The drug verapamil. Verapamil Latin name. Isoptin for injections

VERAPAMIL Verapamil

Active substance

›› Verapamil* (Verapamil*)

Latin name

›› C08DA01 Verapamil

Pharmacological group: Calcium channel blockers

Nosological classification (ICD-10)

›› I10-I15 Diseases characterized by high blood pressure
›› I20 Angina pectoris [angina pectoris]
›› I25 Chronic ischemic heart disease
›› I25.2 Past myocardial infarction
›› I47.2 Ventricular tachycardia
›› I49.4 Other and unspecified premature depolarization
›› R07.2 Pain in the region of the heart

Composition and form of release

1 dragee contains verapamil hydrochloride 40 or 80 mg; in bottles of 30 or 50 pcs. respectively, in a cardboard box 1 bottle.
1 ampoule with 2 ml solution for injection - 5 mg; in a blister 5 pcs., in a cardboard box 2 blisters.
1 tablet retard - 240 mg; in bottles of 20 pcs., in a cardboard box 1 bottle.

pharmachologic effect

pharmachologic effect- hypotensive, antianginal, antiarrhythmic. Blocks calcium channels.

Indications

Arterial hypertension, ischemic heart disease, angina pectoris, paroxysmal tachycardia, extrasystole, postinfarction period.

Contraindications

Wolff-Parkinson-White syndrome, cardiogenic shock, hypotension, AV block, congestive heart failure.

Side effects

Dizziness, nausea, headache, hyperemia, hypotension, AV blockade, bradycardia, constipation.

Dosage and administration

Inside, adults - 80-160 mg (pellets) 3 times a day 30 minutes before meals or in the morning, on an empty stomach - 1 table retard (dose is selected individually), additionally (if necessary) - 1/2-1 table .retard (in the evening). The maximum daily dose is 480 mg.
Children under 14 years old - 40 mg (pellets) 2-3 times a day, infants and young children - 20 mg (pellets) 2-3 times a day.
In / in slowly, for adults - 5-10 mg, maintenance dose - in / in drip (previously dissolved in 100-150 ml of isotonic sodium chloride solution) at a rate of 5-10 mg / h (no more than 100 mg / day). Children: newborns - 0.75-1 mg, up to 1 year - 0.75-2 mg, 1-5 years - 2-3 mg, 6-14 years - 2.5-5 mg.

Best before date

Storage conditions

List B.: In a place protected from light, at a temperature of 15-25 ° C.

