Isoptin tablets - instructions for use. Isoptin preparation: the correct dosage is the key to a healthy cardiovascular system Isoptin instructions for use in ampoules

C.08.D.A.01 Verapamil

C.08.D.A Phenylalkylamine derivatives

When our blood pressure rises and other cardiac disorders are observed that cause a deterioration in the general condition, we turn to drugs that have a positive effect on the cardiovascular system for help. "Isoptin" just belongs to the category of cardiac drugs that normalize the work of the heart and blood vessels.

ATX code

C08DA01 Verapamil

Active ingredients

Verapamil

Pharmacological group

Calcium channel blockers

pharmachologic effect

Antianginal drugs

Antihypertensive drugs

Antiarrhythmic drugs

Indications for use Isoptin

Indications for the use of "Isoptin" are also slightly different if they are considered in relation to what is prescribed by the doctor: taking pills or injections.

So, for example, the appointment of tablets is justified in such situations:

• diagnosed with arterial hypertension (stable high blood pressure),
• with a hypertensive crisis,
• thickening of the wall of one of the heart ventricles (diagnosis: hypertrophic cardiomyopathy),
• for the treatment of cardiac ischemia (vasospastic, chronic stable and unstable angina pectoris),
• with heart rhythm disturbances: sudden attacks of palpitations (paroxysmal supraventricular tachycardia (PNT), which is one of the variants of arrhythmia), tachyarrhythmic form of atrial fibrillation (atrial fibrillation and flutter), the appearance of additional defective heart contractions (supraventricular extrasystole).

"Isoptin" in the form of a solution for injection is used as monotherapy for mild forms of hypertension and as part of complex treatment for its severe, complicated manifestations, for angiospastic angina (against the background of vasospasm) and exertional angina. But most often it is used to treat supraventricular tachyarrhythmias, when restoration of a normal heart rhythm is required in PNT, as well as to correct heart rate in atrial fibrillation of the tachyarrhythmic type (with the exception of Wolff-Parkinson-White and Lawn-Ganong-Levin syndromes).

Release form

On sale you can find the following dosage forms of the drug "Isoptin":

Ordinary tablets 40 mg (white, film-coated, round-shaped, convex on both sides, the number 40 is engraved on one side, and the triangle sign on the other). Tablets are placed in blisters:

• 20 pieces (in a package either 1 or 5 blisters).

Ordinary tablets 80 mg (white, film-coated, round-shaped, convex on both sides, on one side the inscription "ISOPTIN 80" is engraved, on the other - "KNOOL" and a line for dividing the tablet into 2 parts). Tablets are packaged in blisters:

• 10 pieces (in a package either 2 or 10 blisters),
• 20 pieces (in a package either 1 or 5 blisters),
• 25 pieces (pack of 4 blisters).

Tablets СР240 of prolonged (long-term) action 240 mg (light green shade, oblong shape resembling capsules, 2 identical triangles are engraved on one side, there are risks for division on both sides). Tablets in blister packs:

• 10 pieces (in a package of 2,3,5 or 10 blisters),
• 15 pieces (in a package of 2,3,5 or 10 blisters),
• 20 pieces (in a package of 2,3.5 or 10 blisters).

Solution for intravenous administration in colorless glass ampoules of 2 ml (a clear liquid that does not have a specific color). Ampoules are placed in transparent pallets of 5, 10 and 50 pieces. Each pallet is packed in a separate thin cardboard box.

The main active ingredient of the drug "Isoptin" is verapamil, presented in the form of hydrochloride. He is known to many by the drug of the same name.

The composition of "Isoptin" has certain differences depending on the form of release of the drug. So tablets can contain 40, 80 or 240 mg of the main active ingredient plus excipients present in the composition of the tablet or its shell.

Auxiliary components in tablets "Isoptin":

• pyrogenic, or colloidal silicon dioxide as an adsorbent,
• dicalcium phosphate dihydrate as a light source of calcium,
• croscarmellose sodium as a leavening agent,
• microcrystalline cellulose to cleanse the body,
• magnesium stearate to give the composition of the tablets a uniform consistency.

In turn, the film shell of the tablets consists of talc, hypromellose 3 MPa, sodium lauryl sulfate, macrogol and titanium dioxide.

Ampoule solution "Isoptin" in addition to verapamil hydrochloride in the amount of 5 mg contains: NaCl and hydrochloric acid (HCl) with a concentration of 36%, diluted with water for injection.

Pharmacodynamics

"Isoptin" refers to a group of antianginal drugs, which are called calcium antagonists. These drugs help to reduce the need for oxygen in the main heart muscle, provide a vasodilating effect on the coronary arteries and protect against overloading them and the heart muscle with calcium. The drug is able to limit the flow of calcium ions through the membrane into the muscle tissue of the heart and blood vessels.

Possessing a vasodilating effect, it helps to reduce blood pressure by reducing the resistance of peripheral vessels without increasing the heart rate (a common reflex reaction). The antiangial effect of Isoptin in the treatment of angina pectoris is based on its relaxing effect on cardiomyocytes (muscle cells that make up the heart wall), as well as on a decrease in peripheral vascular tone, thereby reducing the load on the atria. A reduction in the flow of calcium ions into myocytes leads to inhibition of the conversion of energy into work, and hence to a slowing of the heart rate.

The use of "Isoptin" in the treatment of supraventricular tachyarrhythmias is justified due to its ability to delay the passage of nerve impulses through the atrioventricular node, block the conduction of the sinoatrial node and reduce the duration of the refractory period in the atrioventricular plexus. In this way, an optimal heart rate is achieved and a normal (sinus) heart rhythm is restored.

The drug has a selective effect and belongs to the group of dose-dependent drugs. If the disease proceeds with the preservation of normal heart rate indicators, then taking the drug will not affect them in any way, and if the heart rate decreases, then only slightly.

In addition to antiangial and vasodilating (relaxation of vascular muscles) action, the drug has a diuretic (diuretic) effect.

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Pharmacokinetics

The active substance of the drug "Isoptin" is almost 90% absorbed in the intestine, while its absorption does not depend on food intake. The bioavailability of the drug ranges from 10 to 35% both with oral administration of tablets and with intravenous infusion of the solution.

With IHD and hypertension, there is no relationship between the content of verapamil in the patient's blood and the resulting therapeutic effect.

Metabolism of the drug occurs in the parenchymal cells of the liver, where it is almost completely biotransformed. Able to relatively easily pass through the tissues of the placenta, since about 25% of the drug is found in the vessels of the navel.

The only active metabolite of Isoptin is norverapamil. Its maximum concentration in the blood is observed 6 hours after taking 1 dose of the drug. Half-life indicators can vary significantly (2.5-7.5 hours with a single dose and 4.5-12 hours with repeated administration). When using a solution for intravenous injection, the half-life of the drug can be from 4 minutes to 5 hours.

Therapeutic concentration of the drug in the blood is observed on the 5th day after repeated administration of the drug.

