Side effects of the substance verapamil. Indications and instructions for use of the drug verapamil - composition of tablets and ampoules, side effects, analogues Medicine verapamil indications

Selective class I calcium channel blocker, diphenylalkylamine derivative
Drug: VERAPAMIL

Active substance of the drug: verapamil
ATX coding: C08DA01
KFG: Calcium channel blocker
Registration number: P No. 013974/01
Registration date: 08/14/08
Owner reg. credential: SHREYA LIFE SCIENCES Pvt.Ltd. (India)

Verapamil release form, drug packaging and composition.

Film-coated tablets 1 tab. verapamil hydrochloride 40 mg - "- 80 mg
Excipients: disubstituted calcium phosphate, starch, butylated hydroxyanisole, purified talc, magnesium stearate, gelatin, methylparaben, hydroxypropyl methylcellulose, titanium dioxide, indigo carmine.
10 pieces. - blisters (1) - cardboard packs.
10 pieces. - blisters (5) - cardboard packs.

DESCRIPTION OF THE ACTIVE SUBSTANCE.
All information provided is provided for information only about the drug; you should consult your doctor about the possibility of use.

Pharmacological action Verapamil

Selective class I calcium channel blocker, diphenylalkylamine derivative. 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, peripheral arterial resistance). Blockade of calcium entry into the cell leads to a decrease in the transformation of energy contained in macroergic bonds of ATP into mechanical work and a decrease in myocardial contractility. Reduces myocardial oxygen demand, has a vasodilating, negative ino- and chronotropic effect.
Verapamil significantly reduces AV conduction, prolongs the refractory period and suppresses the automaticity of the sinus node. Increases the period of diastolic relaxation of the left ventricle, reduces the tone of the myocardial wall (is an auxiliary agent for the treatment of hypertrophic obstructive cardiomyopathy). Has an antiarrhythmic effect in supraventricular arrhythmias.

Pharmacokinetics of the drug.

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 the saturation of liver enzyme systems and an increase in the concentration of verapamil in the blood plasma). After IV administration, the initial T1/2 is about 4 minutes, the final T1/2 is 2-5 hours.
It is excreted mainly by the kidneys and 9-16% through the intestines.

Indications for use:

Angina pectoris (tension, stable without vasospasm, stable vasospastic), supraventricular tachycardia (including paroxysmal, with WPW syndrome, Lown-Ganong-Levine syndrome), sinus tachycardia, atrial fibrillation, atrial flutter, atrial extrasystole, arterial hypertension, hypertensive crisis (iv administration), hypertrophic obstructive cardiomyopathy, primary hypertension in the pulmonary circulation.

Dosage and method of administration of the drug.

Individual. Orally for adults - at an initial dose of 40-80 mg 3 times a day. For long-acting dosage forms, the single dose should be increased and the frequency of administration reduced. Children aged 6-14 years - 80-360 mg/day, up to 6 years - 40-60 mg/day; frequency of administration - 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 severe liver dysfunction, the daily dose of verapamil should not exceed 120 mg.
Maximum dose: adults when taken orally - 480 mg/day.

Side effects of Verapamil:

From the cardiovascular system: bradycardia (less than 50 beats/min), marked decrease in blood pressure, development or worsening 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 ventricular fibrillation and flutter); with rapid intravenous administration - third degree AV block, asystole, collapse.
From 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), gum hyperplasia (bleeding, pain, swelling), increased appetite, increased activity of liver transaminases and alkaline phosphatase.
Allergic reactions: skin itching, skin rash, facial skin flushing, erythema multiforme exudative (including Stevens-Johnson syndrome).
Other: weight gain, very rarely - agranulocytosis, gynecomastia, hyperprolactinemia, galactorrhea, arthritis, transient loss of vision against the background of Cmax, pulmonary edema, asymptomatic thrombocytopenia, peripheral edema.

Contraindications to the drug:

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

Use during pregnancy and lactation.

Verapamil is contraindicated during pregnancy and lactation.

Special instructions for the use of Verapamil.

Caution should be used in case of AV blockade of the first degree, bradycardia, severe stenosis of the aortic mouth, chronic heart failure, mild or moderate arterial hypotension, myocardial infarction with left ventricular failure, hepatic and/or renal failure, in elderly patients, in children and adolescents under 18 years of age (the effectiveness and safety of use have not been studied).
If necessary, combination 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.
Impact on the ability to drive vehicles and operate machinery
After taking verapamil, individual reactions are possible (drowsiness, dizziness), affecting the patient’s ability to perform work that requires high concentration and speed of psychomotor reactions.

Interaction of Verapamil with other drugs.

When used simultaneously with antihypertensive drugs (vasodilators, thiazide diuretics, ACE inhibitors), the antihypertensive effect is mutually enhanced.
When used simultaneously with beta-blockers, antiarrhythmic drugs, and inhalation anesthesia agents, the risk of developing bradycardia, AV blockade, severe arterial hypotension, and heart failure increases due to the mutual increase in the inhibitory effect on the automatism of the sinoatrial node and AV conduction, contractility and conductivity. myocardium.
When verapamil is administered parenterally to patients who have recently received beta-blockers, there is a risk of developing arterial hypotension and asystole.
When used simultaneously with nitrates, the antianginal effect of verapamil is enhanced.
When used simultaneously with amiodarone, the negative inotropic effect, bradycardia, conduction disturbances, and AV block are enhanced.
Since verapamil inhibits the CYP3A4 isoenzyme, which is involved in the metabolism of atorvastatin, lovastatin and simvastatin, drug interactions due to increased plasma concentrations of statins are theoretically possible. Cases of rhabdomyolysis have been described.
When used simultaneously with acetylsalicylic acid, cases of increased bleeding time due to additive antiplatelet effect have been described.
When used simultaneously with buspirone, the concentration of buspirone in the blood plasma increases, and its therapeutic and side effects increase.
With simultaneous use, cases of increased concentrations of digitoxin in the blood plasma have been described.
When used simultaneously with digoxin, the concentration of digoxin in the blood plasma increases.
When used concomitantly with disopyramide, severe 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 effects.
When used simultaneously 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.
When used simultaneously with imipramine, the concentration of imipramine in the blood plasma increases and there is a risk of developing undesirable 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.
When used simultaneously with carbamazepine, the effect of carbamazepine is enhanced 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.
When used simultaneously with clonidine, cases of cardiac arrest in patients with arterial hypertension have been described.
When used simultaneously 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 have been described.
The vasodilating 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 pharmacokinetic interaction: an increase in the 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.
When used simultaneously with tubocurarine chloride and vecuronium chloride, the muscle relaxant effect may be enhanced.
When used simultaneously with phenytoin and phenobarbital, a significant decrease in the concentration of verapamil in the blood plasma is possible.
When used simultaneously 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 arterial hypotension have been 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 concentrations. This is accompanied by an increased immunosuppressive effect, and a decrease in the manifestations of nephrotoxicity is noted.
When used simultaneously with cimetidine, the effects of verapamil are enhanced.
When used simultaneously with enflurane, prolongation of anesthesia is possible.
When used simultaneously with etomidate, the duration of anesthesia increases.

Verapamil is a drug that has antihypertensive ( reduces pressure in blood vessels), antiarrhythmic ( prevents the occurrence of various heart rhythm disorders) and antianginal effect ( reduces symptoms of coronary heart disease). This medication belongs to the group of slow calcium channel blockers, which affect the functioning of the cardiovascular system. It is worth noting that verapamil has a greater effect on the heart muscle ( myocardium) than on vessels.