* * *

VERAPAMIL (Verapamilum) *. 5-[(3,4-Dimethoxyphenethyl)-methylamino]-2-(3,4-dimethoxyphenyl)-2-isopropylvaleronitrile hydrochloride. Synonyms: Verpamil, Isoptin, Falicard, Phenoptin, Calan, Cardilax, Dilacoran, Falicard, Finoptin, Ikacor, Iproveratril, Isopine, Isoptin, Manidon, Vasolan, Vepamil, Verapamilhydrochlorid, Verapamil, etc. According to the chemical structure, the verapamil molecule can be considered as a complicated version of the phenylalkylamine molecule (see Senzit). The drug has antiadrenergic activity. Previously, it was believed that its therapeutic effect is due to the weakening of sympathetic impulses to the blood vessels, heart and other organs. Currently, it is classified as a calcium ion antagonist, and it is one of the main drugs in this group. Verapamil causes expansion of the coronary vessels of the heart and increases coronary blood flow; lowers the heart's need for oxygen. In ischemic processes in the myocardium, the drug helps to reduce the disproportion between the need and supply of the heart with oxygen, both by increasing blood supply and by better utilization and more economical consumption of the delivered oxygen. The drug reduces myocardial contractility, but due to the expansion of peripheral vessels and a decrease in vascular resistance, cardiac output does not change significantly. The drug inhibits platelet aggregation. Verapamil affects the conduction system of the heart, inhibits sinoatrial and atrioventricular conduction. Has antiarrhythmic effect; refers to antiarrhythmic drugs of group IV (see Antiarrhythmic drugs). In addition, it has some natriuretic and diuretic effect by reducing tubular reabsorption. In the mechanism of the antianginal action of verapamil, along with antagonism towards calcium ions, an increase in the content of potassium ions in myocardial cells also plays a role. Verapamil is well absorbed when taken orally. Peak plasma concentration is detected after 1-3 hours. However, there are significant individual differences in the pharmacokinetics of the drug. The elimination half-life varies from 2.5 to 7.5 hours after a single dose and from 4.5 to 12 hours after repeated administration. A constant therapeutic concentration in the blood is usually reached after 4 days from the start of repeated oral administration. The drug is extensively metabolized in the liver. With impaired liver function, the release time of the drug is significantly prolonged. About 5% of the drug is excreted unchanged. Apply verapamil inside and in the form of injections. Inside taken with chronic coronary artery disease to prevent attacks of angina pectoris, especially in combination with atrial extrasystole and a tendency to tachycardia. As an antiarrhythmic agent, it is prescribed mainly for atrial arrhythmias: for supraventricular tachycardia, extrasystole. With ventricular arrhythmias, including with ventricular extrasystole; the drug is ineffective. It is also recommended for arterial hypertension, but as an antihypertensive agent for severe hypertension, nifedipine is more effective (see). Intravenously used for acute attacks of angina pectoris, attacks of supraventricular paroxysmal tachycardia and hypertensive crises. Inside take 30 minutes before meals. Doses, especially taking into account possible fluctuations in pharmacokinetics, are selected individually. In mild forms of angina pectoris, 0.04-0.08 g (40-80 mg) is prescribed 3-4 times a day. If necessary, increase a single dose to 0.12 - 0.16 g (120 - 160 mg). Usually the daily dose is 0.24 - 0.48 g (240 - 480 mg). Maintenance therapy (smaller, individually selected doses) is carried out for a long time. It was noted that tolerance does not develop with the use of verapamil (unlike organic nitrates and nifedipine). On the contrary, the anti-ischemic effect increases with regular use of verapamil. Intravenously, to stop the paroxysm of supraventricular tachycardia, adults are slowly injected with 2–4 ml of a 0.25% solution (5–10 mg). Repeatedly for maintenance therapy is administered 1 time per day drip at a rate of 0.005 mg / kg per minute, not earlier than 30 minutes after the jet injection. A solution of verapamil is prepared by diluting 2 ml of a 0.25% solution of the drug (1 ampoule) in 100-150 ml of isotonic sodium chloride solution or 5% glucose solution. Children are prescribed the drug in smaller doses: up to 4 years, they usually give orally 0.02 g (20 mg) 2 to 3 times a day; up to 14 years - 0.04 (40 mg) 2 - 3 times a day. Intravenously administered at the age of 1 to 5 years, 0.002 - 0.003 g (2 - 3 mg), from 6 to 14 years - 0.025 - 0.05 g (2.5 - 5 mg). Verapamil is generally well tolerated. However, nausea, vomiting, dizziness, increased fatigue, the development of peripheral edema, allergic reactions are possible, relatively often (especially with prolonged use) constipation of an atonic nature occurs. Large doses can cause arterial hypotension, atrioventricular blockade. Contraindications: cardiac shock, severe hypotension, acute myocardial infarction with atrioventricular blockade; the first 3 months of pregnancy and the period of breastfeeding. Caution should be exercised with the simultaneous use of verapamil and b-blockers (due to the possible summation of the effect on the conduction and contractility of the heart). Verapamil is administered intravenously under the control of hemodynamic parameters. Release form tablets of 0.04 g (40 mg); 0.08 g (80 mg) and 0.12 g (120 mg) in a package of 30 and 100 pieces; 0.25% solution in ampoules of 2 ml (5 mg) in a package of 5 ampoules; prolonged action tablets of 0.2 g (200 mg) and 0.24 g (240 mg). Storage: list B. In a place protected from light.

