Raenom, pills 7.5mg 56pcs

Composition

Active ingredient:

ivabradine hydrobromide – 8,795 mg (equivalent to ivabradine 7.5 mg).

Auxiliary substances:

lactose-41.675 mg,

mannitol-44.530 mg,

maltodextrin -3.000 mg,

croscarmellose sodium-1,000 mg,

colloidal silicon dioxide-0.500 mg,

magnesium stearate-0.500 mg.

Tablet shell:

Opadray pink-3,000 mg (contains: polyvinyl alcohol -1.050 mg, talc-0.716 mg, titanium dioxide-0.705 mg, macrogol-3350-0.360 mg, methacrylic acid copolymer (type C) – 0.120 mg, iron oxide yellow dye -0.038 mg, iron oxide red dye-0.007 mg, sodium bicarbonate-0.004 mg).

Pharmacological action

Ivabradine is a medication that slows down the heart rate. The mechanism of action of ivabradiia is selective and specific inhibition of If channels of the sinus node, which control spontaneous diastolic depolarization in the sinus node and regulate heart rate (HR).

Ivabradine has a selective effect on the sinus node, without affecting the timing of impulses along the atrioventricular, atrioventricular and intraventricular pathways, as well as the contractility of the myocardium and ventricular repolarization. Ivabradine can also interact with Ih, retinal channels that are similar in structure to the / / – channels of the heart. They are involved in the mechanisms of temporary adaptation of the visual perception system by changing the retinal response to bright light stimuli.

Under provoking circumstances (for example, a sharp change in the intensity of illumination in the visual field area), partial inhibition of If channels by ivabradine leads to the phenomenon of changing light perception (photopsiam). Photopsy is characterized by a transient change in brightness in a limited area of the visual field (see the section “Side effect”).

The main pharmacological effect of ivabradiia is a dose-dependent decrease in heart rate. The analysis of the dependence of the heart rate decrease on the dose of the drug was carried out with a gradual increase in the dose of ivabradiia to 20 mg 2 times a day and revealed a tendency to achieve a “plateau” effect (no increase in the therapeutic effect with a further increase in the dose of the drug), which reduces the risk of developing severe bradycardia (heart rate less than 40 beats/min) (see the section “Side effect”).

When using the drug in the recommended doses, the degree of heart rate reduction depends on its initial value and is approximately 10-15 beats / min, both at rest and during physical exertion, as a result of which the heart function and myocardial oxygen demand decrease. Ivabradine does not affect viutracardial conduction, myocardial contractility (does not have a negative inotronic effect) and the process of ventricular repolarization.

In clinical electrophysiological studies, ivabradine did not affect the timing of impulses along the atrioventricular or intraventricular pathways, as well as the adjusted QT intervals. Studies in patients with left ventricular dysfunction (left ventricular ejection fraction (LVEF) 30-45%) have shown that ivabradine does not affect myocardial contractility. It was found that ivabradine at a dose of 5 mg 2 times a day improved the performance of exercise tests after 3-4 weeks of treatment.

Efficacy was also confirmed for a dose of 7.5 mg 2 times a day. An additional effect of increasing the dose from 5 mg to 7.5 mg 2 times a day was established in a comparative study with atepolol. The time to perform physical activity increased by approximately I minute after 1 month of ivabradine use at a dose of 5 mg 2 times a day, while after an additional 3-month course of ivabradine use at a dose of 7.5 mg 2 times a day, a further increase in this indicator by 25 seconds was noted.

The anti-anginal and anti-ischemic activity of ivabradine was also confirmed in patients aged 65 years and older. The efficacy of ivabradine at doses of 5 mg and 7.5 mg 2 times a day was observed for all indicators of exercise tests (total duration of physical activity, time to limiting angina attack, time to the onset of angina attack and time to the development of ST segment depression by 1 mm) and was accompanied by a decrease in the frequency of angina attacks by approximately 70%.

The use of ivabradine 2 times a day provided constant therapeutic efficacy for 24 hours. In patients taking ivabradine, additional efficacy was shown in relation to all indicators of load tests when atenolol (50 mg) was added to the maximum dose when its therapeutic activity decreased (12 hours after oral use).

