Raenom, 5 mg 56 pcs.

Antianginal drug.

A selective inhibitor of sinus node If channels

Indications

Stable angina
Treatment of stable angina in patients with normal sinus rhythm:
– if you are intolerant or have contraindications to the use of beta-blockers;
– in combination with beta-blockers with inadequate control of symptoms of stable angina pectoris against the background of the optimal dose of beta-blocker.

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

Pharmacological effect

Antianginal drug.

Selective inhibitor of sinus node If channels

Special instructions

Heart rhythm disturbance

Ivabradine is not effective for the treatment or prevention of arrhythmias. Its effectiveness decreases against the background of the development of tachyarrhythmia (for example, ventricular or supraventricular tachycardia). Raenom® is not recommended for patients with atrial fibrillation (atrial fibrillation) or other types of arrhythmias associated with sinus node function.

During therapy with Raen®, patients should be clinically monitored to detect atrial fibrillation (paroxysmal or permanent). If clinically indicated (eg, worsening angina, palpitations, irregular heart rhythm), an ECG should be included in routine monitoring.

The risk of developing atrial fibrillation may be higher in patients with CHF taking Raenom®. Atrial fibrillation was more common among patients who were taking amiodarone or class I antiarrhythmic drugs concomitantly with ivabradine. Patients with CHF and intraventricular conduction disorders (left or right bundle branch block) and ventricular dyssynchrony should be monitored.

Use in patients with bradycardia

Ivabradine is contraindicated if, before starting therapy, the resting heart rate is less than 60 beats/min. If during therapy the resting heart rate decreases to values ​​less than 50 beats/min or the patient experiences symptoms associated with bradycardia (such as dizziness, fatigue or hypotension), the dose of the drug should be reduced. If, when the dose of the drug is reduced, the heart rate remains less than 50 beats/min or symptoms associated with bradycardia persist, then taking Raenom® should be discontinued.

Combined use as part of antianginal therapy

The use of Raenom® in combination with BMCCs that reduce heart rate, such as verapamil or diltiazem, is contraindicated. With the combined use of ivabradine with nitrates and BMCA, dihydropyridine derivatives, such as amlodipine, no changes in the safety profile of the therapy were noted. It has not been established that combined use with BMCC increases the effectiveness of ivabradine.

Stroke

It is not recommended to prescribe Raenom® immediately after a stroke, because There are no data on the use of the drug during this period.

Functions of visual perception

Ivabradine affects the function of the retina. To date, no toxic effects of ivabradine on the retina have been identified. However, there is no data on the effect of ivabradine on the retina with long-term use (more than 1 year). If visual impairments that are not described in these instructions occur, you should consider stopping taking the drug Raenom®. Patients with retinitis pigmentosa should take Raenom® with caution.

Arterial hypotension

Raenom® should be prescribed with caution to patients with arterial hypotension (due to insufficient clinical data).

Raenom® is contraindicated in severe arterial hypotension (systolic blood pressure less than 90 mm Hg and diastolic blood pressure less than 50 mm Hg).

Atrial fibrillation (atrial fibrillation) – cardiac arrhythmias

An increase in the risk of developing severe bradycardia with the use of ivabradine during pharmacological cardioversion to restore sinus rhythm has not been proven. However, due to insufficient data, if it is possible to delay planned electrical cardioversion, use of the drug Raenom should be stopped 24 hours before it is performed.

Use in patients with congenital long QT syndrome or in patients taking drugs that prolong the QT interval

The drug Raenom® should not be used for congenital long QT interval syndrome, or in combination with drugs that can prolong the QT interval. If simultaneous use of such drugs is necessary, strict ECG monitoring is necessary. A decrease in heart rate due to the use of the drug Raenom® may aggravate the prolongation of the QT interval, which, in turn, can provoke the development of a severe form of arrhythmia, in particular, polymorphic ventricular tachycardia of the “pirouette” type.

Patients with hypertension who require switching to another antihypertensive drug

When changing antihypertensive therapy in patients with CHF taking Raenom®, blood pressure monitoring is required at appropriate intervals.

Chronic heart failure

Before deciding on the use of the drug Raenom®, the course of heart failure must be stable. Caution should be exercised when using the drug Raenom® in patients with CHF functional class IV according to the NYHA classification due to limited data on the use of the drug in this category of patients.

Moderate liver failure

In case of moderately severe liver failure (less than 9 points on the Child-Pugh scale), therapy with Raen® should be carried out with caution.

Severe renal failure

In case of severe renal failure (creatinine clearance less than 15 ml/min), therapy with Raen® should be carried out with caution.

Excipients

Raenom® contains lactose and is therefore not recommended for patients with lactase deficiency, lactose intolerance and glucose/galactose malabsorption syndrome.

Impact on the ability to drive vehicles and operate machinery

Ivabradine does not affect the ability to drive vehicles or perform work requiring a high speed of psychomotor reactions. However, one should remember about the possibility of photopsia occurring with a sharp change in lighting intensity, especially when driving at night.

