Isoptin for the treatment of arterial hypertension in the form of tablets and solution. Out of stock Isoptin instructions for use Belarus

Composition and form of release

1 ampoule with 2 ml of injection solution contains verapamil hydrochloride 5 mg; in a box of 5 or 50 pcs.

1 coated tablet - 40 and 80 mg; in a blister 20 pcs., in a box of 5 blisters.

pharmachologic effect

It inhibits the transmembrane flow of calcium ions in the cells of the myocardium and vascular smooth muscles (causes vasodilation), reduces peripheral vascular resistance without a reflex increase in heart rate, reduces myocardial contractility.

Indications for Isoptin ®

Arterial hypertension, ischemic heart disease, atrial fibrillation (paroxysmal supraventricular tachycardia).

Contraindications

Cardiogenic shock, acute complicated myocardial infarction, severe conduction disorders, sick sinus syndrome.

Use during pregnancy and lactation

With caution, especially in the first trimester.

Side effects

Myocardial rhythm and conduction disturbances, heart failure, hypotension, edema, myalgia, arthralgia, allergic reactions, etc.

Interaction

Increases the effects (including side effects) of beta-blockers. Increases hypotension when co-administered with other antihypertensive drugs.

Dosage and administration

Tablets: inside - 40-80 mg 3-4 times a day after meals; maintenance dose can be used for a long period.

Injection: in / in, under the control of ECG and blood pressure, either slowly (within 2 minutes) at an initial dose of 5 mg (if ineffective - again 5 mg after 5-10 minutes), or drip (to maintain the effect) - 5-10 mg / h in saline, glucose solution or other solutions with a pH less than 6.5, the total dose is 100 mg / day.

Storage conditions of the drug Isoptin ®

Keep out of the reach of children.

Shelf life of Isoptin ®

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

Synonyms of nosological groups

Isoptin is a synthetic antianginal drug that is used to treat arrhythmias, angina pectoris, and lower blood pressure. Available in the form of tablets (Isotropin 40 and 80), capsules (Isotropin CP 240), solution for intravenous administration and dragees.

Pharmacological action of Isoptin

In accordance with the instructions for Isoptin, the active ingredient in the preparation is verapamil hydrochloride.

Isoptin has antihypertensive and antianginal effects on the body. It is a blocker of the transmembrane entry of calcium ions into myocardial cells and vascular smooth muscle cells.

The antianginal effect of the drug is due to the direct effect of the active substance that is part of the drug on peripheral hemodynamics and myocardium. Both Isoptin 240 and Isoptin 40 contribute to a decrease in peripheral arterial tone and overall peripheral vascular resistance.

The antihypertensive effect of the drug is associated with a decrease in peripheral vascular resistance without an increase in the heart rate. In accordance with the instructions for Isoptin, a decrease in blood pressure occurs on the first day of treatment. Preservation of the therapeutic effect is observed with long-term therapy.

Isoptin has vasodilating, negative inotropic and chronotropic properties.

The drug has an antiarrhythmic effect, which is due to its effect on the small channels of the cells of the conduction system of the heart, which is especially effective in supraventricular arrhythmias.

Isoptin has a high ability to be absorbed from the small intestine and cross the placental barrier. With repeated administration, the bioavailability of the drug increases by 2 times in comparison with a single dose. The binding of Isoptin to plasma proteins is about 90%. The drug is metabolized almost completely. The period of complete elimination of Isoptin from the body with a single dose is from 6 to 14 hours, with multiple doses it increases by 2 times. The drug is excreted through the kidneys.

Indications for use Isoptin

The instructions for Isoptin indicate that the drug is prescribed for the treatment of:

• Arterial hypertension: as monotherapy with mild or moderate degree, as part of combined treatment - with severe;
• stable angina;
• Angiospastic angina (Prinzmetal's angina);
• Paroxysmal supraventricular tachycardia;
• Atrial fibrillation and flutter, which are accompanied by tachyarrhythmia (with the exception of WPW syndrome).

Method of application and dosage

Isoptin SR 240 in the form of a solution is intended for intravenous administration only. The injection is carried out slowly, for at least 2 minutes, with simultaneous control of pressure and ECG. The time of administration in elderly patients increases to 3 minutes. A single dose of Isoptin 240 is 5-10 mg. If the expected therapeutic effect does not occur, it is recommended to re-administer the drug after 30 minutes.

A single dose of Isoptin for intravenous administration for infants is 0.7 - 2 mg; from 1 to 5 years - 2-3 mg; from 6 to 14 years - 2.5-3.5 mg.

Isoptin 40 or 80 tablets should be taken with or immediately after meals, swallowed whole and washed down with water. It is recommended to take Isoptin 40/80 three times a day for 40-80 mg. The average daily dose is 120-240 mg.

In the treatment of angina caused by vasospasm, chronic stable angina, Prinzmetal's angina, Isoptin 240 is prescribed at a dose of 240-480 mg per day, which should be divided into 2 doses with an interval of 12 hours.

For the treatment of mild arterial hypertension, Isoptin 240 mg is prescribed 1 tablet once a day in the morning. To slowly lower blood pressure, start with 120 mg per day (1/2 tablet).

For the treatment of atrial fibrillation and flutter, as well as paroxysmal supraventricular tachycardia, Isoptin SR 240 is prescribed at 120-240 mg 2 times a day. The interval between doses should be at least 12 hours.

The duration of therapy with Isoptin and analogues of the drug is not limited.

Side effects of Isoptin

When taking Isoptin, various side effects may occur: bradycardia, fainting, headache, constipation, depression, nausea, peripheral edema, skin allergic reactions, collapse, increased heart rate, muscle and joint pain, angina pectoris.

Contraindications for use

This drug, as well as analogues of Isoptin, is not prescribed to patients who have:

• Bradycardia, left ventricular failure, severe arterial hypotension;
• Cardiogenic shock;
• AV blockade 2 and 3 degrees;
• Sinoatrial blockade;
• Syndrome of bradycardia-tachycardia.

