Active substance

Verapamil hydrochloride (verapamil)

Release form, composition and packaging

Excipients: dibasic calcium phosphate, starch, butylhydroxyanisole, purified talc, magnesium stearate, gelatin, methyl paraben, hydroxypropyl methylcellulose, titanium dioxide, indigo carmine.

Excipients: dibasic calcium phosphate, starch, butylhydroxyanisole, purified talc, magnesium stearate, gelatin, methyl paraben, hydroxypropyl methylcellulose, titanium dioxide, indigo carmine.

10 pieces. - blisters (1) - packs of cardboard.
10 pieces. - blisters (5) - packs of cardboard.

pharmachologic effect

Verapamil is one of the main drugs of the blocker group. calcium channels. It has antiarrhythmic, antianginal and antihypertensive activity.

The drug reduces myocardial oxygen demand by reducing myocardial contractility and reducing heart rate. Calls an extension coronary vessels heart and increases coronary blood flow; reduces the tone of the smooth muscles of the peripheral arteries and the total peripheral vascular resistance.

Verapamil significantly slows down AV conduction, inhibits automatism sinus node, which allows the use of the drug for the treatment of supraventricular arrhythmias.

Verapamil is the drug of choice for the treatment of vasospastic angina (Prinzmetal's angina). It has an effect in angina pectoris, as well as in the treatment of angina pectoris with supraventricular arrhythmias.

Pharmacokinetics

When taken orally, more than 90% of the dose taken is absorbed. It is metabolized during the "first pass" through the liver. Protein binding - 90%. T 1/2 when taking a single dose is 2.8 -7.4 h; when taking repeated doses - 4.5-12 hours. It is excreted mainly by the kidneys and 9-16% through the intestines. The main metabolite is norverapamil, which has less pronounced hypotensive activity than unchanged verapamil.

Indications

- treatment and prevention of rhythm disturbances: paroxysmal supraventricular tachycardia, atrial flutter and fibrillation (tachyarrhythmic variant), supraventricular extrasystole;

– treatment and prevention of chronic stable angina pectoris (angina pectoris), unstable angina(rest angina); vasospastic angina (Prinzmetal's angina, variant angina);

- treatment of arterial hypertension.

Contraindications

- severe bradycardia;

- chronic heart failure stage IIB-III;

- cardiogenic shock (except for that caused by arrhythmia);

- sinotrial blockade;

- AV blockade II and III degree(excluding patients with an artificial pacemaker);

- syndrome of weakness of the sinus node;

- Wolff-Parkinson-White syndrome;

- Morgagni-Adams-Stokes syndrome;

- acute heart failure;

- simultaneous use (in / in);

— childhood up to 18 years;

— hypersensitivity to the components of the drug.

Carefully it is necessary to prescribe the drug to patients with AV blockade of the 1st degree, chronic heart failure of the 1st and 2nd degrees, arterial hypotension (systolic pressure below 100 mm Hg), bradycardia, severe liver dysfunction.

Dosage

Verapamil is taken orally during or after a meal with a small amount of water.

The dosage regimen and duration of treatment are set individually depending on the patient's condition, severity, characteristics of the course of the disease and the effectiveness of therapy.

For prevention of angina attacks, arrhythmias and in the treatment of arterial hypertension the drug is prescribed adults in the initial dose of 40-80 mg 3-4 times / day. If necessary, increase a single dose to 120-160 mg. The maximum daily dose of the drug is 480 mg.

At patients with severe liver dysfunction the excretion of verapamil from the body is slow, so it is advisable to start treatment with minimal doses. Daily dose the drug should not exceed 120 mg.

Side effects

From the side of cardio-vascular system: reddening of the face, severe bradycardia, AV blockade, arterial hypotension, the appearance of symptoms of heart failure when using the drug in high doses especially in predisposed patients.

From the side digestive system: nausea, vomiting, constipation; in individual cases- transient increase in the activity of hepatic transaminases in the blood.

From the side of the central nervous system: dizziness, headache, in rare cases - increased nervous excitability, lethargy, increased fatigue.

Allergic reactions: skin rash, itching.

Others: development of peripheral edema.

Overdose

Symptoms: large doses (taking up to 6 g of the drug) can cause a deep loss of consciousness, arterial hypertension, sinus bradycardia, turning into aAV blockade, sometimes asystole.

Treatment: in the event of arterial hypotension and / or complete AV blockade - in / in the introduction of fluid, dopamine, isoproterenol or norepinephrine. Treatment is symptomatic and depends on clinical picture overdose. Hemodialysis is not effective.

drug interaction

With the simultaneous use of Verapamil c:

- antiarrhythmic drugs, beta-blockers and inhalation anesthetics, there is an increase in the cardiotoxic effect (increased risk of atrioventricular blockade, a sharp decrease in heart rate, the development of heart failure, a sharp drop blood pressure);

- antihypertensive agents and diuretics may increase the hypotensive effect of Verapamil;

- it is possible to increase the level of digoxin concentration in the blood plasma due to the deterioration of its excretion by the kidneys (therefore, it is necessary to monitor the level of digoxin in the blood plasma in order to identify its optimal dosage and prevent intoxication);

- cimetidine and ranitidine increase the level of concentration of Verapamil in the blood plasma;

- rifampicin, phenobarbital may reduce the concentration in blood plasma and weaken the action of Verapamil;

- theophylline, prazosin, cyclosporine may increase the concentration of these substances in the blood plasma;

- muscle relaxants may enhance the muscle relaxant action;

- acetysalicylic acid increases the possibility of bleeding;

- quinidine increases the level of concentration of quinidine in the blood plasma, increases the risk of lowering blood pressure, and in patients with hypertrophic cardiomyopathy possible occurrence of severe arterial hypotension;

- Carbamazepine and lithium increase the risk of neurotoxic effects.

special instructions

During treatment, it is necessary to control the function of the cardiovascular and respiratory systems blood glucose and electrolyte levels, circulating blood volume, and urine output.

Pregnancy and lactation

The use of Verapamil during pregnancy is possible only if the expected benefit to the mother outweighs the potential risk to the fetus. Terms of dispensing from pharmacies

The drug is dispensed by prescription.

Terms and conditions of storage

Store in a dry place, at a temperature not exceeding 25°C. The drug should be stored out of the reach of children. Shelf life - 3 years.

Reg certificate P No. 014947/01-2003 dated April 28, 2003

Trade name of the drug: Verapamil

International non-proprietary name:

Verapamil

Dosage form:

dragee

Composition:

1 dragee contains the active substance - verapamil (in the form of hydrochloride) 40 mg or 80 mg; Excipients- lactose, potato starch, gelatin, avicel, silicon dioxide, magnesium stearate, talc, gum arabic, sucrose, polyvidone K25, polyethylene glycol, Chinolingelblack E 104, paraffin..

Description: yellow dragee

Pharmacotherapeutic group:

blocker of "slow" calcium channels. ATC code: [С08DA01]

Pharmachologic effect:

Pharmacodynamics

Verapamil has antiarrhythmic, antiangial and hypotensive effects. Inhibits the penetration of Ca ++ ions through the membrane of myocardial cells, affecting the conduction system of the heart, leads to vasodilation, negative inotropic action, reduced afterload, inhibition of sinoatrial and atrioventricular conduction.

Verapamil causes an expansion of the coronary vessels of the heart and increases coronary blood flow, reduces myocardial oxygen demand. The antihypertensive effect is enhanced by the natriuretic and diuretic effect of verapamil by reducing calcium reabsorption.

Pharmacokinetics:

Verapamil is almost completely (95%) absorbed from gastrointestinal tract. The maximum concentration of the drug in the blood plasma is reached 1-2 hours after ingestion. Verapamil crosses the blood-brain barrier and the placental barrier. Communication with blood plasma proteins - 90%. Rapidly metabolized in the liver with the formation of several metabolites. The main metabolites are norverapamil, N-dealkylverapamil and N-dealkylnorverapamil. The accumulation of the drug and its metabolites in the body explains the increased effect during course treatment. After a single dose, the half-life is 3-7 hours, with prolonged use - up to 4-12 hours. It is excreted in a small amount unchanged (3-4%), the rest - in the form of metabolites (70%) through the kidneys, about 25% - with bile. Secretion with breast milk is low.