"Isoptin" is able to penetrate and be excreted from the body along with breast milk, but its content there is so small that it does not cause unwanted symptoms in a nursing infant. The half-life in this case will be about 3-7 hours, but with repeated administration, it can increase to 14 hours.

Most of the drug "Isoptin" and its metabolites are excreted by the kidneys and only 16% is eliminated through the intestines.

In the case of prolonged-release tablets, the excretion of the drug from the body is slower. 50% of the administered dose of the drug is removed from the body during the first day. On the second day, 60% excretion was noted, and on the 5th day - 70% of the drug.

In patients with renal insufficiency and severe forms of liver failure, an increase in the half-life and an increase in bioavailability are noted.

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Isoptin use during pregnancy

The use of the drug "Isoptin" during pregnancy and breastfeeding is considered unsafe due to the lack of proven data on its effect on pregnancy and fetal health. Theoretically, the drug is considered quite safe, so if the risk from using the drug is presumably less than the expected benefit, it can be prescribed in tablet form, according to the doctor, during pregnancy. But breastfeeding for the duration of drug therapy will have to be stopped.

Contraindications

"Isoptin", like most heart drugs, has quite a few contraindications for use, which must be taken into account in order to avoid sad, and sometimes tragic consequences.

General contraindications for all forms of the drug are:

• violation of the conduction of nerve impulses from the atria to the ventricles (atrioventricular blockade of the 2nd and 3rd degree), if it is not controlled by a special pacemaker,
• weakness of the pacemaker, as the sinus node is called, with alternating episodes of tachycardia and bradycardia,
• atrial fibrillation in the presence of additional pathways in the heart, which is typical for Wolff-Parkinson-White and Lown-Ganong-Levin syndromes,
• intolerance to individual components of the drug.

The drug is not used for the treatment of patients under 18 years of age. This is due to the lack of information about the effect of "Isoptin" on the children's body.

It is undesirable to prescribe the drug to patients with 1 degree atrioventricular blockade, as well as to those whose heart rate is less than 50 beats per minute. If the upper pressure indicator in the patient is below 90 mm Hg. he will also have to choose another drug.

Taking pills is also contraindicated:

• in acute myocardial infarction against the background of greatly reduced pressure and pulse, complicated by insufficiency of the function of the left heart ventricle,
• severe cases of left ventricular failure (cardiogenic shock),
• in the treatment of "colchicine", used to treat gout.

Contraindications for the use of the drug in the form of a solution:

• stable low blood pressure (arterial hypotension),
• cardiogenic shock, if it was not due to a heart rhythm disorder,
• syncope caused by a sudden acute heart rhythm disturbance (Morgagni-Adams-Stokes syndrome),
• slowing down or complete cessation of the supply of an impulse from the sinus node to the atria (sinoauricular block),
• an increase in heart rate due to the rapid work of the heart ventricles (ventricular tachycardia),
• chronic heart failure, if its cause is not supraventricular tachycardia,
• periods of pregnancy and lactation,

Injections of "Isoptin" are not done within 2 days after the end of therapy with "Disopyramide". The simultaneous administration of Isoptin and beta-blockers is not practiced either.

Side effects of Isoptin

It is possible that even the correct administration of the drug, depending on the individual characteristics of the patient's body and his reaction to a particular drug, may be accompanied by symptoms that are not related to the main purpose of the drug. We are talking about the side effects of drugs, which can be positive (beneficial), but most often the situation is exactly the opposite.

So, taking "Isodinite" may be accompanied by some unpleasant symptoms that occur with varying frequency.

The gastrointestinal tract may react to the drug with some digestive problems. Most often, patients taking Isoptin experience stool disorders in the form of constipation, nausea, and diarrhea is much less common. Some note an increase in appetite, in others, while taking the drug, a noticeable swelling of the gums appears, which subsequently begin to hurt and bleed, and others complain of intestinal obstruction. If the patient has certain disorders in the liver, there may be an increase in the blood level of enzymes (hepatic transaminase and alkaline phosphatase).

Some undesirable disorders can also be observed in the work of the cardiovascular system. The most common of these are bradycardia (pulse less than 50 beats per minute) or, conversely, increased heart rate at rest (tachycardia), a sufficiently strong decrease in pressure (hypotension), and increased symptoms of heart failure. But the appearance or strengthening of signs of angina pectoris is rare, although sometimes such a condition against the background of severe damage to the coronary arteries can be accompanied by myocardial infarction. Far from frequent are cases of cardiac arrhythmias, including flickering / fluttering of the ventricles (arrhythmias).

It was noted above that intravenous injections should be carried out slowly, otherwise the following life-threatening conditions may occur: complete cessation of the flow of impulses from the atrium to the ventricles (AV blockade of the 3rd degree), a strong decrease in pressure with the development of acute vascular insufficiency (collapse), stop heart (asystole).

The central and peripheral nervous systems may react to Isonidin with headaches, dizziness, short-term loss of consciousness (fainting). Some patients note increased fatigue, inhibition of reactions and drowsiness, while in others, taking the medication can cause depressive states with increased anxiety. Also, in some cases, there are tremors of the arms and hands, impaired swallowing function, kinetic disorders in the work of the upper and lower extremities, shuffling gait, etc.

Among the reactions of the immune system, one can distinguish such allergic manifestations as skin rashes, itching, redness of the skin, the development of Stevens-Johnson syndrome.

Other side effects of the drug include weight gain, swelling of the lungs and limbs, increased platelet levels (thrombocytopenia), decreased white blood cells (agranulocytosis), breast enlargement (gynecomastia) and the appearance of secretions from them (galactorrhea), increased prolactin hormone (hyperprolactinemia) , joint pathology.

With intravenous administration of large doses of the drug, with their accumulation in the blood plasma, a temporary loss of vision may be observed.

Dosage and administration

To help your heart do its hard work and not bring on other troubles, you need to carefully listen to the doctor's recommendations regarding medication. The advice of girlfriends and neighbors will come in handy when it comes to a recipe for a delicious cake or roast, but not about taking any other drugs, especially heart medications. When it comes to our “motor”, strict dose and method of administration of cardiac drugs is the key to not only effective, but also safe treatment.

"Isoptin" refers to drugs that improve the functioning of the heart, which means that all of the above applies to it in full.

So, how to take the drug correctly so that having cured one, not to cripple the other. The instructions for the drug noted that it is advisable to combine Isoptin tablets with a meal, or take the drug immediately after a meal. In this case, the tablet form of the drug is not intended for resorption or grinding it when taken. Tablets (regular and prolonged action) should be swallowed whole with plenty of water (usually take half a glass of water). This ensures a gentle effect on the gastric mucosa, and creates optimal conditions for the absorption of this dosage form.

Tablets are taken orally orally, i.e. through the mouth. They are not used for any other purpose. The dosage depends on the age of the patient and, of course, on the diagnosis.

Adult patients: the initial daily dose for angina pectoris, atrial fibrillation and hypertension, depending on the severity of the pathology and the reaction of the body, ranges from 120 to 240 mg. In case of hypertension, the dosage (according to the indications of the attending physician) can be increased to 480 mg, and in case of cardiomyopathy temporarily even up to 720 mg per day. The recommended frequency of administration is 3 times a day.