Relative contraindications to the use of the drug Isoptin are:

• AV blockade 1 degree;
• Arterial hypotension with systolic blood pressure less than 90 mm Hg;
• Bradycardia with heart rate less than 50 beats per minute;
• Heart failure;
• Atrial flutter and fibrillation associated with WPW syndrome.

Overdose

When taking Isoptin in amounts exceeding those recommended, shock, bradycardia and a drop in blood pressure may occur.

The reaction of the body to an overdose of Isoptin depends on the dose taken, the state of the cardiovascular system and the age of the patient.

Isoptin's analogs

Analogues of Isoptin in terms of therapeutic effect and chemical composition are Verapamil hydrochloride, Atsupamil, Veratard, Danistol, Verapamil Sopharma, Mival, Lekoptin, Kaveril, Veramil, Falicard.

Additional Information

With intravenous administration of Isoptin SR, a transient decrease in blood pressure may occur, accompanied by dizziness.

The drug affects the reaction rate and the ability to control heavy machinery.

The instructions for Isoptin indicate that the drug must be stored in a dry, cool and out of the reach of children. Shelf life - 3 years.

Isoptin is released from pharmacies by prescription.

Composition and form of release

in a blister 10, 15 or 20 pieces; in a cardboard box 1, 2, 3, 5 or 10 blisters.

Description of the dosage form

Light green capsule-shaped tablets, film-coated. Tablets on both sides have transverse risks. On one side are two "7" signs.

pharmachologic effect

Blocks calcium channels.

Pharmacodynamics

Verapamil inhibits the transmembrane current of calcium ions into smooth muscle cells. The antianginal effect is associated with a direct effect on the myocardium and the effect on peripheral hemodynamics (reduces the tone of peripheral arteries, OPSS). The blockade of the entry of calcium ions 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.

The antihypertensive efficacy of Isoptin SR 240 is due to a decrease in peripheral vascular resistance without an increase in heart rate as a reflex response. Blood pressure begins to decrease immediately on the first day of treatment; this effect persists with long-term therapy. Isoptin SR 240 is indicated for the treatment of all types of hypertension: for monotherapy of mild or moderate hypertension in combination with other antihypertensive agents, especially diuretics and, according to recent observations, ACE inhibitors in more severe hypertension. It has a vasodilatory, hypotensive, negative foreign and chronotropic effect. The drug Isoptin SR 240 has a pronounced antiarrhythmic effect, especially in supraventricular arrhythmia. It delays the conduction of the impulse in the AV node. As a result, sinus rhythm is restored and / or the ventricular rate is normalized, depending on the type of arrhythmia. Normal heart rate does not change or slightly decreases.

Pharmacokinetics

Verapamil, the active substance of Isoptin SR 240, is rapidly and almost completely absorbed in the small intestine. The degree of absorption is 90-92%. T 1/2 - from 3 to 7 hours after a single dose of the drug inside. With multiple doses, T 1/2 of verapamil can almost double compared to a single dose.

Verapamil is almost completely metabolized. The main metabolite is norverapamil, which has pharmacological activity, other metabolites are mostly inactive.

Verapamil and its metabolites are excreted mainly through the kidneys; only 3-4% - unchanged. Within 24 hours, 50% of the administered dose of the drug is excreted in the urine, within 48 hours - 55-60% and within 5 days - 70%. Up to 16% is excreted in the feces. Recent results indicate that there are no differences in the pharmacokinetics of verapamil in individuals with normal renal function and in patients with end-stage renal disease.

In coronary artery disease and arterial hypertension, no correlation was found between the therapeutic effect and the concentration of the drug in the blood plasma; there is only a certain relationship between the level of the drug in blood plasma and the effect on the PR interval. After administration of sustained-release dosage forms, the plasma concentration curve of verapamil stretches and becomes flatter than with the administration of normal-release dosage forms.

Approximately 90% of the drug binds to plasma proteins.

Bioavailability

After oral administration, verapamil undergoes significant first-pass metabolism, which occurs almost exclusively in the liver.

The average absolute bioavailability in healthy volunteers after a single dose of the drug is 22%. Recent studies in patients with atrial fibrillation or angina showed that the average levels of bioavailability are 35 and 24% after a single oral and intravenous dose, respectively.

With repeated administration of the drug, bioavailability increases by almost 2 times compared with a single dose. This effect is probably due to partial saturation of the liver enzyme systems and / or a transient increase in blood circulation in the liver after a single dose of verapamil. In patients with hepatic insufficiency, compared with individuals with normal liver function, the bioavailability of verapamil was much higher and a delay in drug excretion was observed.

Crossing the placenta

Verapamil crosses the placental barrier; the concentration found in plasma from the umbilical vein was 20-92% of the concentration in maternal plasma.

Excretion with breast milk

Verapamil is excreted in breast milk, but at therapeutic doses its concentration is so low that a clinical effect in newborns is unlikely.

Indications for Isoptin SR 240

arterial hypertension;

chronic stable angina pectoris (classic angina pectoris);

angina due to vasospasm (Prinzmetal's angina, variant);

paroxysmal supraventricular tachycardia;

atrial fibrillation / flutter, accompanied by tachyarrhythmia (with the exception of WPW syndrome a, see "Contraindications").

Contraindications

Absolute:

cardiogenic shock;

complicated acute myocardial infarction (bradycardia, severe arterial hypotension, left ventricular failure);

AV block II-III degree;

sinus node weakness syndrome (bradycardia-tachycardia syndrome);

sinoatrial blockade.

Relative:

AV block I degree;

bradycardia (<50 сокращений в минуту);

arterial hypotension (SBP<90 мм рт. ст. );

atrial fibrillation / flutter with WPW syndrome (risk of ventricular tachycardia);

heart failure (if necessary, cardiac glycosides are prescribed before starting treatment with Isoptin SR 240);

children's age (currently there are no convincing data on the safety of the drug in children under the age of 18 years).

Use during pregnancy and lactation

During pregnancy (especially in the first trimester) and during breastfeeding, the potential benefit of taking the drug Isoptin SR 240 should be analyzed regarding the possible risk to the mother and child. During lactation, the drug must be discontinued.