Medicine Dictionary. 2005 .

Synonyms:

See what "VERAPAMIL" is in other dictionaries:

IUPAC chemical compound? Gross formula? ATX classification ... Wikipedia

Ex., number of synonyms: 15 azupamil (1) antiarrhythmic (5) veramyl (1) ... Synonym dictionary

verapamil- a drug that normalizes heart rhythm, lowers blood pressure and improves blood supply to the heart muscle. It is used for arterial hypertension, angina pectoris, arrhythmias. It is a cheap analogue of ISOPTIN and FINOPTIN ... Analogues of expensive drugs

- (isopropyl hydrochloride [(N methyl N homoveratril) aminopropyl] 3,4 dimethoxyphenyl acetonitrile; isoptin; finoptin), mol. m. 491.1; colorless crystals; m.p. 146 ... Chemical Encyclopedia

VERAPAMIL- (verapamil) calcium antagonist; used to treat hypertension, angina pectoris and arrhythmias. Assigned inside; possible side effects: constipation, nausea and hypotension. Trade names: cordilox (Cordilox), sekuron (Securon), uni (Univer) … Explanatory Dictionary of Medicine- n., number of synonyms: 1 verapamil (15) ASIS Synonym Dictionary. V.N. Trishin. 2013 ... Synonym dictionary

calcium antagonist; used to treat hypertension, angina pectoris and arrhythmias. Assigned inside; possible side effects: constipation, nausea and hypotension. Trade names: cordilox (Cordilox), securon (Securon), uni (Univer).

Verapamil: instructions for use and reviews

Latin name: Verapamil

ATX Code: C08DA01

Active substance: verapamil (verapamil)

Producer: OJSC "Biosintez", Obolenskoye, STI-MED-SORB, Irbit chemical pharmaceutical plant, AVVA-RUS (Russia), Hemofarm concern A.D. (Yugoslavia), Pharbita (Netherlands), BASF Generics (Germany), Alkaloid JSC (Republic of Macedonia)

Description and photo update: 16.08.2019

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

Release form and composition

Verapamil is available in the following dosage forms:

Film-coated tablets (10 pieces in blisters, 1 or 5 blisters in a carton 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 carton box).

The composition of 1 tablet includes:

Active ingredient: verapamil hydrochloride - 40 or 80 mg;
Auxiliary components: dibasic calcium phosphate, starch, butylhydroxyanisole, purified talc, magnesium stearate, gelatin, methyl paraben, hydroxypropyl methylcellulose, titanium dioxide, indigo carmine.

The composition of 1 ampoule of the 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.

Pharmacological properties

Pharmacodynamics

Verapamil is a drug with antiarrhythmic, antihypertensive and antianginal effects. It is a blocker of slow calcium channels. It 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 the blockade of the slow channels of the cardiac conduction system. The electrical activity of the sinoatrial and atrioventricular nodes is affected by the entry of calcium into the cells through slow channels. Verapamil inhibits calcium entry, 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 the re-entry of excitation in the AV node and helps restore the correct sinus rhythm in patients suffering from paroxysmal supraventricular tachycardia, including Wolff-Parkinson-White syndrome.

Reception of Verapamil does not affect the conduction of the impulse along the accessory 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, speed of depolarization and impulse conduction in the altered atrial fibers. Verapamil does not cause spasms of peripheral arteries, does not change the total concentration of calcium in the blood serum. The active substance helps to reduce afterload and myocardial contractility. The negative inotropic effect of verapamil in most patients (including those with organic heart disease) is offset by a decrease in afterload. Usually, the heart index does not decrease, however, in severe or moderate chronic heart failure (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 at 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 the filling pressure of the left ventricle was recorded.