Indications for use:

Treatment and prevention of cardiac arrhythmias

• paroxysmal supraventricular tachycardia;
• atrial fibrillation and flutter (tachyarrhythmic variant);
• supraventricular extrasystole.

Treatment and prevention

• chronic stable angina pectoris (angina pectoris);
• unstable angina (rest angina);
• vasospastic angina (Prinzmetal's angina, variant angina). Treatment of arterial hypertension.

Contraindications:

Hypersensitivity to the drug, arterial hypotension, bradycardia, heart failure IIB - III degree, acute heart failure, acute infarction myocardium, cardiogenic shock (with the exception of that caused by arrhythmia), sinoauricular blockade, atrioventricular blockade II-III st. (excluding patients with an artificial pacemaker), sick sinus syndrome, aortic stenosis, Morgagni-Adams-Stokes syndrome, Wolff-Parkinson-White syndrome, simultaneous use of intravenous beta-blockers, digitalis intoxication, pregnancy, lactation, children under 18 years.

With caution - in patients with severe liver dysfunction, patients with AV blockade I stage, chronic heart failure I and II degree.

Dosage and administration:

Dragee should be taken orally, without sucking or chewing, with a small amount of liquid, preferably before meals or immediately after meals.

The dose of verapamil should be selected individually, depending on the patient's condition, severity, characteristics of the course of the disease and the effectiveness of therapy. The drug is taken at 40-80 mg 3 times a day - for angina pectoris and supraventricular tachycardia in 3 doses, for arterial hypertension - in 2 doses, the daily dose for arterial hypertension is up to 320 mg. With long-term therapy, the daily dose should not exceed 480 mg. Exceeding the dose is possible only for very a short time under close medical supervision.

In patients with impaired liver function, the excretion of verapamil from the body is slow, so it is advisable to start treatment with minimal doses. The daily dose of the drug should not exceed 120 mg.

Side effect:

Verapamil may cause dizziness, headache, redness of the face, nausea and constipation. In rare cases, nervousness, lethargy, fatigue, allergic reactions (pruritus, rash), a transient increase in blood activity of "liver" transaminases and alkaline phosphatase in blood plasma, gynecomastia, hyperprolactinemia, gingival hyperplasia, development of peripheral edema. When using large doses of verapamil, especially in predisposed patients, severe bradycardia, atrioventricular blockade, a pronounced decrease in blood pressure, and symptoms of heart failure may occur.

Overdose.

Symptoms: bradycardia, atrioventricular block, pronounced decrease in blood pressure, heart failure, shock, asystole, SA blockade.

Treatment: with early detection- gastric lavage, Activated carbon; in violation of the rhythm and conduction - intravenous infusion of isoprenaline, norepinephrine, atropine, 10-20 ml of 10% calcium gluconate solution, artificial pacemaker; intravenous infusion of plasma-substituting solutions. To increase blood pressure in patients with hypertrophic cardiomyopathy, alpha-agonists (phenylephrine) are prescribed; do not use isoprenaline and norepinephrine.

Hemodialysis is not effective.

Interaction with other drugs:

Increases the concentration in the blood of digoxin, theophylline, prazosin, cyclosporine, carbamazepine, muscle relaxants.

Cimetidine increases the bioavailability of verapamil by almost 40-50% (due to a decrease in hepatic metabolism), and therefore it may be necessary to reduce the dose of the latter.

Rifampicin, barbiturates, nicotine, accelerating metabolism in the liver, lead to a decrease in the concentration of verapamil in the blood, reduce the severity of antianginal, hypotensive and antiarrhythmic actions.

With simultaneous use with inhalation anesthetics, the risk of developing bradycardia, AV blockade, and heart failure increases.

The combination with beta-blockers, antiarrhythmic drugs can lead to an increase in the negative inotropic effect, an increase in the risk of developing AV conduction disorders, bradycardia.

With simultaneous use with antihypertensive drugs and diuretics, it is possible to increase the hypotensive effect of verapamil, with acetylsalicylic acid- the possibility of bleeding increases.

Special instructions:

During treatment, it is necessary to control the function of the cardiovascular and respiratory systems, the content of glucose and electrolytes in the blood, the volume of circulating blood and the amount of urine excreted.

Release form:

Dragee 40 mg - 30 pieces per pack, dragees 80 mg - 50 pieces per pack.

Storage conditions:

List B.

Store at a temperature of 15 - 25°C, protected from light and moisture.

Keep out of the reach of children.

Best before date:

5 years. Do not use after the date indicated on the package.

Conditions for dispensing from pharmacies:

By prescription.

Manufactured:

Hemofarm concern A.D., Yugoslavia

26300 Vrsac, Beogradsky way bb, Yugoslavia

tel.: 13/821345, tel./fax: 13/821424

Catad_pgroup Calcium channel blockers

Isoptin for injections - official instruction by application

Currently, the drug is not listed in the State Register medicines or specified registration number excluded from the register.

Registration number:

P N015547/01

Active substance:

Verapamil

Dosage form:

solution for intravenous administration

Composition:

For 2 ml of solution:

active substance: verapamil hydrochloride 5.0 mg;

Excipients: sodium chloride 17.0 mg, 36% hydrochloric acid - to adjust the pH, water for injection - up to 2 ml.

Description:

Clear colorless solution.

Pharmacotherapeutic group:

Blocker of "slow" calcium channels

ATH:

C.08.D.A.01

Pharmacodynamics:

Verapamil blocks the transmembrane entry of calcium ions (and possibly sodium ions) through "slow" channels into the cells of the myocardial conduction system and smooth muscle cells of the myocardium and blood 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 atrioventricular (AV) nodes largely depends on calcium entering the cells through "slow" channels. By inhibiting this supply of calcium,
verapamil slows atrioventricular (AV) conduction and increases the effective refractory period in the AV node in proportion to heart rate (HR). 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 the AV node,
verapamil can restore correct sinus rhythm in patients with paroxysmal supraventricular tachycardia, including Wolff-Parkinson-White (WPW) syndrome.

Verapamil has no effect on accessory conduction pathways, does not affect the normal atrial action potential or intraventricular conduction time, but reduces the amplitude, rate of depolarization, and conduction in altered atrial fibers.

Verapamil does not cause spasm of the peripheral arteries and does not change the total calcium content in the blood serum. Reduces afterload and myocardial contractility. In most patients, including patients with organic heart disease, the negative inotropic effect of verapamil is offset by a decrease in afterload, cardiac index usually does not decrease, but in patients with moderate to severe heart failure (wedge pressure in pulmonary artery more than 20 mm Hg. Art., the ejection fraction of the left ventricle is less than 35%), acute decompensation of chronic heart failure can be observed.

Maximum therapeutic effect observed 3-5 minutes after bolus intravenous administration of verapamil.

Standard therapeutic doses of verapamil 5-10 mg when administered intravenously cause a transient, usually asymptomatic, decrease in normal blood pressure (BP), systemic vascular resistance and contractility; the filling pressure of the left ventricle slightly increased.

Pharmacokinetics:

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

Norverapamil is one of 12 metabolites found in urine. The pharmacological activity of norverapamil is 10-20% of the pharmacological activity of verapamil, and the proportion of norverapamil is 6% of the excreted drug. Steady-state plasma concentrations of norverapamil and verapamil are similar. Equilibrium concentration with prolonged use once a day is reached after 3-4 days.

Distribution

Verapamil is well distributed in body tissues, the volume of distribution (Vd) in healthy volunteers is 1.8-6.8 l / kg. Communication with blood plasma proteins is about 90%.

Metabolism

Verapamil undergoes intensive metabolism. Metabolic Research in vitro showed that
Verapamil is metabolized by CYP3A4, CYP1A2, CYP2C8, CYP2C9 and CYP2C18 cytochrome P450 isoenzymes.