Side effects

Sometimes when taking verapamil in high doses or in the presence of any cardiovascular disorders, there may be observed: arrhythmia against the background of bradycardia (sinus bradycardia, sinoatrial block, AV block I, II or III degree or bradyarrhythmia with atrial fibrillation), arterial hypotension, palpitations , tachycardia, development or worsening of symptoms of heart failure.

It is reported about a fairly frequent occurrence of constipation when taking the drug inside; in rare cases, nausea, vomiting, intestinal obstruction, pain or discomfort in the abdomen, dizziness or drowsiness, fatigue, increased nervousness / tremor, leg swelling, erythromelalgia or paresthesia may develop.

In rare cases, dizziness, headache and flushing may occur. In very rare cases, myalgia and arthralgia may occur.

Rarely reported allergic reactions (exanthema, urticaria, urticaria, angioedema, Stevens-Johnson syndrome). A reversible increase in the levels of hepatic transaminases and/or alkaline phosphatase, an increase in the level of prolactin has also been described.

In rare cases, elderly patients with long-term therapy developed gynecomastia, which in all cases was completely reversible after discontinuation of the drug. Cases of galactorrhea and impotence have been reported.

In extremely rare cases, gingival hyperplasia may develop during long-term treatment, which is completely reversible after discontinuation of the drug.

Interaction

Research in vitro indicate that verapamil hydrochloride is metabolized by CYP3A4 isoenzymes, CYP1A2, CYP2C8, CYP2C9 and CYP2C18 cytochrome P450. A clinically significant interaction was noted with the simultaneous use of CYP3A4 inhibitors, which caused an increase in plasma levels of verapamil, while CYP3A4 inducers reduced its plasma concentration. Accordingly, with the simultaneous use of such agents, the possibility of interaction should be taken into account.

The table provides a list of possible interactions between drugs and verapamil due to changes in their pharmacokinetic parameters.

Possible drug interactions with verapamil

* in patients with progressive neoplasms, verapamil does not affect the level or clearance of doxorubicin; in patients with small cell lung cancer, verapamil reduced T 1/2 and C max of doxorubicin.

Antiarrhythmic drugs, beta-blockers. Mutual enhancement of effects on the cardiovascular system is possible (more pronounced AV blockade, a more significant decrease in heart rate, the development of heart failure and increased hypotension).

Antihypertensives, diuretics, vasodilators. Strengthening of hypotensive action.

Prazosin, terazosin. Additive hypotensive action.

Antivirals and agents for the treatment of HIV infection. Ritonavir and antiviral drugs can inhibit the metabolism of verapamil, resulting in an increase in its plasma concentration. In this regard, the dose of verapamil should be reduced.

Quinidine. Hypotension.

Patients with hypertrophic obstructive cardiomyopathy may develop pulmonary edema.

Carbamazepine. Increased plasma levels of carbamazepine and increased neurotoxicity. Adverse reactions characteristic of carbamazepine, such as diplopia, headache, ataxia or dizziness, may be observed.

Lithium. Increased neurotoxicity of lithium.

Rifampicin.

Sulfinpyrazone. May reduce the hypotensive effect of verapamil.

Muscle relaxants. The effect of muscle relaxants may be enhanced.

Aspirin (acetylsalicylic acid). Increased bleeding.

Ethanol (alcohol). Increased plasma ethanol levels.

HMG-CoA reductase inhibitors (statins). Simvastatin/Lovastatin. Simultaneous use with verapamil may lead to an increase in serum levels of simvastatin or lovastatin.

In patients receiving verapamil, treatment with HMG-CoA reductase inhibitors (i.e., simvastatin/lovastatin) should be started at the lowest possible dose and increased further. If it is necessary to prescribe verapamil to patients already receiving HMG-CoA reductase inhibitors, it is necessary to review and reduce their doses in accordance with the concentration of cholesterol in the blood serum. Similar tactics should be followed when prescribing verapamil with atorvastatin (although there are no clinical data confirming the interaction of verapamil and atorvastatin), since pharmacokinetic studies are precisely known, confirming that verapamil similarly affected the level of atorvastatin.

Fluvastatin, pravastatin and rosuvastatin are not metabolized by CYP3A4 isoenzymes, so their interaction with verapamil is the least likely.

Dosage and administration

inside, swallowed whole with water, preferably during a meal or immediately after a meal.

Doses of verapamil should be used depending on the clinical picture of the disease; many years of clinical experience has shown that the average dose for all indications is 240-360 mg / day.

With long-term treatment, a daily dose of 480 mg should not be exceeded; a temporary increase in dose above this level is possible.

In patients with impaired liver function, the effect of verapamil increases and becomes longer as a result of slow drug metabolism, which depends on the severity of liver dysfunction. In such cases, the dose should be set with extreme caution and treatment should be started at lower doses (i.e., patients with cirrhosis of the liver are initially prescribed 1 film-coated tablet of Isoptin 40 mg 2-3 times a day).

The duration of application is not limited.

Overdose

Symptoms of poisoning as a result of an overdose of the drug Isoptin depend on the amount of the drug taken, the time of detoxification measures and on myocardial contractility (depending on age). Fatal cases have been reported as a result of an overdose.

The following symptoms: drop in blood pressure (in some cases to levels that cannot be measured); shock, loss of consciousness; AV block I and II degree, often with Wenckebach periods with or without escape rhythm; complete AV block with complete AV dissociation, escape rhythm, cardiac arrest; sinus bradycardia, sinus node arrest.

Treatment. Therapeutic activities should be carried out depending on the duration and method of taking the drug Isoptin and on the nature and severity of symptoms of poisoning.

In case of overdose with a large number of tablets, coated, prolonged action (i.e. Isoptin SR 240), it must be borne in mind that the active substance is released and absorbed in the intestine within 48 hours after oral administration. Depending on the time of oral administration, separate conglomerates of swollen tablet residues, acting as active depots, are likely to be located throughout the gastrointestinal tract.

General activities.

If there is no motility of the stomach and intestines (signs of peristalsis during auscultation), then it is advisable to wash the stomach even 12 hours after taking the drug inside. If there is a suspicion of an overdose of the drug Isoptin CP 240, then appropriate measures are shown to eliminate the drug, for example, induce vomiting, flush the stomach and intestines in combination with an endoscopic examination, take laxatives, emetics.