Pharmacokinetics

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 effect of the first pass through the liver. The content in the blood plasma increases gradually. The maximum plasma concentration is 81.34 ng / ml. The average time to reach the maximum concentration is 4.75 hours. 1 day after taking the drug, sufficiently high therapeutic concentrations (51.6 ng / ml) are found in the blood plasma. 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 the drug is taken again, from 4.5 to 12 hours. In elderly patients, the half-life increases. Verapamil crosses the blood-brain and placental barriers, is excreted into breast milk;
metabolism: metabolized in the liver (first pass effect). 12 verapamil metabolites have been identified, the main of which is the pharmacologically active norverapamil. Other metabolites are mostly inactive;
excretion: approximately 70% of the dose of Verapamil is excreted in the urine, and approximately 16% or more is excreted in the feces for 5 days after oral administration of the drug. In unchanged form, 3-4% is excreted from the body.

When administered intravenously:

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 CYP1A2, CYP3A4, CYP2C8, CYP2C18 and CYP2C9 isoenzymes of the cytochrome P 450 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 the O- and N-dealkylated forms of verapamil derivatives. In studies in dogs, only norverapamil was found to be the pharmacologically active metabolite (about 20% of the parent compound). Verapamil crosses the blood-brain and placental barriers, is excreted in small amounts into breast milk;
excretion: the curve of change in the content of verapamil in the blood has a bi-exponential character with a fast early phase of distribution (half-life - about 4 minutes), as well as a slower terminal phase of elimination (half-life - from 2 to 5 hours). Within 24 hours, approximately 50% of the dose of the drug is excreted by the kidneys, within 5 days - 70%. About 16% of the dose of verapamil is excreted through the intestines. In unchanged form, 3-4% of verapamil is excreted from the body. The total clearance of verapamil approximately corresponds to the hepatic blood flow - about 1 l / h / kg (range from 0.7 to 1.3 l / h / kg).

In case of impaired renal function, the pharmacokinetic parameters of verapamil do not change, which was recorded during studies in two groups of patients: without impaired renal function and with renal failure in the terminal stage. Norverapamil and verapamil are not excreted by hemodialysis.

The age indicator may change the pharmacokinetic parameters of verapamil in the case of its use in patients with arterial hypertension. In elderly patients, the elimination half-life may be increased. The relationship between age and the antihypertensive effect of the drug has not been identified.

Indications for use

Tablets

Heart rhythm disorders, including paroxysmal supraventricular tachycardia, atrial fibrillation and flutter (tachyarrhythmic variant), supraventricular extrasystole - for treatment and prevention;
Unstable angina (rest angina), chronic stable angina (angina pectoris), vasospastic angina (variant angina, Prinzmetal's 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 premature beats, paroxysms of flutter and atrial fibrillation.

Contraindications

Absolute:

Chronic heart failure IIB-III stage;
Morgagni-Adams-Stokes syndrome;
Sinoatrial blockade;
Sick sinus syndrome;
Cardiogenic shock (other than that 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 degree (except for patients with an artificial pacemaker) (for tablets);
Arterial hypotension (for injection solution);
Acute myocardial infarction (for injection solution);
Stenosis of the aortic orifice (for injection solution);
Digitalis intoxication (for injection solution);
Ventricular tachycardia (for injection solution);
Lown-Ganong-Levin syndrome or Wolff-Parkinson-White syndrome in combination with flutter or atrial fibrillation (excluding patients with a pacemaker) (for injection solution);
Porphyria (for injection solution);
Simultaneous therapy with intravenous administration of 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):

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

Instructions for use Verapamil: method and dosage

Tablets

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

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 in the treatment of arterial hypertension and for the prevention of angina attacks, arrhythmias 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).

With severe functional disorders of the liver, it is advisable to start therapy with the smallest doses (maximum - 120 mg per day).

injection solution

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 administration of the solution should be carried out for at least 3 minutes.

