessary to determine the concentration and titration of the dose of sirolimus
Tacrolimus	It is possible to increase the concentration of tacrolimus
*Hypolipidemic agents (inhibitors of HMG-CoA reductase)*
Atorvastatin	Perhaps an increase in the concentration of atorvastatin in blood plasma, an increase in AUCverapamil (43%)	Additional information is provided below.
Lovastatin	It is possible to increase the concentration of lovastatin and AUCverapamil (63%) and C_max (32%) in the blood plasma
Simvastatin	Increase AUC (2.6 times) and FROM_max simvastatin (4.6 times)
*Serotonin Receptor Agonists*
Almotriptan	The increase in AUC (20%) and C_max(24%) of the almotriptan
*Urikozuric means*
Sulfinpyrazone	The administration of verapamil intravenously does not affect the pharmacokinetics	Antihypertensive effect may decrease
*Other*
Grapefruit juice	The increase in AUC R- (49%) and S- (37%) verapamil and C_max R- (75%) and S- (51%) of verapamil	T_1/2and renal clearance did not change. Grapefruit juice should not be taken with verapamil
St. John's wort perforated	Reduction of AUC R- (78%) and S- (80%) verapamil with a corresponding decrease in C_max

Other drug interactions

Antiviral drugs for the treatment of HIV infection

Ritonavir and other antiviral drugs for the treatment of HIV infection can inhibit the metabolism of verapamil, which leads to an increase in its concentration in the blood plasma. Therefore, with the simultaneous use of such drugs and verapamil should be careful or reduce the dose of verapamil.

Lithium

An increase in neurotoxicity of lithium was observed with the simultaneous use of verapamil and lithium in the absence of changes or an increase in the concentration of lithium in serum.However, an additional dose of verapamil also led to a decrease in serum lithium concentration in patients taking lithium drugs for a long time inside. With the simultaneous use of these drugs, careful monitoring of patients is necessary.

Neuromuscular blocking agents

Clinical data and the results of preclinical studies suggest that verapamil can potentiate the effect of drugs that block neuromuscular conduction (such as curare-like and depolarizing muscle relaxants). In this connection, it may be necessary to reduce the dose of verapamil and / or a dose of drugs that block neuromuscular conduction when they are used simultaneously.

Acetylsalicylic acid (as an antiplatelet agent)

Increased risk of bleeding.

Ethanol

Increase in the concentration of ethanol in the blood plasma and slowing its elimination. Therefore, the effect of ethanol can be enhanced.

Inhibitors of HMG-CoA reductase (statins)

Patients receiving verapamil, treatment with statins (ie simvastatin, atorvastatin or lovastatin) should begin with the lowest possible dose, which is then increased. If it is necessary to appoint verapamil patients who are already receiving statins should be reviewed and reduced their doses according to the concentration of cholesterol in the blood serum.

Fluvastatin, pravastatin and rosuvastatin not metabolized by isoenzyme CYP3A4, so their interaction with verapamil is less likely.

Means that bind to blood plasma proteins

Verapamil as a means, highly binding to blood proteins (including coumarin and indanedione derivatives, non-steroidal anti-inflammatory drugs, quinine, salicylates, sulfinpyrazone), should be applied with caution while taking with other drugs having this ability.

Means for inhalation of general anesthesia

With the simultaneous use of funds for inhalation anesthesia and blockers of "slow" calcium channels, which include verapamil, the dose of each agent should be carefully titrated to achieve the desired effect in order to avoid excessive inhibition of the cardiovascular system.

Hypotensive drugs, diuretics, vasodilators

Increased antihypertensive action.

Cardiac glycosides

Verapamil for intravenous administration was used in conjunction with cardiac glycosides. Because these drugs slow down AV conductivity, it is necessary to monitor patients for timely detection AV blockade or severe bradycardia.

Quinidine

Verapamil for intravenous administration was administered to a small group of patients receiving quinidine inside. There are several reports of cases of pronounced blood pressure lowering with simultaneous use of quinidine inwards and verapamil intravenously, so this combination of drugs should be used with caution.

Flecainide

A study involving healthy volunteers showed that with the combined use of verapamil and flecainide, an additive effect is possible with a decrease in myocardial contractility, slowing AV conductivity and repolarization of the myocardium.

Disopyramide

Prior to receiving data on the possible interaction between verapamil and disopyramide, do not prescribe disopyramide 48 hours before or 24 hours after using verapamil (see "Contraindications").

Dabigatran

With simultaneous use with dabigatran - an increase (FROM_maxup to 90% to 70% of dabigatran.The risk of bleeding may increase.

Iwabradine

Simultaneous use with ivabradine is contraindicated due to the development of an additional negative chronotropic effect of verapamil to ivabradine.

Beta-blockers

Verapamil for intravenous administration was given to patients receiving beta-blockers inwards. It is necessary to take into account the possibility of adverse interactions, because both drugs can reduce myocardial contractility or AV-conductivity. The simultaneous use of verapamil and beta-blockers intravenously led to the development of serious adverse reactions, especially in patients with severe cardiomyopathy, CHF, or after a previous myocardial infarction (see section "Contraindications").

