Verapamil, 40 mg, film-coated tablets, 50 pcs.

Prescription of Verapamil

The abstract advises the use of the medication:

• with supravenricular and sinus tachycardia;
• stable angina pectoris and pathology with supraventricular rhythm disturbances;
• atrial fibrillation;
• hypertensive crisis;
• supraventricular extrasystole;
• hypertension.

Verapamil is contraindicated in patients:

• with a pronounced slow heartbeat;
• disorders of the left ventricle;
• intolerance to the component composition;
• low blood pressure levels.

The drug is not prescribed to pregnant and nursing mothers. Particular caution is needed during therapeutic procedures in patients with bradycardia, sinoatrial, atrioventricular block, chronic heart, renal, and liver failure. Doctor's supervision is required in old age.

Verapamil, 40 mg, film-coated tablets, 50 pcs.

When used simultaneously:

- increases the AUC (area under the concentration-time curve) of carbamazepine in patients with persistent partial epilepsy (risk of side effects such as diplopia, headache, ataxia and dizziness).

- increases AUC, Css (clearance) and Cmax (maximum drug concentration) of cyclosporine.

— increases the AUC and Cmax of glibenclamide.

- increases the concentration of sirolimus and tacrolimus.

— significantly increases the AUC and Cmax of buspirone and midazolam.

- increases the concentration of theophylline (due to decreased clearance), ethanol (and prolongs its effect), the concentration of quinidine (risk of a pronounced decrease in blood pressure).

- may increase concentrations of atorvastatin and lovastatin.

— significantly increases the AUC and Cmax of simvastatin.

— increases the AUC and Cmax of almotriptan.

- increases the concentration of cardiac glycosides (requires careful monitoring and reduction in the dose of glycosides).

- increases the AUC and Cmax of metoprolol and propranolol in patients with angina pectoris.

- increases the plasma concentration of colchicine (a substrate for CYP 3 A and p-glycoprotein).

— when taken orally, it significantly increases the AUC and Cmax of doxorubicin.

- slightly increases the AUC of imipramine; does not affect the concentration of the active metabolite, desipramine.

— increases the Cmax of prazosin and terazosin and the AUC of terazosin.

- CYP3A inhibitors (including erythromycin, ritonavir and other antiviral HIV drugs), teligomycin increase plasma concentrations of verapamil.

- grapefruit juice increases the AUC and Cmax of the R - and S - isomer of verapamil.

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

- Rifampicin can significantly reduce the bioavailability (up to 92%), as well as the AUC and Cmax of verapamil.

- phenobarbital increases the clearance of verapamil by 5 times.

- sulfinpyrazone increases the clearance of verapamil by approximately 3 times and reduces bioavailability (60%).

- preparations of St. John's wort reduce the AUC R - and S - isomer of verapamil and, accordingly, C max.

- when used simultaneously with inhalational anesthetics, the risk of developing bradycardia, atrioventricular block, and heart failure increases.

- combination with beta-blockers can lead to an increased negative inotropic effect, increasing the risk of developing atrioventricular conduction disorders, bradycardia (administration of verapamil and beta-blockers must be carried out at intervals of several hours).

- prazosin and other alpha-blockers, as well as other antihypertensive drugs (ATP inhibitors, vasodilators, diuretics, beta-blockers) enhance the hypotensive effect.

- disopyramide and flecainide should not be administered within 48 hours or 24 hours after the use of verapamil (the sum of the negative inotropic effect, including death).

- increases the risk of the neurotoxic effect of lithium preparations.

- enhances the effect of peripheral muscle relaxants (a change in dosage regimen may be required)

- with simultaneous use with acetylsalicylic acid (ASA), a slightly greater increase in bleeding time was observed than with the use of ASA alone.

- carbamazepine and lithium increase the risk of neurotoxic effects.

Adverse reactions

The drug can become a source of non-standard responses in the body. Veramil provokes:

• slowing of cardiac activity;
• cephalgia with dizziness;
• dyspeptic disorders;
• facial hyperemia;
• weight gain.

Less commonly, the medication leads to the appearance of:

• digestive disorders, gum tissue hyperplasia;
• lethargy, nervousness, fatigue;
• skin rash, obsessive itching;
• gynecomastia, arthritis, galactorrhea.

The drug causes the development of pulmonary and peripheral edema.