The effective dose for extended-release tablets ranges from 240 to 360 mg. Long-term use of the drug does not allow increasing the dose above 480 mg per day, except for a short time.

If the patient has abnormalities in the liver, it is recommended to take tablets with a minimum dosage. The daily dose with 2-3 times the intake will be 80-120 mg.

The solution "Isoptin" can only be used for intravenous injections. Slow administration of the drug is shown, for at least 2 minutes. In this case, it is necessary to control the indicators of blood pressure and heart rate. In elderly patients, the administration of the drug should be even slower (at least 3 minutes).

The effective initial dose is calculated based on the ratio: 0.075 to 0.15 mg of the drug in solution per 1 kg of the patient's weight. Usually it is 2-4 ml (1-2 ampoules or 5-10 mg of verapamil hydrochloride). If the expected result has not come within half an hour, it's time to make another injection with a dosage of the drug 10 ml.

The duration of the therapeutic course is set individually by the attending physician.

Children: the dosage depends on the age of the small patient. Despite the fact that "Isoptin" can be used even for the treatment of newborns, doctors prefer to resort to this practice extremely rarely, if there are no other options for therapy at the moment, in order to avoid possible serious consequences (isolated cases of death of a child after injection have been noted). The dosage for newborns is from 0.75 to 1 mg (for babies up to 12 months - up to 2 mg), which, in terms of the solution, will be 0.3-0.4 (0.3-0.8) ml.

The effective dose of "Isoptin" for babies over a year old (up to 5 years old) is 2-3 mg (in the form of a solution - 0.8-1.2 ml), for children over 5 years old (up to 14 years old) - from 2.5 to 5 mg (as a solution - from 1 to 2 ml).

Before using the drug "Isoptin" in children, it is desirable to conduct a course of preparations based on digitalis or its derivatives, which will help reduce the symptoms of heart failure and reduce the course of treatment with "Isoptin".

Overdose

In principle, therapy with large doses of Isoptin should be carried out in a hospital under the supervision of the attending physician, which in most cases excludes an overdose of the drug. If, nevertheless, for some reason this happened, it is urgent to take all necessary measures in order to remove drug particles from the body as soon as possible.

How to determine that there is an overdose? Most likely based on the following:

• a very strong drop in blood pressure, up to critical indicators,
• complete loss of consciousness while taking the drug,
• state of shock
• the appearance of symptoms of AV blockade of the heart of 1 or 2 degrees, and sometimes even the onset of a complete blockade (degree 3) is possible,
• the appearance of signs of ventricular tachycardia,
• sinus bradycardia with a pulse rate below 55 beats per minute.

Sometimes during the reception of "Isoptin" in large doses (especially when administered intravenously), cases of cardiac arrest were noted. And not always patients could be saved.

The severity of overdose symptoms depends on the dose of the drug taken by the patient, the age of the patient, the timeliness and completeness of first aid, which consists of stopping the process of intoxication of the body.

If everything points to an overdose of Isoptin tablets, you must first take measures to remove the drug from the gastrointestinal tract. For this purpose, it is possible to induce vomiting in the patient (by means of a mechanical effect on the root of the tongue or by taking emetics), to carry out measures to wash the stomach and empty the intestines (enemas, laxatives). With critically weak intestinal motility and in the case of using prolonged-release tablets, gastric lavage measures are relevant even within 12 hours after taking the drug.

If a prolonged form of the drug was used in the treatment of diseases, it should be borne in mind that its effect may be felt over the next 2 days, during which the particles of the tablets will be released in the intestine, where they are absorbed and transported into the blood. Individual particles of the drug can be located along the entire gastrointestinal tract, creating additional foci of poisoning, which cannot be removed by conventional gastric lavage.

In case of cardiac arrest, the usual resuscitation measures (direct and indirect heart massage, artificial respiration) are carried out.

A specific antidote for verapramil is calcium gluconate, a 10% solution of which is injected in a volume of 10 to 30 ml. Re-introduction of calcium is carried out drip (injection rate of 5 mmol per hour).

Cardiac arrest, AV blockade, sinus bradycardia, in addition to electrical stimulation of the heart, require the appointment of the following drugs: Isoprenaline, Orciprenaline, atropine drugs.

With a strong decrease in blood pressure indicators, Dopamine, Dobutamine, Norepinephrine are used. If there is a persistent symptomatology of myocardial insufficiency, the first 2 drugs in combination with calcium intake will be useful.

Interactions with other drugs

The cardiac drug "Isoptin" tends to react with many drugs, so you should inform your doctor about taking any other drug during therapy with the use of "Isoptin" in order to avoid unpleasant and dangerous consequences, including an overdose of verapramil.

So, the simultaneous use of "Isoptin" and drugs that lower blood pressure leads to the fact that the effect of both drugs is markedly enhanced, which can lead to a sharp drop in blood pressure.

The likelihood of developing various complications in the form of a drop in heart rate and blood pressure, the development of AV heart block or heart failure increases if Isoptin is taken together with beta-blockers, arrhythmia drugs, drugs for inhalation anesthesia. This is due to an increase in the inhibitory effect of drugs on the conductivity and work of the sinus node and cardiac myocardium.

"Isoptin" with the parallel administration of certain drugs (antihypertensive drugs aliskiren ("Rasilez"), tranquilizers based on buspirone ("Spitomin", "Buspirone"), cardiac glycoside "Digoxin", antitumor antibiotic "Doxorubicin", means for the treatment of gout "Colchicine ", the bronchodilator "Theophylline" and the antiarrhythmic agent "Quinidine") is able to increase their concentration in the blood plasma, enhancing their action and provoking the development of side effects. Most often, there is an excessive drop in pressure or the development of AV block.

An increase in the concentration of drugs in the blood under the action of Isoptin is also observed when it is taken simultaneously with alpha-blockers Prazosin and Terazosin, the immunosuppressant Cyclosporine, the anticonvulsant Karmazepin, the antiepileptic drug Valproic acid and muscle relaxants.

It is possible to increase the blood content of the active substance of the sedative drug "Midazolam" and ethanol with simultaneous therapy with these drugs and "Isoptin".

Simultaneous use of "Isoptin" with antiarrhythmic drugs "Amidarone" and "Desopyramid" provokes a significant decrease in the strength of heart contractions, causing bradycardia and collapse, a decrease in the conduction of impulses in the heart, and AV blockade of varying degrees.

Simultaneous therapy with Isoptin and the antiarrhythmic drug Flecainide can adversely affect the contractility of the main heart muscle and slow down AV conduction.

"Isoptin" can enter into drug interactions with some statins (atorvastatin, lovastatin, simvastatin), because it extinguishes the action of the CYP3A4 isoenzyme, which is involved in the metabolism of the above statins. At the same time, the level of statins in the blood plasma rises, which can lead to the destruction of muscle tissue cells.

With intravenous administration of veraptamil preparations to patients undergoing treatment with beta-blockers, there is a high risk of a strong drop in blood pressure and cardiac arrest.