There was no improvement in the effectiveness of ivabradine when added to the maximum dose of amlodnpiia at a decrease in its therapeutic activity (12 hours after oral use), while at the maximum activity of amlodinine (3-4 hours after oral use), additional effectiveness of ivabradine was proved.

In studies of the clinical efficacy of ivabradine, its therapeutic effect was completely preserved during 3-4 months of therapy. There were no signs of decreased efficacy during treatment, and no withdrawal symptoms were observed after discontinuation of treatment. The anti-anginal and anti-ischemic effects of ivabradine were associated with both a dose-dependent HR reduction and a significant reduction in the work product (HR x systolic blood pressure). both in mowing and during physical exertion.

The effect on blood pressure (BP) and total peripheral vascular resistance (OPSS) was insignificant and clinically insignificant. A steady decrease in heart rate was observed in patients who took ivabradine for at least 1 year. No effect on carbohydrate metabolism and lipid profile was observed.

In patients with diabetes mellitus, the efficacy and safety indicators of ivabradine were similar to those in the general population. There were no differences between the groups of patients taking ivabradine to standard therapy, and in patients with stable angina and left ventricular dysfunction (FVLI less than 40%),86.9% of whom received bsta-adrenoblokatory a and a placebo, but the total frequency of deaths from cardiovascular disease, hospitalization for acute myocardial infarction, hospitalization for about the emergence of new cases of heart failure or worsening of chronic heart failure (CHF) and in the subgroup of patients with heart rate of at least 70 beats/min.

Ivabradine treatment in patients with a heart rate of at least 70 beats/min has been shown to reduce the frequency of hospitalizations for fatal and non-fatal myocardial infarction by 36% and the frequency of revascularization by 30%. In patients with tension-type angina, ivabradine decreased the relative risk of complications (the incidence of deaths from cardiovascular diseases, hospitalization for acute myocardial infarction, hospitalization for new cases of heart failure or worsening of the course of CHF) by 24%.

The noted therapeutic advantage is achieved primarily by reducing the frequency of hospitalizations for acute myocardial infarction by 42%. The decrease in the frequency of hospitalizations for fatal and non-fatal myocardial infarction in patients with a heart rate of more than 70 beats / min is even more significant and reaches 73%.

In general, good tolerability and safety of the drug were noted. When ivabradine was used in patients with NYIIA functional class II-IV CSF with LVEF less than 35%, a clinically and statistically significant reduction in the relative risk of complications (the frequency of deaths from cardiovascular diseases and a decrease in the frequency of hospitalizations due to worsening of the course of CSF) by 18% was shown. The absolute risk reduction was 4.2%.

A pronounced therapeutic effect was observed 3 months after the start of ivabradine therapy. A decrease in mortality from cardiovascular diseases and the frequency of hospitalizations due to the worsening course of CHF was observed regardless of age, iol, functional class of CSF, use of beta-blockers, ischemic or non-ischemic etiology of CSF. a history of diabetes or arterial hypertension.

Patients with symptomatic CSF with sinus rhythm and heart rate below 70 beats / min received standard therapy, which included beta-blockers (89%), angiotensin-converting enzyme inhibitors (A%^%11%^%F) and/or angiotensin II receptor antagonists (91%), diuretics (83%) and aldosterone antagonists (60%).

It has been shown that the use of ivabradine for 1 year can prevent one death or one hospitalization due to cardiovascular disease for every 26 patients taking the drug. Against the background of ivabradine use, an improvement in the functional class of HCI according to the NYHA classification was shown. In patients with a heart rate of 80 beats/mip, a decrease in heart rate by an average of 15 beats/min was noted.

Indications

Stable angina pectoris

Therapy of stable angina in patients with normal sinus rhythm: if they are intolerant or have contraindications to the use of bsta-blockers; in combination with beta-blockers, if the symptoms of stable angina are not adequately controlled against the background of an optimal dose of beta-blockers.