Special instructions:

It is rare to develop life-threatening side effects (atrial fibrillation / flutter with a high incidence of ventricular contraction, with the presence of additional pathways, severe arterial hypotension, or severe bradycardia / asystole).

Acute myocardial infarction

Verapamil should be used with caution in patients with acute myocardial infarction complicated by bradycardia, severe lowering of blood pressure, or left ventricular dysfunction.

Heart block / Atrioventricular block of degree I / Bradycardia / Asystole

Verapamil affects AV and SA nodes and slows down AV conductivity. A drug Verapamil should be used with caution, as development AV II and III degrees (see the section "Contraindications") or a single-bundle, two-beam or three-beam blockade of the legs of the bundle of Hisb require the termination of the use of verapamil and appropriate therapy if necessary.

Verapamil affects AV and SA nodes and in rare cases can cause development AV blockades of II and III degree, bradycardia and, in extreme cases, asystole. These phenomena are most likely in patients with sinus node weakness syndrome, which is more common in elderly patients.

Asystole in patients who do not have sinus node weakness is usually short-term (several seconds) with spontaneous recoveryatrioventricular or normal sinus rhythm. If the sinus rhythm is not restored in time, it is necessary to immediately prescribe the appropriate treatment.

Beta-blockers and antiarrhythmics

Mutual strengthening of influence on the cardiovascular system (AV blockade of a high degree, significant reduction in heart rate, exacerbation of the course of heart failure and pronounced decrease in blood pressure). Asymptomatic bradycardia (36 beats per minute) with rhythm migration in the atrium was observed in a patient simultaneously receiving timolol (beta-blocker) in the form of eye drops and verapamil inside.

Digoxin

In the case of simultaneous reception of verapamil with digoxin, the dose of digoxin should be reduced (see the section "Interaction with other medicinal products").

Heart failure

Patients with heart failure and a left ventricular ejection fraction greater than 35% should achieve a stable condition before starting the drug Verapamil and conduct appropriate therapy in the future.

Arterial hypotension

Intravenous administration of the drug Verapamil often causes a decrease in blood pressure below the initial values, usually short-term and asymptomatic, but may be accompanied by dizziness.

Inhibitors of HMG-CoA reductase (statins)

See section "Interaction with other medicinal products".

Violations of neuromuscular transmission

A drug Verapamil should be used with caution in patients with diseases affecting neuromuscular transmission (myasthenia gravis gravis, Lambert-Eaton syndrome, Duchenne muscular dystrophy).

Renal impairment

Comparative studies have demonstrated that the pharmacokinetics of verapamil remains unchanged in patients with terminal stage of renal failure. However, some of the available to assume that the drug Verapamil in patients with impaired Kidney function should be used with caution and careful monitoring. Verapamil not excreted by hemodialysis.

Dysfunction of the liver

A drug Verapamil Use with caution in patients with severe impairment of liver function.

Ventricular tachycardia

Intravenous administration of the drug Verapamil patients with ventricular tachycardia with wide complexes QRS (more than 0.12 seconds) can lead to a marked deterioration in the parameters of hemodynamics and ventricular fibrillation. Before the start of treatment, it is mandatory to conduct proper diagnosis and exclude ventricular tachycardia with wide complexes QRS.

In the treatment it is necessary to control the function of the cardiovascular and respiratory system, the concentration of glucose and electrolytes in the blood, the volume of circulating blood and the amount of urine released.

Effect on the ability to drive transp. cf. and fur:

With caution apply during work drivers of vehicles and people whose profession is associated with increased concentration of attention (reduces the reaction rate).

Form release / dosage:

Solution for intravenous administration, 2.5 mg / ml.

Packaging:

2 ml per ampoule of colorless neutral glass type I with a colored break ring or with a colored dot and a notch or without a kink ring, a colored dot and a notch. One, two or three color rings and / or a two-dimensional bar code, and / or alphanumeric coding or without additional color rings, a two-dimensional bar code, and alphanumeric coding can additionally be applied to the ampoules.

5 ampoules per circuit cell packaging made of polyvinylchloride film and aluminum foil foil or polymer film or without foil and without film. Or 5 ampoules are placed in a prefabricated form (tray) made of cardboard with cells for laying ampoules.

1 or 2 contour squares or cardboard tracks together with the instruction for use and a scarifier or knife with an ampoule, or without a scarifier and an ampoule knife are placed in a cardboard box (bundle).

Storage conditions:

In the dark place at a temperature of no higher than 25 ° C. Do not freeze.

Keep out of the reach of children.

Shelf life:

2 of the year.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-003640

Date of registration:20.05.2016

Expiration Date:20.05.2021

The owner of the registration certificate:ATOLL, LLC ATOLL, LLC Russia

Manufacturer: & nbsp

OZONE, LLC Russia

Information update date: & nbsp28.01.2017

Illustrated instructions

Instructions

Verapamil (Verapamil)