When arresting paroxysmal cardiac arrhythmias, 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 a 0.25% solution of Verapamil, use 100-150 ml of a 0.9% solution of sodium chloride.

Side effects

Tablets

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 hepatic transaminases in the blood plasma;
Cardiovascular system: redness of the face, AV blockade, 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 hepatic transaminases and alkaline phosphatase;
Central nervous system: increased fatigue, anxiety, headache, dizziness, fainting, extrapyramidal disorders, lethargy, asthenia, depression, drowsiness;
Cardiovascular system: severe bradycardia (not less than 50 beats per minute), a pronounced decrease in blood pressure, aggravation or development of heart failure, tachycardia; possibly - 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 the rapid introduction of the solution - asystole, atrioventricular blockade of the III degree, collapse;
Allergic reactions: flushing of the skin of the face, rash, pruritus, erythema multiforme exudative (including Stevens-Johnson syndrome);
Others: 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, atrioventricular block I or II degree (wenckebach periods are often observed with or without escape rhythm), complete atrioventricular block, accompanied by complete atrioventricular dissociation, cardiac arrest, sinus arrest, sinus bradycardia, heart failure, sinoatrial block, asystole.

In case of early detection (it should be borne in mind 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 the application. With reduced motility of the gastrointestinal tract (in the absence of intestinal noises), this measure can be carried out in later periods.

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

Calcium is a specific antidote. For the treatment of overdose, a solution of calcium gluconate 10% (10–30 ml) is administered intravenously or slowly as a drip infusion. If necessary, the procedure can be repeated.

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

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

special instructions

During therapy, it is necessary to control 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, a prolongation of the PQ interval is possible at plasma concentrations above 30 mg / ml.

Verapamil should be used with caution by drivers of vehicles and people whose profession is associated with increased concentration of attention (due to a decrease in the reaction rate).

Use during pregnancy and lactation

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, direct or indirect toxic effects on the reproductive system have not been identified. 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 higher than the expected risk to the child.

The drug is characterized by penetration through the placental barrier, 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 data available, the dose of Verapamil that an infant receives with milk is quite low (from 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 can be used during breastfeeding only in cases where the potential benefit to the mother is higher than the expected risk to the child.

Application in childhood

It is forbidden to use Verapamil for the treatment of patients under the age of 18 years.

For impaired renal function

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

For impaired liver function

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

Use in the elderly

drug interaction

With the simultaneous use of Verapamil with certain drugs, the following effects may occur:

Antiarrhythmic drugs, beta-blockers and inhalation anesthetics: increased cardiotoxic effect (the risk of developing atrioventricular blockade, a sharp decrease in heart rate, the development of heart failure, a sharp decrease in blood pressure increases);
Antihypertensive agents and diuretics: increased hypotensive effect of Verapamil;
Digoxin: an increase in the level of 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: an increase in the level of concentration of Verapamil in the blood plasma;
Theophylline, prazosin, cyclosporine: an increase in their concentration in blood plasma;
Muscle relaxants: increased muscle relaxant action;
Rifampicin, phenobarbital: a decrease in the concentration of Verapamil in the blood plasma and a weakening of its action;
Acetylsalicylic acid: increased likelihood of bleeding;
Quinidine: an increase in the level of concentration of quinidine in the blood plasma, an increased risk of lowering blood pressure, with hypertrophic cardiomyopathy - the development of severe arterial hypotension;
Carbamazepine, lithium: increased risk of neurotoxic effects.

Analogues

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

Terms and conditions of storage

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

Shelf life - 3 years.