In healthy volunteers after oral administration
Verapamil undergoes extensive metabolism in the liver, with 12 metabolites detected, most of which are in trace amounts. The main metabolites have been identified as the N and O-dealkylated forms of verapamil. Among the metabolites, only norverapamil has pharmacological action(about 20% compared to the parent compound), which was found in a study on dogs.

breeding

With intravenous administration, the curve of change in the concentration of verapamil in the blood is biexponential in nature with a fast early distribution phase (half-life (T 1/2) - about 4 minutes) and a slower terminal elimination phase (T 1/2 - 2-5 hours).

Within 24 hours, about 50% of the dose of verapamil is excreted by the kidneys, within five days - 70%. Up to 16% of a dose of verapamil is excreted through the intestines. Approximately 3-4% of verapamil is excreted by the kidneys unchanged. The total clearance of verapamil approximately coincides with the hepatic blood flow, i.e. about 1 l/h/kg (range: 0.7-1.3 l/h/kg).

Special groups patients

Elderly patients

Age may affect the pharmacokinetic parameters of verapamil when administered to patients with arterial hypertension. T 1/2 may be increased in elderly patients. The relationship between the antihypertensive effect of verapamil and age has not been identified.

Impaired kidney function

Impaired renal function does not affect the pharmacokinetic parameters of verapamil, which was revealed in the course of comparative studies involving patients with terminal stage kidney failure and patients with normal function kidneys.
Verapamil and norverapamil are practically not excreted during hemodialysis.

Indications for use

For the treatment of supraventricular tachyarrhythmias, including:

Recovery sinus rhythm with paroxysmal supraventricular tachycardia, including conditions associated with the presence of additional pathways in Wolff-Parkinson-White (WPW) and Lown-Ganong-Levin (LGL) syndromes.

In the presence of clinical indications it is advisable before using the drug Isoptin® to try to influence nervus vagus(for example, the Valsalva maneuver);

Temporary control of the frequency of ventricular contractions in atrial flutter and fibrillation (tachyarrhythmic variant), except in cases where atrial flutter or fibrillation is associated with the presence of additional pathways (WPW and LGL syndromes).

Contraindications

Hypersensitivity to active substance or auxiliary components drug;

Cardiogenic shock;

Atrioventricular block II or III degree, with the exception of patients with an artificial pacemaker;

Sick sinus syndrome, with the exception of patients with an artificial pacemaker;

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

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

Atrial fibrillation / flutter in the presence of additional pathways (Wolf-Parkinson-White, Lown-Ganong-Levin syndromes). These patients are at risk of developing ventricular tachyarrhythmia, incl. ventricular fibrillation in the case of verapamil;

Ventricular tachycardia with wide QRS complexes (> 0.12 sec.) (see section " special instructions");

Simultaneous use with beta-blockers, intravenously.
Verapamil and beta-blockers should not be administered simultaneously (within a few hours), since both drugs can reduce myocardial contractility and AV conduction (see section "Interaction with other medicines");

The use of disopyramide 48 hours before and 24 hours after taking verapamil;

Pregnancy, period breastfeeding(effectiveness and safety not established);

Age up to 18 years (efficacy and safety not established).

Carefully:

Severe decrease in blood pressure, acute myocardial infarction, left ventricular dysfunction, AV block I degree, bradycardia, asystole, hypertrophic obstructive cardiomyopathy, heart failure.

Impaired kidney function and/or severe violations liver function.

Diseases affecting the neuromuscular transmission (myasthenia gravis, Lambert-Eaton syndrome, Duchenne muscular dystrophy).

Simultaneous administration with cardiac glycosides, quinidine, flecainide, simvastatin, lovastatin, atorvastatin; ritonavir and others antiviral drugs for the treatment of HIV infection; beta-blockers for oral administration; means that bind to plasma proteins (see section "Interactions with other drugs").

Elderly age.

Pregnancy and lactation:

There are no sufficient data on the use of the drug Isoptin® in pregnant women. Animal studies do not reveal direct or indirect toxic action on the reproductive system. Due to the fact that the results of drug studies in animals do not always predict the response to treatment in humans, the drug Isoptin® can be used during pregnancy only if the benefit to the mother outweighs the potential risk to the fetus / child.

Verapamil crosses the placental barrier and is found in the blood of the umbilical vein during childbirth.
Verapamil and its metabolites are excreted in breast milk. The limited data available regarding the oral administration of Isoptin® indicate that the dose of verapamil given to infants with mother's milk is quite low (0.1-1% of the dose of verapamil taken by the mother), and the use of verapamil may be compatible with feeding breast. However, a risk to newborns and infants cannot be ruled out.

Given the possibility of serious side effects in infants, the drug Isoptin® during breastfeeding should be used only if the benefit to the mother outweighs the potential risk to the child.

Dosage and administration

Only intravenously.

Intravenous administration should be carried out slowly over at least 2 minutes with continuous monitoring of the ECG (electrocardiogram) and blood pressure.

In elderly patients and the introduction is carried out for at least 3 minutes to reduce the risk unwanted effects.

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

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

Stability

Isoptin® is compatible with the most commonly used solutions for parenteral administration large volume and chemically stable in them for at least 24 hours at 25 °C, protected from light.

Before use dosage form for parenteral administration, evaluate visually for sediment and discoloration. Do not use if solution is cloudy or vial seal is broken.

The remaining unused solution should be destroyed immediately after taking a portion of the contents of any volume.

Incompatibility

In order to avoid compromising stability, it is not recommended to dilute Isoptin® with sodium lactate solutions for injection in polyvinyl chloride bags. Mixing with solutions of albumin, amphotericin B, hydralazine hydrochloride or trimethoprinem and sulfamethoxazole should be avoided.

Verapamil precipitates in any solution with a pH greater than 6.0.

Side effect

Side effects identified during clinical research and with post-marketing use of the drug Isoptin®, are presented below by organ systems and the frequency of their occurrence in accordance with the WHO classification: very often (> 1/10); often (from? 1/100 to<1/10); нечасто (от?1/1000 до <1/100); редко (от?1/10000 до <1/1000); очень редко (<1/10000); частота неизвестна (невозможно определить на основании доступных данных).

The following side effects were most often observed: headache, dizziness, nausea, constipation, abdominal pain, bradycardia, tachycardia, palpitations, a pronounced decrease in blood pressure, flushing of blood to the skin of the face, peripheral edema and increased fatigue.

Immune system disorders:

frequency unknown: hypersensitivity.

Metabolic and nutritional disorders:

frequency unknown: hyperkalemia.

Mental disorders:

rarely: drowsiness.

Nervous system disorders:

often: dizziness, headache;

rarely: paresthesia, tremor;

frequency unknown: extrapyramidal disorders, paralysis (tetraparesis) 1, convulsive seizures.

Hearing disorders and labyrinth disorders:

rarely: tinnitus;

frequency unknown: twitches.

Heart disorders:

often: bradycardia;

infrequently: palpitations, tachycardia;

frequency unknown: AV blockade I, II, III degree; heart failure, sinus arrest ("sinus arrest"), sinus bradycardia, asystole.

Vascular disorders:

often: "flushing" of blood to the skin of lime, a pronounced decrease in blood pressure.

Respiratory, thoracic and mediastinal disorders:

frequency unknown: bronchospasm, shortness of breath.

Gastrointestinal disorders:

often: constipation, nausea;

infrequently: abdominal pain;

rarely: vomiting;

frequency unknown: abdominal discomfort, gingival hyperplasia, intestinal obstruction.

Skin and subcutaneous tissue disorders:

rarely: hyperhidrosis;

frequency unknown: angioedema, Stevens-Johnson syndrome, erythema multiforme, alopecia, pruritus, pruritus, purpura. maculopapular rash, urticaria.

Musculoskeletal and connective tissue disorders:

frequency unknown: arthralgia, muscle weakness, myalgia.

Renal and urinary tract disorders:

frequency unknown: renal failure.

Genital and breast disorders:

frequency unknown: erectile dysfunction, galactorrhea, gynecomastia.