Common emergency resuscitation measures include chest compressions, artificial respiration, and electrical cardiac stimulation.

Special events.

Exclusion of effects associated with inhibition of cardiac function, arterial hypotension and bradycardia.

Calcium is a specific antidote: 10-30 ml of a 10% solution of calcium gluconate is administered as an intravenous injection (2.25-4.5 mmol), if necessary, administered repeatedly or as a slow drip infusion (for example, 5 mmol / h).

The following activities may be required.

In case of AV block II or III degree, sinus bradycardia, cardiac arrest: atropine, isoprenaline, orciprenaline or cardiac stimulation.

In case of arterial hypotension: dopamine, dobutamine, norepinephrine.

In case of persistent signs of myocardial insufficiency: dopamine, dobutamine, additional calcium injections as needed.

Precautionary measures

Influence on the ability to drive a car and work with mechanisms

Treatment of arterial hypertension with Isoptin SR 240 requires regular medical supervision. Depending on the individual response to treatment, the patient's ability to drive or use machines may be reduced. This is especially important in the initial period of treatment when transferring from one drug to another and taking it in combination with alcohol.

Storage conditions of the drug Isoptin SR 240

Keep out of the reach of children.

Shelf life of the drug Isoptin SR 240

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

Synonyms of nosological groups

Dosage form

Film-coated tablets, 40 mg

Compound

One tablet contains

active substance - verapamil hydrochloride 40 mg,

excipients: calcium hydrogen phosphate dihydrate, microcrystalline cellulose, anhydrous colloidal silicon dioxide, 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.

Pharmacotherapeutic group

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

ATX code С08D A01

Pharmacological properties

Pharmacokinetics

Verapamil hydrochloride is a racemic mixture that consists of equal parts of the R-enantiomer and S-enantiomer. Verapamil is actively metabolized. Norverapamil is one of 12 metabolites that are determined in the urine, has 10-20% of the pharmacological activity of verapamil and accounts for 6% of the excreted drug. Steady-state plasma concentrations of norverapamil and verapamil are the same. The equilibrium concentration is reached 3-4 days after repeated administration of the drug 1 time per day.

Absorption

More than 90% of verapamil after oral administration is rapidly and almost completely absorbed in the small intestine. The average bioavailability in healthy volunteers after a single dose of the drug is 23%, which is explained by extensive first-pass hepatic metabolism. Bioavailability increases 2-fold after multiple doses.

After taking immediate-release tablets, the maximum plasma concentration of verapamil is reached after 1-2 hours, norverapamil - after 1 hour. Eating does not affect the bioavailability of verapamil.

Distribution

Verapamil is widely distributed in body tissues, in healthy volunteers the volume of distribution ranges from 1.8 to 6.8 l / kg. Plasma protein binding of verapamil is approximately 90%.

Metabolism

Verapamil is actively metabolized. In vitro metabolism studies have shown that verapamil is metabolized via cytochrome P450 CYP3A4, CYP1A2, CYP2C8, CYP2C9 and CYP2C18. It has been established that after oral administration of the drug to healthy male volunteers, verapamil hydrochloride undergoes intensive metabolism in the liver with the formation of 12 metabolites, most of which were determined in trace amounts. The main metabolites were identified as various N- and O-dealkylated products of verapamil. Among these metabolites, only norverapamil has a pharmacological effect (approximately 20% of the initial compound), which was found in studies in dogs.

breeding

After oral administration, the elimination half-life is 3-7 hours. About 50% of the administered dose is excreted by the kidneys within 24 hours, 70% within 5 days. Up to 16% of the dose is excreted in the faeces. About 3-4% of the drug, which is excreted by the kidneys, is excreted unchanged. The total clearance of verapamil is almost as high as hepatic circulation, at approximately 1 L/hr/kg (range 0.7-1.3 L/hr/kg).

Special patient groups

Children. Data on the pharmacokinetics of verapamil in children are limited. After oral administration of the drug, steady-state plasma concentrations in children are slightly lower than in adults.

Elderly patients. Age may affect the pharmacokinetics of verapamil in hypertensive patients. The elimination half-life may be prolonged in elderly patients. It has been established that the antihypertensive effect of verapamil does not depend on age.

Patients with renal insufficiency. Impaired renal function does not affect the pharmacokinetics of verapamil, as demonstrated in comparative studies in patients with end-stage renal disease and those with normal renal function. Verapamil and norverapamil are not removed by hemodialysis.

Patients with liver failure. The half-life of verapamil is increased in patients with impaired hepatic function due to low clearance and large volume of distribution.

Pharmacodynamics

Isoptin® blocks the transmembrane flow of calcium ions into cardiomyocytes and vascular smooth muscle cells. Isoptin® directly reduces myocardial oxygen demand by influencing energy-consuming metabolic processes in myocardial cells and indirectly affects afterload reduction. By blocking the calcium channels of the smooth muscle cells of the coronary arteries, blood flow to the myocardium increases, even in post-stenotic areas, and spasm of the coronary arteries is eliminated. 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. Isoptin® has an antiarrhythmic effect, especially in supraventricular arrhythmia. Isoptin® causes a delay in the conduction of an impulse in the atrioventricular node, as a result of which, depending on the type of arrhythmia, the sinus rhythm resumes and / or the frequency of ventricular contractions normalizes. The normal level of heart rate does not change or decreases slightly.

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 without heart failure unless beta-blockers are indicated

Rhythm disturbances: paroxysmal supraventricular tachycardia, atrial flutter/fibrillation with rapid atrioventricular conduction, except for Wolf-Parkinson-White syndrome (WPW) or Lowne-Ganong-Levin syndrome (LGL)

Arterial hypertension

Dosage and administration

The dose of verapamil hydrochloride is selected individually for each patient in accordance with the severity of the disease. 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.

Isoptin® should not be taken in the supine position.

In patients with angina pectoris after myocardial infarction, Isoptin® can be used only 7 days after acute myocardial infarction.