Chronic heart failure

To reduce the incidence of cardiovascular complications (mortality from cardiovascular diseases and hospitalization due to worsening of the course of CHF) in patients with chronic heart failure, with a sinus rhythm and heart rate of at least 70 beats/min.

Contraindications

Hypersensitivity to ivabradine or any of the excipients of the drug; Bradycardia (resting heart rate less than 60 beats / min (before starting treatment));

Cardiohsnny shock;

Acute myocardial infarction;

Severe arterial hypotension (systolic blood pressure less than 90 mm Hg and diastolic blood pressure less than 50 mm Hg);

Severe liver failure (more than 9 points on the Child-Pugh scale);

 Use in women of reproductive age who do not use reliable methods and contraception;

Age up to 18 years (the efficacy and safety of the drug in this age group has not been studied);

lactase deficiency, lactose intolerance, glucose-galactose malabsorption syndrome.

With caution Moderate hepatic insufficiency (less than 9 points on the Child-Pugh scale); severe renal insufficiency (creatinine clearance less than 15 ml/min); congenital prolongation of the QT interval (see the section “Interaction with other drugs”); concomitant use of drugs that prolong the QT interval; concomitant use of moderate inhibitors and inducers of cytochrome CYP3A4 isoenzymes and grapefruit juice; concomitant use with potassium-sparing diuretics; asymptomatic left ventricular dysfunction; grade II atrioventricular block; recent stroke; NYHA functional class IV CHF; retinitis pigmentosa’, arterial hypotension; age over 75 years.

Side effects

The most frequent side effects of ivabradine, bradycardia and photopsia, were dose-dependent and were due to the mechanism of its pharmacological action.

Undesirable side effects are presented by systemic organ classes according to the MedDRA classification and with the frequency of occurrence: very common (>1/10); often (>>1/100, >><1/10); infrequently (>1/1,000, <1/10); infrequently (><1/100); rarely (>1/10,000, <1/100); rarely (><1/1,000); very rarely (

Nervous system disorders Common: headache (especially in the first month of therapy), dizziness, possibly associated with bradycardia; Infrequent: vertigo, muscle spasms; Frequency unknown: syncope, possibly associated with bradycardia.

Visual disturbances Very common: changes in light perception (photopsies); Common: blurred vision; Frequency unknown: diplopia, visual disturbances.

Disorders of the heart and blood vessels Often:Bradycardia, grade I atrioventricular block, ventricular extrasystole, short-term increase in blood pressure; Infrequently: 0009 palpitation, supraventricular extrasystole, prolongation of the QT interval on the ECG; Very rare: atrial fibrillation, atrioventricular (AV) block of N-W degree, sinus node weakness syndrome; Frequency unknown: marked decrease in blood pressure, possibly associated with bradycardia.

The following are adverse events identified in clinical trials that occurred with the same frequency in both the ivabradine-treated group and the control group, suggesting that they are associated with the disease itself, and not with ivabradine: sinus arrhythmia, angina pectoris, including unstable angina, atrial fibrillation, myocardial ischemia, myocardial infarction, and ventricular tachycardia.

Respiratory, thoracic and mediastinal disorders

Infrequently: shortness of breath.

Disorders of the gastrointestinal tract

Infrequently: nausea, constipation, diarrhea.

Skin and subcutaneous tissue disorders

Frequency unknown: skin rash, pruritus, erythema, angioedema, urticaria.

Musculoskeletal and connective tissue disorders

Infrequently: muscle spasms.

Effects on the results of laboratory and instrumental studies Infrequently: hyperuricemia, eosinophilia, increased serum creatinine concentration.

General disorders and disorders at the injection

site Frequency unknown: asthenia, increased fatigue, malaise, possibly associated with bradycardia.

Interaction

Undesirable drug combinations Medications that prolong the OT interval Antiarrhythmic drugs that prolong the QT interval (for example, hipidine, disopyramide, bspridil, sotalol, ibutilide, amiodarone); Medications that prolong the QT interval that are not related to antiarrhythmic drugs (for example, pimozide, ziprasidone, sertindol, mefloquine, halofantrine, pentamidine, cisapride, erythromycin for intravenous use).