Verapamil is a white crystalline powder that is highly soluble in water. This drug dissolves quite quickly and almost completely in the digestive tract. Verapamil has its maximum effect on the body during the first 2 to 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	A country	Release form	Dosage
*Avexima*	*Verapamil*	*Russia*	Film-coated tablets.	Selected individually. The medication should be taken 30–40 minutes before meals. 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 of age, the daily dose is 80–360 milligrams, and children up to six years old inclusive are prescribed 40–60 milligrams. Frequency of tablet intake ( children from six to fourteen years old) is 3 – 4 times a day.
*North Star*	*Verapamil*	*Russia*
*Chemical and 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 meals 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 to 480 milligrams ( treatment must be carried out in a hospital). The frequency of administration is 2 – 3 times a day. It should be noted that the initial dose for patients with impaired renal and liver function should not exceed 120 milligrams.
*Eskom*	*Verapamil-Eskom*	*Russia*	Solution for intravenous administration.	Inject slowly, over at least 2–3 minutes. Heart rate and blood pressure should be monitored continuously during administration. Adults are administered 5–10 milligrams ( single dosage). If there is no desired effect, the administration should be repeated at the same dosage. The maximum daily dosage for adults should not exceed 480 milligrams. The starting dose for people with impaired renal and liver 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, from six to fourteen years old - 2.5 - 3.5 milligrams.
*Biosynthesis*	*Verapamil*	*Russia*	Solution for intravenous administration.

The mechanism of therapeutic action of the drug

Verapamil is a slow L-type calcium channel blocker ( is a calcium antagonist), which are located in the heart muscle, as well as in the blood 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 disturbances. These changes inevitably lead to an excessive increase in oxygen consumption by the heart muscle, which is subsequently manifested by a decrease in blood supply to the heart tissues ( ischemia) and oxygen starvation ( hypoxia). Verapamil reduces myocardial demand ( heart muscle) in oxygen, which consumes more than 10% of all inspired oxygen, and is also able to correct the imbalance between oxygen supply and oxygen consumption 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 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 ( vessels supplying the heart), and also dilates peripheral arterial vessels ( arteries and arterioles). There is also a decrease in total peripheral vascular resistance ( hypotensive effect).

It should be noted that verapamil is well absorbed in the body, but due to significant individual differences, this medication may exert its effect after a different period of time ( from 1 to 4 hours). When verapamil enters liver cells, it is actively metabolized ( undergoes enzymatic breakdown). Subsequently, once in the blood, it binds to plasma proteins ( 90% ). The required 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 bile ( 25% ), with urine ( 70% ), as well as unchanged ( 4 – 5 % ). The elimination period of verapamil is significantly increased in people with various liver dysfunctions.

When administered intravenously, the antiarrhythmic effect is achieved within the first 5 minutes and lasts about two hours ( verapamil is a group IV antiarrhythmic drug). Hypotensive effect ( 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 the prevention, as well as for the treatment of various heart rhythm disorders, for coronary heart disease ( impaired blood supply to the myocardium due to damage to the coronary vessels), as well as for some other heart diseases.

Use of verapamil

Indications for use	Mechanism of action	Dosage
*Prevention and treatment of coronary heart disease ( IHD)*
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 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 old 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 during any physical activity and against the background of complete rest)*
Vasospastic angina *(spasm of the vessels supplying the heart, which occurs at rest)*
Prevention and treatment of certain heart rhythm disorders
Paroxysmal supraventricular tachycardia *(sudden and paroxysmal increase in heart rate)*	Reduces the excitability of ectopic foci ( These lesions have their own excitability and can disrupt the normal heart rhythm). Normalizes and significantly reduces heart rate.	Most often used intravenously. During jet injection, it is necessary to monitor electrocardiogram readings, blood pressure, and also count the pulse for 2–3 minutes. A single dosage for adults is 5 – 10 milligrams. If the desired effect is not observed within the first 5 to 10 minutes, it is necessary to re-administer the medication in the same dosage. The frequency of administration should be selected by the attending physician. Children under one year of age 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 orderly contraction of the atria of the heart)*		Used both intravenously and orally.
Prevention and treatment of hypertensive conditions
Hypertension *(increase in blood pressure over 140/90 mm Hg. Art.)*	Directly affects arterial vessels of medium and small caliber and blocks the release of calcium in them, which leads to their reflex expansion. Also dilates coronary arteries.	Most often used intravenously ( to achieve faster results).
Hypertensive crisis *(excessive increase in pressure, which can lead to damage to various organs and systems)*
Other heart diseases
Hypertrophic cardiomyopathy *(thickening of the muscle layer of the left and sometimes right ventricle of the heart)*	Helps 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 intravenous injections.

How to use the medicine?

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

Verapamil tablets are most often prescribed for the prevention or treatment of coronary heart disease. The 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 must 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. The tablets are taken twice or thrice daily. In rare cases, a single dose can be increased to 120 – 160 milligrams ( only after consulting a doctor). Verapamil tablets can also be prescribed to children. For children under six years of age, a single dose is 15–20 milligrams, and for children from six to fourteen years of age – 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 lower blood pressure ( for hypertension), as well as for the prevention of attacks of angina and supraventricular tachycardia. The daily dose of verapamil prolonged action is 240 – 360 milligrams. The medication should be taken in the morning during or immediately after meals. The tablet should also be taken with a small amount of liquid ( 50 – 100 milligrams). It should be noted that in persons with impaired liver function, as well as in the elderly, the single dose should be reduced.

For the treatment and prevention of various heart rhythm disorders ( 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 over at least 2 to 3 minutes under constant monitoring of heart rate and blood pressure. Adults are given a one-time dose of 5 or 10 milligrams of the drug, and if there is no effect, the same dose is repeated. Children under one year old are given a one-time dose of 0.75–2 milligrams, from one to five years old 2–3 milligrams, from six to fourteen years old 2.5–3.5 milligrams of verapamil. For elderly people, as well as patients with impaired liver and kidney function, the single and daily dose should be reduced ( less than 120 milligrams per day).

Possible side effects

The effects of verapamil on the cardiovascular system can in some cases lead to serious consequences. That is why intravenous administration of this medication should only be carried out in a hospital ( under the direct supervision of a physician). Verapamil can also 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

Taking verapamil can sometimes lead to significant disturbances in heart rhythm. It is worth noting that these disorders most often occur with intravenous use of the drug.

The following side effects from the cardiovascular system are distinguished:

hypotension;
angina pectoris;
atrioventricular heart block;
asystole.

Bradycardia represents a pronounced decrease in heart rate ( less than 50 beats per minute). Bradycardia occurs due to decreased 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 pre-syncope and fainting, which is caused by a decrease in the supply of oxygen to the brain tissues ( brain hypoxia).

Hypotension characterized by a decrease in blood pressure ( below 90/60 mm Hg. 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. Subsequently, blood stagnation occurs at the level of the entire body. If failure of the left ventricle of the heart occurs, this leads to shortness of breath, hemoptysis and cyanosis ( the skin and mucous membranes acquire a bluish tint). With failure of the right ventricle of the heart, shortness of breath and hepatomegaly are observed ( increase in liver size), swelling of the extremities. Fast growing ( acute) heart failure can lead to complications such as cardiac asthma ( attack of suffocation due to impaired contractility of the heart), cardiogenic shock ( shock condition caused by a significant decrease in the contractile function of the left ventricle) or pulmonary edema. It is worth noting 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 activity. Also, angina pectoris can appear against the background of psycho-emotional stress or after eating. Angina pectoris can manifest itself not only as pain in the chest, but also as a feeling of discomfort behind the sternum. The pain can usually spread ( radiate) in the left hand, between the shoulder blades, in the neck or in the lower jaw. The duration of pain during angina pectoris does not exceed 15 minutes. It is worth noting that angina pectoris can lead to myocardial infarction due to damage to the coronary arteries of the heart.

Atrioventricular heart block is one of the types of heart block, in which there is a disruption in the conduction of impulses from the atria of the heart to the ventricles. Atrioventricular block most often leads to heart rhythm disturbances. It is worth noting that there are three degrees of atrioventricular node blockade. Improper intravenous administration of verapamil can cause third-degree atrioventricular block, which is characterized by a decrease in heart rate to 20 or lower. 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 causes cardiac arrest in approximately 3–5% of cases.