General disorders:

often: peripheral edema;

infrequently: increased fatigue.

Laboratory and instrumental data:

frequency unknown: increased concentration of prolactin, increased activity of liver enzymes.

1 - in the period of post-registration use of Isoptina®, a single case of paralysis (tetraparesis) associated with the combined use of verapamil and colchicine was reported. This could be due to the penetration of colchicine through the blood-brain barrier due to the suppression of the activity of the CYP3A4 isoenzyme and P-glycoprotein under the action of verapamil (see section "Interaction with other drugs").

Overdose:

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

Treatment: supportive symptomatic therapy should be carried out. For clinically significant hypotensive reactions or AV block, vasopressor drugs or pacing should be given, respectively. Asystole should be treated with beta-adrenergic stimulation (isoprenaline), other vasopressor drugs, or resuscitation. Hemodialysis is ineffective.

Interaction

In patients with severe cardiomyopathy, chronic heart failure or after myocardial infarction, the simultaneous administration of verapamil and intravenous beta-blockers or disopyramide has rarely led to the development of serious adverse events.

The simultaneous use of intravenous verapamil with drugs that suppress adrenergic function may lead to an increase in the antihypertensive effect.

Metabolic Research in vitro testify that
Verapamil is metabolized by the action of cytochrome P450 isoenzymes CYP3A4, CYP1A2, CYP2C8, CYP2C9 and CYP2C18.

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

The table below provides data on possible drug interactions due to pharmacokinetic parameters.

Possible interactions associated with the CYP-450 isoenzyme system
A drug	Possible drug interaction	A comment
Alpha blockers
Prazosin	An increase in C m ax of prazosin (~40%) does not affect T 1/2 of prazosin.	Additional antihypertensive action.
Terazosin	An increase in the AUC of terazosin (-24%) and C m ax (~ 25%).
Antiarrhythmic drugs
Flecainide	Minimal effect on plasma clearance of flecainide (<~10 %); не влияет на клиренс верапамила в плазме крови.
	Decreased oral clearance of quinidine (~35%).	Pronounced decrease in blood pressure. Pulmonary edema may occur in patients with hypertrophic obstructive cardiomyopathy.
Means for the treatment of bronchial asthma
Theophylline	Decreased oral and systemic clearance (~20%).	Decreased clearance in smoking patients (~11%).
Anticonvulsants / antiepileptics
Carbamazepine	Increased AUC of carbamazepine (~46%) in patients with sustained 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	Decreased plasma concentrations of verapamil.
Antidepressants
Imipramine	Increase in AUC of imipramine (~15%).	Does not affect the concentration of the active metabolite, desipramine.
Hypoglycemic agents
Glibenclamide	An increase in C m ax of glibenclamide (-28%), AUC (~26%).
Antigout agents
Colchicine	Increase in AUC of colchicine (~ 2.0 times) and C m ah (~ 1.3 times).	Reduce the dose of colchicine (see instructions for use of colchicine).
Antimicrobials
Clarithromycin
Erythromycin	An increase in the concentration of verapamil is possible.
Rifampicin	Decreased AUC (~97%), Cmax (~94%), bioavailability (~92%) of verapamil.
Telithromycin	An increase in the concentration of verapamil is possible.
Anticancer drugs
Doxorubicin	An increase in AUC (104%) and C m ax (61%) of doxorubicin.	In patients with small cell lung cancer.
Barbiturates
Phenobarbital	Increase in oral clearance of verapamil ~ 5 times.
Benzodiazepines and other tranquilizers
Buspirone	Increase in AUC and C m ah buspirone ~ 3.4 times.
Midazolam	Increase in AUC (~ 3 times) and Cmax (~ 2 times) of midazolam.
Beta blockers
metoprolol	An increase in AUC (-32.5%) and Cmax (-41%) of metoprolol in patients with angina pectoris.	See section "Special Instructions".
propranolol	An increase in AUC (-65%) and C m ax (-94%) of propranolol in patients with angina pectoris.
cardiac glycosides
Digitoxin	Decreased total clearance (-27%) and extrarenal clearance (-29%) of digitoxin.
Digoxin	An increase in C m ax (by -44%), C 12 h (by -53%), C ss (by -44%) and AUC (by -50%) of digoxin in healthy volunteers.	Reduce the dose of digoxin. See section "Special Instructions".
H 2 receptor antagonists
Cimetidine	An increase in the AUC of R- (-25%) and S- (-40%) verapamil with a corresponding decrease in the clearance of R- and S-verapamil.
Immunological/immunosuppressive agents
Cyclosporine	Increase in AUC, C ss , C max (by - 45%) of cyclosporine.
everolimus	Everolimus: increase in AUC (~ 3.5 times) and Cmax (~ 2.3 times) Verapamil: increase in Chough (the concentration of the drug in the blood plasma immediately before taking its next dose) (~ 2.3 times).	It may be necessary to determine the concentration and titrate the dose of everolimus.
Sirolimus	Increase in AUC of sirolimus (~ 2.2 times); increase in AUC S-verapamil (~ 1.5 times).	It may be necessary to determine the concentration and titrate the dose of sirolimus.
Tacrolimus	An increase in the concentration of tacrolimus is possible.
Lipid-lowering agents (HMG-CoA reductase inhibitors)
Atorvastatin	It is possible to increase the concentration of atorvastatin in the blood plasma, an increase in the AUC of verapamil - 43%.	Additional information is provided below.
Lovastatin	It is possible to increase the concentration of lovastatin and the AUC of verapamil (~ 63%) and C m ax (~ 32%) in plasma
Simvastatin	Increase in AUC (~ 2.6 times) and C m ah (~ 4.6 times) of simvastatin.
Serotonin receptor agonists
Almotriptan	Increase in AUC (~20%) and C m ah (~24%) of almotriptan.
Uricosuric agents
Sulfinpyrazone	An increase in oral clearance of verapamil (~ 3 times), a decrease in its bioavailability (~ 60%).	The antihypertensive effect may decrease.
Other
Grapefruit juice	An increase in AUC R- (~ 49%) and S- (~ 37%) of verapamil and C m x R- (~ 75%) and S-C-51%) of verapamil.	T 1/2 and renal clearance did not change. Grapefruit juice should not be taken with verapamil.
St. John's wort	A decrease in AUC R- (~ 78%) and S- (~ 80%) of verapamil with a corresponding decrease in C m ax.

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 blood plasma. Therefore, with the simultaneous use of such drugs and verapamil, care should be taken or the dose of verapamil should be reduced.

Lithium

An increase in lithium neurotoxicity was observed during the simultaneous administration of verapamil and lithium in the absence of changes or an increase in the concentration of lithium in the blood serum. However, the addition of verapamil also led to a decrease in serum lithium concentrations in patients taking oral lithium for a long time. With the simultaneous use of these drugs, careful monitoring of patients is necessary.

Drugs that block neuromuscular conduction

Clinical data and preclinical studies suggest that
verapamil may potentiate the effect of drugs that block neuromuscular conduction (such as curariform and depolarizing muscle relaxants). Therefore, it may be necessary to reduce the dose of verapamil and / or the dose of drugs that block neuromuscular conduction, while using them simultaneously.

Acetylsalicylic acid (as an antiplatelet agent)

Increased risk of bleeding.

Ethanol (alcohol)

Increasing the concentration of ethanol in the blood plasma and slowing down its excretion. Therefore, the effect of ethanol can be enhanced.

HMG-CoA inhibitors - reductases (statins)

Patients receiving
verapamil, treatment with HMG-CoA reductase inhibitors (i.e., simvastatin, atorvastatin, or lovastatin) should be started at the lowest possible dose, which is then increased. If it is necessary to assign
Verapamil patients already receiving HMG-CoA reductase inhibitors should be reviewed and their doses reduced according to the concentration of cholesterol in the blood serum.

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

Plasma protein-binding agents

Verapamil, as a highly protein-binding agent, should be used with caution when taken concomitantly with other drugs with a similar ability.