An increase in the antianginal effect of Isoptin is observed against the background of the parallel intake of nitrates used to treat cardiac ischemia.

Taking acetylsalicylic acid against the background of Isoptin therapy increases the likelihood of various bleeding.

The combination of "Isoptin" with the muscle relaxant "Dantrolene" is also considered potentially dangerous, since their interaction can cause the patient's death associated with the development of ventricular fibrillation.

Non-steroidal anti-inflammatory drugs ("Diclofenac"), the anti-tuberculosis drug "Rifampicin", barbiturates ("Phenytoin", "Phenobarbital") and nicotine can reduce the content of verapamil in the blood, to a greater extent due to the acceleration of its metabolism in the liver and rapid excretion from the body. In this regard, all the useful actions of Isoptin are noticeably weakened.

But the antiulcer drug "Cimetidine", on the contrary, enhances the effect of verapamil, which is part of the tablets "Isoptin". But it does not have any effect on the kinetic features of "Isoptin" when administered intravenously.

The results of the interaction of "Isoptin" and the antidepressant "Imipramine" ("Melipramine") are visible on the cardiogram in the form of indicators indicating a decrease in atrioventricular conduction.

It is undesirable to conduct simultaneous therapy with the anti-herpentic agent "Clonidine" ("Clonidine"), since there is a risk of cardiac arrest.

It is difficult to predict the results of drug interactions with lithium preparations (lithium carbonate). Such dangerous situations as the development of severe bradycardia and a violation of the structure and functions of the nervous system (neurotoxicity) are possible. Sometimes there is a decrease in the content of lithium in the blood, which negatively affects the mental health of the patient.

Taking the neuroleptic "Sertindole" ("Serdolect") against the background of therapy with "Isoptin" increases the likelihood of developing ventricular arrhythmias.

"Isoptin" is able to enhance the muscle relaxant effect of tubocurarine and vecuronium chlorides.

Estrogens and sympathomimetics can significantly reduce the hypotensive effect of Isoptin.

The use of anesthetics ("Enfluran", "Etomidat") during treatment with "Isoptin" should be carried out with caution, since the latter can prolong the effect of anesthesia, significantly inhibiting the activity of the cardiovascular system.

I20 Angina pectoris [angina pectoris]

I21 Acute myocardial infarction

I25 Chronic ischemic heart disease

I47.1 Supraventricular tachycardia

I49.4 Depolarization other and unspecified

I49.9 Cardiac arrhythmia, unspecified

R07.2 Pain in the region of the heart

Manufacturer

Abbvi Deutschland GmbH & Co. KG for "Abbot Laboratories GmbH", Germany

with the same active ingredient. So, let's take a closer look at the indications and contraindications for taking the drug Isoptin, its instructions, analogues, prices and reviews of patients and doctors about it.

Features of the drug

Compound

The chemical composition of the Isoptin tablet consists of the active (active) substance, excipients to facilitate absorption in the mucosa of the gastrointestinal tract and the substances that make up the tablet shell. The active substance of Isoptin is verapamil hydrochloride. The excipients are calcium hydrophosphate dihydrate, magnesium stearic, colloidal silicon oxide, cellulose in microcrystals, croscarmellose sodium disintegrant NF.

According to the pharmacological classifier, the drug is known under the code C08DA01 Verapamil.

The chemical composition of the tablet shell is formed by titanium oxide, talc, an ethylene glycol-based polymer - macrogol, sodium lauryl sulfate, hypromellose.

Dosage forms

The drug Isoptin is offered by pharmaceutical production in two forms: injection and tablet.

• Isoptin solution is packaged in ampoules with a capacity of 2 ml. Ampoule cartons contain 5 to 50 ampoules. The content of verapamil hydrochloride in each ampoule is 5 mg.
• One tablet of Isoptin contains 40 or 80 mg of active ingredient. Tablets are in blisters of 20 pieces. The cardboard box contains 5 blisters. The tablets are white in color, the shape is biconvex, round. The number 40 is engraved on one side of the tablet, and a triangle is engraved on the other. Verapamil hydrochloride 80mg tablets are marked "80" on one side. The other side has a separating mark and the inscription "KNOLL".

Prices for the drug vary depending on the manufacturer, the number of tablets or ampoules in the package. The average price for Isoptin prolonged action in tablets (30 pieces per pack) is 390 rubles.

pharmachologic effect

• Verapamil hydrochloride inhibits the influx of calcium ions to the smooth muscle cells of the coronary arteries and striated myofibrils of the cardiac myocardium.
• Reduces oxygen consumption by the muscles of the heart by reducing oxidative phosphorylation in muscle mitochondria and reducing the amount of afterload on the muscles of the heart.
• By limiting the influx of calcium ions to the myofibrils of the heart and cardiac vessels, verapamil causes an increase in the throughput of the heart in relation to blood. Perfusion increases even in those areas that have been affected by stenosis.
• Verapamil relieves cardiac spasms.
• Vascular resistance decreases, resulting in a decrease in systolic pressure without an increase in heart rate. A decrease in blood pressure does not occur with its normal indicators.
• The heart rate practically does not change (in some cases it changes slightly) under the action of Verapamil. The drug normalizes heart rhythms in the presence of pathologies ().
• There is a delay in the conduction of an electrical impulse in the atrioventricular node, as a result of which the normal rhythm of the heart as a whole and in separate sections is restored.

Pharmacodynamics of Isoptin

A single application of Verapamil in voluntary subjects reveals a bioavailability rate of 22%. Systemic use of the drug increases the bioavailability rate up to 45%. The change in dynamic parameters is explained by the effect of the first passage through hepatic hepatocytes. The absorption of the active substance in the microvilli of the small intestine is 90%.

The maximum concentration of the active substance is found 1.5 hours after the use of Isoptin. Complexes with proteins form 90% verapamil. The half-life of the compound is 3 hours (minimum), 7 hours (maximum). Intermediate decomposition products of Verapamil do not have pharmacological activity, with the exception of norverapamil, the activity of which varies within 20% of the active substance.

Pharmacokinetics

84% of the active substance is excreted through the urinary system, the rest is removed by the intestines. On the first day, about half of Verapamil is excreted, after five days - 70%. In its original form, no more than 4% of the drug is excreted. Verapamil freely passes the hematomilk and hematoplacental barriers.

Patients suffering from hepatic diseases have a higher half-life due to insufficient clearance of oral origin. The drug is not excreted during the hemodialysis procedure. The indicators of renal excretion of the drug did not reveal differences in patients with healthy kidneys and those with severe pathologies.

Indications

• systolic hypertension;
• supraventricular arrhythmias in the form;
• atrial flutter with a pronounced increase in rhythm;
• various forms (, chronic, unstable,).

Lactation after taking Isoptin is stopped. The drug is not prescribed to pregnant women and children under 18 years of age. Use is justified during pregnancy if the risk to a woman's life outweighs the risk of fetal death.