Active ingredient

Ivabradin

Composition

1 tab. ivabradine hydrobromide 8.795 mg, which corresponds to the content of ivabradine 7.5 mg

Excipients:

lactose – 41.675 mg,

mannitol – 44.53 mg,

maltodextrin – 3 mg,

croscarmellose sodium – 1 mg,

colloidal silicon dioxide – 0.5 mg,

magnesium stearate – 0.5 mg.

Shell composition:

Opadry pink – 3 mg (polyvinyl alcohol – 1.05 mg, talc – 0.716 mg, titanium dioxide – 0.705 mg, macrogol-3350 – 0.36 mg, methacrylic acid copolymer (type C) – 0.12 mg, iron dye yellow oxide – 0.038 mg, iron dye red oxide – 0.007 mg, sodium bicarbonate – 0.004 mg).

Contraindications

— bradycardia (heart rate at rest less than 60 beats/min (before treatment));

– cardiogenic 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);

— SSSU;

– sinoatrial blockade;

— presence of an artificial pacemaker;

– unstable angina;

— AV block of the third degree;

– simultaneous use with powerful inhibitors of the CYP3A4 isoenzyme, such as antifungals of the azole group (ketoconazole, itraconazole), macrolide antibiotics (clarithromycin, erythromycin for oral administration, josamycin, telithromycin), HIV protease inhibitors (nelfinavir, ritonavir) and nefazodone;

– simultaneous use with slow calcium channel blockers (SCBCs) that reduce heart rate, such as verapamil or diltiazem;

– pregnancy;

– lactation period (breastfeeding);

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

– age under 18 years (the effectiveness and safety of the drug in this age group has not been studied);

– lactase deficiency, lactose intolerance, glucose/galactose malabsorption syndrome;

– hypersensitivity to ivabradine or any of the auxiliary components of the drug.

The drug should be prescribed with caution for moderate liver failure (less than 9 points on the Child-Pugh scale); severe renal failure (creatinine clearance less than 15 ml/min); congenital prolongation of the QT interval; simultaneous use of drugs that prolong the QT interval; simultaneous use of moderate inhibitors and inducers of CYP3A4 and grapefruit juice; simultaneous use with potassium-sparing diuretics; asymptomatic left ventricular dysfunction; AV blockade of the second degree; recent stroke; CHF functional class IV according to the NYHA classification; pigmentary degeneration of the retina (retinitis pigmentosa); arterial hypotension; patients over 75 years of age.

Side Effects

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

Undesirable adverse reactions are presented by system-organ classes in accordance with the MedDRA classification and with the frequency of occurrence: very often (≥1/10); often (≥1/100, <1/10); uncommon (≥1/1000, <1/100); rare (≥1/10,000, <1/1000); very rare (<1/10,000); frequency unknown (insufficient data to estimate the frequency of development).

From the nervous system: often – headache (especially in the first month of therapy), dizziness, possibly associated with bradycardia; infrequently – vertigo, muscle spasms; frequency unknown – syncope, possibly associated with bradycardia.

From the organ of vision: very often – changes in light perception (photopsia1); often – blurred vision; frequency unknown – diplopia, visual impairment.

From the cardiovascular system: often – bradycardia2, AV block of the first degree, ventricular extrasystole, short-term increase in blood pressure; infrequently – palpitations, supraventricular extrasystole, prolongation of the QT interval on the ECG; very rarely – atrial fibrillation, AV block of II-III degree, CCCV; frequency unknown – excessive decrease in blood pressure, possibly associated with bradycardia.

The following are adverse events identified in clinical studies that occurred with the same frequency in both the group of patients receiving ivabradine and in the control group, which suggests their connection with the disease as such, and not with taking ivabradine: sinus arrhythmia, angina pectoris, incl. unstable angina, atrial fibrillation, myocardial ischemia, myocardial infarction and ventricular tachycardia.

From the respiratory system: infrequently – shortness of breath.

From the digestive system: infrequently – nausea, constipation, diarrhea.

From the musculoskeletal system: infrequently – muscle spasms.

Allergic reactions: frequency unknown – skin rash, itching, erythema, angioedema, urticaria.

From laboratory and instrumental studies: infrequently – hyperuricemia, eosinophilia, increased creatinine concentration in the blood serum.

Other: frequency unknown – asthenia, fatigue, malaise, possibly associated with bradycardia.

1 Photopsia is a transient change in brightness in a limited area of ​​the visual field. As a rule, such phenomena are provoked by a sharp change in the intensity of illumination in the visual field. Most often, photopsia appeared in the first 2 months of therapy with subsequent repetition. The severity of photopsia was usually mild or moderate. Photopsia disappeared during therapy or after its completion.

2 Bradycardia was observed more often in the first 2-3 months of therapy, and only some patients developed severe bradycardia with a heart rate of no more than 40 beats/min.