Means for inhalation general anesthesia

With the combined use of drugs for inhalation anesthesia and blockers of "slow" calcium channels, which include
verapamil, the dose of each agent should be carefully titrated until the desired effect is achieved in order to avoid excessive oppression of the cardiovascular system.

Antihypertensives, diuretics, vasodilators

Enhancement of antihypertensive action.

cardiac glycosides

Verapamil for intravenous administration was used in conjunction with cardiac glycosides. Because these drugs slow AV conduction, patients should be monitored for early detection of AV block or severe bradycardia.

Quinidine

Intravenous verapamil has been administered to a small group of patients receiving
quinidine inside. There are several reports of cases of a pronounced decrease in blood pressure when quinidine is taken orally and verapamil intravenously, so this combination of drugs should be used with caution.

Flecainide

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

Disopyramide

Before receiving data on a possible interaction between verapamil and disopyramide, disopyramide should not be administered 48 hours before or 24 hours after the use of verapamil (see section "Contraindications").

Beta blockers

Verapamil for intravenous administration was prescribed to patients receiving oral beta-blockers. The possibility of adverse interactions must be considered, since both drugs can reduce myocardial contractility or AV conduction. The simultaneous administration of verapamil and intravenous beta-blockers has led to the development of serious adverse reactions, especially in patients with severe cardiomyopathy, chronic heart failure or after myocardial infarction (see section "Contraindications").

Special instructions:

Rarely, life-threatening side effects may develop (atrial fibrillation / flutter with a high ventricular rate, with the presence of additional pathways, severe arterial hypotension or severe bradycardia / asystole).

Acute myocardial infarction

Isoptin® should be used with caution in patients with acute myocardial infarction complicated by bradycardia, severe hypotension or left ventricular dysfunction.

Heart block / AV block I degree / Bradycardia / A systole

Verapamil affects the AV and SA nodes and slows down AV conduction. The drug Isoptin® should be used with caution, since the development of AV block II or III degree (see section "Contraindications") or single-beam, two-beam or three-beam blockade of the His bundle legs requires discontinuation of verapamil and appropriate therapy if necessary.

Verapamil affects the AV and SA nodes and, in rare cases, can cause second or third degree AV block, bradycardia, and, in extreme cases, asystole. These events are most likely in patients with sick sinus syndrome, which is more common in older patients.

Asystole in patients without sinus node weakness is usually brief (several seconds) with spontaneous return to atrioventricular or normal sinus rhythm. If sinus rhythm is not restored in a timely manner, appropriate treatment should be instituted immediately.

Beta-blockers and antiarrhythmics

Mutual strengthening of the effect on the cardiovascular system (high-degree AV blockade, a significant decrease in heart rate, exacerbation of heart failure and a pronounced decrease in blood pressure). Asymptomatic bradycardia (36 beats/min) with rhythm migration along the atrium was observed in a patient taking
timolol (beta-blocker) in the form of eye drops and
verapamil inside.

Digoxin

In the case of simultaneous administration of verapamil with digoxin, the dose of digoxin should be reduced. See section "Interaction with other drugs".

Heart failure

Patients with heart failure and a left ventricular ejection fraction of more than 35% should be stable before starting Isoptin® and should be treated appropriately thereafter.

Pronounced decrease in blood pressure

Intravenous administration of the drug Isoptin® often causes a decrease in blood pressure below baseline values, usually transient and asymptomatic, but may be accompanied by dizziness.

HMG-CoA reductase inhibitors (statins)

See section "Interaction with other drugs".

Neuromuscular Transmission Disorders

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

Impaired kidney function

Conducted comparative studies demonstrate that the pharmacokinetics of verapamil remains unchanged in patients with end-stage renal disease. However, some reports suggest that Isoptin should be used with caution and under close supervision in patients with impaired renal function.
Verapamil is not excreted by hemodialysis.

Impaired liver function

Isoptin should be used with caution in patients with severe hepatic impairment.

Ventricular tachycardia

Intravenous administration of the drug Isoptin® to patients with ventricular tachycardia with wide QRS complexes (> 0.12 sec.) Can lead to a pronounced deterioration in hemodynamics and ventricular fibrillation. Before starting treatment, proper diagnosis and exclusion of wide QRS ventricular tachycardia is mandatory.

Influence on the ability to drive a vehicle:

The drug Isoptin® can affect the speed of psychomotor reactions due to the antihypertensive effect and as a result of individual sensitivity. During the period of treatment, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require increased concentration of attention and speed of psychomotor reactions. This is especially important at the beginning of treatment, when increasing the dose or when switching from therapy with another drug.

Release form:

Solution for intravenous administration, 5 mg/2 ml.

Package:

2 ml in colorless type I hydrolytic glass ampoules with a blue break point.

5, 10 or 50 ampoules in a cardboard tray or PVC or polystyrene blister, closed with paper foil, together with instructions for use in a cardboard box.

Storage conditions:

Store at a temperature not exceeding 25 °C.

Keep out of the reach of children.

Best before date:

Do not use after the expiry date stated on the package.

Conditions for dispensing from pharmacies:

On prescription

Registration certificate holder:

Registration Authorization Holder: Abbott GmbH & Co. KG

Manufacturer

EBEWE PHARMA, Ges.m.b.H.Nfg.KG Austria
EBEWE PHARMA GmbH Nfg KG. Austria Representation: ABBOTT LABORATORIES LLC Verapamil is a drug that has antihypertensive ( reduces pressure in blood vessels), antiarrhythmic ( prevents the occurrence of various cardiac arrhythmias) and antianginal action ( reduces symptoms of coronary heart disease). This medication belongs to the group of slow calcium channel blockers that affect the functioning of the cardiovascular system. It should be noted that verapamil has a greater effect on the heart muscle ( myocardium) than on vessels.


Verapamil is a white crystalline powder, which is highly soluble in water. This drug is quite quickly and almost completely dissolved in the digestive tract. Verapamil has a maximum effect on the body during the first 2-4 hours after oral administration ( inside).

Types of medication, commercial names of analogues, release forms

Due to the fact that verapamil is well absorbed when taken orally, it is most often prescribed in tablet form. Verapamil is also available as a solution for intravenous administration.

It is worth mentioning that verapamil is also produced under other names - Veratard, Verogalid, Isoptin, Kaveril, Lekoptin, Finoptin, etc.

Manufacturers of verapamil

Company manufacturer	Commercial name of the drug	The country	Release form	Dosage
Aveksima	Verapamil	Russia	Coated tablets.	Selected individually. The medication should be taken 30-40 minutes before a meal. Adults and adolescents over 15 years of age are prescribed 0.04 - 0.08 grams ( 40 - 80 milligrams) three times a day. If necessary, the doctor can increase the dose to 0.12 - 0.16 grams ( 120 - 160 milligrams). The daily dosage should not exceed 240 - 480 milligrams. For children from six to fourteen years old, the daily dose is 80 - 360 milligrams, and for children up to six years old, 40 - 60 milligrams are prescribed. The frequency of taking pills ( children from six to fourteen years old) is 3-4 times a day.
North Star	Verapamil	Russia
Chemical-Pharmaceutical Plant AKRIKHIN	Verapamil	Russia
alkaloid	Verapamil	Macedonia
Obolenskoe	Verapamil	Russia
Unipharm	Verapamil-Sopharma	Bulgaria	Film-coated tablets ( film coating is less than 10% of the weight of the entire tablet).
Valenta Pharmaceuticals	Verapamil	Russia
Serena Pharma	Verapamil	India
alkaloid	Verapamil	Macedonia	Tablets, long-term ( prolonged) actions.	Should be taken before or after a meal with a small amount of water ( 50 - 100 milliliters). As a rule, a daily dose of 240 to 360 milligrams is used. This dosage can be increased up to 480 milligrams ( treatment should be in a hospital). The multiplicity of reception is 2 - 3 times a day. It should be noted that the initial dose for patients with impaired renal and hepatic function should not exceed 120 milligrams.
Eskom	Verapamil-Eskom	Russia	Solution for intravenous administration.	Enter slowly, at least 2 - 3 minutes. When administered, heart rate and blood pressure should be constantly monitored. Adults are administered 5 - 10 milligrams ( single dosage). In the absence of the desired effect, the administration should be repeated at the same dosage. The maximum daily dosage for adults should not exceed 480 milligrams. The initial dose for people with impaired renal and hepatic function should not exceed 120 milligrams. A single dose for children under one year old is 0.75 - 2 milligrams, from one to five years old, 2 - 3 milligrams each, from six to fourteen years old - 2.5 - 3.5 milligrams.
Biosynthesis	Verapamil	Russia

