Verapamil - instructions for use, dose, side effects, contraindications

The antianginal effect is associated with both direct action on the myocardium and with influence on peripheral hemodynamics (reduces the tone of peripheral arteries, total peripheral vascular resistance). The blockade of calcium intake into the cell leads to a decrease in the transformation of the energy encapsulated in the macroergic ATP bonds into mechanical work, a decrease in myocardial contractility. Reduces the need for myocardium in oxygen, has a vasodilating, negative foreign and chronotropic effect. Increases the period of diastolic relaxation of the left ventricle, reduces the tone of the wall of the myocardium.

Decrease total peripheral resistance of blood vessels may also be due to the antihypertensive effect of verapamil.

Verapamil significantly reduces AV-conduction, prolongs the period of refractoriness and suppresses the automatism of the sinus node. Has antiarrhythmic effect in supraventricular arrhythmia.

Pharmacokinetics:

If ingested, more than 90% of the dose is absorbed. Binding to proteins - 90%. It is metabolized by the "first pass" through the liver. The main metabolite is noraverapamil, which has less pronounced hypotensive activity than the unchanged verapamil.

Half-life when taking a single dose of 2.8-7.4 hours, when taking repeated doses - 4,5-12 hours (in connection with the saturation of the enzyme systems of the liver and increased concentration of verapamil in the blood plasma). After intravenous administration, the initial half-life - about 4 minutes, the final - 2-5 hours.

It is excreted mostly by the kidneys and 9-16% by the intestine.

Indications:

Treatment and prevention of ischemic heart disease: chronic stable angina (stress angina), unstable angina, vasospastic angina (Prinzmetal angina / variant angina).

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

Arterial hypertension. Hypertensive crisis.

Hypertrophic cardiomyopathy.

ICD-10

IX.I10-I15.I10 Essential [primary] hypertension

IX.I20-I25.I20.1 Angina with documented spasm

IX.I20-I25.I20.8 Other forms of angina pectoris

IX.I26-I28.I27.0 Primary pulmonary hypertension

IX.I30-I52.I42 Cardiomyopathy

IX.I30-I52.I45.6 Syndrome of premature agitation

IX.I30-I52.I47.1 Nadzheludochkovaya tachycardia

IX.I30-I52.I48 Atrial fibrillation and flutter

IX.I30-I52.I49.4 Other and unspecified depolarization

Contraindications:

- cardiogenic shock, heart failure, severe contractility of the left ventricle, severe arterial hypotension (systolic blood pressure less than 90 mm Hg), bradycardia;

- syndrome of weakness of the sinus node, sinoatrial blockade, AV-blockade of II and III degree (except for patients with a pacemaker);

- flutter and atrial fibrillation in combination with WPW-syndrome or Laun-Ganong-Levin syndrome (except for patients with a pacemaker);

- simultaneous reception with colchicine, dantrolene, aliskiren, sertindole;

- pregnancy, lactation (breastfeeding);

- Hypersensitivity to verapamil.

Carefully:

FROM caution should be used for AV blockade of the first degree, bradycardia, severe stenosis of the aortic aorta, chronic heart failure, with mild or moderate arterial hypotension, acute phase myocardial infarction, obstructive hypertrophic cardiomyopathy, with hepatic and / or renal insufficiency, in elderly patients , in children and adolescents under the age of 18 (efficacy and safety of use not investigated).

Pregnancy and lactation:

FDA Action Category - C.

The use of verapamil in pregnancy is possible only if the expected benefit to the mother exceeds the potential risk to the fetus.

For the duration of treatment, breastfeeding should be discontinued (verapamil excreted in breast milk).

Dosing and Administration:

Inside adults - in an initial dose of 40-80 mg 3 times a day. For dosage forms of prolonged action, the single dose should be increased and the frequency of administration reduced.Children aged 6-14 years - 80-360 mg per day, up to 6 years - 40-60 mg per day; frequency of reception - 3-4 times a day.

If necessary verapamil can be administered intravenously struino (slowly, under the control of blood pressure, heart rate and ECG). A single dose for adults is 5-10 mg, in the absence of effect after 20 minutes, repeated administration in 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 impairment of liver function, the daily dose of verapamil should not exceed 120 mg.

The maximum daily dose for adults with oral administration is 480 mg.

Side effects:

From the side of the cardiovascular system and blood (hematopoiesis, hemostasis): arterial hypotension, bradycardia (sinus), AV blockade, the appearance of symptoms of heart failure (when used in high doses).

From the nervous system and sensory organs: headache, dizziness, nervousness, retardation, drowsiness, weakness, fatigue, paresthesia.

On the part of organs GIT: nausea, dyspeptic phenomena, constipation; rarely - gingival hyperplasia, increased activity of hepatic transaminases, alkaline phosphatase.