Pharmacological action - antianginal, hypotensive, antiarrhythmic.
It blocks calcium channels (acts from the inside of the cell membrane) and lowers the transmembrane calcium current. Interaction with the channel is determined by the degree of membrane depolarization: it more effectively blocks the open calcium channels of the depolarized membrane. To a lesser extent, it affects the closed channels of the polarized membrane, preventing their activation. Slightly affects sodium channels and alpha-adrenergic receptors. Reduces contractility, frequency of the pacemaker of the sinus node and the speed of conduction in the AV node, sinoatrial and AV conduction, relaxes smooth muscles (more arterioles than veins), causes peripheral vasodilation, lowers peripheral vascular resistance, reduces afterload. Increases myocardial perfusion, reduces the disproportion between the need and supply of oxygen to the heart, promotes regression of left ventricular hypertrophy, lowers blood pressure. Prevents the development and eliminates spasm of the coronary arteries in variant angina pectoris. In patients with uncomplicated hypertrophic cardiomyopathy, it improves the outflow of blood from the ventricles. Reduces the frequency and severity of headaches of vascular origin. It inhibits neuromuscular transmission in Duchenne pseudohypertrophic myopathy and prolongs the recovery period after the use of vecuronium. In vitro, it blocks the P170 enzyme and partially eliminates the resistance of cancer cells to chemotherapeutic agents.
After oral administration, more than 90% of the dose is absorbed, bioavailability is 20-35% due to first-pass metabolism through the liver (increases with long-term use in large doses). Tmax is 1-2 hours (tablets), 5-7 hours (prolonged-release tablets) and 7-9 hours (prolonged-release capsules). Contacts proteins of plasma for 90%. It is metabolized in the liver to form norverapamil, which has 20% of the hypotensive activity of verapamil, and 11 other metabolites (determined in trace amounts). T1 / 2 when administered as a single dose - 2.8-7.4 hours, with repeated doses - 4.5-12 hours (due to saturation of the liver enzyme systems). With intravenous administration, T1 / 2 is biphasic: early - about 4 minutes, final - 2-5 When ingested, the onset of action is noted after 1-2 min), hemodynamic effects - within 3-5 minutes. The duration of action is 8-10 hours (tablets) or 24 hours (capsules and tablets of prolonged action). With intravenous administration, the antiarrhythmic effect lasts about 2 hours, the hemodynamic effect lasts 10-20 minutes. Excreted mainly by the kidneys and faeces (about 16%). Penetrates into breast milk, passes through the placenta and is determined in the blood of the umbilical vein during childbirth. Rapid intravenous administration causes hypotension in the mother, leading to fetal distress. With prolonged use, clearance decreases and bioavailability increases. Against the background of severe liver dysfunction, plasma clearance decreases by 70% and T1 / 2 increases to 14-16.
According to the results obtained in 2-year studies in rats at doses 12 times the MRDH and in the Ames bacterial test (5 studied strains, dose - 3 mg per cup, with or without metabolic activation), it is not carcinogenic and mutagenic activity. In experiments on rats at doses 6 times higher than those recommended for humans, it slows down fetal growth and increases the frequency of intrauterine fetal death.

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

The active substance of the drug: verapamil
ATX encoding: C08DA01
CFG: Calcium Channel Blocker
Registration number: P No. 013974/01
Date of registration: 14.08.08
The owner of the reg. Credit: 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: 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.

DESCRIPTION OF THE ACTIVE SUBSTANCE.
All the information provided is provided only for familiarization with the drug, you should consult a doctor about the possibility of using it.

Pharmacological action Verapamil

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 the macroergic bonds of ATP 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 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 the liver enzyme systems and an increase in the concentration of verapamil in the blood plasma). 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.

Indications for use:

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.

Dosage and method of application of the drug.

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.
Maximum dose: adults when taken orally - 480 mg / day.

Side effects of Verapamil:

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 ventricular fibrillation and 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.

Contraindications to the drug:

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.

Use during pregnancy and lactation.

Verapamil is contraindicated during pregnancy and lactation.

Special instructions for the use of Verapamil.

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.

Interaction of Verapamil with other drugs.

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.