The mechanism of the therapeutic action of the drug

Verapamil is an L-type calcium channel blocker ( is a calcium antagonist), which are located in the heart muscle, as well as in the vessels. In the heart, calcium channels are located in the sinoatrial and atrioventricular nodes, as well as in the Purkinje fibers ( these structures are part of the conduction system of the heart and support its normal contractile function). The increased rate of penetration of calcium ions from the intercellular space into the cells of the conduction system of the heart leads to rhythm disturbance. These changes inevitably lead to an excessive increase in oxygen consumption by the heart muscle, which is further manifested by a decrease in blood supply to the heart tissues ( ischemia) and oxygen starvation ( hypoxia). Verapamil reduces myocardial demand ( cardiac muscle) in oxygen, which consumes more than 10% of all inhaled oxygen, and is also able to correct the imbalance between the supply and consumption of oxygen in cardiomyocytes ( myocardial cells). Along with the above mechanisms in cardiomyocytes, there is an increase in the concentration of potassium ions, which is necessary for a normal heart rhythm.

Inhibition of the penetration of calcium ions into the cells of the vascular wall leads to a reflex expansion of the coronary arteries of the heart ( blood vessels that feed the heart), and also dilates peripheral arterial vessels ( arteries and arterioles). There is also a decrease in total peripheral vascular resistance ( hypotensive action).

It should be noted that verapamil is well absorbed in the body, but due to significant individual differences, this medication can exert its effect after a different period of time ( 1 to 4 hours). Verapamil, when it enters the liver cells, is actively metabolized ( undergoes enzymatic degradation). Later, once in the blood, it binds to plasma proteins ( 90% ). The necessary constant concentration of the drug in the blood is achieved, as a rule, on the fourth day after repeated use of the drug. Verapamil is excreted through the bile ( 25% ), with urine ( 70% ), as well as in unchanged form ( 4 – 5 % ). The period of release of verapamil is significantly increased in people with various liver dysfunctions.

With intravenous administration, the antiarrhythmic effect is achieved already in the first 5 minutes and lasts about two hours ( verapamil is a group IV antiarrhythmic drug.). hypotensive action ( lowering blood pressure) is observed after 3-6 minutes and lasts no more than 25 minutes. In most cases, verapamil is well tolerated.

Indications for use

Verapamil is prescribed for prevention, as well as for the treatment of various cardiac arrhythmias, with coronary heart disease ( violation of blood supply to the myocardium against the background of damage to the coronary vessels), as well as some other heart diseases.

The use of verapamil

Indication for use	Mechanism of action	Dosage
Prevention and treatment of coronary heart disease ( ischemic heart disease)
Chronic stable angina (the occurrence of pain behind the sternum caused by the same type of physical activity)	Reduces the release of calcium ions in the coronary vessels and thereby relieves spasm. Increases the concentration of potassium ions in myocardial cells, which also helps to reduce the contractility of the heart muscle and reduce pain. Reduces the total peripheral vascular resistance, which leads to a decrease in pressure in the arteries.	The dosage should be selected individually. When used internally parenterally) the drug should be taken half an hour before meals. A single dosage for adolescents under 15 years of age and for adults is 40 - 80 milligrams. The medication should be taken up to three times a day. Sometimes a single dosage can be increased to 120 - 160 milligrams. Children under six years of age are prescribed 40 - 60 milligrams, and from six to fourteen years old, 80 - 360 milligrams per day. Children and adolescents under 14 years of age take the drug up to four times a day.
Unstable angina (pain behind the sternum can occur both with any physical exertion, and against the background of complete rest)
Vasospastic angina (spasm of blood vessels supplying the heart, which occurs at rest)
Prevention and treatment of certain heart rhythm disorders
Paroxysmal supraventricular tachycardia (sudden and sudden increase in heart rate)	Reduces the excitability of ectopic foci ( these foci have their own excitability and can disrupt the normal rhythm of the heart). Normalizes and significantly reduces the heart rate.	Most often used intravenously. During a jet injection, it is necessary to monitor the electrocardiogram, blood pressure, and count the pulse for 2 to 3 minutes. A single dosage for adults is 5 - 10 milligrams. If during the first 5-10 minutes the desired effect is not observed, it is necessary to re-introduce the drug in the same dosage. The frequency of administration should be selected by the attending physician. Children under one year are prescribed 0.75 - 2 milligrams. Children from one to five years old, 2 - 3 milligrams. Children from six to fourteen years old, 2.5 - 3.5 mg.
Supraventricular extrasystole (the appearance of extraordinary incomplete contractions of the heart against the background of increased excitability of ectopic foci)
Chronic form of atrial fibrillation and flutter (frequent and regular atrial contraction of the heart)		Apply both intravenously and orally.
Prevention and treatment of hypertension
Hypertension (increased blood pressure over 140/90 mm Hg. Art.)	Directly affects the arterial vessels of medium and small caliber and blocks the release of calcium in them, which leads to their reflex expansion. It also dilates the coronary arteries.	Most commonly used intravenously for a faster effect).
Hypertensive crisis (excessive increase in pressure, which can lead to damage to various organs and systems)
Other heart conditions
Hypertrophic cardiomyopathy (thickening of the muscle layer of the left, and sometimes the right ventricle of the heart)	It helps to reduce the contractility of the heart muscle by reducing excitability in the conduction system of the heart. Reduces the rate of calcium release in the vessels of the heart, as well as in peripheral arteries.	Can be used orally or as an intravenous injection.

How to apply the medication?

Depending on the pathology, verapamil can be prescribed in tablet form, as well as as intravenous injections.

Verapamil tablets are most commonly prescribed to prevent or treat coronary heart disease. Tablets should be taken before meals in 30 - 40 minutes), while washing them down with a small amount of liquid ( 50 - 100 milliliters). The dosage should be selected individually, taking into account the type and severity of the pathology. A single dosage for adults and adolescents over 15 years of age is, on average, 40 - 80 milligrams. Tablets are taken twice or thrice a day. In rare cases, a single dose can be increased to 120 - 160 milligrams ( only after consulting a doctor). Verapamil tablets can also be given to children. For children under six years of age, a single dose is 15-20 milligrams, and for children from six to fourteen years old - 20-80 milligrams ( 3 - 4 times a day).

In some cases, your doctor may prescribe long-acting or extended-release verapamil. Most often it is prescribed to reduce pressure ( with hypertension), as well as for the prevention of angina attacks and supraventricular tachycardia. The daily dose of long-acting verapamil is 240-360 milligrams. The medication should be taken in the morning during or immediately after a meal. Also, the tablet should be taken with a small amount of liquid ( 50 - 100 milligrams). It should be noted that in persons with impaired hepatic function, as well as for the elderly, a single dose should be reduced.

For the treatment and prevention of various cardiac arrhythmias ( supraventricular extrasystole, paroxysmal supraventricular tachycardia, chronic form of atrial fibrillation and flutter), as well as in hypertensive crisis, verapamil is used intravenously. Verapamil is administered for at least 2-3 minutes under constant monitoring of heart rate and blood pressure. Adults are given a single dose of 5 or 10 milligrams of the drug, and if there is no effect, repeat at the same dose. Children under one year of age are administered 0.75-2 milligrams at a time, from one to five years, 2-3 milligrams each, from six to fourteen years, 2.5-3.5 milligrams of verapamil. Elderly people, as well as patients with impaired liver and kidney function, a single and daily dose should be reduced ( less than 120 milligrams per day).

