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

Excipients: lactose monohydrate 20.87 mg or 41.74 mg, potato starch 12.87 mg or 25.74 mg, copovidone 4.80 mg or 9.60 mg, talc 0.73 mg or 1.46 mg, calcium stearate - 0.73 mg or 1.46 mg,

shell: Opadrai II (series 85) - 2.00 mg or 4.00 mg: polyvinyl alcohol partially hydrolysed - 40.00%, macrogol-3350 - 20.20%, talcum 14.80%, titanium dioxide E 171-19, 50%, iron coloring oxide yellow E 172 - 0.10%, aluminum lacquer based on quinoline yellow dye E 104 - 5.40%.

Description:Round biconvex tablets, coated with a yellow coating. On the cross-section the nucleus is white.

Pharmacotherapeutic group:The blocker of "slow" calcium channels

ATX: & nbsp

C.08.D.A.01 Verapamil

C.08.D.A Phenylalkylamine derivatives

Pharmacodynamics:

The blocker of "slow" calcium channels (inhibits the transmembrane transport of calcium 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 resistance of the vessels).

The blockade of calcium intake into the cell leads to a decrease in the transformation of the adenosine triphosphate (ATP) encapsulated in macerergic bonds into mechanical work, a decrease in myocardial contractility. Reduces the need for myocardium in oxygen, has a vasodilating, negative, foreign and chronotropic effect. Significantly reduces atrioventricular (AV) conductivity, prolongs the period of refractoriness 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).

The onset of the effect 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 oral intake is 24-35% (due to intensive metabolism in the "primary passage" through the liver). With prolonged use (including with increasing dose), bioavailability may increase in 1,5-2 times. The maximum concentration of verapamil in the blood plasma after ingestion (80-400 ng / ml) is achieved after 1-2 hours. Binding to blood plasma proteins - 90%. Penetrates through the blood-brain barrier, hematoplacental barrier (20-92% of the 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 (12 metabolites were identified in a human). The accumulation of verapamil and its metabolites in the body explains the intensification of action in course treatment. The main pharmacologically active metabolite is noraverapamil (provides 20% of hypotensive activity of verapamil). In the metabolism of verapamil, isozymes participate CYP3A4, CYP3A5 and CYP3A7.

The half-life (T1 / 2) with a single oral intake is 3-7 hours,when taking repeated doses of T1 / 2 increases to 4-12 hours (in connection with the saturation of the enzyme systems of the liver and increased plasma concentrations of verapamil). With hepatic insufficiency increases bioavailability and increases T1 / 2. It is mainly excreted by the kidneys - 70% (3-5% unchanged) and 16-25% - with bile. Hemodialysis is not effective.

Indications:

- arterial hypertension;

- ischemic heart disease, including chronic stable angina (classic angina pectoris), unstable angina, angina due to vasospasm (Prinzmetal angina);

- paroxysmal supraventricular tachycardia;

- atrial fibrillation / flutter accompanied by tachyarrhythmia (with the exception of Wolff-Parkinson-White syndrome and Laun-Ganong-Levin syndrome).

Contraindications:

- hypersensitivity to the components of the drug;

- lactose intolerance, lactase deficiency, glucose-galactose malabsorption;

- severe left ventricular dysfunction;

- acute myocardial infarction complicated by bradycardia, severe arterial hypotension and left ventricular failure;

- chronic heart failure;

- arterial hypotension (systolic blood pressure (BP) less than 90 mm Hg) or cardiogenic shock, AV FP blockade, sinus node weakness syndrome (except for patients with a pacemaker), Wolff-Parkinson-White syndrome or Laun-Ganong-Levin syndrome in combination with atrial flutter or fibrillation (except for patients with a pacemaker);

- simultaneous reception of colchicine;

- pregnancy;

- lactation period;

- children under 18 years of age (efficacy and safety of use not investigated).

Carefully:

AV blockade of the 1st degree, bradycardia, idiopathic hypertrophic subaortal stenosis (IGSS), expressed violations of the liver and kidney function, diseases related to neuromuscular transmission (myasthenia gravis gravis, Lambert-Eaton syndrome, Duchenne muscular dystrophy), elderly age (over 60 years).

Pregnancy and lactation:

Determined that verapamil penetrates the hematoplacental barrier. The use of verapamil during pregnancy is contraindicated. If necessary, use inErupamil during lactation should stop breastfeeding.

Dosing and Administration:

Inside, not dissolving and not chewing, squeezed with a small amount of liquid, preferably before eating or immediately after eating.

Dosing regimen and duration of treatment are established individually depending on the patient's condition, severity, the features of the course of the disease and the effectiveness of therapy.

The initial dose is 40-80 mg 3 times a day. If necessary, increase the single dose to 120-160 mg.

With prolonged treatment, the daily dose of 480 mg should not be exceeded. The maximum daily dose of verapamil is 480 mg. In the maximum daily dose verapamil must be taken only in the hospital.

With angina and supraventricular tachycardia, a daily dose is recommended in 3 divided doses, with arterial hypertension - in 2 divided doses.

In patients with severe hepatic impairment, excretion of verapamil from the body is slowed, so it is advisable to start treatment with minimal doses. The daily dose of verapamil should not exceed 120 mg.