Interaction

Undesirable combinations

Drugs that prolong the QT interval

– antiarrhythmic drugs that prolong the QT interval (for example, quinidine, disopyramide, bepridil, sotalol, ibutilide, amiodarone);

– drugs that prolong the QT interval that are not antiarrhythmic drugs (for example, pimozide, ziprasidone, sertindole, mefloquine, halofantrine, pentamidine, cisapride, erythromycin for intravenous administration).

The simultaneous use of ivabradine and these drugs should be avoided, since a decrease in heart rate may cause further prolongation of the QT interval. If simultaneous use of these drugs is necessary, ECG readings should be carefully monitored.

Isoenzyme CYP3A4

Ivabradine is metabolized in the liver with the participation of the CYP3A4 isoenzyme and is a very weak inhibitor of this cytochrome. Ivabradine does not have a significant effect on the metabolism and plasma concentrations of other substrates (strong, moderate and weak inhibitors) of the CYP3A4 isoenzyme. 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 has been found that inhibitors of the CYP3A4 isoenzyme increase, and inducers of the CYP3A4 isoenzyme reduce the concentration of ivabradine in the blood plasma.

Increasing the concentration of ivabradine in blood plasma may increase the risk of developing severe bradycardia.

Contraindicated combinations

Potent CYP3A4 inhibitors

Concomitant use of ivabradine with potent inhibitors of the CYP3A4 isoenzyme, such as antifungals of the azole group (ketoconazole, itraconazole); macrolide antibiotics (clarithromycin, erythromycin for oral administration, josamycin, telithromycin); HIV protease inhibitors (nelfinavir, ritonavir) and nefazodone are contraindicated. Potent inhibitors of the CYP3A4 isoenzyme – ketoconazole (200 mg 1 time / day) or josamycin (1 g 2 times / day) – increase the average concentration of ivabradine in the blood plasma by 7-8 times.

Moderate CYP3A4 inhibitors

The simultaneous use of ivabradine and diltiazem or verapamil (drugs that slow heart rate) in healthy volunteers and patients was accompanied by an increase in ivabradine AUC by 2-3 times and an additional decrease in heart rate by 5 beats/min. The use of these combinations is contraindicated.

Combinations requiring caution

The use of ivabradine in combination with other moderate inhibitors of the CYP3A4 isoenzyme (for example, fluconazole) is possible provided that the resting heart rate is more than 60 beats/min. The recommended starting dose of ivabradine is 2.5 mg 2 times a day. Heart rate control is required.

Concomitant 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. With the combined use of ivabradine and preparations containing St. John’s wort, a twofold decrease in the AUC of ivabradine was noted. During therapy with Raen®, you should, if possible, avoid the use of drugs and products containing St. John’s wort.

The drug should be used with caution simultaneously with potassium-sparing diuretics (diuretics of the thiazide group and loop diuretics), because Hypokalemia may increase the risk of developing arrhythmia. Because ivabradine can cause bradycardia, the combination of hypokalemia and bradycardia is a predisposing factor for the development of severe arrhythmia, especially in patients with long QT syndrome, either congenital or caused by exposure to any substances.

Combined use with other drugs

The absence of a clinically significant effect on the pharmacodynamics and pharmacokinetics of ivabradine has been shown with the simultaneous use of the following drugs: proton pump inhibitors (omeprazole, lansoprazole), PDE5 inhibitors (for example, sildenafil), HMG-CoA reductase inhibitors (for example, simvastatin), BMCC – dihydropyridine derivatives (for example, amlodipine, lacidipine), digoxin and warfarin. It has been shown that ivabradine does not have a clinically significant effect on the pharmacokinetics of simvastatin, amlodipine, lacidipine, the pharmacokinetics and pharmacodynamics of digoxin, warfarin and the pharmacodynamics of acetylsalicylic acid.

Ivabradine has been used in combination with ACE inhibitors, angiotensin II receptor antagonists, beta-blockers, diuretics, aldosterone antagonists, short-acting and long-acting nitrates, HMG-CoA reductase inhibitors, fibrates, proton pump inhibitors, oral hypoglycemic agents, acetylsalicylic acid and other antiplatelet agents. means. The use of the above drugs was not accompanied by a change in the safety profile of the therapy.

Other interactions requiring caution when used together

When taking grapefruit juice, there was a twofold increase in the concentration of ivabradine in the blood plasma. During therapy with Raen®, you should avoid drinking grapefruit juice if possible.

Overdose

Symptoms: An overdose of ivabradine can lead to severe and prolonged bradycardia.

Treatment: therapy for severe bradycardia is symptomatic, carried out in specialized departments.

In case of development of bradycardia in combination with hemodynamic disturbances, symptomatic treatment with intravenous administration of beta-adrenergic agonists, such as isoprenaline, is indicated.

If necessary, an artificial pacemaker can be installed.

Manufacturer

Gedeon Richter, Hungary