Isoptin injection solution is also used in childhood after the dosage is prescribed by the attending pediatrician. Due to changes in hemodynamic blood parameters up to death in children, the use of the drug in pediatric practice has become a rare occurrence. Read more about how to take Isoptin.

Instructions for use

• Isoptin tablets are not subject to resorption or chewing.
• Isoptin is taken orally with a small amount of purified water.
• Do not take on an empty stomach, after a meal or at the time of a meal - the best time to consume Isoptin.
• The duration of the treatment course is determined by the attending doctor.

Isoptin is usually prescribed at a dosage of 40 mg or 80 mg 3 times a day. The dosage can be increased only in a hospital setting. The maximum daily dose of the drug is 480 mg. Patients with liver pathologies can take Isoptin 40 mg 2 times a day.

Instructions for use of tablets and Isoptin solution also speaks of some contraindications, let's look at them below.

The use of Isoptin sometimes causes side effects.

• Allergic reactions in persons prone to exposure to allergens are not excluded.
• The nervous system detects pain and circling in the head, tremors of the limbs, increased fatigue.
• Some patients after using Isoptin complained of ringing in the ears.
• Sometimes there is pain and discomfort in the joints, muscles.
• In patients taking the drug, disorders of the digestive organs in the form of nausea and vomiting, diarrhea or constipation are not excluded.
• The list of side effects from the dermatological side is the richest: itching, rash, redness of the skin, urticaria, swelling, alopecia, etc.

special instructions

• When taking Isoptin, it is better to temporarily abandon work that requires attention and accuracy.
• Driving should be temporarily stopped.
• The peculiarity of taking the drug is the categorical abrupt withdrawal of the drug, the dosage should be reduced smoothly.

APPROVED

By order of the chairman
Medical and
pharmaceutical activities

Ministry of Health

Republic of Kazakhstan

From "_____" ____________20 g

№____________

Instructions for medical use

medicinal product

ISOPTIN®

Tradename

Isoptin®

International non-proprietary name

Verapamil

Dosage form

Film-coated tablets, 40 mg, 80 mg.

Compound

One tablet contains

active substance- verapamil hydrochloride 40 mg or 80 mg,

Excipients: calcium dihydrogen phosphate dihydrate, microcrystalline cellulose, colloidal anhydrous silica, croscarmellose sodium, magnesium stearate,

Shell composition: hypromellose, sodium lauryl sulfate, macrogol 6000, talc, titanium dioxide (E 171).

Description

White, round biconvex film-coated tablets, marked "40" on one side and a triangle on the other (for a dosage of 40 mg). White, round biconvex film-coated tablets, marked "ISOPTIN 80" on one side and marked "KNOLL" on the other side above the break line (for a dosage of 80 mg).

Pharmacotherapeutic group

Blockers of "slow" calcium channels are selective with a direct effect on cardiomyocytes. Phenylalkylamine derivatives.

ATC code С08D A01

Pharmacological properties

Pharmacokinetics

Verapamil is rapidly and almost completely absorbed in the small intestine. The degree of absorption is 80-90%. Binding to plasma proteins - 90%. Bioavailability - 10-20%. The maximum plasma concentration is reached 1-2 hours after taking the drug. Due to the extensive metabolism of verapamil, a large number of metabolites are formed. Of the metabolites, only norverapamil is pharmacologically active (approximately 20% of the hypotensive activity of verapamil). The elimination half-life is 3-7 hours for a single dose and 4.5-12 hours for a course. Verapamil and its metabolites are excreted mainly through the kidneys; only 3-4% is excreted unchanged. Up to 16% of the drug is excreted in the faeces.

There is no difference in the pharmacokinetics of verapamil in people with healthy kidneys and in patients with end-stage renal disease. The elimination half-life is increased in patients with cirrhosis due to low clearance and large volume of distribution.

Pharmacodynamics

Verapamil, the active ingredient of Isoptin®, blocks the transmembrane flow of calcium ions into cardiomyocytes and vascular smooth muscle cells. It directly reduces myocardial oxygen demand by influencing energy-consuming metabolic processes in myocardial cells and indirectly affects afterload reduction. Due to the blocking of calcium channels in the smooth muscles of the coronary arteries, blood flow to the myocardium increases, even in post-ischemic areas, and the spasm of the coronary arteries is relieved. These properties determine the anti-ischemic and antianginal efficacy of Isoptin® in all forms of coronary heart disease.

The antihypertensive efficacy of Isoptin® is due to a decrease in peripheral vascular resistance without an increase in heart rate as a reflex response. Undesirable changes in the physiological values ​​of blood pressure are not observed.

The drug Isoptin® has a pronounced antiarrhythmic effect, especially in supraventricular arrhythmia. It delays the conduction of the impulse in the atrioventricular node, as a result of which, depending on the type of arrhythmia, the sinus rhythm is restored and / or the frequency of ventricular contractions is normalized.

Indications for use

Ischemic heart disease: stable exertional angina, unstable angina (progressive angina, rest angina), vasospastic angina (variant angina, Prinzmetal's angina), post-infarction angina in patients outside a heart attack, unless ?-blockers are indicated

Rhythm disturbances: paroxysmal supraventricular tachycardia, atrial flutter/fibrillation with rapid atrioventricular conduction, with the exception of Wolf-Parkinson-White (WPW) syndrome

Arterial hypertension

Dosage and administration

Doses are selected individually for each patient. The drug should be taken without sucking or chewing with a sufficient amount of liquid (for example, a glass of water, in no case grapefruit juice), preferably during or immediately after a meal.

Adults and adolescents weighing more than 50 kg:

Ischemic heart disease, paroxysmal supraventricular tachycardia, atrial flutter/fibrillation:

Arterial hypertension

Pediatric use (only for cardiac arrhythmias):

Children under 6 years of age from 80 to 120 mg divided into 2 to 3 doses.

Children 6-14 years 80-360 mg per day divided into 2-4 single doses.

Elderly patients.

Elderly patients may be more sensitive to the effects of verapamil hydrochloride when using the usual adult dose, so a dose reduction is possible.

Liver dysfunction

In patients with limited liver function, depending on the severity, the effect of verapamil hydrochloride is enhanced and prolonged due to the slowing down of the disintegration of the drug. Therefore, in such cases, the dosage should be set with extreme caution and start with small doses (for example, for patients with limited liver function, first 40 mg 2-3 times a day, respectively, 80-120 mg per day).

After prolonged therapy, the drug should be discontinued, gradually reducing the dose.

Side effects

Adverse events are classified by frequency of occurrence: very often > 10%, often > 1% -< 10%, иногда > 0.1% - < 1 %, редко >0.01% - <0.1 %, очень редко >0.01%, including special cases.