Allergic manifestations

Drug allergies can occur to almost any drug. As a rule, drug allergies are manifested by the occurrence of skin rashes 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 ( allergic reaction mediator), which is involved in increasing the permeability of the vascular wall of capillaries ( small vessels), which leads to swelling of the surrounding tissues. The skin rash is most often symmetrical in nature and resembles blisters from a nettle burn. After stopping the medication, the skin rash completely disappears.

Stevens–Johnson syndrome, or erythema malignant exudative, is a fairly serious allergic reaction. This syndrome is manifested by the appearance of pinkish-red blisters on the skin and mucous membranes of the eyes, mouth, pharynx, and genitals ( papules), which can have different sizes ( from a few millimeters to several centimeters). The skin most often affected is the forearms, hands, feet, legs and face. After opening these papules, severely painful bleeding areas remain on the mucous membranes and 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.

Disorders of the central and peripheral nervous system

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. When the pumping function of the heart decreases, arterial blood does not sufficiently nourish the nerve tissues of the brain, which can lead to various disorders and pathological conditions.
bleeding, pain, and swelling of the gums. Hyperplasia occurs due to disruption of the release of calcium from the gum tissue, which subsequently leads to poor circulation. Ultimately, the functional gum tissue is replaced by connective tissue ( collagen).

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

Increased liver tests occurs due to the fact that verapamil is metabolized in the liver. The breakdown products of this drug can interfere with 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 the medicine

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	Average cost of medicine
City	Pills	Long-acting 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

Active ingredient: Verapamil.

White crystalline powder. It dissolves well in water, methyl alcohol, and chloroform.

Chemical formula: C 27 H 38 N 2 O 4.

Name: alpha-methylamino]propyl]-3,4-dimethoxy-alpha-(1-methylethyl)benzeneacetonitrile.

In this drug, Verapamil is presented in the form of hydrochloride.

Mechanism of action

One of its many functions is the contraction of muscle fibers (smooth, skeletal, myocardial). Calcium ensures the interaction of muscle contractile proteins – actin and myosin. These proteins take the form of thread-like formations (filaments) located in the muscle fiber (myofibril).

Under the influence of Calcium ions, thin (actin) and thick (myosin) filaments overlap each other, and the muscle fibril shortens and thickens. As a result, the muscle contracts . Of course, a muscle cannot be contracted for any length of time - after the spasm there must be relaxation, for which it is necessary that calcium be removed from the cytoplasm of the myofibrils.

The required energy is obtained through the breakdown of ATP. Thanks to calcium-dependent ATPase, the concentration of calcium outside the cell is 25 times higher than inside the cell.

To ensure the next contraction, calcium re-enters the cell and ensures the interaction of filaments. The passage of calcium through the membrane of nerve fibers is accompanied by changes in the transmembrane charge and the passage of an impulse along the nerve fiber.

From a biochemical point of view, these channels are nothing more than carrier proteins. They are located on the surface of the cell membrane, and, combining with calcium, transport it into the cell.

Verapamil blocks slow, long-lived L-channels located in the myocardium, in the conduction system of the heart, in blood vessels, as well as in the smooth muscles of internal organs. Its main points of application are: the myocardium, the cardiac conduction system, and the muscular choroid.

Dilatation of arterioles leads to a decrease in total peripheral vascular resistance (TPR) and to hypotension - a decrease in blood pressure (BP). In addition, Verapamil blocks alpha-1 adrenergic receptors of arterioles, which leads to their additional expansion and increases hypotension.

Verapamil has a depressing effect on the myocardial conduction system. Under its action, the generation of impulses in the pacemaker, in the sinus node, slows down.

This drug also slows sinoatrial (sinus-atrial) and atrioventricular (atrioventricular) conduction. Clinically, this is manifested by a decrease in HR (heart rate).

As a result, the load on the myocardium is reduced. After all, under the influence of the drug, it does less work - it beats weaker and slower. At the same time, cardiac output does not decrease - the heart works more efficiently against the background of decreased OPS and hypotension.

Reducing the load on the myocardium is of great importance for patients suffering from IHD (coronary heart disease). In IHD, the delivery of oxygen through the blood to the myocardium is impaired.

Verapamil also solves this problem. Firstly, a slowdown in heart rate is accompanied by an extension of the relaxation phase (diastole) of the myocardium. But the myocardium receives blood through the coronary arteries during diastole.

Blood flow through the coronary arteries also improves as a result of their dilatation. Reducing the load on the myocardium, hypotension, improving coronary blood flow - all this leads to a number of positive effects. Blood pressure decreases, the frequency and intensity of angina attacks decreases - unstable angina, exertional angina, Prinzmetal angina (caused by spasm of the coronary arteries).

With long-term use of the drug, such a negative process as left ventricular myocardial hypertrophy is eliminated. The mechanism is the same - reducing the load on the myocardium and improving its blood supply.

The risk of myocardial infarction is also reduced. The leading cause of heart attack is coronary thrombosis. Platelets also contain calcium channels. Their blockade prevents platelet aggregation (their combination into conglomerates) and the formation of blood clots. Dilatation of the renal arteries leads to improved blood supply to the kidneys. In the kidneys, Verapamil partially blocks sodium channels. Increased excretion of sodium, and with it water, complements the hypotensive effect.

Verapamil, like other calcium antagonists, relaxes the muscles of the bronchi, genitourinary system, and gastrointestinal tract. True, these effects are insignificantly expressed.

The effect on cerebral vessels is also not great. However, Verapamil can be used to relieve headaches. Verapamil also does not affect the condition of skeletal muscles in healthy people.

However, the condition of patients with muscle pathology (Duchenne myopathy) may worsen. In addition, this drug may prolong the action of muscle relaxants, drugs used to relax skeletal muscles.

History of creation

A year later, in 1962, its effect on the strength of heart contractions and heart rate was discovered. In 1963, it was officially recommended for use in clinical practice as an antianginal agent for the treatment of coronary artery disease.

Since then it has been widely used in Russia, the USA and the West. Europe. Being a representative of the first generation of calcium antagonists, Verapamil is not without its drawbacks. These are relatively low bioavailability, short duration of action, and side effects that limit its use.

Subsequently, more effective and safe drugs from this group were introduced into clinical practice. However, Verapamil is still very often used today in the treatment of cardiovascular pathology.

In this regard, local injections of Verapamil are used to resolve keloid scars on the skin. The same injections into the penis are made for fibrous deformation - Peyronie's disease.

Synthesis technology

Verapamil is obtained through several reactions involving complex organic substances. To make tablets, in addition to the main substance, auxiliary substances are used: disubstituted calcium phosphate, gelatin, methylparaben, starch, talc, titanium dioxide, magnesium stearate, hydroxypropyl methylcellulose, indigo carmine.

Release forms

Tablets and dragees 40 and 80 mg;
Verapamil 240 mg extended release tablets;
Ampoules 2 ml of 0.25% injection solution.

Although it is not at all necessary that Russian pharmaceutical manufacturers produce low-grade drugs. Of the foreign patented drugs, the most famous tablets are Isoptin (Abbott-Knoll, Germany) and Finoptin (Orion, Finland). Abroad, the drug may be called Azupamil, Vergamma, Veradil, Lekoptin, and many others.

Indications

Arterial hypertension;
Tachyarrhythmias (supraventricular extrasystole, paroxysmal supraventricular tachycardia, atrial fibrillation and flutter);
Prevention and treatment of coronary artery disease, unstable angina, variant Prinzmetal angina.

Dosages

The tablets are taken regardless of food, not chewed, and washed down with water. The recommended dose is 40-80 mg 3-4 times a day. If there is no effect, single doses are gradually increased to 120 and 160 mg. The daily dose usually ranges from 240 to 360 mg. The maximum daily dose is 480 mg. It is not recommended to exceed it to avoid unwanted effects.

Long-acting verapamil (Isoptin SR 240) is taken in a daily dose of 240-480 mg, which is divided into 2 doses with an interval of 12 hours.