The duration of treatment with the drug is not limited. After prolonged use, treatment with Isoptin® should not be abruptly discontinued, it is recommended to gradually reduce the dose.

Adults and adolescents weighing more than 50 kg:

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

Pediatric use (only for cardiac arrhythmias):

Children of older preschool age up to 6 years: 40 to 120 mg per day, divided into 2-3 doses.

Children 6–14 years: 80–360 mg daily, divided into 2–4 doses.

Impaired kidney function

The available data are described in the Special Instructions section. Patients with renal insufficiency should take Isoptin® with caution and under the close supervision of a physician.

Liver dysfunction

In patients with impaired liver function, the metabolism of the drug slows down depending on the severity of the violations, as a result of which the effect of the drug Isoptin® is enhanced and prolonged. Therefore, in such cases, the dose should be selected with extreme caution and start with small doses (for example, for patients with impaired liver function, first 2-3 times a day, 40 mg, respectively, 80-120 mg per day), see section "Special instructions ".

Side effects

The following side effects have been reported during clinical trials, post-marketing use of the drug Isoptin® or in phase IV clinical trials.

Adverse reactions are classified according to the frequency of reports: very often (≥1/10), often (≥1/100 to<1/10), нечасто (≥1/1000 до <1/100), редко (≥1/10000 до <1/1000), очень редко (<1/10000), частота неизвестна (частоту нельзя установить из имеющихся данных) и для каждой системы органов.

The most frequently observed adverse reactions were: headache, dizziness; gastrointestinal disorders: nausea, constipation and abdominal pain; also bradycardia, tachycardia, palpitations, low blood pressure, hyperemia, peripheral edema and fatigue.

Adverse reactions reported in clinical studies with the use of the drug Isoptin® and post-marketing observations.

1 In post-marketing experience, paralysis (tetraparesis) associated with the combined use of verapamil and colchicine has been reported once. This may be due to the penetration of colchicine through the blood-brain barrier as a result of inhibition of CYP3A4 and P-gp by verapamil, see the section "Drug Interactions".

Note

In patients with pacemakers, an increase in the stimulation threshold and susceptibility with the use of Isoptin cannot be ruled out.

Patients with pre-existing cardiovascular disorders such as severe cardiomyopathy, congestive heart failure, or recent myocardial infarction are at increased risk of severe adverse events during concomitant use of intravenous beta-blockers or disopyramide with intravenous verapamil, as these two drug classes have a cardiodepressant effect. action (see also section "Drug Interactions").

Contraindications

Known hypersensitivity to verapamil or to any component of the drug

Cardiogenic shock

Atrioventricular block II or III degree (except for patients with a functioning pacemaker).

Sick sinus syndrome (excluding patients with a functioning pacemaker)

Heart failure with reduced ejection fraction less than 35% and/or pulmonary artery wedge pressure greater than 20 mmHg. (unless the condition is secondary to supraventricular tachycardia that is treatable with Isoptin®)

Atrial flutter/fibrillation with additional

pathways (eg, WPW syndrome, LGL syndrome). In such patients, when using Isoptin®, there is a risk of developing ventricular tachycardia, including ventricular fibrillation.

Use in combination with ivabradine (see "Drug Interactions")

During treatment with Isoptin®, intravenous beta-blockers should not be used (except in cases of intensive care; see section "Drug Interactions")

I and II trimester of pregnancy

Drug Interactions

An in vitro metabolism study of Isoptin® showed that verapamil hydrochloride is metabolized by cytochrome P450 CYP3A4, CYP1A2, CYP2C8, CYP2C9 and CYP2C18. Isoptin® is an inhibitor of CYP3A4 and P-glycoprotein (P-gp) enzymes. Clinically significant interactions have been reported with CYP3A4 inhibitors, which were accompanied by an increase in plasma levels of verapamil hydrochloride, while CYP3A4 inducers caused a decrease in plasma levels of verapamil hydrochloride, so it is necessary to monitor interactions with other drugs.

Potential Interactions Associated with the CYP-450 Enzyme System

Prazosin: increase in Cmax of prazosin (~40%) without affecting the half-life. Additive hypotensive effect.

Terazosin: increased AUC (~24%) and Cmax (~25%) of terazosin. Additive hypotensive effect.

Quinidine: decreased clearance of quinidine (~35%) when taken orally. Possible development of arterial hypotension, and in patients with hypertrophic obstructive cardiomyopathy - pulmonary edema.

Flecainide: minimal effect on plasma clearance of flecainide (<~10 %); не влияет на клиренс верапамила в плазме крови (см. раздел «Особые указания»).

Amiodarone: Increased plasma levels of amiodarone

Theophylline: decrease in oral and systemic clearance by approximately 20%, in smokers by 11%.

Carbamazepine: increased AUC of carbamazepine (~46%) in patients with refractory partial epilepsy; increased levels of carbamazepine, which may cause side effects of carbamazepine such as diplopia, headache, ataxia, or dizziness.

Phenytoin: Decreased plasma concentrations of verapamil.

Imipramine: Increased AUC (~15%) of imipramine without affecting the active metabolite desipramine.

Glibenclamide: an increase in Cmax of glibenclamide by approximately 28%, AUC by 26%, an increase in plasma levels of verapamil hydrochloride.

Colchicine: increase in AUC (approximately 2 times) and Cmax (approx. 1.3 times) of colchicine. It is recommended to reduce the dose of colchicine (see the instructions for medical use of colchicine), the simultaneous use of colchicine and verapamil hydrochloride is not recommended.

Clarithromycin, erythromycin, telithromycin: May increase verapamil levels.

Rifampicin: possible decrease in hypotensive effect. Decrease in AUC (~97%), Cmax (~94%) and bioavailability after oral administration (~92%) of verapamil.

Doxorubicin: with the simultaneous use of doxorubicin and Isoptin® (orally), AUC (~ 104%) and Cmax (~ 61%) of doxorubicin in blood plasma increase in patients with small cell lung cancer.

Clotrimazole, ketoconazole, itraconazole: possible increase in verapamil levels.

Phenobarbital: approximately 5-fold increase in oral clearance of verapamil.