Concomitant use of ivabradine and these medications should be avoided, since a decrease in heart rate may cause an additional prolongation of the QT interval. If the simultaneous use of these drugs is necessary, ECG indicators should be carefully monitored.

The CYP3A4 isoenzyme of the cytochrome P450 system Ivabradine is metabolized in the liver with the participation of the CYP3A4 isoenzyme of the cytochrome P450 system and is a very weak inhibitor of this cytochrome.

Ivabradine does not significantly affect the metabolism and plasma concentrations of other substrates (potent, moderate and weak inhibitors) of the CYP3A4 isoenzyme. 13 At the same time, inhibitors and inducers of the CYP3A4 isoenzyme can interact with ivabradine and have a clinically significant effect on its metabolism and pharmacokinetic properties.

It was found that inhibitors of the CYP3A4 isoenzyme increase, and inducers of the CYP3A4 isoenzyme reduce the concentration of ivabradine in blood plasma. an increase in the concentration of ivabradine in blood plasma may increase the risk of developing severe bradycardia (see the section “Precautions for use”).

Concomitant use of ivabradine with potent inhibitors of the CYP3A4 isocyermcnt, such as azole antifungal agents (ketocoiazole, itraconazole); macrolide antibiotics (clarithromycin, oral erythromycin, josamycin, telithromycin); HIV protease inhibitors (nelfipavir, ritonavir) and nefazodone, is contraindicated (see the section “Contraindications”).

Powerful inhibitors of the CYP3A4 isoenzyme-ketocoiazole (200 mg 1 time a day) or josamycin (1 g 2 times a day) – increase the average concentration of ivabradine in blood plasma by 7-8 times. Moderate inhibitors of the CYP3A4 isoenzyme Simultaneous use of ivabradine and diltiazem or verapamil (drugs that reduce heart rate) in healthy volunteers and patients was accompanied by an increase in the AUC of ivabradine by 2-3 times and an additional reduction in heart rate by 5 beats / min.

The use of these combinations is contraindicated (see the section “Contraindications”). Drug combinations requiring caution Moderate inhibitors of the CYP3A4 isoenzyme. Ivabradine can be used in combination with other moderate inhibitors of the CYP3A4 isoenzyme (for example, fluconazole), provided that the mowing heart rate is more than 60 beats / min. The recommended initial dose of ivabradine is 2.5 mg 2 times a day.

Heart rate monitoring is required. Simultaneous use with inducers of the CYP3A4 isoenzyme. such as rifampicin, barbiturates, phenytoin, and herbal remedies containing St. John’s wort (Hypericum perforatum) may lead to a decrease in the plasma concentration and activity of ivabradine and require the selection of a higher dose of ivabradine.

When ivabradine was co-administered with preparations containing St. John’s wort, a twofold decrease in ivabradine AUC was observed. During therapy with Raen, the use of drugs and products containing St. John’s Wort should be avoided as much as possible.

How to take, course of use and dosage

Inside,2 times a day (morning and evening), with meals.

The initial recommended daily dose is 10 mg per day (5 mg 2 times a day). Depending on the therapeutic effect, after 3 to 4 weeks, the daily dose can be increased to 15 mg (7.5 mg 2 times a day).

If during therapy the heart rate decreases to less than 50 / min or symptoms associated with bradycardia occur (dizziness, fatigue, or a decrease in blood pressure), a lower dose of the drug should be used.

If the heart rate does not return to normal when the dose is reduced and remains less than 50/min, the drug is discontinued.

In elderly patients, treatment should begin with an initial dose of 2.5 mg (1/2 tablet of 5 mg) 2 times a day; it is possible to increase the daily dose depending on the patient’s condition.

Form of production

Light orange, round, biconvex film-coated tablets with the inscription “SK 4” on one side.

On the cross-section, the tablet core is white.

Active ingredient

Ivabradin

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

For adults as directed by your doctor

Indications

Heart Failure, Angina, Arrhythmia