In patients with impaired liver function, the metabolism of Verapamil slows down. The daily dose in such cases should not exceed 120 mg.

It is divided into 3 doses of 40 mg. Tablets are taken in a long course from 2 weeks to 6-8 months. The injection solution is administered intravenously slowly in 2-4 ml (1-2 ampoules). If there is no effect, the jet injection can be repeated after half an hour. The same amount of solution can be diluted in 100-200 m of saline. solution and administered intravenously.

Pharmacodynamics

The maximum concentration in the blood plasma is formed after 1-2 hours of taking the usual forms of the drug. For prolonged forms this figure is 3-5 hours. The hypotensive effect is observed already in the first week of systematic use of Verapamil, and reaches its maximum by 3-4 weeks.

The half-life is initially in the range of 2-6 hours. With repeated administration, Verapamil accumulates in the body, and the half-life slows down to 4.5-12 hours. Because of this, it may be necessary to reduce the daily dose by approximately 2 times. The same picture is observed in liver failure, when the metabolism and excretion of Verapamil slow down, and the content of the free fraction in the blood, on the contrary, increases. In these cases, the dose of Verapamil is also reduced.

Side effects

The cardiovascular system: hypotension, bradycardia, atrioventricular block, facial flushing, worsening existing heart failure, the appearance of shortness of breath and peripheral edema;
CNS: headache, dizziness, general weakness, increased excitability, fatigue;
Gastrointestinal tract: nausea, vomiting, constipation, increased levels of liver enzymes-transaminases;
Leather: allergic rash, itching.

Contraindications

Individual intolerance to Verapamil;
Cardiogenic shock;
Acute heart failure;
Chronic heart failure stage IIB-III;
Atrioventricular block II-III degree;
Sinoatrial block;
SSS – sick sinus syndrome;
Morgagni-Adams-Stokes syndrome;
WPW (Wolf-Parkinson-White) syndrome;
Acute myocardial infarction (Verapamil is prescribed no earlier than the 7th day after the development of this disease);
Age up to 18 years

The drug is prescribed with extreme caution for hypotension and bradycardia, for liver failure, as well as for the initial degree of chronic heart failure and atrioventricular block.

Interaction with other drugs

Antihypertensive drugs of other groups, diuretics - increased hypotensive effect;
Inhalation anesthetics, beta-blockers, inhaled anesthetics – toxic effect on the myocardium, risk of arrhythmias;
Digoxin – slower excretion of this drug by the kidneys, increased concentration in the blood plasma, risk of arrhythmias;
Cyclosporine, Prazosin, Theophylline - increase the concentration of these substances in the blood plasma;
Ranitidine, Cimetidine - increased levels of Verapamil in the blood plasma;
Quinidine - increased concentration of this drug in the blood plasma, hypotension;
Acetylsalicylic acid - danger of bleeding;
Muscle relaxants – their effect is enhanced;
Lithium preparations, Carbamazepine – toxic effects on the central nervous system.

During treatment with Verapamil, you should not drink grapefruit juice, because it increases the bioavailability of the drug.

Pregnancy and lactation

Verapamil penetrates the placental barrier and into breast milk. In some cases, it is prescribed to pregnant women for therapeutic and obstetric indications.

Dear visitors of the Farmamir website. This article does not constitute medical advice and should not serve as a substitute for consultation with a physician.

Verapamil is a calcium channel blocker. It has antihypertensive, antianginal and antiarrhythmic effects. Due to the decrease in heart rate and myocardial contractility, this drug helps reduce its oxygen demand. Verapamil increases coronary blood flow, reduces the tone of peripheral arteries, dilates cardiac vessels and reduces vascular resistance. It helps to suppress the automatism of the sinus node, as a result of which it can be used in the treatment of various types of arrhythmias.

When this medication is taken orally, you can notice a positive effect after 1 to 2 hours. It is excreted primarily by the kidneys, and 16% is excreted in feces. Verapamil crosses the placenta, is detected during childbirth in the blood of the umbilical vein and enters the baby's body through breast milk. Therefore, it is highly not recommended for pregnant women and nursing mothers.

Compound

The main active ingredient of this drug is verapamil hydrochloride, and additional ingredients are indigo carmine, talc, disubstituted calcium phosphate, butylated hydroxyanisole, methylparaben, starch, gelatin, magnesium stearate and titanium dioxide.

What do Verapamil tablets help with?

in the prevention and treatment of heart rhythm disorders;
in a condition characterized by a sudden, paroxysmal increase in heart rate;
if there is a disturbance in the heart rhythm in the AV junction or in the tissues of the atria;
to prevent the occurrence and treatment of angina pectoris;
as a therapeutic therapy for high blood pressure.

It is important to know the conditions in which taking this medication can do much more harm than good. Contraindications to the use of Verapamil include the following:

heart failure;
bradycardia;
hypersensitivity to the constituent components of the drug;
sinoatrial block;
cardiogenic shock;
Morgagni-Adams-Stokes syndrome, Wolff-Parkinson-White syndrome and sinus node weakness;
children under 18 years of age;
childbearing and lactation.

Interaction with other drugs

Simultaneous use of the drug with other blood pressure-normalizing drugs is accompanied by an increase in their antihypertensive effect.
When combined with antiarrhythmic drugs and beta-blockers, the risk of developing AV block and bradycardia significantly increases.
The antianginal effect of the drug is enhanced by simultaneous use of nitrates.
The combined use of Verapamil with lithium carbonate is fraught with unpredictable drug interactions.

Therefore, if you are taking any medication and have been prescribed Verapamil, be sure to inform your doctor!

Directions for use and adverse reactions

The dosage of this drug is established by a medical specialist and depends on a number of factors: treatment or prevention of any disease, the age of the patient, his complaints, etc. Verapamil tablets are taken orally with water after or during meals.

As a prophylactic agent to prevent attacks of arrhythmia, angina pectoris, as well as in the treatment of high blood pressure, the medication should be taken in an initial dosage of 40–80 mg 3 to 4 times a day. If necessary, the doctor can increase the single dosage to 120 – 160 mg. The maximum daily dose is 480 mg.

In patients with liver dysfunction, it is more advisable to start treatment with minimal dosages, since the process of removing the drug components from the body is slowed down. In this case, the maximum permissible daily dose is 120 mg.

In some cases, while taking this medicine, patients may experience the following side effects:

redness of the facial skin;
lethargy;
a sharp increase in blood pressure;
constipation;
vomit;
headache;
dizziness;
itching and skin rash.

If side effects occur, you should immediately stop taking this medication and seek medical help.

Verapamil is a drug that has antihypertensive (

reduces pressure in blood vessels

), antiarrhythmic (

prevents the occurrence of various heart rhythm disorders

) and antianginal effect (

reduces symptoms of coronary heart disease

). This medication belongs to the group of slow calcium channel blockers, which affect the functioning of the cardiovascular system. It is worth noting that verapamil has a greater effect on the heart muscle (

) than on vessels.

Verapamil is a white crystalline powder that is highly soluble in water. This drug dissolves quite quickly and almost completely in the digestive tract. Verapamil has its maximum effect on the body during the first 2 to 4 hours after oral administration (

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	A country	Release form	Dosage
Avexima	Verapamil	Russia	Film-coated tablets.	Selected individually. The medication should be taken 30–40 minutes before meals. 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 of age, the daily dose is 80–360 milligrams, and children up to six years old inclusive are prescribed 40–60 milligrams. The frequency of taking tablets (for children from six to fourteen years old) is 3 to 4 times a day.
North Star	Verapamil	Russia
Chemical and pharmaceutical plant AKRIKHIN	Verapamil	Russia
Alkaloid	Verapamil	Macedonia
Obolenskoe	Verapamil	Russia
Unipharm	Verapamil-Sopharma	Bulgaria	Film-coated tablets (the 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 (prolonged) action.	Should be taken before or after meals, while washing down the tablet 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 to 480 milligrams (treatment should be carried out in a hospital). The frequency of administration is 2 – 3 times a day. It should be noted that the initial dose for patients with impaired renal and liver function should not exceed 120 milligrams.
Eskom	Verapamil-Eskom	Russia	Solution for intravenous administration.	Inject slowly, over at least 2–3 minutes. Heart rate and blood pressure should be monitored continuously during administration. Adults are administered 5–10 milligrams (single dosage). If there is no desired effect, the administration should be repeated at the same dosage. The maximum daily dosage for adults should not exceed 480 milligrams. The starting dose for people with impaired renal and liver 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, from six to fourteen years old - 2.5 - 3.5 milligrams.
Biosynthesis	Verapamil	Russia	Solution for intravenous administration.