Buspirone: an increase in AUC and Cmax of buspirone by approximately 3.4 times.

Midazolam: approximately 3-fold increase in midazolam AUC and 2-fold increase in Cmax. Increased plasma levels of verapamil hydrochloride.

Metoprolol: an increase in the AUC of metoprolol (~ 32.5%) and Cmax (~ 41%) in patients with angina pectoris (see section "Special Instructions"). Increased plasma levels of verapamil hydrochloride

Propranolol: an increase in AUC of propranolol (~ 65%) and Cmax (~ 94%) in patients with angina pectoris (see section "Special Instructions"). Increased plasma levels of verapamil hydrochloride

Digoxin: in healthy volunteers, an increase in Cmax (~44%), C12h (~53%), Css (~44%) and AUC (~50%) of digoxin. It is recommended to reduce the dose of digoxin (see also section "Special Instructions").

Digitoxin: Decreased digitoxin clearance (~27%) and extrarenal clearance (~29%).

Cimetidine: AUC of R-verapamil (~25%) and S-verapamil (~40%) increases with a corresponding decrease in the clearance of R- and S-verapamil.

Cyclosporine: increase in AUC, Cmax, CSS of cyclosporine by approximately 45%.

Everolimus: increase in AUC (approximately 3.5 times) and Cmax (approximately 2.3 times) of everolimus. Increase in Ctrough of verapamil (approximately 2.3 times). It may be necessary to accurately determine the concentration and dose of everolimus.

Sirolimus: increase in AUC (approximately 2.2 times) of sirolimus, increase in AUC (approximately 1.5 times) of S-verapamil. It may be necessary to determine the concentrations and dose adjustment of sirolimus.

Tacrolimus: Plasma levels of this drug may increase.

Atorvastatin: An increase in the level of atorvastatin is possible. Atorvastatin increases the AUC of verapamil by approximately 43%.

Lovastatin: An increase in lovastatin levels is possible. Increase in AUC (~63%) and Cmax (~32%) of verapamil.

Simvastatin: increase in AUC of simvastatin approximately 2.6 times, Cmax of simvastatin - 4.6 times.

Almotriptan: increase in AUC of almotriptan by 20%, Cmax by 24%. Increased plasma levels of verapamil hydrochloride.

Sulfinpyrazone: increased oral clearance of verapamil (approximately 3 times), decreased bioavailability of verapamil by 60%. There may be a decrease in the hypotensive effect.

Dabigatran: Verapamil in the form of immediate-release tablets increases Cmax (up to 180%) and AUC (up to 150%) of dabigatran. The risk of bleeding may increase. When co-administered with oral verapamil, a reduction in the dose of dabigatran may be necessary (see the dabigatran prescribing information for dosage recommendations).

Ivabradine: concomitant use with ivabradine is contraindicated due to the additional heart rate-lowering effect of verapamil (see "Contraindications").

Grapefruit juice: AUC of R-verapamil (~49%) and S-verapamil (~37%) increases, Cmax of R-verapamil (~75%) and S-verapamil (~51%) increases without changing the half-life and renal clearance. Grapefruit juice should be avoided with Isoptin®.

St. John's wort: AUC of R-verapamil (~78%) and S-verapamil (~80%) decreases with a corresponding decrease in Cmax.

Other interactions

Antiviral (HIV) agents: Due to the ability of some antiviral agents used in HIV infections, such as ritonavir, to suppress metabolism, plasma concentrations of verapamil may increase. The drug should be administered with caution or it may be necessary to reduce the dose of Isoptin®.

Lithium: Increased lithium neurotoxicity has been reported with concomitant use of lithium preparations with verapamil hydrochloride, with or without elevated plasma lithium levels. However, in patients who consistently took the same dose of oral lithium, the addition of verapamil hydrochloride resulted in a decrease in plasma lithium levels. Patients who receive both drugs should be under close medical supervision.

Neuromuscular blockers: Clinical data and animal studies indicate that Isoptin® may potentiate the activity of neuromuscular blockers (curare-like and depolarizing). It may be necessary to reduce the dose of Isoptin® and / or the dose of a neuromuscular blocker while using them.

Acetylsalicylic acid: increased chance of bleeding.

Ethanol (alcohol): increased plasma ethanol levels.

Antihypertensive agents, diuretics, vasodilators: increased hypotensive effect.

Lipid-lowering agents (HMG-CoA reductase inhibitors (statins)): Treatment with HMG-CoA reductase inhibitors (simvastatin, atorvastatin, lovastatin) in patients taking Isoptin® should be started at the lowest possible dose and gradually increased. If a patient already taking Isoptin® needs to be prescribed an HMG-CoA reductase inhibitor, the necessary reduction in the dose of statins should be taken into account and dosage should be adjusted in accordance with the concentration of cholesterol in the blood plasma.

When verapamil and simvastatin are co-administered at high doses, the risk of myopathy/rhabdomyolysis is increased. Accordingly, the dose of simvastatin should be adjusted accordingly (see the manufacturer's information on the drug; see also the section "Special Instructions")

Fluvastatin, pravastatin and rosuvastatin are not metabolized by cytochrome CYP3A4 and are less likely to interact with Isoptin®.

Antihypertensives, diuretics, vasodilators:

Increased antihypertensive effect with the risk of excessive reduction in blood pressure.

Antiarrhythmics (eg, flecainide, disopyramide), beta blockers (eg, metoprolol, propranolol), inhalational anesthetics:

Mutual potentiation of cardiovascular effects (severe atrioventricular blockade, a significant slowdown in heart rate, the development of heart failure, a pronounced hypotensive effect).

special instructions

Acute myocardial infarction

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

Heart block / atrioventricular block I degree / bradycardia / asystole

Isoptin® affects the atrioventricular and sinoatrial nodes and prolongs the time of atrioventricular conduction. Caution should be exercised because the development of atrioventricular block II or III degree (contraindication), or single-beam, two-beam or three-beam block of the pedicle of His, requires the cancellation of the following doses of verapamil hydrochloride and the appointment of appropriate therapy if necessary.