Allergic reactions: skin rash, hives, itching; rarely - angioedema, Stevens-Johnson syndrome.

Other: hyperemia of the facial skin, bronchospasm (with intravenous injection), peripheral edema, very rarely - gynecomastia, increased prolactin secretion (isolated cases).

Overdose:

Symptoms: arterial hypotension, bradycardia, AV-blockade, cardiogenic shock, coma, asystole.

Treatment: as a specific antidote is used calcium gluconate (10-20 ml of a 10% solution intravenously); with bradycardia and AV-blockade is introduced atropine, isoprenaline or orciprenaline; at a hypotension - plazmozameshchajushchie solutions, dopamine, norepinephrine; when manifestations of heart failure - dobutamine.

Interaction:

When used simultaneously with antihypertensive drugs (vasodilators, thiazide diuretics, ACE inhibitors), there is a mutual increase in antihypertensive action.

With simultaneous use with beta-blockers, antiarrhythmics, means for inhalation anesthesia, the risk of bradycardia, AV blockade, severe arterial hypotension,heart failure, due to the mutual reinforcement of the inhibitory effect on the automatism of the sinoatrial node and AV-conduction, contractility and conductivity of the myocardium.

When parenteral administration of verapamil, patients who have recently received beta-blockers have a risk of developing arterial hypotension and asystole.

With simultaneous use with nitrates, the antianginal effect of verapamil increases.

With simultaneous use with aliskiren increases its concentration in the plasma and increases the risk of side effects.

With simultaneous use with amiodarone, a negative inotropic effect, bradycardia, conduction disturbance, AV blockade is intensified.

Because the verapamil inhibits the isoenzyme CYP3A4, which is involved in the metabolism of atorvastatin, lovastatin and simvastatin, theoretically possible manifestations of drug interaction caused by increased concentrations of statins in blood plasma. The cases of development of rhabdomyolysis are described.

With simultaneous use with acetylsalicylic acid, cases of increased bleeding time due to additive antiaggregant action are described.

With simultaneous application with buspirone, the concentration of buspirone in the blood plasma increases, its therapeutic and side effects are intensified.

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

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

With simultaneous use with disopyramide, severe arterial hypotension and collapse are possible, especially in patients with cardiomyopathy or decompensated heart failure. The risk of developing severe manifestations of drug interaction is apparently associated with an increase in the negative inotropic effect.

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

When used simultaneously with imipramine, the concentration of imipramine in the blood plasma increases and there is a risk of unwanted changes in the ECG. Verapamil improves 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.

With simultaneous use with carbamazepine, the action of carbamazepine is increased and the risk of side effects from the CNS is increased due to the inhibition of carbamazepine metabolism in the liver under the influence of verapamil.

With simultaneous use with clonidine, cases of cardiac arrest in patients with arterial hypertension have been described.

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

With simultaneous application of lithium carbonate, the manifestations of drug interaction are ambiguous and unpredictable. The cases of amplification of lithium effects and development of neurotoxicity, reduction of lithium concentration in blood plasma, severe bradycardia are described.

The vasodilating effect of alpha-blockers and calcium channel blockers can be additive or synergistic. With simultaneous application of terazosin or prazosin and verapamil development of pronounced arterialhypotension is partly due to pharmacokinetic interaction: an increase in C_max and AUC terazosin and prazosin.

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

With simultaneous application with sertindol, the risk of ventricular arrhythmias, especially ventricular arrhythmias such as pirouettes, increases.

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

With the simultaneous application of tubocurarine chloride, vecuronium chloride, the enhancement of myorelaxing action is possible.

With simultaneous use with phenytoin, phenobarbital, a significant decrease in the concentration of verapamil in the blood plasma is possible.

With simultaneous use with fluoxetine, side effects of verapamil are increased due to the slowing of its metabolism under the influence of fluoxetine.

With simultaneous application verapamil inhibits the metabolism of cyclosporine in the liver, which leads to a decrease in its excretion and an increase in the concentration in the blood plasma.This is accompanied by increased immunosuppressive action, a decrease in manifestations of nephrotoxicity.

With simultaneous use with cimetidine, the effects of verapamil are enhanced.

With simultaneous application with enflurane, prolongation of anesthesia is possible.

When used simultaneously with etomidate, the duration of anesthesia is increased.

Special instructions:

If necessary, combined therapy of angina and arterial hypertension with verapamil and beta-blockers is possible. However, intravenous beta-blockers should be avoided with verapamil.

Impact on the ability to drive vehicles and manage mechanisms

After taking verapamil, individual reactions (drowsiness, dizziness) that affect a patient's ability to perform work requiring high concentration of attention and speed of psychomotor reactions are possible.

Instructions

Verapamil (Verapamilum)