Bradycardia, 1st, 2nd, or 3rd degree AV block, or bradyarrhythmia with

Atrial fibrillation, hypotension/hypotension, sinus arrest, asystole

Nausea, flatulence, constipation

Dizziness, headache

Development or exacerbation of heart failure, significant

Decreased blood pressure and/or orthostatic reactions

Impotence, erectile dysfunction, gynecomastia

Galactorrhea

Decreased glucose tolerance

Vomiting, abdominal discomfort

Allergic reactions (erythema multiforme, pruritus, urticaria,

Maculopapular rash), bronchospasm, accompanied by itching and

Urticaria

alopecia

erythromelalgia

Myalgia, arthralgia, muscle weakness

Tachycardia

Rarely

Palpitations, peripheral edema, flushing

Abdominal pain, intestinal obstruction

Headache, nervousness, dizziness, drowsiness, fatigue,

Sensory disturbances (tinnitus, paresthesia, neuropathy and tremor,

Extrapyramidal syndrome, sweating, erythema multiforme,

redness of the skin and a feeling of heat)

Bleeding into the skin or mucous membranes (purpura), photodermatitis

Gingival hyperplasia (gingivitis and bleeding) that resolves after withdrawal

drug, allergic hepatitis

Elevated liver enzymes and blood prolactin levels

In single cases

Elderly patients with long-term therapy developed

Gynecomastia, which completely resolved after discontinuation of the drug

Angioedema, Stevens-Johnson syndrome

Hypersensitivity

Contraindications

Cardiogenic shock

Acute myocardial infarction with complications (bradycardia, hypotension,

left ventricular failure)

Severe conduction disorders (sinoatrial or

Atrioventricular block II and III degree)

Sick sinus syndrome (unless artificial

pacemaker)

Known hypersensitivity to verapamil or to any component of the drug

Chronic heart failure IIB-III st.

Atrial flutter/fibrillation and the presence of additional

pathways (WPW-syndrome, LGL-syndrome) - the risk of

Ventricular tachycardia

During treatment with Isoptin, do not simultaneously use intravenous beta-blockers (with the exception of intensive care).

Drug Interactions

Verapamil is a substrate and inhibitor of cytochrome P450 3A4. While taking simvastatin, which is metabolized through cytochrome P450 3A4, verapamil can increase the level of simvastatin in the blood.

Antiarrhythmic drugs, beta-blockers, inhalation anesthesia drugs:

Mutual enhancement of cardiovascular effects (atrioventricular blockade of a high degree, a significant decrease in heart rate, induction of heart failure, a significant decrease in blood pressure). During treatment with the drug, do not simultaneously use intravenous beta-blockers (with the exception of intensive care).

Antihypertensive drugs, diuretics, vasodilators: increased hypotensive effect.

Prazosin, terazosin: additional hypotensive effect.

Antiviral (HIV) agents: Plasma concentrations of verapamil may increase. Assign with caution, it may be necessary to reduce the dose of verapamil.

Digoxin, digitoxin: Increased plasma levels of digoxin caused by reduced renal excretion. Pay special attention to the symptoms of an overdose of digoxin/digitoxin and, if necessary, reduce the dose of the glycoside.

Cimetidine: the area under the concentration-time curve increases, the clearance of verapamil decreases.

Quinidine: possibly enhanced lowering of blood pressure. In patients with hypertrophic obstructive cardiomyopathy, pulmonary edema may occur. Increased plasma levels of quinidine.

Carbamazepine: increased levels of carbamazepine, increased neurotoxic side effects of carbamazepine, diplopia, headache, ataxia, dizziness.

Lithium: increased neurotoxicity of lithium.

Antidiabetic drugs (glyburide): Cmax of glyburide is increased by approximately 28%.

Rifampicin: weakening of the hypotensive effect.

Erythromycin, telithromycin: possible increase in verapamil levels.

Colchicine: Combination with verapamil is not recommended due to increased colchicine exposure.

Muscle relaxants: possible increased effect.

Acetylsalicylic acid: increased bleeding.

Doxorubicin: Co-administration of oral doxorubicin and verapamil increases the bioavailability and peak plasma levels of doxorubicin in patients with small cell lung cancer. In patients in the stage of a progressive tumor, significant changes in the pharmacokinetics of doxorubicin with simultaneous intravenous use of verapamil are not observed.

Almotriptan: the area under the concentration-time curve increases, Cmax increases.

Phenobarbital: Increases the clearance of verapamil.

Sulfipyrazone: there may be a decrease in the hypotensive effect.

Ethanol: the breakdown of ethanol is delayed and the plasma ethanol level rises, thereby verapamil enhances the effect of alcohol.

HMG-CoA reductase inhibitors:

Treatment with HMG-CoA reductase inhibitors (simvastatin, atorvastatin, lovastatin) in patients taking verapamil should be initiated at the lowest possible dose. If a patient already taking verapamil needs an HMG-CoA reductase inhibitor (simvastatin, atorvastatin, lovastatin), consider reducing the statin dose and titrate against plasma cholesterol levels.

Grapefruit juice: the area under the concentration-time curve increases, the Cmax of verapamil increases.

Hypericum perforatum: the area under the concentration-time curve decreases with a corresponding decrease in Cmax.

Immunological drugs (cyclosporine, everolimus, sirolimus, tacrolimus): levels of these drugs may increase.

Interaction based on cytochrome P450 isoenzyme 3A4.

Verapamil hydrochloride is metabolized in the liver by cytochrome P450 isoenzyme 3A4 and inhibits this enzyme.

In this regard, attention should be paid to the following interactions:

Other inhibitors of cytochrome P450 isoenzyme 3A4, such as azole fungicides (eg, clotrimazole or ketoconazole), protease inhibitors (eg, ritonavir or indinavir), macrolides (eg, erythromycin or clarithromycin), and cimetidine: increased plasma levels of verapamil hydrochloride and /or the level of these drugs in plasma arises due to the effect on their metabolism.

Inducers of cytochrome P450 isoenzyme 3A4, such as phenytoin, rifampicin, phenobarbital, carbamazepine: a decrease in plasma levels of verapamil hydrochloride and a weakening of the action of verapamil hydrochloride.

Substrates of cytochrome P450 isoenzyme 3A4, e.g. antiarrhythmics (e.g. amiodarone or quinidine), CSE inhibitors (e.g. lovastatin or atorvastatin), midazolam, cyclosporine, theophylline, prazosin: increased plasma levels of these drugs.

special instructions

Verapamil should be used with caution in patients:

With AV block I degree;

With arterial hypotension (systolic blood pressure< 90 мм рт. ст.);

With bradycardia (heart rate less than 50 beats per minute);

With severe liver failure;

With disorders of neuromuscular conduction (myasthenia gravis, Eaton-Lambert syndrome, progressive Duchenne muscular dystrophy).

Although data from validated comparative studies have shown that renal insufficiency does not affect the pharmacokinetics of verapamil in patients with end-stage renal disease, there have been several reports indicating that verapamil in patients with renal insufficiency should be used with caution and under close supervision. Verapamil cannot be removed by hemodialysis.

During the use of the drug, you should avoid eating food and drinks with grapefruit. Grapefruit may increase plasma levels of verapamil hydrochloride.

Use during pregnancy and lactation

The drug should not be taken in the first and second trimesters of pregnancy. Reception in the third trimester of pregnancy only in case of emergency, when the result exceeds the risk to the mother and child, and should not be taken during breastfeeding, since the biologically active substance penetrates into mother's milk.