Isoptin affects the atrioventricular and sinoatrial nodes and can rarely cause second or third degree atrioventricular block, bradycardia and, in extreme cases, asystole. These symptoms are more likely to occur in patients with sick sinus syndrome (sinoatrial node disease), which is more common in older patients.

Asystole in patients who do not have sick sinus syndrome is usually short-term (several seconds or less), with spontaneous return to the atrioventricular node or normal sinus rhythm. If this phenomenon does not disappear quickly, appropriate therapy should be started immediately (see section "Side Effects").

Antiarrhythmic drugs, b-blockers and inhalation anesthetics

Antiarrhythmic drugs (eg, flecainide, disopyramide), beta-blockers (eg, metoprolol, propranolol) and inhalation anesthetics, when used simultaneously with verapamil hydrochloride, may increase cardiovascular effects (severe atrioventricular block, significant slowing of heart rate, development of heart failure , increased hypotension) (see also Drug Interactions).

Asymptomatic bradycardia (36 beats/min.) Was observed in one patient with an established migrating/vagrant atrial pacemaker, who simultaneously used eye drops containing timolol (b-blocker) along with verapamil hydrochloride.

Digoxin

With the simultaneous use of the drug Isoptin® with digoxin, the dose of digoxin should be reduced (see the section "Drug Interactions").

Heart failure

Before starting treatment with Isoptin®, it is necessary to compensate for heart failure in patients with an ejection fraction greater than 35% and to adequately control it throughout the entire period of treatment.

HMG-CoA reductase inhibitors (statins)

See section "Drug Interactions".

Diseases in which neuromuscular transmission is impaired

Isoptin® should be used with caution in the presence of diseases with impaired neuromuscular conduction (myasthenia gravis), Lambert-Eaton syndrome, progressive Duchenne muscular dystrophy).

Lowering blood pressure

In case of hypotension (systolic blood pressure less than 90 mm Hg).

kidney failure

Although reliable comparative studies have not established the effect of impaired renal function on the pharmacokinetics of verapamil in patients with end-stage renal disease, there have been several reports that indicate that Isoptin® should be used with caution and under supervision in patients with impaired renal function. careful observation.

Isoptin® is not excreted by hemodialysis.

Liver failure

Patients with severe hepatic impairment should use Isoptin® with caution (see section "Method of administration and doses").

Isoptin® 40 mg can be used in children only for cardiac arrhythmias (see section "Method of administration and doses")

Use during pregnancy and lactation

Pregnancy. Isoptin® can cross the placental barrier. The concentration in the blood plasma of the umbilical vein is from 20% to 92% of the concentration in the mother's blood plasma. There is insufficient experience with the use of the drug during pregnancy. However, data from a limited number of women taking the drug by mouth during pregnancy do not suggest a teratogenic effect. Animal studies have shown reproductive toxicity

Thus, Isoptin® should not be used during the first and second trimesters of pregnancy. The drug can be used in the third trimester of pregnancy only in case of special indications, taking into account the risk to the mother and child.

lactation period. Isoptin® and its metabolites pass into breast milk (the concentration in milk is approximately 23% of the concentration in the mother's blood plasma). Limited oral human data suggest that the neonatal dose of verapamil is low (0.1% to 1% of the maternal dose), so Isoptin may be compatible with breastfeeding, but there is a risk to neonates/infants cannot be excluded. Taking into account the risk of serious adverse reactions in newborns who are breastfeeding, Isoptin® should be used during breastfeeding only if absolutely necessary for the mother.

There is evidence that in some cases verapamil can cause hyperprolactinemia and galactorrhea.

Features of the influence of the drug on the ability to drive a vehicle or potentially dangerous mechanisms

Due to the antihypertensive effect of the drug Isoptin®, depending on the individual reaction, the ability to drive vehicles, operate machinery or work in hazardous conditions may be impaired. This is especially true of periods of initiation of treatment, dose increases, drug changes, as well as simultaneous administration of the drug with alcohol. Isoptin® can increase the level of alcohol in the blood plasma and slow down its excretion, so the effect of alcohol may be enhanced.

Overdose

Symptoms: Symptoms of intoxication after poisoning with the drug Isoptin® progress depending on the amount of the drug taken, the time when detoxification measures are applied, and the contractile function of the myocardium (depending on age).

In case of severe poisoning, the following symptoms were observed:

Sudden decrease in blood pressure, heart failure, brady, or tachyarrhythmias (eg, junctional rhythm with atrioventricular dissociation and high-degree atrioventricular block), which can lead to cardiovascular shock and cardiac arrest.

Impaired consciousness progressing to coma, hyperglycemia, hypokalemia, metabolic acidosis, hypoxia, cardiogenic shock with pulmonary edema, impaired renal function and convulsions. Occasionally deaths have been reported.

Treatment of drug overdose

Urgent treatment includes detoxification and restoration of a stable state of the cardiovascular system.

Therapeutic measures depend on the time and method of application, as well as the type and severity of symptoms of intoxication.

In case of intoxication with the use of a large number of drugs of prolonged action, it should be noted that the active substance can be released and absorbed in the intestine even longer than 48 hours after ingestion.

After intoxication with the use of the oral drug Isoptin®, gastric lavage is recommended, and even later than 12 hours after ingestion, if signs of gastrointestinal motility (bowel noise) are not detected. If intoxication is suspected due to the use of drugs with prolonged action, complex elimination measures are indicated, such as inducing vomiting, aspiration of the contents of the stomach and small intestine under endoscopic control, bowel lavage, emptying, high enema.

Since Isoptin® is not excreted by dialysis, hemodialysis is not recommended, but hemofiltration and, if possible, plasmapheresis (high plasma protein binding) are recommended.

Usual intensive care and resuscitation measures such as chest compressions, ventilation, defibrillation, and cardiac pacing.

Special Measures

Elimination of cardiodepressive effects, hypotension and bradycardia.

Bradyarrhythmias are treated symptomatically with atropine and/or beta-sympathomimetics (isoprenaline, orciprenaline); in the event of a life-threatening bradyarrhythmia, temporary pacing is required. Asystole should be treated with conventional methods, including beta-adrenergic stimulation (isoprenaline).