Possible side effects

The effect of verapamil on the cardiovascular system can in some cases lead to serious consequences. That is why the intravenous administration of this medication should only be carried out in a hospital ( under the direct supervision of a doctor). Also, verapamil can lead to drug allergies.

Verapamil can cause the following side effects:

• disorders of the cardiovascular system;
• allergic manifestations;
• disorders of the central and peripheral nervous system;
• disorders of the digestive tract;

Cardiovascular disorders

Reception of verapamil will sometimes burn to lead to significant disturbances in the rhythm of cardiac activity. It should be noted that these violations most often occur with intravenous use of the drug.

There are the following side effects from the cardiovascular system:

• hypotension;
• angina;
• atrioventricular heart block;
• asystole.

Bradycardia is a pronounced decrease in heart rate ( less than 50 beats per minute). Bradycardia occurs due to a decrease in the conductivity of the sinoatrial node, which normally generates 60 - 90 heartbeats. Subjectively, bradycardia may not cause any sensations, but most often this condition is manifested by symptoms such as dizziness, severe weakness, cold sweat, as well as fainting and fainting, which is caused by a decrease in oxygen supply to the brain tissues ( brain hypoxia).

Hypotension characterized by a decrease in blood pressure below 90/60 mmHg Art.). A decrease in the excitability of the entire conduction system of the heart inevitably leads to a decrease in the pumping function performed by the heart muscle. Due to a decrease in blood pressure, tissues and organs experience oxygen starvation, which can significantly disrupt their activity.

Heart failure is a condition in which the contractile function of the heart is significantly impaired. In the future, blood stagnation occurs at the level of the whole organism. If left ventricular failure occurs, this leads to dyspnea, hemoptysis, and cyanosis ( skin and mucous membranes become bluish). With insufficiency of the right ventricle of the heart, shortness of breath, hepatomegaly ( an increase in the size of the liver), swelling of the extremities. fast growing ( acute) heart failure can lead to complications such as cardiac asthma ( asthma attack against the background of a violation of the contractile activity of the heart), cardiogenic shock ( shock caused by a significant decrease in the contractile function of the left ventricle) or pulmonary edema. It should be noted that acute heart failure can directly threaten a person's life and even lead to death.

angina pectoris(angina pectoris) is a pain syndrome that usually occurs after intense physical exertion. Also, angina pectoris can appear on the background of psycho-emotional stress or after eating. Angina pectoris can be manifested not only by pain in the chest, but also by a feeling of discomfort behind the sternum. The pain can usually spread ( irradiate) in the left arm, between the shoulder blades, in the neck or in the lower jaw. The duration of pain in angina pectoris does not exceed 15 minutes. It should be noted that angina pectoris can lead to myocardial infarction against the background of damage to the coronary arteries of the heart.

Atrioventricular heart block is a type of heart block in which there is a violation of the impulse from the atria of the heart to the ventricles. Atrioventricular blockade most often leads to a violation of the heart rhythm. It is worth noting that there are three degrees of blockade of the atrioventricular node. Incorrect intravenous administration of verapamil can cause atrioventricular blockade of the 3rd degree, which is characterized by a decrease in heart rate to 20 or below. Complete atrioventricular block lack of conduction of electrical impulses to the ventricles) leads to complete cardiac arrest and death.

Asystole represents a complete cessation of cardiac activity. Ventricular asystole is the cause of cardiac arrest in about 3-5% of cases.

Allergic manifestations

Drug allergies can occur to almost any drug. As a rule, drug allergy is manifested by the appearance of a skin rash and itching.

When taking verapamil, the following allergic manifestations may occur:

• Stevens-Johnson syndrome.

Hives characterized by the appearance of itchy blisters on the skin ( skin rash ). This form of allergic reaction occurs due to the release of large amounts of histamine ( mediator of an allergic reaction), which is involved in increasing the permeability of the capillary vascular wall ( small vessels), which leads to swelling of the surrounding tissues. The skin rash is most often symmetrical and resembles blisters with a nettle burn. After stopping the medication, the skin rash disappears completely.

Stevens-Johnson syndrome, or malignant exudative erythema, is a fairly serious allergic reaction. This syndrome is manifested by the appearance of pinkish-red vesicles on the skin and mucous membranes of the eyes, mouth, pharynx, genitals ( papules), which can have different sizes ( from a few millimeters to several centimeters). Most often, the skin of the forearms, hands, feet, lower legs and face is affected. After opening these papules, severely painful bleeding areas remain on the mucous membranes and on the skin. It should be noted that this type of skin rash is accompanied by severe itching. Also, Stevens-Johnson syndrome is often accompanied by fever, headache, and joint pain.

Central and peripheral nervous system disorders

A decrease in heart rate inevitably leads to oxygen starvation of the brain. Nerve cells ( neurons) are very sensitive to the lack of oxygen, which is necessary for their normal functioning. With a decrease in the pumping function of the heart, arterial blood does not adequately nourish the nerve tissues of the brain, which can lead to various disorders and pathological conditions.
bleeding, soreness, and swelling of the gums. Hyperplasia occurs due to a violation of the release of calcium from the tissues of the gums, which further leads to impaired blood circulation. Ultimately, functional gum tissue is replaced by connective tissue ( collagen).

Constipation occurs most often with long-term use of verapamil. As a rule, constipation has an atonic character, which is characterized by a decrease in the tone of the intestinal muscles. Stopping verapamil in the vast majority of cases normalizes bowel function.

Elevation of liver tests occurs due to the fact that verapamil is metabolized in the liver. The breakdown products of this drug can disrupt the normal functioning of liver cells ( hepatocytes). As a result, various enzymes enter the blood from hepatocytes ( alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase), which normally should practically not penetrate into the bloodstream.

Approximate cost of medication

Verapamil and its analogues can be found in almost any city in the Russian Federation. Depending on the form of release, the price of this medication may vary slightly.

Average cost of verapamil

City	The average cost of a drug
	Tablets	Prolonged release tablets	Solution for intravenous administration
Moscow	21 ruble	142 rubles	23 rubles
Kazan	20 rubles	140 rubles	21 ruble
Krasnoyarsk	20 rubles	138 rubles	20 rubles
Samara	19 rubles	137 rubles	20 rubles
Tyumen	22 rubles	142 rubles	24 rubles
Chelyabinsk	24 rubles	145 rubles	26 rubles

C08DA01 (Verapamil)
C09BB10 (Trandolapril in combination with verapamil)

You should consult your doctor before using VERAPAMIL. These instructions for use are for informational purposes only. For more information, please refer to the manufacturer's annotation.

Clinical and pharmacological groups

01.048 (Antihypertensive drug)
01.015 (Calcium channel blocker)

pharmachologic effect

Selective blocker of calcium channels of class I, a derivative of diphenylalkylamine. It has antianginal, antiarrhythmic and antihypertensive effects.

The antianginal effect is associated both with a direct effect on the myocardium and with an effect on peripheral hemodynamics (reduces the tone of peripheral arteries, OPSS). The blockade of calcium entry into the cell leads to a decrease in the transformation of the energy contained in macroergic ATP bonds into mechanical work, and a decrease in myocardial contractility. Reduces myocardial oxygen demand, has a vasodilating, negative foreign and chronotropic effect.

Verapamil significantly reduces AV conduction, prolongs the refractory period and suppresses the automatism of the sinus node. Increases the period of diastolic relaxation of the left ventricle, reduces the tone of the myocardial wall (is an adjuvant for the treatment of hypertrophic obstructive cardiomyopathy). It has an antiarrhythmic effect in supraventricular arrhythmias.

Pharmacokinetics

When taken orally, more than 90% of the dose is absorbed. Protein binding - 90%. It is metabolized during the "first pass" through the liver. The main metabolite is norverapamil, which has less pronounced hypotensive activity than unchanged verapamil.

T1 / 2 when taking a single dose is 2.8-7.4 hours, when taking repeated doses - 4.5-12 hours (due to saturation of the liver enzyme systems and an increase in plasma concentration). After intravenous administration, the initial T1 / 2 is about 4 minutes, the final one is 2-5 hours.