Verapamil therapy

The instructions include the exact dosage of the drug and the specifics of its administration. The standards depend on the type of tablet:

1. With a standard duration of action - before meals from 40 to 80 mg, three times a day for registered angina or increased heart rate. For hypertension, the daily dose is divided into two procedures and is 480 mg. For children under five years of age, no more than 60 mg of medication is allowed per day.
2. With prolonged action - for hypertension, 240 mg in the morning, therapy begins with a dosage of 120 mg, which is gradually increased. The dose is increased after 14 days, the maximum volume of the drug does not exceed 480 mg (taken in 2 doses, observing a twelve-hour break).

An intravenous solution is used to suppress the symptoms of a hypertensive crisis. From 5 to 10 ml of Verapamil is injected in a stream. A similar amount is used for paroxysmal pathologies; in the absence of the expected result, the procedure is duplicated.

Maintenance therapy involves the use of the drug in conjunction with sodium chloride or dextrose. When treating children under 5 years of age, the dosage does not exceed 3 mg.

Verapamil 240 mg 20 pcs. extended-release film-coated tablets

pharmachologic effect

Selective class I calcium channel blocker, diphenylalkylamine derivative.
It has antianginal, antiarrhythmic and antihypertensive effects. The antianginal effect is associated both with a direct effect on the myocardium and with an effect on peripheral hemodynamics (reduces the tone of peripheral arteries, peripheral arterial resistance). Blockade of calcium entry into the cell leads to a decrease in the transformation of energy contained in macroergic bonds of ATP into mechanical work and a decrease in myocardial contractility. Reduces myocardial oxygen demand, has a vasodilating, negative ino- and chronotropic effect. Increases the period of diastolic relaxation of the left ventricle, reduces the tone of the myocardial wall.

A decrease in peripheral vascular resistance may also be due to the antihypertensive effect of verapamil.

Verapamil significantly reduces AV conduction, prolongs the refractory period and suppresses the automaticity of the sinus node. Has an antiarrhythmic effect in supraventricular arrhythmias.

Composition and release form Verapamil 240 mg 20 pcs. extended-release film-coated tablets

Tablets - 1 tablet: verapamil hydrochloride 240 mg.

20 pcs per package, cardboard packs.

Description of the dosage form

Film-coated tablets.

Directions for use and doses

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

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

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

Pharmacokinetics

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

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

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

Indications for use Verapamil 240 mg 20 pcs. extended-release film-coated tablets

Treatment and prevention of coronary artery disease: chronic stable angina (angina pectoris), unstable angina, vasospastic angina (Prinzmetal angina/variant angina).

Treatment and prevention of heart rhythm disturbances: paroxysmal supraventricular tachycardia, chronic form of atrial flutter and fibrillation (tachyarrhythmic variant), supraventricular extrasystole.

Arterial hypertension. Hypertensive crisis.

Hypertrophic cardiomyopathy.

Contraindications

Cardiogenic shock, heart failure, severe impairment of contractile function of the left ventricle, severe arterial hypotension (systolic blood pressure less than 90 mm Hg), bradycardia; SSSU, sinoatrial block, AV block of II and III degrees (except for patients with a pacemaker); atrial flutter and fibrillation in combination with WPW syndrome or Lown-Ganong-Levine syndrome (except for patients with a pacemaker); simultaneous use with colchicine, dantrolene, aliskiren, sertindole; pregnancy, lactation (breastfeeding); hypersensitivity to verapamil.

Application Verapamil 240 mg 20 pcs. extended-release film-coated tablets during pregnancy and lactation

Verapamil is contraindicated during pregnancy and lactation.

Use in children

Use with caution in children and adolescents under 18 years of age (the effectiveness and safety of use have not been studied).

special instructions

Caution should be used in case of AV blockade of the first degree, bradycardia, severe stenosis of the aortic mouth, chronic heart failure, with mild or moderate arterial hypotension, in the acute phase of myocardial infarction, obstructive hypertrophic cardiomyopathy, with hepatic and/or renal failure, in elderly patients age, in children and adolescents under the age of 18 years (the effectiveness and safety of use have not been studied).

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

Impact on the ability to drive vehicles and operate machinery

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

Side effects Verapamil 240 mg 20 pcs. extended-release film-coated tablets

From the cardiovascular system: bradycardia (less than 50 beats/min), marked decrease in blood pressure, development or worsening of heart failure, tachycardia; rarely - angina pectoris, up to the development of myocardial infarction (especially in patients with severe obstructive lesions of the coronary arteries), arrhythmia (including ventricular fibrillation and flutter); with rapid intravenous administration - third degree AV block, asystole, collapse.