Calcium can be used as a specific antidote, for example, 10 to 20 ml of 10% calcium gluconate solution intravenously (2.25 to 4.5 mmol), repeated if necessary, or as a continuous drip infusion (for example, 5 mmol / hour).

Arterial hypotension resulting from cardiogenic shock and arterial vasodilation is treated with dopamine (up to 25 micrograms per kg of body weight per minute), dobutamine (up to 15 micrograms per kg of body weight per minute), epinephrine or norepinephrine. The doses of these drugs are determined only by the effect achieved. Serum calcium levels should be maintained within the upper limit of normal to slightly elevated levels. At an early stage, due to arterial vasodilation, additional fluid replacement (Ringer's solution or sodium chloride solution) is performed.

Release form and packaging

Film-coated tablets 40 mg No. 100.

25 tablets in a blister pack made of PVC film and aluminum foil.

Name and country of the manufacturing organization

FAMAR A.V.E. Anthousa, Greece

Anthousa Avenue, 7 15344 Anthousa, Athens

Isoptin is a synthetic antianginal drug that is used to treat arrhythmias, angina pectoris, and lower blood pressure.

Available in the form of tablets (Isotropin 40 and 80), capsules (Isotropin CP 240), solution for intravenous administration and dragees.

In this article, we will consider why doctors prescribe Isoptin, including instructions for use, analogues and prices for this drug in pharmacies. Real REVIEWS of people who have already used Isoptin can be read in the comments.

Composition and form of release

Isoptin is available in the form of tablets and solution for intravenous administration, the main active ingredient of the preparations is verapamil hydrochloride, its content is:

• 40, 80 mg - in 1 tablet;
• 5 mg - in 2 ml of solution.

Clinical and pharmacological group: calcium channel blocker.

What helps Isoptin?

According to the instructions for Isoptin, the use of tablets is indicated for patients in the treatment of:

1. arterial hypertension;
2. Paroxysmal supraventricular tachycardia;
3. Ischemic heart disease, including unstable and stable angina pectoris or caused by vasospasm;
4. Tachyarrhythmias caused by atrial fibrillation or flutter, except for Wolff-Parkinson-White and Lown-Honong-Levin syndromes.

Isoptin solution is prescribed for intensive therapy of supraventricular tachyarrhythmias in case of:

1. Wolff-Parkinson-White and Lown-Hongong-Levin syndromes;
2. Paroxysmal supraventricular tachycardia in violation of sinus rhythm;
3. The need to control the frequency of ventricular contractions during flutter and atrial fibrillation, if they are not associated with the presence of additional pathways.

pharmachologic effect

Isoptin is an antianginal drug related to calcium channel blockers (active ingredient is verapamil hydrochloride). Reduces blood pressure, is used for arrhythmias, has an antianginal effect. Under the action of the drug, blocking of the transmembrane flow of calcium ions into smooth myocytes of blood vessels and the heart is observed.

The effect of lowering blood pressure is associated with a decrease in peripheral vascular resistance, and there is no effect of increasing heart rate in the form of a reflex reaction.

Instructions for use

Isoptin in the form of tablets is taken orally, swallowed whole (can not be chewed or dissolved) and washed down with water. It is preferable to take the drug during or immediately after a meal.

The scheme of Isoptin application is determined individually, taking into account the severity of the disease and the clinical picture.

• 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; frequency of admission - 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.

Contraindications

Contraindications to the use of Isoptin are:

• sinoauricular blockade;
• simultaneous use of beta-blockers (in / in);
• preliminary (within 48 hours) use of disopyramide;
• pregnancy;
• lactation period;
• arterial hypotension or cardiogenic shock (except for those caused by arrhythmia);
• AV block II and III degree (excluding patients with an artificial pacemaker);
• Morgagni-Adams-Stokes syndrome;
• sinus node weakness syndrome (excluding patients with an artificial pacemaker);
• age up to 18 years (efficacy and safety have not been established);
• hypersensitivity to the drug and its components;
• Wolf-Parkinson-White (WPW) and Lown-Ganong-Levin (LGL) syndrome in combination with atrial flutter or fibrillation (except for patients with a pacemaker);
• ventricular tachycardia with wide QRS complexes (> 0.12 sec);
• chronic heart failure stage IIB-III (with the exception of supraventricular tachycardia caused by verapamil treatment).

Side effects

During therapy, the development of disorders from some body systems is possible:

1. Musculoskeletal system: pain in the muscles / or joints, swelling of the legs;
2. Nervous system: general weakness, anxiety, depression, drowsiness, extrapyramidal disorders (stiffness of the legs or arms, ataxia, shuffling gait, mask-like face, difficulty swallowing, trembling of the hands and fingers), headache, dizziness, convulsions during drug administration, tremor , paresthesia; in rare cases - lethargy, increased nervous excitability, fatigue;
3. Reproductive system: gynecomastia, galactorrhea, hyperprolactinemia, impotence;
4. Skin lesions: exanthema, angioedema, urticaria, Stevens-Johnson syndrome;
5. Cardiovascular system: severe bradycardia, redness of the face, atrioventricular blockade, a marked decrease in blood pressure, the appearance of symptoms of heart failure when using high doses of the drug, especially in predisposed patients; palpitations, tachycardia, sinus arrest; rarely - arrhythmia (including flutter and ventricular fibrillation), angina pectoris up to the development of myocardial infarction (especially in patients with severe obstructive lesions of the coronary arteries), bradycardia;
6. Digestive system: nausea, vomiting, increased values ​​of hepatic transaminases and alkaline phosphatase, intestinal obstruction, discomfort and pain in the abdomen, constipation, gingival hyperplasia.
7. Other: erythromelalgia, hot flashes.

Most of the listed side effects are typical for all dosage forms of Isoptin.

Isoptin's analogs

Analogues of Isoptin in terms of therapeutic effect and chemical composition are Verapamil hydrochloride, Atsupamil, Veratard, Danistol, Verapamil Sopharma, Mival, Lekoptin, Kaveril, Veramil, Falicard.

Prices

The average price of IZOPTIN, SR 240 240 mg tablets in pharmacies (Moscow) is 440 rubles.