Side effects:

From the cardiovascular system: AV blockade I, II, III degree, stopping the sinus node, peripheral edema, tachycardia,sinus bradycardia, heart failure, pronounced lowering of blood pressure, "tides" of blood to the skin of the face, a feeling of palpitations.

From the nervous system: tremor, paresthesia, dizziness, headache, fainting, anxiety, inhibition, 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: pain and discomfort in the abdomen, intestinal obstruction, nausea, constipation, diarrhea, gingival hyperplasia (bleeding, soreness, swelling), increased appetite, increased activity of "liver" transaminases and alkaline phosphatase.

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

Other: weight gain, agranulocytosis, gynecomastia, hyperprolactinaemia, galactorrhea, arthritis, pulmonary edema, thrombocytopenia (without clinical manifestations), peripheral edema, purpura, alopecia, muscle weakness, myalgia, arthralgia, erectile dysfunction, ringing in the ears.

Overdose:

Symptoms: marked decrease in blood pressure, sinus bradycardia, changing into AV blockade of a high degree, stopping the sinus node, hyperglycemia, stupor and metabolic acidosis. Reported lethal cases as a result of an overdose.

Treatment: should be symptomatic and supportive therapy, including gastric and intestinal flushing, the reception of activated charcoal, parenteral administration of calcium preparations and beta-adrenomimetics. Verapamil is not excreted by hemodialysis.

Interaction:

When used simultaneously with carbamazepine in patients with persistent partial epilepsy due to inhibition of the metabolism of carbamazepine in the liver verapamil strengthens its effect (risk of side effects from the central nervous system, such as diplopia, headache, ataxia and dizziness).

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.

With simultaneous application verapamil increases the concentration of theophylline (due to lower clearance).

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

With simultaneous application verapamil increases the concentration of ethanol in blood plasma and lengthens its effect.

Because the verapamil inhibits isoenzyme CYP3A4, which is involved in the metabolism of atorvastatin, lovastatin and simvastatin, there may be manifestations of drug interaction caused by an increase in the concentrations of statins in the blood plasma (rhabdomyolysis).

With simultaneous application verapamil increases the concentration in the blood plasma of almotriptan, glibenclamide.

With simultaneous application verapamil increases the concentration in blood plasma of sirolimus and tacrolimus.

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

With simultaneous application verapamil increases the concentration of metoprolol and propranolol in patients with angina.

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

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

With the simultaneous use of verapamil with imipramine, the concentration of imipramine in the blood plasma increases (the risk of unwanted changes caused by the additive inhibitory effect of verapamil and imipramine on AV conductivity). Does not affect the concentration of the active metabolite, desipramine.

Verapamil increases the concentration of prazosin and terazosin with simultaneous use (risk of development of severe arterial hypotension).

With the simultaneous use of verapamil with buspirone or midazolam, their concentration in the blood plasma increases (the risk of side effects).

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

Grapefruit juice increases the concentration in the blood plasma R- and Sisomer of verapamil. Cimetidine or does not alter, or reduces the clearance of verapamil (possibly enhancing the effects of verapamil).

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

Phenobarbital increases the clearance of verapamil 5 times.

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

Drugs of St. John's wort cut the concentration R- and Sisomer of verapamil in blood plasma.

With the simultaneous use of verapamil with inhalational anesthetics, the risk of bradycardia increases, AV blockade, heart failure. The combination of verapamil with beta-blockers can lead to an increase in the negative inotropic effect, an increased risk of violations AV conduction, bradycardia (the use of verapamil and beta-blockers should be done at intervals of several hours).

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

With the simultaneous use of verapamil with disopyramide and flecainide, severe arterial hypotension and collapse are possible, up to a lethal outcome. The risk of developing severe manifestations of drug interaction is associated with an increase in the negative inotropic effect. Do not administer dysopyramide and flecainide for 48 hours before or 24 hours after the use of verapamil.

Verapamil increases the risk of neurotoxic effect of lithium preparations.

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

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

Special instructions:

Before starting therapy for heart failure, it is necessary to achieve a state of compensation.

In the treatment it is necessary to monitor the function of the cardiovascular and respiratory systems, the concentration of glucose and blood electrolytes, the volume of circulating blood and the amount of excreted urine.

In patients with impaired renal function, monitoring of renal function is necessary. Verapamil can not be abruptly abolished, it is recommended to gradually reduce the dose to the complete withdrawal of verapamil.

Effect on the ability to drive transp. cf. and fur:Considering the possible occurrence of side effects, care should be taken when driving vehicles or other potentially dangerous mechanisms.

Form release / dosage:

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

Packaging:

For 10 tablets in a contour mesh box made of polyvinylchloride film and aluminum foil printed lacquered.

5 contour mesh packages together with the instruction for use are placed in a pack of cardboard.

Storage conditions:

In the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

5 years.

Do not use after expiry date, indicated on the package.

Terms of leave from pharmacies:On prescription

Registration number:P N001232 / 01

Date of registration:19.11.2007 / 12.05.2012

Expiration Date:Unlimited

The owner of the registration certificate:VALENTA PHARM, PAO VALENTA PHARM, PAO Russia

Manufacturer: & nbsp

VALENTA PHARMACEUTICS, JSC Russia

Information update date: & nbsp26.01.2017

Illustrated instructions

Instructions

Verapamil (Verapamil)