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

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

Allergic reactions: skin itching, skin rash, facial skin flushing, erythema multiforme exudative (including Stevens-Johnson syndrome).

Other: weight gain, very rarely - agranulocytosis, gynecomastia, hyperprolactinemia, galactorrhea, arthritis, transient loss of vision against the background of maximum plasma concentration (with intravenous administration), pulmonary edema, asymptomatic thrombocytopenia, peripheral edema.

Drug interactions

When used simultaneously with antihypertensive drugs (vasodilators, thiazide diuretics, ACE inhibitors), the antihypertensive effect is mutually enhanced.

When used simultaneously with beta-blockers, antiarrhythmic drugs, and inhalation anesthesia agents, the risk of developing bradycardia, AV blockade, severe arterial hypotension, and heart failure increases due to the mutual increase in the inhibitory effect on the automatism of the sinoatrial node and AV conduction, contractility and conductivity. myocardium.

When verapamil is administered parenterally to patients who have recently received beta-blockers, there is a risk of developing arterial hypotension and asystole.

When used simultaneously with nitrates, the antianginal effect of verapamil is enhanced.

When used simultaneously with aliskiren, its plasma concentration increases and the risk of side effects increases.

When used simultaneously with amiodarone, the negative inotropic effect, bradycardia, conduction disturbances, and AV block are enhanced.

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

When used simultaneously with acetylsalicylic acid, cases of increased bleeding time due to additive antiplatelet effect have been described.

When used simultaneously with buspirone, the concentration of buspirone in the blood plasma increases, and its therapeutic and side effects increase.

With the simultaneous administration of verapamil and dantrolene (iv) in experimental studies in animals, ventricular fibrillation was observed with a fatal outcome. This combination is potentially dangerous.

When used simultaneously with digoxin, cases of increased concentrations of digitoxin in the blood plasma have been described.

When used simultaneously with digoxin, the concentration of digoxin in the blood plasma increases.

When used concomitantly with disopyramide, severe hypotension and collapse are possible, especially in patients with cardiomyopathy or decompensated heart failure. The risk of developing severe manifestations of drug interactions is apparently associated with increased negative inotropic effects.

When used simultaneously with diclofenac, the concentration of verapamil in the blood plasma decreases; with doxorubicin - the concentration of doxorubicin in the blood plasma increases and its effectiveness increases.

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

When used simultaneously with carbamazepine, the effect of carbamazepine is enhanced and the risk of side effects from the central nervous system increases due to inhibition of the metabolism of carbamazepine in the liver under the influence of verapamil.

When used simultaneously with clonidine, cases of cardiac arrest in patients with arterial hypertension have been described.

Increases plasma concentrations of colchicine (substrate of the isoenzyme CYP3A and P-glycoprotein).

When used simultaneously with lithium carbonate, the manifestations of drug interactions are ambiguous and unpredictable. Cases of increased effects of lithium and the development of neurotoxicity, a decrease in the concentration of lithium in the blood plasma, and severe bradycardia have been described.

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

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

When used simultaneously with sertindole, the risk of developing ventricular cardiac arrhythmias, especially ventricular arrhythmias, increases.

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

When used simultaneously with tubocurarine chloride and vecuronium chloride, the muscle relaxant effect may be enhanced.

When used simultaneously with phenytoin and phenobarbital, a significant decrease in the concentration of verapamil in the blood plasma is possible.

When used simultaneously with fluoxetine, the side effects of verapamil increase due to a slowdown in its metabolism under the influence of fluoxetine.

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

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

When used simultaneously with cimetidine, the effects of verapamil are enhanced.

When used simultaneously with enflurane, prolongation of anesthesia is possible.

When used simultaneously with etomidate, the duration of anesthesia increases.

Overdose symptoms, interactions

Accidentally exceeding the recommended volume of Verapamil leads to a slow heartbeat, a drop in blood pressure, asystole, etc. Therapeutic measures include:

• gastric lavage and use of sorbents;
• administration of Atropine, Calcium Gluconate into a vein - in case of impaired conductivity;
• prescribing alpha-adrenergic agonists to normalize blood pressure levels.

In some cases, an artificial pacemaker is used.

The instructions indicate the following therapeutic nuances:

• combination with Cyclosporine, Theophylline, Quinidine, Caramazepine increases their concentration;
• the inclusion of lithium preparations leads to increased neurotoxic effects;
• Cimetidine, Rifampicin reduce the bioavailability of verapamil;
• inhalation anesthetics and beta-blockers - provoke the development of heart failure and bradycardia.

