Raenom, 5 mg 56 pcs.

Antianginal drug.

A selective inhibitor of sinus node If channels

Indications

Stable angina pectoris
The therapy of stable angina pectoris in patients with normal sinus rhythm:
– In intolerance or contraindications to the use of beta-adrenoblockers;
– In combination with beta-adrenoblockers in inadequate control of symptoms of stable angina against optimal dose of beta-adrenoblocker.

Chronic heart failure
– to decrease the incidence of cardiovascular complications (cardiovascular mortality and hospitalization due to worsening course of CHF) in patients with chronic heart failure, with sinus rhythm and HR of at least 70 bpm.

Active ingredient

Composition

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

Assisted substances:

Lactose – 41.675 mg,

Mannitol – 44.53 mg,

maltodextrin – 3 mg,

croscarmellose sodium – 1 mg,

colloidal silica – 0.5 mg,

magnesium stearate – 0.5 mg.

Shell composition:

Opadray 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 oxide yellow dye – 0.038 mg, iron oxide red dye – 0.007 mg, sodium hydrogen carbonate – 0.004 mg).

How to take, the dosage

The drug is taken orally 2 times a day, morning and evening, with meals.

The decision to initiate therapy and dose titration should be made with regular HR and ECG monitoring.

In stable angina, the recommended initial dose of the drug is 10 mg/day (1 tablet of 5 mg 2 times/day) for patients less than 75 years of age. After 3-4 weeks of using the drug, depending on the therapeutic effect, the daily dose may be increased to 15 mg (1 tablet of 7.5 mg twice daily).

If during the treatment by Raenom® HR at rest slows down to values less than 50 bpm or if the patient shows symptoms associated with bradycardia (such as dizziness, increased fatigability or marked BP decrease), the drug dose of Raenom® should be decreased (for example, to 2.5 mg (1/2 tablet of 5 mg) 2 times per day). If the HR remains less than 50 bpm or symptoms of marked bradycardia persist when the drug dose is reduced, the drug administration of Raenom® should be discontinued.

If symptoms of angina pectoris persist for 3 months after therapy, the drug should be discontinued.

In chronic heart failure, the recommended starting dose of Raenom® is 10 mg/day (1 tablet of 5 mg 2 times/day) for patients less than 75 years of age. Treatment should be started only in patients with stable CHF. After 2 weeks of use the daily dose of Raenom® can be increased up to 15 mg (1 tablet of 7.5 mg 2 times per day), if resting HR is stable more than 60 bpm.

If the resting HR is stable to less than 50 bpm or if there are symptoms of bradycardia, such as dizziness, increased fatigue, or hypotension, the dose may be decreased to 2.5 mg (1/2 tablet of 5 mg) 2 times daily.

If the HR is between 50 and 60 bpm, the recommended dose is Raenom® 5 mg 2 times daily.

If the resting HR is consistently less than 50 bpm during therapy or if the patient has symptoms of marked bradycardia, the drug dose should be reduced for patients taking the drug at 5 mg 2 times daily or 7.5 mg 2 times daily.

If patients receiving Raenom® at a dose of 2.5 mg (1/2 tablet of 5 mg) 2 times/day or 5 mg 2 times/day have a resting HR steadily greater than 60 bpm, the dose may be increased.

If the resting HR is less than 50 bpm or if symptoms of bradycardia persist, the use of Raenom® should be discontinued.

In Patients 75 years and older, the recommended starting dose of the drug is 2.5 mg (1/2 tablet of 5 mg) 2 times daily. There may be an increase in the dose later.

In patients with a CK of more than 15 ml/min the recommended initial dose of the drug is 10 mg/day (1 tablet of 5 mg 2 times/day). After 3-4 weeks of the drug use, depending on the therapeutic effect, the daily dose may be increased to 15 mg (1 tablet of 7.5 mg 2 times per day). In patients with CKD less than 15 ml/min the drug should be used with caution (because of insufficient clinical data).

Patients with mild hepatic impairment (up to 7 points on the Child-Pugh scale) are recommended to administer Raenom® in the usual dose.

The recommended initial dose of the drug is 10 mg/day (1 tablet of 5 mg 2 times/day). After 3-4 weeks of using the preparation and depending on the therapeutic effect the daily dose can be increased up to 15 mg (1 tablet of 7.5 mg 2 times per day).

Caution should be exercised when using Raenom® in patients with moderate hepatic impairment (7-9 points by Child-Pugh score). Raenom® is contraindicated in patients with severe hepatic impairment (greater than 9 Child-Pugh score), since there are no data on the use of ivabradine in this group of patients (a significant increase in plasma concentration of ivabradine can be expected).

Interaction

Unwanted combinations

Drugs that prolong the QT interval

– Antiarrhythmic drugs that prolong the QT interval (e.g., quinidine, disopyramide, bepridil, sotalol, ibutilide, amiodarone);

– Drugs that prolong the QT interval that are not antiarrhythmic drugs (e.g., pimozide, ziprasidone, sertindole, mefloquine, halofantrine, pentamidine, cisapride, intravenous erythromycin).

