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

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.

special instructions

Arterial hypotension, decreased neuromuscular transmission (for example, Duchenne muscular dystrophy), atrioventricular (AV) block I stage, bradycardia, idiopathic hypertrophic subaortic stenosis (IGSS), hypertrophic obstructive cardiomyopathy, simultaneous use with cardiac glycosides, quinidine, flecainide, ritonavir , lovastatin, simvastatin, atorvastatin; elderly age, age under 18 years (efficacy and safety of use have not been studied), chronic heart failure, liver and/or kidney failure

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 CYP2CI8. Verapamil is an inhibitor of the CYP3A4 isoenzyme and P-glycoprotein. Clinically significant interactions were observed when used concomitantly with inhibitors of the CYP3A4 isoenzyme, and an increase in the concentration of verapamil in the blood plasma was observed, while inducers of the CYP3A4 isoenzyme decreased the concentration of verapamil in the blood plasma, therefore monitoring patients for drug interactions is necessary. 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).

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

A study involving healthy volunteers showed that the combined use of verapamil and flecainide may have an additive effect with a decrease in myocardial contractility, a slowdown in atrioventricular conduction and myocardial repolarization.

Disopyramide

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

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 has been 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 serum.

Fluvastatin, pravastatin and rosuvastatin are not metabolized by the CYP3A4 isoenzyme, 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.

Directions for use and doses

Administer intravenously only, slowly, over at least 2 minutes, with continuous monitoring of the electrocardiogram, heart rate and blood pressure.

In elderly patients, administration is carried out over at least 3 minutes to reduce the risk of unwanted effects.

To relieve paroxysmal cardiac arrhythmias or hypertensive crisis, 2-4 ml of a solution of 2.5 mg/ml (5-10 mg) is administered intravenously, in a stream (under ECG and blood pressure control). If there is no effect, repeated administration after 30 minutes at the same dose is possible. A verapamil solution is prepared by diluting 2 ml of a 2.5 mg/ml solution of the drug in 100-150 ml of 0.9% sodium chloride solution.

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.