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 (

vessels supplying the heart

), and also dilates peripheral arterial vessels (

arteries and arterioles

). There is also a decrease in total peripheral vascular resistance (

hypotensive effect

It should be noted that verapamil is well absorbed in the body, but due to significant individual differences, this medication may exert its effect after a different period of time (

from 1 to 4 hours

). When verapamil enters liver cells, it is actively metabolized (

undergoes enzymatic breakdown

). Subsequently, once in the blood, it binds to

). The required 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 bile (

), with urine (

), as well as unchanged (

). The elimination period of verapamil is significantly increased in people with various liver dysfunctions.

When administered intravenously, the antiarrhythmic effect is achieved within the first 5 minutes and lasts about two hours (

verapamil is a group IV antiarrhythmic drug

). Hypotensive effect (

lowering blood pressure

) is observed after 3 – 6 minutes and lasts no more than 25 minutes. In most cases, verapamil is well tolerated.

Verapamil is prescribed for the prevention, as well as for the treatment of various heart rhythm disorders, for coronary heart disease (

impaired blood supply to the myocardium due to damage to the coronary vessels

), as well as for some other heart diseases.

Use of verapamil

Indications for use	Mechanism of action	Dosage
Prevention and treatment of coronary heart disease (CHD)
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 total peripheral vascular resistance, which leads to a decrease in pressure in the arteries.	The dosage should be selected individually. When used orally (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 old 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 during any physical activity 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 (sharp and paroxysmal 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 heart rate.	Most often used intravenously. During jet injection, it is necessary to monitor the electrocardiogram, blood pressure, and also count the pulse for 2–3 minutes. A single dosage for adults is 5 – 10 milligrams. If the desired effect is not observed within the first 5 to 10 minutes, it is necessary to re-administer the medication in the same dosage. The frequency of administration should be selected by the attending physician. Children under one year of age 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 orderly contraction of the atria of the heart)		Used both intravenously and orally.
Prevention and treatment of hypertensive conditions
Hypertension (increased blood pressure over 140/90 mmHg)	Directly affects arterial vessels of medium and small caliber and blocks the release of calcium in them, which leads to their reflex expansion. Also dilates coronary arteries.	Most often used intravenously (to achieve a faster effect).
Hypertensive crisis (excessive increase in pressure, which can lead to damage to various organs and systems)
Other heart diseases
Hypertrophic cardiomyopathy (thickening of the muscle layer of the left and sometimes right ventricle of the heart)	Helps 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 intravenous injections.

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

Verapamil tablets are most often prescribed for the prevention or treatment of coronary heart disease. The 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 must 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. The tablets are taken twice or thrice daily. In rare cases, a single dose can be increased to 120 – 160 milligrams (

only after consulting a doctor

). Verapamil tablets can also be prescribed to children. For children under six years of age, a single dose is 15–20 milligrams, and for children from six to fourteen years of age – 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 lower blood pressure (

for hypertension

), as well as for the prevention of attacks

angina pectoris

and supraventricular

tachycardia

The daily dose of verapamil prolonged action is 240 – 360 milligrams. The medication should be taken in the morning during or immediately after meals. The tablet should also be taken with a small amount of liquid (

50 – 100 milligrams

). It should be noted that in persons with impaired liver function, as well as in the elderly, the single dose should be reduced.

For the treatment and prevention of various heart rhythm disorders (

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 over at least 2 to 3 minutes under constant monitoring of heart rate and blood pressure. Adults are given a one-time dose of 5 or 10 milligrams of the drug, and if there is no effect, the same dose is repeated. Children under one year old are given a one-time dose of 0.75–2 milligrams, from one to five years old 2–3 milligrams, from six to fourteen years old 2.5–3.5 milligrams of verapamil. For elderly people, as well as patients with impaired liver and kidney function, the single and daily dose should be reduced (

less than 120 milligrams per day

under the direct supervision of a physician

). Verapamil can also lead to drug-induced

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;

The following side effects from the cardiovascular system are distinguished:

bradycardia;
hypotension;
heart failure;
angina pectoris;
atrioventricular heart block;
asystole.

Bradycardia represents a pronounced decrease in heart rate (less than 50 beats per minute). Bradycardia occurs due to decreased 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 pre-syncope and fainting, which is caused by a decrease in the supply of oxygen to the brain tissues (cerebral hypoxia).

Hypotension characterized by a decrease in blood pressure (

below 90/60 mm Hg. 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.

Hemoptysis and cyanosis (

the skin and mucous membranes acquire a bluish tint

). With failure of the right ventricle of the heart, shortness of breath and hepatomegaly are observed (

increase in liver size

limbs. Fast growing (

) heart failure can lead to complications such as cardiac asthma (

attack of suffocation due to impaired contractility of the heart

), cardiogenic shock (

shock condition caused by a significant decrease in the contractile function of the left ventricle

pulmonary edema

It is worth noting 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 activity. Also, angina pectoris can appear against the background of psychoemotional

or after eating. Angina pectoris can manifest itself not only as pain in the chest, but also as a feeling of discomfort behind the sternum. The pain can usually spread (

radiate

) in the left hand, between the shoulder blades, in the neck or in the lower jaw. The duration of pain during angina pectoris does not exceed 15 minutes. It is worth noting that angina pectoris can lead to

myocardial infarction

against the background of damage to the coronary arteries of the heart.

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 causes cardiac arrest in approximately 3–5% of cases.

Drug allergies can occur to almost any drug. As a rule, drug allergies are manifested by the occurrence of skin

When taking verapamil, the following allergic manifestations may occur:

hives;
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 a large amount of histamine (a mediator of the allergic reaction), which is involved in increasing the permeability of the vascular wall of capillaries (small vessels), which leads to swelling of the surrounding tissues. The skin rash is most often symmetrical in nature and resembles blisters from a nettle burn. After stopping the medication, the skin rash completely disappears.

), which can have different sizes (

from a few millimeters to several centimeters

). Most often affected

forearms, hands, feet, legs and face. After opening these papules, severely painful bleeding areas remain on the mucous membranes and 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

joint pain

A decrease in heart rate inevitably leads to oxygen starvation of the brain. Nerve cells (

) are very sensitive to the lack of oxygen, which is necessary for their normal functioning. When the pumping function of the heart decreases, arterial blood does not sufficiently nourish the nerve tissues of the brain, which can lead to various disorders and pathological conditions.

The effect of oxygen starvation on nerve tissue can lead to the following disorders:

dizziness;
headache;
inhibited state;
increased fatigue;
increased excitability;
depression;
drowsiness.

Verapamil can also cause other disorders of the digestive system:

gum hyperplasia;
constipation;
increased liver tests.

Gingival hyperplasia is a pathological growth of gums. This condition is manifested by bleeding, pain, and swelling of the gums. Hyperplasia occurs due to disruption of the release of calcium from the gum tissue, which subsequently leads to poor circulation. Ultimately, the functional gum tissue is replaced by connective tissue (collagen).

Increased liver tests occurs due to the fact that verapamil is metabolized in the liver. The breakdown products of this drug can interfere with the normal functioning of liver cells (

hepatocytes

). As a result, various

enzymes

alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase

), which normally should practically not penetrate into the bloodstream.