The ability to influence the reaction rate when driving vehicles or operating other mechanisms.

Depending on the individual response, the ability to drive vehicles or operate machinery may be impaired. This is especially true of the initial phase of treatment, when changing the antihypertensive drug, as well as while taking the drug with alcohol.

Overdose

Symptoms depend on the amount of drug taken, the time when detoxification measures were taken, and the age of the patient.

Symptoms: a significant decrease in blood pressure, cardiac arrhythmias (bradycardia, borderline rhythms with atrioventricular dissociation and high-degree atrioventricular block), which can lead to shock and cardiac arrest; confusion to coma, stupor, hyperglycemia, hypokalemia, metabolic acidosis, hypoxia, cardiogenic shock with pulmonary edema, renal dysfunction and convulsions.

Treatment is aimed at removing the substance from the body and restoring the stability of the cardiovascular system.

General measures: gastric lavage is recommended even if more than 12 hours have passed since the moment of taking the drug and the motility of the gastrointestinal tract is not determined (no bowel sounds). General resuscitation measures include chest compressions, artificial respiration, defibrillation, and pacing. Hemodialysis is not indicated. Hemofiltration and possibly plasmaphoresis may be helpful (calcium antagonists bind well to plasma proteins).

Special measures: elimination of cardiodepressive influences, hypotension and bradycardia. Calcium is a specific antidote: 10-20 ml of a 10% solution of calcium gluconate (2.25-4.5 mmol) is injected intravenously. If necessary, you can repeat the introduction or conduct an additional drip infusion (eg, 5 mmol / hour).

Additional measures: for AV block II and III degree, sinus bradycardia, cardiac arrest, atropine, isoproterenol, orciprenaline, or pacing are used. In case of hypotension as a result of cardiogenic shock and arterial vasodilation, dopamine (up to 25 mcg/kg/min), dobutamine (up to 15 mcg/kg/min), or noradrenaline is used. Serum calcium concentrations should be within the upper limit of normal or slightly above normal. In connection with vasodilation in the early stages, the introduction of replacement fluid (Ringer's solution or saline) is carried out.

Name and country of the marketing authorization holder

Abbott Laboratories S.A., Switzerland

Name and country of the packaging organization

Abbott GmbH & Co. KG, Germany

Address of the organization accepting claims from consumers on the quality of products (goods) on the territory of the Republic of Kazakhstan

Representation of Abbott Laboratories S.A. in the Republic of Kazakhstan

Almaty, Dostyk Ave. 117/6, BC Khan Tengri 2

Tel.: +7 727 244 75 44

Catad_pgroup Calcium channel blockers

Isoptin tablets - instructions for use

Currently, the drug is not listed in the State Register of Medicines or the specified registration number has been excluded from the register.

Registration number:

P N015403/01

Active substance:

Dosage form:

Compound:

One tablet contains:

Active substance: verapamil hydrochloride 40 or 80 mg.

Excipients tablets 40 mg: calcium hydrophosphate dihydrate - 70.0 mg; microcrystalline cellulose - 23.0 mg; colloidal silicon dioxide - 0.7 mg; croscarmellose sodium - 1.8 mg; magnesium stearate - 1.5 mg.

Film-coated tablet 40 mg: hypromellose 3 MPa - 1.7 mg; sodium lauryl sulfate - 0.1 mg; macrogol 6000 -2.0 mg; talc-4.0 mg; titanium dioxide - 1.0 mg.

Excipients tablets 80 mg: calcium hydrophosphate dihydrate - 140.0 mg; microcrystalline cellulose - 46.0 mg; colloidal silicon dioxide - 1.4 mg; croscarmellose sodium - 3.6 mg; magnesium stearate - 3.0 mg.

Film coating of 80 mg tablet: hypromellose 3 MPa - 2.0 mg; sodium lauryl sulfate - 0.1 mg; macrogol 6000 - 2.3 mg; talc - 4.5 mg; titanium dioxide -1.1 mg.

Description:

Tablets 40 mg. Round, biconvex, white film-coated tablets, debossed with "40" on one side and a triangle on the other side.

Tablets 80 mg. Round, biconvex, white film-coated tablets, debossed with "ISOPTIN 80" on one side and "KNOLL" above the score line on the other side.

Pharmacotherapeutic group:

ATH:

Pharmacodynamics:

Verapamil blocks the transmembrane entry of calcium ions (and possibly sodium ions) through "slow" channels into the cells of the myocardial conduction system and smooth muscle cells of the myocardium and blood vessels. The antiarrhythmic effect of verapamil is probably due to its effect on the "slow" channels in the cells of the conduction system of the heart.

The electrical activity of the sinoatrial (SA) and atrioventricular (AV) nodes largely depends on calcium entering the cells through "slow" channels. By inhibiting this supply of calcium,
verapamil slows atrioventricular (AV) conduction and increases the effective refractory period in the AV node in proportion to heart rate (HR). This effect results in a decrease in ventricular rate in patients with atrial fibrillation and/or atrial flutter. Terminating the re-entry of excitation in the AV node,
verapamil can restore correct sinus rhythm in patients with paroxysmal supraventricular tachycardia, including Wolff-Parkinson-White (WPW) syndrome.

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

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

Pharmacokinetics:

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

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

Suction

More than 90% of verapamil is rapidly absorbed in the small intestine after oral administration. The average systemic bioavailability after a single oral dose of verapamil is 22%, due to the pronounced effect of "primary passage" through the liver. The bioavailability of verapamil with repeated use increases by approximately 2 times. The time to reach the maximum concentration (TC max) of verapamil in plasma is 1-2 hours. Peak plasma concentrations of norverapamil are reached approximately 1 hour after ingestion of verapamil. Eating does not affect the bioavailability of verapamil.

Distribution

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

Metabolism

Verapamil undergoes intensive metabolism. Metabolic studies in vitro have shown that
Verapamil is metabolized by CYP3A4, CYP1A2, CYP2C8, CYP2C9 and CYP2C18 cytochrome P450 isoenzymes. In healthy volunteers after oral administration
Verapamil undergoes extensive metabolism in the liver, with 12 metabolites detected, most of which are in trace amounts. The main metabolites have been identified as the N and O-dealkylated forms of verapamil. Among the metabolites, only norverapamil has a pharmacological effect (about 20% compared to the parent compound), which was revealed in a study in dogs.

breeding

The half-life (T 1/2) after taking verapamil orally is 3-7 hours. Within 24 hours, about 50% of the dose of verapamil is excreted by the kidneys, within five days - 70%. Up to 16% of a dose of verapamil is excreted through the intestines. Approximately 3-4% of verapamil is excreted by the kidneys unchanged. The total clearance of verapamil approximately coincides with the hepatic blood flow, i.e. about 1 l/h/kg (range: 0.7 - 1.3 l/h/kg).

Special patient groups

Elderly patients

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

Impaired kidney function

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

Impaired liver function

In patients with impaired liver function, T 1/2 is prolonged due to the lower oral clearance of verapamil and the larger V d .

