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.

Description of the drug VERAPAMIL-BELMED

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:

• increased 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.

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

In vitro metabolic studies indicate that verapamil is metabolized by the cytochrome P450 isoenzymes CYP3A4, CYP1A2, CYP2C8, CYP2C9 and CYP2C18.

Verapamil is an inhibitor of the CYP3A4 isoenzyme and P-glycoprotein. Clinically significant interactions were observed with simultaneous use with inhibitors of the CYP3A4 isoenzyme, and an increase in the concentration of verapamil in the blood plasma was observed, while inducers of CYP3A4 decreased the concentration of verapamil in the blood plasma. When using such drugs simultaneously, the possibility of this interaction should be taken into account.

The combined use of verapamil and a drug that is metabolized by the CYP3A4 isoenzyme or is a P-gp substrate may be accompanied by an increase in drug concentrations. This may result in increased or prolonged duration of both therapeutic and side effects of the drug used in conjunction with verapamil.

The table below presents data on possible drug interactions caused by pharmacokinetic parameters (where Cmax is the maximum concentration in the blood plasma, Css is the average equilibrium concentration in the blood plasma, AUC is the area under the pharmacokinetic concentration-time curve).

Possible interactions with verapamil:

Other possible types of interaction

Dabigatran

When dabigatran etexilate was co-administered with verapamil administered orally, the Cmax and AUC values ​​of dabigatran increased, depending on the time of use and the dosage form of verapamil. The greatest increase in dabigatran values ​​was observed when the first dose of immediate-release verapamil was taken 1 hour before dabigatran etexilate (Cmax increased by 180% and AUC increased by 150%).

When using the sustained release formulation of verapamil, this effect was progressively reduced (Cmax increased by 90% and AUC by 70%), as well as when using multiple doses of verapamil (Cmax increased by 60% and AUC by 50%), which may be explained by the induction of P-glycoprotein in the gastrointestinal tract with long-term use of verapamil. When verapamil was administered 2 hours after taking dabigatran etexilate, no clinically significant interaction was observed (Cmax increased by 10% and AUC by 20%) since dabigatran was completely absorbed after 2 hours. In a study in patients with atrial fibrillation, dabigatran concentrations increased by no more than 21%, and no increase in the risk of bleeding was observed. There are no data on the interaction of dabigatran etexilate with verapamil administered parenterally; no clinically significant interaction is expected

With regard to the prolongation of blood coagulation, the use of verapamil, as a rule, did not affect the plasma concentration-effect relationship of dabigatran. No unexpected safety data were obtained when dabigatran etexilate was co-administered with verapamil.

Drugs that bind to plasma proteins

Verapamil, as a drug that is highly bound to plasma proteins, should be used with caution when taken simultaneously with other drugs that have a similar ability. It is possible to increase the concentrations in the blood plasma of drugs characterized by a high degree of protein binding (including coumarin and indanedione derivatives, non-steroidal anti-inflammatory drugs, quinine, salicylates, sulfinpyrazone).

Means for inhalation general anesthesia

With the simultaneous use of drugs for inhalation anesthesia and BMCA, which include verapamil, the risk of developing bradycardia, atrioventricular block, and heart failure increases, so the dose of each drug should be carefully titrated to achieve the desired effect in order to avoid excessive depression of the cardiovascular system.

Flecainide

When verapamil and flecainide are used together, an additive effect is possible with a decrease in myocardial contractility, a slowdown in atrioventricular conduction and myocardial repolarization.

Disopyramide

Pending evidence of a possible interaction between verapamil and disopyramide, disopyramide should not be administered 48 hours before or 24 hours after verapamil.

Ivabradin

Due to its moderate inhibitory effect on CYP3A4, verapamil (at a dose of 120 mg 2 times a day) when used simultaneously led to an increase in the AUC of ivabradine by 2-3 times.

Both verapamil and ivabradine are heart rate depressants and, therefore, co-administration may worsen the patient's heart rate. The simultaneous use of verapamil with ivabradine is contraindicated due to the development of an additional negative chronotropic effect.

Procainamide, quinidine and other drugs known to prolong the QT interval

Increased risk of developing QT prolongation.

Valproic acid

Verapamil increases the concentration of valproic acid in the blood due to suppression of metabolism involving cytochrome P450.

Nicotine

Nicotine accelerates metabolism in the liver, leads to a decrease in the concentration of verapamil in the blood, and reduces the severity of antianginal, antihypertensive and antiarrhythmic effects.

Ranitidine

The concentration of verapamil in the blood plasma increases.

Calcium preparations

Reduced effectiveness of verapamil.

Nonsteroidal anti-inflammatory drugs (NSAIDs)

NSAIDs reduce the antihypertensive effect of verapamil due to suppression of prostaglandin synthesis, sodium and fluid retention in the body.

Sympathomimetics

Sympathomimetics reduce the antihypertensive effect of verapamil.

Estrogens

Estrogens reduce the antihypertensive effect of verapamil due to fluid retention in the body.

Medicines for the treatment of HIV infection

Some drugs used to treat HIV infection, such as ritonavir, may inhibit the metabolism of verapamil, resulting in increased plasma concentrations of verapamil. Caution should be exercised or the dose of verapamil should be reduced.

Lithium

Increased lithium neurotoxicity was observed during concomitant administration of verapamil and lithium, with no change or increase in serum lithium concentrations. However, additional administration of verapamil also led to a decrease in serum lithium concentrations in patients regularly taking lithium by mouth. Patients taking both drugs should be closely monitored.

Muscle relaxants

Clinical data and preclinical studies suggest that verapamil may enhance the activity of muscle relaxants (such as curare and depolarizing agents). Therefore, it may be necessary to reduce the dose of verapamil and/or the dose of drugs that block neuromuscular conduction when used simultaneously.

Acetylsalicylic acid (as an antiplatelet agent)

Increased risk of bleeding.

Ethanol (alcohol)

Increased concentration of ethanol in blood plasma.

HMG-CoA reductase inhibitors (statins)

For patients receiving verapamil, treatment with HMG-CoA reductase inhibitors (i.e. simvastatin, atorvastatin or lovastatin) should be started at the lowest possible doses and gradually increased during therapy. If it is necessary to prescribe verapamil to patients already receiving HMG-CoA reductase inhibitors (i.e. simvastatin, atorvastatin or lovastatin), then it is necessary to review and reduce their doses according to the concentration of cholesterol in the blood serum.

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

Antihypertensives, diuretics, vasodilators

Strengthening the antihypertensive effect.

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, 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.

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.