It is excreted mainly by the kidneys and 9-16% through the intestines.

VERAPAMIL: DOSAGE

Individual. Inside adults - at an initial dose of 40-80 mg 3 times / day. For dosage forms of prolonged action, a single dose should be increased, and the frequency of administration should be reduced. Children aged 6-14 years - 80-360 mg / day, up to 6 years - 40-60 mg / day; reception frequency - 3-4 times / day.

If necessary, verapamil can be administered intravenously (slowly, under the control of blood pressure, heart rate and ECG). A single dose for adults is 5-10 mg, if there is no effect after 20 minutes, repeated administration at the same dose is possible. A single dose for children aged 6-14 years is 2.5-3.5 mg, 1-5 years - 2-3 mg, up to 1 year - 0.75-2 mg. For patients with severely impaired liver function, the daily dose of verapamil should not exceed 120 mg.

The maximum daily dose for adults when taken orally is 480 mg.

drug interaction

With simultaneous use with antihypertensive drugs (vasodilators, thiazide diuretics, ACE inhibitors), there is a mutual enhancement of the antihypertensive effect.

With simultaneous use with beta-blockers, antiarrhythmic drugs, inhalation anesthesia, the risk of developing bradycardia, AV blockade, severe arterial hypotension, heart failure increases, due to the mutual strengthening of the inhibitory effect on the automatism of the sinoatrial node and AV conduction, contractility and conduction myocardium.

With parenteral administration of verapamil to patients who have recently received beta-blockers, there is a risk of arterial hypotension and asystole.

With simultaneous use with nitrates, the antianginal effect of verapamil is enhanced.

With simultaneous use with amiodarone, the negative inotropic effect, bradycardia, conduction disturbance, and AV blockade increase.

Since verapamil inhibits the CYP3A4 isoenzyme, which is involved in the metabolism of atorvastatin, lovastatin and simvastatin, drug interactions are theoretically possible due to an increase in plasma concentrations of statins. Cases of rhabdomyolysis have been described.

With simultaneous use with acetylsalicylic acid, cases of an increase in bleeding time due to additive antiplatelet action are described.

With simultaneous use with buspirone, the concentration of buspirone in the blood plasma increases, its therapeutic and side effects increase.

With simultaneous use, cases of an increase in the concentration of digitoxin in the blood plasma are described.

With simultaneous use with digoxin, the concentration of digoxin in the blood plasma increases.

With simultaneous use with disopyramide, severe arterial hypotension and collapse are possible, especially in patients with cardiomyopathy or decompensated heart failure. The risk of developing severe manifestations of drug interactions is apparently associated with increased negative inotropic action.

With simultaneous use with diclofenac, the concentration of verapamil in the blood plasma decreases; with doxorubicin - the concentration of doxorubicin in the blood plasma increases and its effectiveness increases.

With simultaneous use with imipramine, the concentration of imipramine in the blood plasma increases and there is a risk of developing unwanted changes on the ECG. Verapamil increases the bioavailability of imipramine by reducing its clearance. Changes in the ECG are due to an increase in the concentration of imipramine in the blood plasma and the additive inhibitory effect of verapamil and imipramine on AV conduction.

With simultaneous use with carbamazepine, the effect of carbamazepine increases and the risk of side effects from the central nervous system increases due to inhibition of the metabolism of carbamazepine in the liver under the influence of verapamil.

With simultaneous use with clonidine, cases of cardiac arrest in patients with arterial hypertension have been described.

With simultaneous use with lithium carbonate, the manifestations of drug interactions are ambiguous and unpredictable. Cases of increased effects of lithium and the development of neurotoxicity, a decrease in the concentration of lithium in the blood plasma, and severe bradycardia are described.

The vasodilatory effects of alpha blockers and calcium channel blockers may be additive or synergistic. With the simultaneous use of terazosin or prazosin and verapamil, the development of severe arterial hypotension is partly due to a pharmacokinetic interaction: an increase in Cmax and AUC of terazosin and prazosin.

With simultaneous use, rifampicin induces the activity of liver enzymes, accelerating the metabolism of verapamil, which leads to a decrease in its clinical effectiveness.

With simultaneous use, the concentration of theophylline in the blood plasma increases.

With simultaneous use with tubocurarine chloride, vecuronium chloride, it is possible to increase the muscle relaxant effect.

With simultaneous use with phenytoin, phenobarbital, a significant decrease in the concentration of verapamil in the blood plasma is possible.

With simultaneous use with fluoxetine, the side effects of verapamil increase due to a slowdown in its metabolism under the influence of fluoxetine.

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

With simultaneous use, verapamil inhibits the metabolism of cyclosporine in the liver, which leads to a decrease in its excretion and an increase in plasma concentration. This is accompanied by an increase in the immunosuppressive effect, a decrease in the manifestations of nephrotoxicity was noted.

With simultaneous use with cimetidine, the effects of verapamil are enhanced.

With simultaneous use with enflurane, prolongation of anesthesia is possible.

With simultaneous use with etomidate, the duration of anesthesia increases.

Pregnancy and lactation

Verapamil is contraindicated during pregnancy and lactation.

VERAPAMIL: SIDE EFFECTS

From the side of the cardiovascular system: bradycardia (less than 50 beats / min), a pronounced decrease in blood pressure, the development or aggravation of heart failure, tachycardia; rarely - angina pectoris, up to the development of myocardial infarction (especially in patients with severe obstructive lesions of the coronary arteries), arrhythmia (including flicker and ventricular flutter); with rapid on / in the introduction - AV blockade of the III degree, asystole, collapse.

From the side of the central nervous system and peripheral nervous system: dizziness, headache, fainting, anxiety, lethargy, fatigue, asthenia, drowsiness, depression, extrapyramidal disorders (ataxia, mask-like face, shuffling gait, stiffness of the arms or legs, trembling of the hands and fingers, difficulty swallowing).

From the digestive system: nausea, constipation (rarely - diarrhea), gingival hyperplasia (bleeding, soreness, swelling), increased appetite, increased activity of hepatic transaminases and alkaline phosphatase.

Allergic reactions: pruritus, skin rash, flushing of the skin of the face, erythema multiforme exudative (including Stevens-Johnson syndrome).

Others: weight gain, very rarely - agranulocytosis, gynecomastia, hyperprolactinemia, galactorrhea, arthritis, transient loss of vision against the background of Cmax, pulmonary edema, asymptomatic thrombocytopenia, peripheral edema.

Indications

Angina (tension, stable without angiospasm, stable vasospastic), supraventricular tachycardia (including paroxysmal, with WPW syndrome, Lown-Ganong-Levin syndrome), sinus tachycardia, tachyarrhythmia fibrillation, atrial flutter, atrial extrasystole, arterial hypertension, hypertensive crisis (in / in the introduction), hypertrophic obstructive cardiomyopathy, primary hypertension in the pulmonary circulation.

Contraindications

Severe arterial hypotension, AV block II and III degree, sinoatrial block and SSS (except for patients with a pacemaker), WPW syndrome or Lown-Ganong-Levin syndrome in combination with atrial flutter or fibrillation (except for patients with a pacemaker), pregnancy, period lactation, hypersensitivity to verapamil.

special instructions

Caution should be used in patients with AV block I degree, bradycardia, severe aortic stenosis, chronic heart failure, mild or moderate arterial hypotension, myocardial infarction with left ventricular failure, hepatic and / or renal insufficiency, in elderly patients, in children and adolescents under the age of 18 years (efficacy and safety of use have not been studied).

If necessary, combined therapy of angina pectoris and arterial hypertension with verapamil and beta-blockers is possible. However, intravenous administration of beta-blockers should be avoided while using verapamil.

Influence on the ability to drive vehicles and control mechanisms

After taking verapamil, individual reactions (drowsiness, dizziness) are possible, affecting the patient's ability to perform work that requires a high concentration of attention and speed of psychomotor reactions.