Gross formula

C 27 H 38 N 2 O 4

Pharmacological group of the substance Verapamil

Nosological classification (ICD-10)

CAS code

53-53-9

Characteristics of the substance Verapamil

A derivative of phenylalkylamine. Verapamil hydrochloride is a white crystalline powder. Soluble in water, chloroform, methanol.

Pharmacology

pharmachologic effect- antianginal, hypotensive, antiarrhythmic.

It blocks calcium channels (acts from the inside of the cell membrane) and lowers the transmembrane calcium current. Interaction with the channel is determined by the degree of membrane depolarization: it more effectively blocks the open calcium channels of the depolarized membrane. To a lesser extent, it affects the closed channels of the polarized membrane, preventing their activation. Slightly affects sodium channels and alpha-adrenergic receptors. Reduces contractility, the frequency of the sinus node pacemaker and the speed of conduction in the AV node, sinoatrial and AV conduction, relaxes smooth muscles (more arterioles than veins), causes peripheral vasodilation, lowers OPSS, reduces afterload. Increases myocardial perfusion, reduces the imbalance between the need and supply of oxygen to the heart, promotes regression of left ventricular hypertrophy, lowers blood pressure. Prevents the development and eliminates spasm of the coronary arteries in variant angina pectoris. In patients with uncomplicated hypertrophic cardiomyopathy, it improves the outflow of blood from the ventricles. Reduces the frequency and severity of headaches of vascular origin. It inhibits neuromuscular transmission in Duchenne pseudohypertrophic myopathy and prolongs the recovery period after the use of vecuronium. In vitro blocks the P170 enzyme and partially eliminates the resistance of cancer cells to chemotherapeutic agents.

After oral administration, more than 90% of the dose is absorbed, bioavailability is 20-35% due to first-pass metabolism through the liver (increases with long-term use in large doses). T max is 1-2 hours (tablets), 5-7 hours (prolonged-release tablets) and 7-9 hours (prolonged-release capsules). Contacts proteins of plasma for 90%. It is metabolized in the liver to form norverapamil, which has 20% of the hypotensive activity of verapamil, and 11 other metabolites (determined in trace amounts). T 1/2 when administered as a single dose - 2.8-7.4 hours, with repeated doses - 4.5-12 hours (due to the saturation of the liver enzyme systems). With intravenous administration, T 1/2 is biphasic: early - about 4 minutes, final - 2-5 hours. When taken orally, the onset of action is noted after 1-2 hours. min (usually less than 2 min), hemodynamic effects - within 3-5 min. The duration of action is 8-10 hours (tablets) or 24 hours (capsules and tablets of prolonged action). With intravenous administration, the antiarrhythmic effect lasts about 2 hours, the hemodynamic effect lasts 10-20 minutes. Excreted mainly by the kidneys and faeces (about 16%). Penetrates into breast milk, passes through the placenta and is determined in the blood of the umbilical vein during childbirth. Rapid intravenous administration causes hypotension in the mother, leading to fetal distress. With prolonged use, clearance decreases and bioavailability increases. Against the background of severe liver dysfunction, plasma clearance decreases by 70% and T 1/2 increases to 14-16 hours.

According to the results obtained in 2-year experiments on rats at doses 12 times higher than the MRDH, and in the Ames bacterial test (5 studied strains, the dose is 3 mg per dish, with or without metabolic activation), it is not carcinogenic and mutagenic activity. In experiments on rats at doses 6 times higher than those recommended for humans, it slows down fetal growth and increases the frequency of intrauterine fetal death.

The use of the substance Verapamil

Paroxysmal supraventricular tachycardia (except for WPW syndrome a), sinus tachycardia, atrial extrasystole, atrial fibrillation and flutter, angina pectoris (including Prinzmetal, tension, post-infarction), arterial hypertension, hypertensive crisis, idiopathic hypertrophic subaortic stenosis, hypertrophic cardiomyopathy.