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

Selective class I calcium channel blocker, diphenylalkylamine derivative
Drug: VERAPAMIL

DESCRIPTION OF THE ACTIVE SUBSTANCE.
All information provided is provided for information only about the drug; you should consult your doctor about the possibility of use.

Verapamil is contraindicated during pregnancy and lactation.

Verapamil is a drug from the group of calcium antagonists, or calcium channel blockers.

Active ingredient: Verapamil. White crystalline powder. It dissolves well in water, methyl alcohol, and chloroform. Chemical formula: C27H38N2O4. Name: alpha-methylamino]propyl]-3,4-dimethoxy-alpha-(1-methylethyl)benzeneacetonitrile. In this drug, Verapamil is presented in the form of hydrochloride.

Calcium antagonism, or blockade of calcium channels by Verapamil, manifests itself in a violation of the flow of calcium into the cell. This creates an obstacle to muscle contraction, and the muscle relaxes. Calcium is one of the intracellular ions. One of its many functions is the contraction of muscle fibers (smooth, skeletal, myocardial). Calcium ensures the interaction of muscle contractile proteins – actin and myosin. These proteins take the form of thread-like formations (filaments) located in the muscle fiber (myofibril).

This is achieved by the action of the enzyme calcium-dependent ATPase, which pushes calcium outside the cytoplasm. To ensure the continuous operation of this enzyme, energy is required - because calcium is transported against the concentration gradient, towards higher concentrations. The required energy is obtained through the breakdown of ATP. Thanks to calcium-dependent ATPase, the concentration of calcium outside the cell is 25 times higher than inside the cell. To ensure the next contraction, calcium re-enters the cell and ensures the interaction of filaments. The passage of calcium through the membrane of nerve fibers is accompanied by changes in the transmembrane charge and the passage of an impulse along the nerve fiber.

Calcium transport through the membrane is ensured by the so-called. calcium channels. There are several types of these channels located in the myocardium, skeletal muscles, in the smooth muscles of internal organs, and in the structures of the central nervous system. From a biochemical point of view, these channels are nothing more than carrier proteins. They are located on the surface of the cell membrane, and, combining with calcium, transport it into the cell. Verapamil blocks slow, long-lived L-channels located in the myocardium, in the conduction system of the heart, in blood vessels, as well as in the smooth muscles of internal organs. Its main points of application are: the myocardium, the cardiac conduction system, and the muscular choroid.

Blockade of L-channels in the myocardium leads to a decrease in the force of heart contractions. A similar process in the smooth muscles of blood vessels is accompanied by an expansion of the lumen of these vessels - vasodilation. The drug acts on the wall of small arterioles. It has virtually no effect on the veins. Dilatation of arterioles leads to a decrease in total peripheral vascular resistance (TPR) and to hypotension - a decrease in blood pressure (BP). In addition, Verapamil blocks alpha-1 adrenergic receptors of arterioles, which leads to their additional expansion and increases hypotension.

Verapamil has a depressing effect on the myocardial conduction system. Under its action, the generation of impulses in the pacemaker, in the sinus node, slows down. This drug also slows sinoatrial (sinus-atrial) and atrioventricular (atrioventricular) conduction. Clinically, this is manifested by a decrease in HR (heart rate). As a result, the load on the myocardium is reduced. After all, under the influence of the drug, it does less work - it beats weaker and slower. At the same time, cardiac output does not decrease - the heart works more efficiently against the background of decreased OPS and hypotension.

Reducing the load on the myocardium is of great importance for patients suffering from IHD (coronary heart disease). In IHD, the delivery of oxygen through the blood to the myocardium is impaired. Verapamil also solves this problem. Firstly, a slowdown in heart rate is accompanied by an extension of the relaxation phase (diastole) of the myocardium. But the myocardium receives blood through the coronary arteries during diastole. Blood flow through the coronary arteries also improves as a result of their dilatation. Reducing the load on the myocardium, hypotension, improving coronary blood flow - all this leads to a number of positive effects. Blood pressure decreases, the frequency and intensity of angina attacks decreases - unstable angina, exertional angina, Prinzmetal angina (caused by spasm of the coronary arteries). With long-term use of the drug, such a negative process as left ventricular myocardial hypertrophy is eliminated. The mechanism is the same - reducing the load on the myocardium and improving its blood supply.

Verapamil, like other calcium antagonists, relaxes the muscles of the bronchi, genitourinary system, and gastrointestinal tract. True, these effects are insignificantly expressed. The effect on cerebral vessels is also not great. However, Verapamil can be used to relieve headaches. Verapamil also does not affect the condition of skeletal muscles in healthy people. However, the condition of patients with muscle pathology (Duchenne myopathy) may worsen. In addition, this drug may prolong the action of muscle relaxants, drugs used to relax skeletal muscles.

Verapamil is the first drug from the group of calcium antagonists. It was synthesized in 1961 by German pharmaceutical scientists. Initially, Verapamil was conceived as an antispasmodic, a more effective analogue of Papaverine. A year later, in 1962, its effect on the strength of heart contractions and heart rate was discovered. In 1963, it was officially recommended for use in clinical practice as an antianginal agent for the treatment of coronary artery disease. Since then it has been widely used in Russia, the USA and the West. Europe. Being a representative of the first generation of calcium antagonists, Verapamil is not without its drawbacks. These are relatively low bioavailability, short duration of action, and side effects that limit its use. Subsequently, more effective and safe drugs from this group were introduced into clinical practice. However, Verapamil is still very often used today in the treatment of cardiovascular pathology.

According to some data, Verapamil increases the sensitivity of atypical tumor cells to chemotherapy. In addition, there is evidence that collagen synthesis is reduced under the influence of this drug. In this regard, local injections of Verapamil are used to resolve keloid scars on the skin. The same injections into the penis are made for fibrous deformation - Peyronie's disease.

Verapamil under the active substance name of the same name is produced by many domestic companies. Some of these companies are virtually unknown, and the quality of their products may be questionable. Although it is not at all necessary that Russian pharmaceutical manufacturers produce low-grade drugs. Of the foreign patented drugs, the most famous tablets are Isoptin (Abbott-Knoll, Germany) and Finoptin (Orion, Finland). Abroad, the drug may be called Azupamil, Vergamma, Veradil, Lekoptin, and many others.

Long-acting verapamil (Isoptin SR 240) is taken in a daily dose of 240-480 mg, which is divided into 2 doses with an interval of 12 hours. In patients with impaired liver function, the metabolism of Verapamil slows down. The daily dose in such cases should not exceed 120 mg. It is divided into 3 doses of 40 mg. Tablets are taken in a long course from 2 weeks to 6-8 months. The injection solution is administered intravenously slowly in 2-4 ml (1-2 ampoules). If there is no effect, the jet injection can be repeated after half an hour. The same amount of solution can be diluted in 100-200 m of saline. solution and administered intravenously.

Bioavailability ranges from 22 to 35%. In case of repeated use of the drug, it can increase by 2 times. Absorption in the gastrointestinal tract is 90% of the amount taken orally. 90% of Verapamil entering the blood binds to plasma proteins. The maximum concentration in the blood plasma is formed after 1-2 hours of taking the usual forms of the drug. For prolonged forms this figure is 3-5 hours. The hypotensive effect is observed already in the first week of systematic use of Verapamil, and reaches its maximum by 3-4 weeks.

In the liver, Verapamil undergoes metabolic transformations. One of the metabolites, norverapamil, also has calcium antagonist properties. However, in its strength it is inferior to the original substance Verapamil. The remaining metabolites are inactive. It is excreted mainly by the kidneys in the form of metabolites, and to a lesser extent (3-4%) – unchanged. 9-16% of the drug is excreted through the intestines. The half-life is initially in the range of 2-6 hours. With repeated administration, Verapamil accumulates in the body, and the half-life slows down to 4.5-12 hours. Because of this, it may be necessary to reduce the daily dose by approximately 2 times. The same picture is observed in liver failure, when the metabolism and excretion of Verapamil slow down, and the content of the free fraction in the blood, on the contrary, increases. In these cases, the dose of Verapamil is also reduced.