Verapamil can enhance the effect of muscle relaxants.

VERAPAMIL

Interaction

When used concomitantly with carbamazepine in patients with persistent partial epilepsy due to inhibition of carbamazepine metabolism in the liver, verapamil increases its effect (risk of side effects from the central nervous system, such as diplopia, headache, ataxia and dizziness).
With simultaneous use, verapamil inhibits the metabolism of cyclosporine in the liver, which leads to a decrease in its excretion and an increase in plasma concentrations. This is accompanied by an increased immunosuppressive effect.

With simultaneous use, verapamil increases the concentration of theophylline (due to decreased clearance).

With simultaneous use of verapamil with quinidine, the concentration of quinidine in the blood plasma increases (risk of a pronounced decrease in blood pressure, especially in patients with IHSS).

With simultaneous use, verapamil increases the concentration of ethanol in the blood plasma and prolongs its effect.

Since verapamil inhibits the CYP3A4 isoenzyme, which is involved in the metabolism of atorvastatin, lovastatin and simvastatin, drug interactions due to increased plasma concentrations of statins (rhabdomyolysis) are possible.

With simultaneous use, verapamil increases the plasma concentration of almotriptan and glibenclamide.

With simultaneous use, verapamil increases the plasma concentrations of sirolimus and tacrolimus.

With simultaneous use, verapamil increases the concentration of cardiac glycosides (requires careful monitoring and reduction in the dose of glycosides).

With simultaneous use, verapamil increases the concentration of metoprolol and propranolol in patients with angina pectoris.

With simultaneous use, verapamil increases the plasma concentration of colchicine (a substrate for the CYP3A isoenzyme and P-glycoprotein).

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

With simultaneous use of verapamil with imipramine, the concentration of imipramine in the blood plasma increases (the risk of developing undesirable changes due to the additive inhibitory effect of verapamil and imipramine on AV conduction). Does not affect the concentration of the active metabolite, desipramine.

Verapamil increases the concentration of prazosin and terazosin when used simultaneously (risk of developing severe arterial hypotension).

When verapamil is used simultaneously with buspirone or midazolam, their concentration in the blood plasma increases (risk of increased side effects).

CYP3A4 inhibitors (including erythromycin, human immunodeficiency virus protease inhibitors), telithromycin increase plasma concentrations of verapamil.

Grapefruit juice increases plasma concentrations of the R- and S-isomers of verapamil. Cimetidine either does not change or reduces the clearance of verapamil (the effects of verapamil may be enhanced).

Rifampin can significantly reduce the bioavailability (up to 92%) as well as the plasma concentration of verapamil, which leads to a decrease in its clinical effectiveness.

Phenobarbital increases the clearance of verapamil by 5 times.

Sulfinpyrazone increases the clearance of verapamil by approximately 3 times and reduces bioavailability by up to 60%.

St. John's wort preparations reduce the concentration of the R- and S-isomer of verapamil in the blood plasma.

With the simultaneous use of verapamil with inhalational anesthetics, the risk of developing bradycardia, AV block, and heart failure increases. The combination of verapamil with beta-blockers can lead to an increased negative inotropic effect, an increased risk of developing AV conduction disorders, bradycardia (the use of verapamil and beta-blockers must be carried out at intervals of several hours).

Prazosin and other alpha-blockers, as well as other antihypertensive drugs (angiotensin-converting enzyme inhibitors, vasodilators, diuretics, beta-blockers) enhance the hypotensive effect of verapamil.

With the simultaneous use of verapamil with disopyramide and flecainide, severe arterial hypotension and collapse, including death, are possible. The risk of developing severe manifestations of drug interactions is associated with increased negative inotropic effects. Disopyramide and flecainide should not be administered within 48 hours before or 24 hours after verapamil.

Verapamil increases the risk of neurotoxic effects of lithium preparations.

Verapamil enhances the effect of peripheral muscle relaxants (may require a change in dosage regimen).

With the simultaneous use of verapamil with acetylsalicylic acid, cases of increased bleeding time have been described.

Manufacturer's instructions

Clinical studies have not shown sufficient information about the effect of the drug on the body of pregnant women. The use of the drug is allowed after assessing the real risk to the health of the fetus and the benefits to the maternal body.

Verapamil is used:

• when there is a threat of spontaneous abortion;
• placental insufficiency;
• nephropathy.

The drug is prescribed by the obstetrician-gynecologist leading the pregnancy strictly according to indications. Self-medication is unacceptable and can provoke any results.