Contraindications

Hypersensitivity, severe hypotension (systolic blood pressure less than 90 mm Hg), cardiogenic shock, II and III degree AV blockade, myocardial infarction (acute or recent and complicated by bradycardia, hypotension, left ventricular failure), severe bradycardia (less than 50 beats ./min), chronic heart failure stage III, atrial flutter and fibrillation and WPW syndrome or Lown-Ganong-Levin syndrome (except for patients with a pacemaker), sick sinus syndrome (if no pacemaker is implanted), sinoatrial blockade, Morgagni syndrome - Adams-Stokes, digitalis intoxication, severe aortic stenosis, pregnancy, breast-feeding.

Application restrictions

AV block I degree, chronic heart failure stages I and II, mild or moderate hypotension, severe myopathy (Duchenne syndrome), renal and / or liver failure, ventricular tachycardia with a wide QRS complex (for intravenous administration).

Use during 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.

At the time of treatment, breastfeeding should be stopped (verapamil is excreted in breast milk).

Side effects of Verapamil

From the side of the cardiovascular system and blood (hematopoiesis, hemostasis): arterial hypotension, bradycardia (sinus), AV blockade, the appearance of symptoms of heart failure (when used in high doses).

From the nervous system and sensory organs: headache, dizziness, nervousness, lethargy, drowsiness, weakness, fatigue, paresthesia.

From the digestive tract: nausea, dyspepsia, constipation; rarely - gingival hyperplasia, increased activity of hepatic transaminases, alkaline phosphatase.

Allergic reactions: skin rash, urticaria, pruritus; rarely - angioedema, Stevens-Johnson syndrome.

Others: hyperemia of the skin of the face, bronchospasm (with intravenous administration), peripheral edema, very rarely - gynecomastia, increased secretion of prolactin (separate cases).

Interaction

Increases plasma levels of digoxin, cyclosporine, theophylline, carbamazepine, reduces - lithium. Weakens the antibacterial activity of rifampicin, the depriming effect of phenobarbital, reduces the clearance of metoprolol and propranolol, enhances the effect of muscle relaxants. Rifampicin, sulfinpyrazone, phenobarbital, calcium salts, vitamin D - weaken the effect. The hypotensive effect is enhanced by antihypertensive drugs (diuretics, vasodilators), tricyclic and tetracyclic antidepressants and antipsychotics: antianginal - nitrates. Beta-blockers, class IA antiarrhythmics, cardiac glycosides, inhalation anesthetics, radiopaque agents potentiate (mutually) inhibitory effect on the automatism of the sinoatrial node, AV conduction and myocardial contractility. With the simultaneous use of verapamil with acetylsalicylic acid - an increase in existing bleeding. Cimetidine increases plasma levels of verapamil.

Overdose

Symptoms: arterial hypotension, bradycardia, AV blockade, cardiogenic shock, coma, asystole.

Treatment: as a specific antidote, calcium gluconate is used (10-20 ml of a 10% solution in / in); for bradycardia and AV blockade, atropine, isoprenaline, or orciprenaline is administered; with hypotension - plasma-substituting solutions, dopamine, norepinephrine; with signs of heart failure - dobutamine.

Verapamil Precautions

Be wary appoint patients with hypertrophic cardiomyopathy, complicated by obstruction of the left ventricle, high wedge pressure in the pulmonary capillaries, paroxysmal nocturnal dyspnea or orthopnea, dysfunction of the sinoatrial node. When administered to patients with severe impairment of liver function and neuromuscular transmission (Duchenne myopathy), constant medical supervision and, possibly, dose reduction are necessary. It is recommended to use with caution during work for drivers of vehicles and people whose profession is associated with increased concentration of attention (reaction speed decreases), it is recommended to exclude alcohol.

special instructions

The injection form is incompatible with albumin, injection forms of amphotericin B, hydralazine, sulfamethoxazole, trimethoprim and may precipitate in solution with a pH above 6.0.