The drug is prescribed with extreme caution for hypotension and bradycardia, for liver failure, as well as for the initial degree of chronic heart failure and atrioventricular block.

During treatment with Verapamil, you should not drink grapefruit juice, because it increases the bioavailability of the drug.

Verapamil penetrates the placental barrier and into breast milk. In some cases, it is prescribed to pregnant women for therapeutic and obstetric indications. Among these indications are initial hypertension, insufficiency of placental circulation, the danger of gestosis and premature birth. However, the drug should be used with extreme caution, focusing on the risk-benefit ratio. If Verapamil is prescribed during breastfeeding, it should be discontinued.

Store at a temperature not exceeding 250C. Shelf life – 3 years. Verapamil is available with a doctor's prescription.

Verapamil is a drug with antiarrhythmic, antianginal and antihypertensive effects.

Verapamil is available in the following dosage forms:

Film-coated tablets (10 pieces in blisters, 1 or 5 blisters in a cardboard box);
Solution for intravenous administration: colorless, transparent (in colorless glass ampoules of 2 ml, 5 ampoules in blister packs, 2 or 10 packs in a cardboard box).

1 tablet contains:

Active ingredient: verapamil hydrochloride – 40 or 80 mg;
Auxiliary components: dibasic calcium phosphate, starch, butylated hydroxyanisole, purified talc, magnesium stearate, gelatin, methylparaben, hydroxypropyl methylcellulose, titanium dioxide, indigo carmine.

The composition of 1 ampoule of injection solution includes:

Active ingredient: verapamil hydrochloride – 5 mg;
Auxiliary components: sodium chloride - 17 mg, sodium hydroxide - 16.8 mg, citric acid monohydrate - 42 mg, concentrated hydrochloric acid - 0.0054 ml, water for injection - up to 2 ml.

Pharmacodynamics

Verapamil is a drug with antiarrhythmic, antihypertensive and antianginal effects. It is a slow calcium channel blocker. Prevents the transmembrane entry of calcium ions (and possibly sodium ions) into the smooth muscle cells of the myocardium and blood vessels, as well as into the cells of the myocardial conduction system. The antiarrhythmic effect of verapamil is probably due to blockade of the slow channels of the cardiac conduction system. The electrical activity of the sinoatrial and atrioventricular nodes is influenced by the entry of calcium into the cells through slow channels. Verapamil inhibits the entry of calcium, slows down atrioventricular conduction, which leads to an increase in the effective refractory period in the AV node depending on the heart rate. In patients with atrial flutter and/or atrial fibrillation, this effect causes a decrease in the ventricular rate. Verapamil prevents reentry of excitation in the AV node and helps restore proper sinus rhythm in patients suffering from paroxysmal supraventricular tachycardia, including Wolff-Parkinson-White syndrome.

Taking Verapamil does not affect the conduction of impulses along additional pathways, and also does not lead to a change in the normal atrial action potential or intraventricular conduction time. In this case, the drug helps to reduce the amplitude, depolarization rate and impulse conduction in the altered atrial fibers. Verapamil does not cause spasms of peripheral arteries and does not change the total concentration of calcium in the blood serum. The active substance helps reduce afterload and myocardial contractility. The negative inotropic effect of verapamil in most patients (including those with organic heart lesions) is offset by a decrease in afterload. Usually, the cardiac index does not decrease, but in severe or moderate chronic heart failure (with wedge pressure in the pulmonary artery over 20 mm Hg and with a left ventricular ejection fraction of up to 35%), there is a possibility of acute decompensation of chronic heart failure. As a result of bolus intravenous administration, the maximum therapeutic effect of verapamil occurs after 3–5 minutes. With intravenous administration of Verapamil in a standard therapeutic dose (5–10 mg), a transient, most often asymptomatic, decrease in normal blood pressure, systemic vascular resistance, and contractility is observed. A slight increase in left ventricular filling pressure was recorded.

When taken orally:

absorption: about 90–92% of the drug is absorbed in the gastrointestinal tract. The bioavailability of verapamil is low (approximately 20%), which is explained by the first pass effect through the liver. The content in blood plasma increases gradually. The maximum concentration in blood plasma is 81.34 ng/ml. The average time to reach maximum concentration is 4.75 hours. 1 day after taking the drug, fairly high therapeutic concentrations are found in the blood plasma (51.6 ng/ml). Communication with plasma proteins – about 90%;
distribution: when taking a single dose, the half-life is from 2.8 to 7.4 hours, and when taking the drug repeatedly - from 4.5 to 12 hours. In elderly patients, the half-life increases. Verapamil crosses the blood-brain and placental barriers and is excreted into breast milk;
metabolism: metabolized in the liver (first pass effect). 12 metabolites of verapamil have been recorded, the main of which is the pharmacologically active norverapamil. Other metabolites are largely inactive;
excretion: approximately 70% of the taken dose of Verapamil is excreted in the urine, and approximately 16% or more is excreted in the feces within 5 days after oral administration of the drug. 3–4% is excreted unchanged from the body.

For intravenous administration:

distribution: verapamil is well distributed in body tissues. In healthy volunteers, the volume of distribution ranges from 1.6 to 1.8 l/kg. About 90% binds to plasma proteins;
metabolism: in vitro metabolic studies have shown that verapamil is metabolized by isoenzymes CYP1A2, CYP3A4, CYP2C8, CYP2C18 and CYP2C9 of the cytochrome P450 family. When administered orally to healthy volunteers, verapamil was extensively metabolized in the liver to form 12 metabolites, most of which were present in trace amounts. The main metabolites include forms of O- and N-dealkylated derivatives of verapamil. Studies on dogs revealed that only norverapamil is a pharmacologically active metabolite (about 20% compared to the parent compound). Verapamil crosses the blood-brain and placental barriers and is excreted in small quantities into breast milk;
elimination: the curve of changes in the content of verapamil in the blood has a bi-exponential character with a fast early distribution phase (half-life - about 4 minutes), as well as a slower terminal elimination phase (half-life - from 2 to 5 hours). Within 24 hours, approximately 50% of the drug dose is excreted by the kidneys, and within 5 days – 70%. About 16% of the verapamil dose is excreted through the intestines. 3–4% of verapamil is excreted unchanged from the body. The total clearance of verapamil approximately corresponds to the hepatic blood flow - about 1 l/h/kg (range 0.7 to 1.3 l/h/kg).

When renal function is impaired, the pharmacokinetic parameters of verapamil do not change, which was recorded in studies in two groups of patients: without impaired renal function and with end-stage renal failure. Norverapamil and verapamil are not eliminated by hemodialysis.

Age may change the pharmacokinetic parameters of verapamil when used in patients with arterial hypertension. In elderly patients, the half-life may be prolonged. The relationship between age and the antihypertensive effect of the drug has not been identified.

Pills

Heart rhythm disturbances, including paroxysmal supraventricular tachycardia, atrial fibrillation and flutter (tachyarrhythmic variant), supraventricular extrasystole - for treatment and prevention;
Unstable angina (rest angina), chronic stable angina (effort angina), vasospastic angina (variant angina, Prinzmetal angina) - for treatment and prevention;
Arterial hypertension - for treatment.

Injection solution

Verapamil in the form of an injection solution is used to relieve attacks of supraventricular paroxysmal tachycardia, atrial extrasystole, paroxysms of flutter and atrial fibrillation.

Absolute:

Chronic heart failure stage IIB-III;
Morgagni-Adams-Stokes syndrome;
Sinoatrial block;
Sick sinus syndrome;
Cardiogenic shock (except caused by arrhythmia) (for tablets);
Severe bradycardia (for tablets);
Wolff-Parkinson-White syndrome (for tablets);
Acute heart failure (for tablets);
Atrioventricular block II and III degrees (except for patients with an artificial pacemaker) (for tablets);
Arterial hypotension (for injection solution);
Acute myocardial infarction (for injection solution);
Aortic stenosis (for injection solution);
Digitalis intoxication (for injection solution);
Ventricular tachycardia (for injection solution);
Lown-Ganong-Levine syndrome or Wolff-Parkinson-White syndrome in combination with atrial flutter or fibrillation (excluding patients with a pacemaker) (for injection solution);
Porphyria (for injection solution);
Simultaneous therapy with intravenous beta-blockers;
Age up to 18 years;
Pregnancy and lactation (for injection solution);
Hypersensitivity to the components of the drug.

