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

Shell composition: hypromellose (hydroxypropylmethylcellulose), macrogol (polyethylene glycol 6000), glycerol (glycerin), talc, titanium dioxide, lactose (milk sugar), tropeoline O.

Description:

The tablets covered with a film cover, yellow color, round, biconcave. On the break the tablets are white or almost white in color.

Pharmacotherapeutic group:The blocker of "slow" calcium channels

ATX: & nbsp

C.08.D.A.01 Verapamil

C.08.D.A Phenylalkylamine derivatives

Pharmacodynamics:

Verapamil - a blocker of "slow" calcium channels (inhibits the transmembrane transport of calcium ions to the contractile fibers of smooth muscle cells), a derivative of diphenylalkylamine. Has antianginal, antiarrhythmic and hypotensive effect. The antianginal effect is associated with both direct action on the myocardium and with influence on peripheral hemodynamics (reduces the tone of the peripheral arteries, the overall peripheral vascular resistance).

The blockade of calcium ions entering the cell leads to a decrease in the transformation of the energy encapsulated in the macroergic ATP bonds into mechanical work, a decrease in the contractility of the myocardium. Reduces the need for myocardium in oxygen, has a vasodilating, negative andbut- and chronotropic actions. Significantly reduces the atrioventricular (A V) conductivity, lengthens the period of refractivity and suppresses the automatism of the sinus node.

Increases the period of diastolic relaxation of the left ventricle, reduces the tone of the wall of the myocardium (it is an auxiliary tool for the treatment of hypertrophic obstructive cardiomyopathy).

Suppresses metabolism involving cytochrome P450.

The beginning of the effect with oral administration - after 1-2 hours, the maximum effect develops after 30-90 minutes (usually within 24-48 hours), the duration of the effect is 8-10 hours. The antianginal effect is dose-dependent, tolerance does not arise.

Pharmacokinetics:

When ingested quickly absorbed in the small intestine, absorption - 90-92%, bioavailability after a single dose of 24-35% due to intensive metabolism during the "first passage" through the liver and increases by 1.5-2 times with prolonged use. With prolonged use in increasing doses bioavailability may increase.

Time to reach the maximum concentration of the drug in the blood plasma - 1-2 hours with oral administration. The maximum concentration of the drug in the blood plasma (C_max) - 80-400 ng / ml. Connection with blood plasma proteins - 90%. Penetrates through the blood-brain barrier, placental barrier (20-92 % concentration in the blood plasma of the mother) and in breast milk (in low concentrations).

Rapidly metabolized in the liver by N-dealkylation and O-demethylation, with the formation of several metabolites (in humans, 12 were identified). Accumulation of the drug and its metabolites in the body explains the increased effect of course treatment. The main pharmacologically active metabolite is noraverapamil (20% of the hypotensive activity of verapamil). In the metabolism of the drug, isozymes participate CYP3A4, CYP3A5 and CYP3A7.

The half-life of the drug is 3-7 hours with a single admission, 4-12 hours with prolonged use (in connection with the saturation of the enzyme systems of the liver and increased plasma concentrations, the half-life of the drug is almost doubled). With hepatic insufficiency increases bioavailability and increases the half-life of the drug.Output 70% of the kidneys (3-5% unchanged), 16-25% - with bile. It is not excreted by hemodialysis.

Indications:

1. Treatment and prevention of cardiac arrhythmias:

paroxysmal supraventricular tachycardia;
flutter and atrial fibrillation (tachyarrhythmic variant); supraventricular extrasystole.

2. Treatment and prevention:

chronic stable angina (stress angina);
unstable angina;
vasospastic angina (Prinzmetal angina, variant angina).

3. Treatment of arterial hypertension.

Contraindications:

Hypersensitivity to verapamil and other components of the drug, severe left ventricular dysfunction, severe arterial hypotension (systolic blood pressure less than 90 mm Hg), or cardiogenic shock, severe bradycardia, atrioventricular blockade of the P-III degree, weakness syndrome of the sinus node (except for patients with a pacemaker), atrial flutter and fibrillation, and Wolff-Parkinson-White syndrome (WPW) or Laun-Ganong-Levin syndrome (except for patients with a pacemaker), pregnancy, lactation, age under 18 (efficacy and safety not established), simultaneous reception of colchicine.

Carefully:

Sinoatrial block, atrioventricular block of the 1st degree, bradycardia, idiopathic hypertrophic subaortic stenosis (IGSS), chronic heart failure, hepatic and / or renal failure, delay of neuromuscular transmission, elderly age.

Dosing and Administration:

Tablets are taken without dissolving and chewing, with a small amount of liquid, preferably before meals or immediately after meals.

40-80 mg 3 times a day - with stenocardia and supraventricular tachycardia in 3 doses, with arterial hypertension - in 2 doses, daily dose for arterial hypertension - up to 480 mg. The maximum daily dose of 480 mg.

For patients with severe hepatic insufficiency, the daily dose should not exceed 120 mg.

Side effects:

From the side of the cardiovascular system: bradycardia (less than 50 beats per minute), marked decrease in blood pressure, development or worsening of heart failure, tachycardia; rarely - angina, up to the development of myocardial infarction (especially in patients with severe obstructive lesions of the coronary arteries), arrhythmia (including fibrillation and flutter of the ventricles).