Indications for use

Arterial hypertension.

Ischemic heart disease, including chronic stable angina (classic angina pectoris); unstable angina; angina pectoris due to spasm of the coronary vessels (Prinzmetal's angina pectoris).

Paroxysmal supraventricular tachycardia.

Atrial fibrillation/flutter accompanied by tachyarrhythmia (with the exception of Wolff-Parkinson-White and Lown-Ganong-Levin syndrome).

Contraindications

Hypersensitivity to the active substance or auxiliary components of the drug.

Cardiogenic shock.

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

Sick sinus syndrome, except in patients with a pacemaker.

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

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

Pregnancy, breastfeeding period (efficacy and safety not established).

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

Carefully:

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

Impaired kidney function and / or severe liver dysfunction.

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

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

Elderly age.

Pregnancy and lactation:

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

Verapamil crosses the placental barrier and is found in the blood of the umbilical vein during childbirth.
Verapamil and its metabolites are excreted in breast milk. The limited data available regarding oral administration of Isoptin® indicate that the dose of verapamil given to breastfed infants is quite low (0.1-1% of the mother's dose of verapamil), and verapamil use may be compatible with feeding. breast.

However, a risk to newborns and infants cannot be ruled out. Given the possibility of serious side effects in infants, the drug Isoptin® during breastfeeding should be used only if the benefit to the mother outweighs the potential risk to the child.

Dosage and administration

Tablets should be swallowed whole with water, preferably taken during a meal or immediately after a meal, they should not be sucked or chewed.

The dose of Isoptin® should be selected individually depending on the clinical picture and the severity of the disease.

Initial dose- 40-80 mg 3-4 times a day.

The average daily dose for all recommended indications for use varies from 240 to 360 mg. With long-term treatment, a daily dose of 480 mg should not be exceeded, however, with short-term therapy, a higher daily dose may be used. At the maximum daily dose, Isoptin® should only be taken in a hospital. There are no restrictions on the duration of taking the drug Isoptin®. It is not necessary to abruptly cancel the drug Isoptin® after prolonged therapy, it is recommended to gradually reduce the dose until the drug is completely discontinued.

Isoptin® 40 mg should be used in patients who are expected to have a satisfactory response to low doses (patients with impaired liver function or elderly patients).

Impaired kidney function

The drug Isoptin® in patients with impaired renal function should be used with caution and under close supervision (See section "Special Instructions").

Impaired liver function

In patients with impaired liver function, the metabolism of verapamil is slowed down to a greater or lesser extent, depending on the severity of the liver dysfunction, which leads to an increase and an increase in the duration of action of verapamil. Therefore, the dose of the drug Isoptin® in patients with impaired liver function should be selected with extreme caution and treatment should be started with lower doses.

Side effect

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

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

Immune system disorders:

frequency unknown: hypersensitivity.

Metabolic and nutritional disorders:

frequency unknown: hyperkalemia.

Mental disorders:

rarely: drowsiness.

Nervous system disorders:

often: dizziness, headache; rarely: paresthesia, tremor;

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

Hearing disorders and labyrinth disorders:

rarely: tinnitus; frequency unknown: vertigo.

Heart disorders:

often: bradycardia; infrequently: palpitations. tachycardia;

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

Vascular disorders:

often: "tides" of blood to the skin of the face, a pronounced decrease in blood pressure;

Respiratory, thoracic and mediastinal disorders:

frequency unknown: bronchospasm, shortness of breath.

Gastrointestinal disorders:

often: constipation, nausea; infrequently: abdominal pain; rarely: vomiting;

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

Skin and subcutaneous disordersskin tissue:

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

Musculoskeletal and connective tissue disorders:

frequency unknown: arthralgia, muscle weakness, myalgia.

Nocturnal and urinary tract disorders:

frequency unknown: renal failure.

Genital and breast disorders:

frequency unknown: erectile dysfunction, galactorrhea, gynecomastia.

General disorders:

often: peripheral edema; infrequently: increased fatigue.

Laboratory and instrumental data:

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

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

Overdose:

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

Treatment: supportive symptomatic therapy should be carried out. In case of overdose, beta-adrenergic stimulation and / or parenteral administration of calcium preparations are effective measures (
calcium chloride). In clinically significant hypotensive reactions or AV blockade, vasopressor drugs or pacing should be given, respectively. Asystole should be treated with beta-adrenergic stimulation (isoprenaline), other vasopressor drugs, or resuscitation. Hemodialysis is not effective.

Interaction

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

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

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

other drug interactions

antiviral drugs for the treatment of hiv infection

ritonavir and other antiviral drugs for the treatment of HIV infection can inhibit the metabolism of verapamil, which leads to an increase in its concentration in blood plasma. therefore, with the simultaneous use of such drugs and verapamil, care should be taken or the dose of verapamil should be reduced.

lithium

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

drugs that block neuromuscular conduction

clinical data and preclinical studies suggest that
verapamil may potentiate the effect of drugs that block neuromuscular conduction (such as curariform and depolarizing muscle relaxants). therefore, it may be necessary to reduce the dose of verapamil and / or the dose of drugs that block neuromuscular conduction when they are used simultaneously.

acetylsalicylic acid (as an antiplatelet agent)

increased risk of bleeding.

ethanol (alcohol)

an increase in the concentration of ethanol in the blood plasma and a slowdown in its excretion. therefore, the effect of ethanol may be enhanced.

hmg-coa reductase inhibitors (statins)

patients receiving
verapamil, treatment with HMG-CoA reductase inhibitors (i.e., simvastatin, atorvastatin, or lovastatin) should be started at the lowest possible dose, which is then increased. if it is necessary to assign
Verapamil patients already receiving HMG-CoA reductase inhibitors should be reviewed and their doses reduced according to the concentration of cholesterol in the blood serum. fluvastatin,
pravastatin and
rosuvastatin is not metabolized by cyp3a4 isoenzymes, so their interaction with verapamil is less likely.

antihypertensives, diuretics, vasodilators

enhancement of the antihypertensive effect.

Special instructions:

Acute myocardial infarction

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

Heart block/Atrioventricular block I degree/Bradycardia/Asystole

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

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

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

Beta-blockers and antiarrhythmic drugs

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

Digoxin

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

Heart failure

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

HMG-CoA reductase inhibitors (statins)

See section "Interaction with other drugs".

Neuromuscular Transmission Disorders

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

Impaired kidney function

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

Impaired liver function

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

Influence on the ability to drive a vehicle:

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

Release form:

Film-coated tablets 40 mg and 80 mg.

Package:

10 tablets in a PVC/A1 foil blister. 2 or 10 blisters in a carton box along with instructions for use.

20 tablets in a PVC/A1 foil blister. 1 or 5 blisters in a cardboard box along with instructions for use.

25 tablets in a PVC/A1 foil blister. 4 blisters in a cardboard box along with instructions for use.

Storage conditions:

Store at a temperature of 15 to 25 °C.

Keep out of the reach of children.

Shelf life:

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

Conditions for dispensing from pharmacies:

Registration certificate holder:

Manufacturer