Ivabradin + Metoprolol - instructions for use, dose, side effects, contraindications

Clinical and pharmacological group: & nbsp

Beta-blockers

Other cardiovascular drugs

Included in the formulation

Implicor®

pills inwards

Servier Laboratories France

АТХ:

C.07.F.X.05 Metoprolol in combination with ivabradine

Pharmacodynamics:

Iwabradine

Selectively and specifically inhibits the f-channels of the sinus node of the heart, controlling spontaneous diastolic repolarization of the sinus node. Reduces the heart rate by 10-15 beats / min, thereby reducing the need for myocardium in oxygen, as the work of the heart decreases. Does not change the interval of QT, does not affect the process of repolarization of the ventricles of the heart, intracardiac conduction and contractility of the myocardium (does not cause negative inotropic effect).

It should be borne in mind that the drug interacts with h-channels of the retina, which are similar in structure to the f-channels of the sinus node of the heart, which can lead to transient impairment of vision - the appearance of photopsias with a sharp change in illumination.

Metoprolol

Selective β1-blocker not having internal sympathomimetic activity. Has antihypertensive, antiarrhythmic, antianginal action. In therapeutic doses does not affect the tone of peripheral arteries.

Reduces the effect of catecholamines on the heart muscle, thereby reducing the heart rate, minute and shock volumes of blood within 24 hours.

Eliminates the effects of arrhythmogenic factors: tachycardia, arterial hypertension, increased content of cyclic AMP.

Antianginal action is due to a decrease in myocardial oxygen demand with prolonged diastole and improved perfusion of the heart muscle.

Pharmacokinetics:

Iwabradine

After oral administration, an empty stomach is absorbed in the gastrointestinal tract up to 100%. The maximum concentration in the blood plasma is reached after 1 hour. The connection with plasma proteins is 70%.

Therapeutic effect develops 2-3 weeks after the start of the procedure. Metabolism in the liver.

T ½ is 2 hours. Elimination by the kidneys and with feces.

Metoprolol

The maximum concentration is achieved in 2-4 hours. Metoprolol binds to plasma proteins up to 16%. Poorly penetrates the blood-brain barrier, penetrates the placenta.

T1 / 2 metoprolol is 3-7 hours. Partially metabolized in the liver, eliminated by the kidneys: 5% unchanged and 95% - in the form of metabolites. When hemodialysis is not excreted from the blood plasma.

Indications:

It is used for the treatment of arterial hypertension, as well as with the goals of arrhythmia prevention, it is used for stable angina, chronic heart failure in patients with sinus rhythm not less than 70 beats / min.

ICD-10

IX.I20-I25.I20 Angina pectoris [angina pectoris]

IX.I20-I25.I20.80 Other forms of angina with hypertension

Contraindications:

Age under 18, pregnancy and lactation, cardiogenic shock, sinoartrial block, weakness syndrome of the sinus node, the presence of the artificial pacemaker, atrioventricular blockade of the II-III degree, hypotension (BP below 95/50 mm Hg), unstable angina , myocardial infarction, severe hepatic insufficiency, chronic heart failure - resistant to the action of cardiac glycosides, bronchial asthma, individual intolerance.

Carefully:

Moderate hepatic insufficiency, renal failure, congenital lengthening of the interval QT, chronic heart failure IV functional class according to the NYHA classification, chronic bronchitis with an asthmatic component, obliterating arterial diseases, atrioventricular blockade of the 1st degree, disturbance of the water-electrolyte balance.

Pregnancy and lactation:

Recommendations for FDA - category - category D without teratogenicity. Not applicable in pregnancy and lactation.

Dosing and Administration:

Inside, 1 tablet 2 times / day, with meals, morning and evening.

The highest daily dose: 2 tablets.

The highest single dose: 1 tablet.

Side effects:

Iwabradine

Central and peripheral nervous system: dizziness, headache; - in the first days of taking the drug. Effects are dose-related, associated with bradycardia. Rarely, convulsions.

Respiratory system: rarely - shortness of breath.

Hemopoietic system: eosinophilia.

The cardiovascular system: a bradycardia in the first 2-3 months of treatment. Rarely AV-blockade I degree, ventricular extrasystole.

Digestive system: nausea, constipation, diarrhea.

Sense organs: transient photopsy during the first 2 months of treatment, blurred vision.

Metoprolol

Central and peripheral nervous system: dizziness, insomnia, asthenia.

Respiratory system: shortness of breath, rarely - bronchospasm

The cardiovascular system: bradycardia, atrioventricular blockade, cold extremities.

Hemopoietic system: neutropenia, thrombocytopenia.

Sense organs: "dry eye syndrome", transient visual impairment.

Digestive system: indigestion, diarrhea, or constipation.

Reproductive system: lowering the potency.

Leather: Hyperhidrosis.

Allergic reactions.

Overdose:

Iwabradine

Development of bradycardia.

Treatment is symptomatic. When the hemodynamic parameters are violated, intravenous administration of β-stimulating agents (isoprenaline) is indicated. In severe cases, temporary use of the pacemaker.

Metoprolol

Pronounced bradycardia, arterial hypotension.

Treatment. Intravenous 1-2 mg. atropine, 2.5 μg / kg dobutamine, intravenously bolus 10 mg glucagon, intravenously drop 10-20 μg isoprenaline at a rate of not more than 5 μg / min.

Interaction:

Iwabradine

It is not recommended simultaneous use with drugs that extend the interval QT: ziprasidone, pimozide, sertinol, halofantrine, pentamine, cisaride, erythromycin (intravenous injection).

The intake of grapefruit juice in the treatment with ivabradine leads to an increase in the concentration of the drug in the blood plasma, which increases the risk of bradycardia.

Simultaneous use with stimulants CYP 3A4, such as barbiturates, rifampicin, phenytoin, St. John's wort (Hypericum perforatum leads to a decrease in the concentration of ivabradine, hence, requires a dose adjustment of ivabradine.

Simultaneous use with non-potassium-sparing diuretics (thiazide and "loop" diuretics) leads to hypokalemia that increases the risk of arrhythmia. Because the ivabradine can cause bradycardia, a combination of hypokalemia and bradycardia is a predisposing factor for the development of severe arrhythmia.

Metoprolol

Increases the concentration of ethanol in the blood and lengthens its excretion.

Potentiates the effect of lidocaine in systemic application.

Negative dromo-, foreign, chromotropic influences are intensified with simultaneous admission with amiodarone, anesthetics, antiarrhythmics, digoxin, diltiazem, verapamil.

Increases the bioavailability of metoprololol with cimetidine.

Special instructions:

Monitoring of liver and kidney function. Regular monitoring of the electrocardiogram to detect atrial fibrillation.

Discontinue taking the drug gradually (for 8-10 days).

Before an operative intervention it is necessary to inform the anesthesiologist about taking the drug by the patient.

During drug treatment, patients are not advised to drive and work with moving machinery.

Instructions

Ivabradine + Metoprolol (Ivabradine + Metoprolol)