From the central nervous system: dizziness, headache, fainting, anxiety, retardation, fatigue, asthenia, drowsiness, depression, extrapyramidal disorders (ataxia, masky face, shuffling gait, stiffness of hands or feet, trembling of hands and fingers, difficulty swallowing).

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

Allergic reactions: skin itch, rash, hyperemia of the skin of the face, multiforme exudative erythema (including Stevens-Johnson syndrome).

Other: weight gain, very rarely - agranulocytosis, gynecomastia, hyperprolactinaemia, galactorrhea, arthritis, pulmonary edema, thrombocytopenia, asymptomatic, peripheral edema.

Overdose:

Symptoms: bradycardia, atrioventricular blockade, marked decrease in blood pressure, heart failure, shock, asystole, sinoatrial blockade.

Treatment: with early detection - gastric lavage, Activated carbon; with rhythm and conduction disturbances - intravenous isoprenaline, norepinephrine, atropine, 10-20 ml of 10% calcium gluconate solution, artificial pacemaker; IV infusion of plasma-substituting solutions. To increase blood pressure in patients with hypertrophic obstructive cardiomyopathy, alpha-adrenergic stimulants (phenylephrine); do not use isoprenaline and norepinephrine. Hemodialysis is ineffective.

Interaction:

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

Raises the AUC, equilibrium concentration (C_ss) and the maximum concentration (C_max) of cyclosporine in blood plasma.

Increases the concentration of theophylline (due to decreased clearance), ethanol (and lengthens its effect), the concentration of quinidine (the risk of a pronounced decrease in blood pressure, especially in patients with IHSS).

It may increase the concentration of atorvastatin and lovastatin when used concomitantly.

Significantly increases AUC and C_max simvastatin.

Raises the AUC and C_max almotriptan.

Increases the concentration of cardiac glycosides (requires careful monitoring anddose of glycosides).

Raises the AUC and C_max metoprolol and propranolol in patients with angina pectoris. Increases the plasma concentration of colchicine (substrate for CYP3A and p-glycoprotein). Significantly increases AUC and C_max doxorubicin.

Slightly increases AUC imipramine, does not affect the concentration of the active metabolite of desipramine.

Raises the C_max prazosin and terazosin and AUC terazosin.

Inhibitors CYP3A4 (incl. erythromycin, ritonavir and other antiviral HIV drugs), telithromycin increase plasma concentrations of verapamil.

Grapefruit juice increases AUC and C_max R- and Sisomers of verapamil.

Cimetidine increases bioavailability of verapamil by almost 40-50 % (due to a decrease in hepatic metabolism), in connection with which it may be necessary to reduce the dose of the latter.

Rifampicin can significantly reduce bioavailability (up to 92%), and AUC and C_max verapamil.

Phenobarbital increases the clearance of verapamil 5 times.

Sulfinpyrazone increases the clearance of verapamil by about 3 times and reduces bioavailability (60 %).

Drug preparations of St. John's wort reduce AUC R- and S- isomers of verapamil and C_max.

With simultaneous use with inhalation anesthetics, the risk of bradycardia, atrioventricular blockade, and heart failure increases.

Combination with beta-blockers can lead to an increase in the negative inotropic effect, an increased risk of violations AV conduction, bradycardia (the administration of verapamil and beta-blockers should be performed at intervals of several hours).

Prazosin and other alpha-blockers, as well as other antihypertensive drugs (ACE inhibitors, vasodilators, diuretics, beta-adrenoblockers) increase the hypotensive effect.

Dysopyramide and flecainide should not be administered within 48 hours before or 24 hours after the use of verapamil (summation of a negative inotropic effect, up to a lethal outcome).

Increases the risk of neurotoxic effect of lithium drugs.

Strengthens the action of peripheral muscle relaxants (may require a change in the dosage regimen).

With simultaneous use with acetylsalicylic acid, there was a slightly greater increase in bleeding time than with acetylsalicylic acid alone.

Special instructions:

Heart failure must first be compensated.

In the treatment it is necessary to monitor the functions of the cardiovascular system, the respiratory system, the content of glucose and electrolytes in the blood, the volume of circulating blood and the amount of excreted urine.

It is not recommended to stop treatment suddenly.

Form release / dosage:

Tablets, film-coated, 40 mg and 80 mg.

Packaging:

For 10 or 20 tablets in a planar cell pack.

1 or 5 contour cell packs of 10 tablets or 1 or 2 contour packs of 20 tablets together with instructions for use in a pack of cardboard.

Storage conditions:

List B. In a dry, the dark place at a temperature of no higher than 25 ° C. Keep out of the reach of children.

Shelf life:

3 of the year. Do not use the drug after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:P N001573 / 01

Date of registration:07.08.2008

Expiration Date:Unlimited

The owner of the registration certificate:AKRIKHIN HFK, JSC AKRIKHIN HFK, JSC Russia

Manufacturer: & nbsp

AKRIKHIN HFK, JSC Russia

Information update date: & nbsp28.01.2017

Illustrated instructions

Instructions

Verapamil (Verapamil)