Relative (Verapamil should be used with caution in the presence of the following conditions/diseases):

First degree atrioventricular block;
Bradycardia;
Severe functional disorders of the kidneys and liver;
Arterial hypotension with systolic pressure below 100 mm Hg. (for tablets);
Chronic heart failure degrees I and II (for tablets) and degrees I and IIA (for injection solution);
Simultaneous use with beta-blockers (for injection solution);
Myocardial infarction with left ventricular failure (for injection solution);
Old age (for injection solution).

Pills

Verapamil is taken orally with a small amount of water, preferably during or after meals.

The doctor sets the dosage regimen and duration of therapy individually depending on the patient’s condition, the severity and characteristics of the course of the disease, as well as the effectiveness of the drug.

The initial adult single dose for the treatment of arterial hypertension and for the prevention of attacks of angina pectoris and arrhythmia is 40-80 mg, the frequency of administration is 3-4 times a day. A single dose, if necessary, is increased to 120-160 mg (maximum 480 mg per day).

In case of severe functional disorders of the liver, it is advisable to start therapy with the lowest doses (maximum 120 mg per day).

Verapamil should be administered intravenously, slowly, over at least 2 minutes, continuously monitoring the electrocardiogram, heart rate and blood pressure. In elderly patients, in order to reduce the risk of developing undesirable effects, the solution should be administered over at least 3 minutes.

When stopping paroxysmal heart rhythm disturbances, Verapamil is administered intravenously in a stream of 2-4 ml of a 0.25% solution (5-10 mg), monitoring the electrocardiogram and blood pressure. In cases of no effect, it is possible to re-administer the same dose of the drug after 30 minutes. To dilute 2 ml of 0.25% Verapamil solution, use 100-150 ml of 0.9% sodium chloride solution.

Pills

Central nervous system: headache, dizziness; in rare cases - lethargy, increased nervous excitability, increased fatigue;
Digestive system: vomiting, nausea, constipation; in some cases - a transient increase in the activity of liver transaminases in the blood plasma;
Cardiovascular system: facial flushing, AV block, severe bradycardia, arterial hypotension, the appearance of symptoms of heart failure (when using high doses of the drug, especially in predisposed patients);
Allergic reactions: itching, skin rash;
Other: peripheral edema.

Injection solution

Digestive system: nausea, increased activity of liver transaminases and alkaline phosphatase;
Central nervous system: increased fatigue, anxiety, headache, dizziness, fainting, extrapyramidal disorders, lethargy, asthenia, depression, drowsiness;
Cardiovascular system: severe bradycardia (at least 50 beats per minute), marked decrease in blood pressure, worsening or development of heart failure, tachycardia; possible - the development of angina pectoris, up to myocardial infarction (especially in patients with severe obstructive lesions of the coronary arteries), arrhythmias (including flutter and ventricular fibrillation); with rapid administration of the solution – asystole, third degree atrioventricular block, collapse;
Allergic reactions: facial skin flushing, rash, itching, exudative erythema multiforme (including Stevens-Johnson syndrome);
Other: pulmonary edema, transient loss of vision against the background of maximum concentration, asymptomatic thrombocytopenia, peripheral edema (including swelling of the ankles, legs and feet).

Overdose

Symptoms: marked decrease in blood pressure (sometimes to a level that cannot be measured), loss of consciousness, shock, escape rhythm, first or second degree atrioventricular block (Wenckebach periods with or without escape rhythm are often observed), complete atrioventricular block accompanied by complete atrioventricular block dissociation, cardiac arrest, sinus node arrest, sinus bradycardia, heart failure, sinoatrial block, asystole.

In case of early detection (it should be taken into account that when taken orally, the release and absorption of verapamil in the intestine occurs within 2 days), gastric lavage is prescribed if no more than 12 hours have passed since administration. With reduced motility of the gastrointestinal tract (in the absence of bowel sounds), this measure can be carried out in later periods.

Treatment is symptomatic and depends on the clinical picture of the overdose.

The specific antidote is calcium. To treat an overdose, a 10% calcium gluconate solution (10–30 ml) is administered intravenously or slowly as a drip infusion. If necessary, the procedure can be repeated.

For sinus bradycardia, atrioventricular block II and III degrees, cardiac arrest, isoprenaline, atropine, orciprenaline or cardiac stimulation are indicated.

For arterial hypotension, norepinephrine (norepinephrine), dobutamine, and dopamine are prescribed. Hemodialysis is ineffective.

During therapy, it is necessary to monitor the function of the respiratory and cardiovascular systems, the level of electrolytes and glucose in the blood, the amount of urine excreted and the volume of circulating blood.

With intravenous administration of Verapamil, an extension of the PQ interval is possible at plasma concentrations above 30 mg/ml.

Verapamil should be used with caution by vehicle drivers and people whose profession involves increased concentration (due to a decrease in reaction speed).

According to the instructions, Verapamil is contraindicated for use during pregnancy and lactation.

There are no data on the use of the drug in pregnant women.

In animal studies, no direct or indirect toxic effects on the reproductive system were detected. Since the results of animal studies do not reliably predict the response to drug therapy in humans, Verapamil can be used during pregnancy only in cases where the potential benefit to the mother is greater than the estimated risk to the child.

The drug is characterized by penetration through the placental barrier, and it is also found in the blood of the umbilical vein during childbirth.

Verapamil and metabolites are excreted into breast milk. According to the limited available data, the dose of Verapamil that an infant receives via milk is quite low (0.1 to 1% of the amount of Verapamil taken by the mother). Since the possibility of complications for infants cannot be excluded, the drug may be used during breastfeeding only in cases where the potential benefit to the mother is higher than the expected risk to the child.

Verapamil should not be used to treat patients under 18 years of age.

In severe renal failure, the drug should be used with caution, prescribing a lower initial dose.

In case of impaired liver function and severe liver failure, the drug should be used with caution, prescribing a lower initial dose.

When Verapamil is used simultaneously with certain medications, the following effects may occur:

Antiarrhythmic drugs, beta-blockers and inhalational anesthetics: increased cardiotoxic effect (increases the risk of developing atrioventricular block, a sharp decrease in heart rate, the development of heart failure, a sharp decrease in blood pressure);
Antihypertensive drugs and diuretics: increased hypotensive effect of Verapamil;
Digoxin: increase in the concentration of digoxin in the blood plasma (to determine the optimal dosage of the drug and prevent intoxication, its level in the blood plasma should be monitored);
Cimetidine and ranitidine: increase in the concentration of Verapamil in the blood plasma;
Theophylline, prazosin, cyclosporine: increase in their concentration in blood plasma;
Muscle relaxants: enhanced muscle relaxant effect;
Rifampicin, phenobarbital: decreasing the concentration of Verapamil in the blood plasma and weakening its effect;
Acetylsalicylic acid: increased likelihood of bleeding;
Quinidine: an increase in the level of quinidine concentration in the blood plasma, an increased risk of lowering blood pressure, and in hypertrophic cardiomyopathy - the development of severe arterial hypotension;
Carbamazepine, lithium: increased risk of developing neurotoxic effects.

Analogues of Verapamil are: Isoptin, Isoptin SR 240, Kaveril, Finoptin, Lekoptin, Gallopamil, Verapamil Sopharma, Verapamil-Eskom, Nifedipine, Nifedipine Retard, Amlodipine, Nicardipine, Riodipine, Nimodipine.

Store in a dry, dark place, out of reach of children, at temperatures up to 25 °C.

Shelf life – 3 years.

Dispensed by prescription.