The concomitant use of ivabradine and these drugs should be avoided because the pacing may cause additional prolongation of the QT interval. ECG should be monitored closely if these drugs must be used at the same time.

CYP3A4 isoenzyme

Ivabradine is metabolized in the liver via CYP3A4 isoenzyme and is a very weak inhibitor of this cytochrome. Ivabradine has no significant effect on the metabolism and plasma concentrations of other substrates (potent, moderate and weak inhibitors) of CYP3A4 isoenzyme. At the same time, inhibitors and inducers of CYP3A4 isoenzyme may interact with ivabradine and have a clinically significant effect on its metabolism and pharmacokinetic properties.

CYP3A4 isoenzyme inhibitors have been found to increase and CYP3A4 isoenzyme inducers to decrease the plasma concentration of ivabradine.

Elevated plasma concentrations of ivabradine may increase the risk of marked bradycardia.

Controlled combinations

Powerful inhibitors of CYP3A4 isoenzyme

Concomitant use of ivabradine with potent inhibitors of CYP3A4 isoenzyme, such as antifungal agents of the azole group (ketoconazole, itraconazole); macrolide antibiotics (clarithromycin, oral erythromycin, jozamycin, telithromycin); HIV protease inhibitors (nelfinavir, ritonavir) and nefazodone, contraindicated. Powerful inhibitors of CYP3A4 isoenzyme – ketoconazole (200 mg 1 time/day) or jozamycin (1 g 2 times/day) – increase average plasma concentrations of ivabradine by 7-8 times.

Moderate inhibitors of CYP3A4 isoenzyme

. Concomitant use of ivabradine and diltiazem or verapamil (heart rate-limiting drugs) in healthy volunteers and patients was accompanied by a 2-3-fold increase in the AUC of ivabradine and an additional heart rate reduction of 5 bpm./min. The use of these combinations is contraindicated.

Combinations requiring caution

The use of ivabradine in combination with other moderate CYP3A4 isoenzyme inhibitors (such as fluconazole) is possible provided that the resting HR is greater than 60 bpm. The recommended starting dose of ivabradine is 2.5 mg twice daily. HR control is necessary.

Special Instructions

Heart rhythm disorders

Ivabradine is ineffective in the treatment or prevention of arrhythmias. Its effectiveness is reduced with the development of tachyarrhythmias (e.g., ventricular or supraventricular tachycardia). The drug Raenom® is not recommended for patients with atrial fibrillation (atrial fibrillation) or other types of arrhythmias associated with sinus node function.

Patients should be clinically monitored for atrial fibrillation (paroxysmal or persistent) during therapy with Raenom®. For clinical indications (e.g., worsening angina, palpitations, irregular heart rhythm), an ECG should be included in ongoing monitoring.

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

Application in patients with bradycardia

Ivabradine is contraindicated if the resting HR is less than 60 bpm before therapy. If during therapy the resting HR falls below 50 bpm or the patient develops bradycardia-related symptoms (such as dizziness, increased fatigue or hypotension) the drug dose should be reduced. If the HR remains less than 50 bpm or the symptoms associated with bradycardia persist when reducing the dose of the drug, Raenom® should be discontinued.

Combined use as part of antianginal therapy

The use of Raenom® together with heart rate-limiting BMCCs such as verapamil or diltiazem is contraindicated. No changes in the safety profile of therapy have been observed with the combined use of ivabradine with nitrates and dihydropyridine derivatives, such as amlodipine. Combined use with BMCC has not been found to increase the efficacy of ivabradine.

Stroke

The use of Raenom® immediately after a stroke is not recommended because there are no data on the use of the drug during this period.

Sight functions

Ivabradine affects the function of the retina. To date, no toxic effects of ivabradine on the retina have been identified. However, there are no data on the effect of ivabradine on the retina during long-term use (more than 1 year). In case of visual impairment not described in these instructions, discontinuation of the drug Raenom® should be considered. Patients with retinal pigmentary degeneration (retinitis pigmentosa) should take Raenom® with caution.

Arterial hypotension

Patients with arterial hypotension (due to insufficient clinical data) should use Raenom® with caution.

Raenom® is contraindicated in severe arterial hypotension (systolic BP less than 90 mmHg and diastolic BP less than 50 mmHg).

Atrial fibrillation (atrial fibrillation) – cardiac arrhythmias

An increased risk of severe bradycardia with ivabradine during pharmacological cardioversion to restore sinus rhythm has not been proven. However, due to insufficient data, if it is possible to postpone planned electric cardioversion, administration of Raenom® should be discontinued 24 hours prior to it.

Application in patients with congenital prolonged QT interval syndrome or in patients taking drugs that prolong the QT interval

Preventive use in patients with congenital prolonged QT interval syndrome.

The drug Raenom® should not be used in congenital long QT interval syndrome or in combination with drugs that may prolong the QT interval. Strict ECG monitoring is required if concomitant use of such drugs is necessary. HR slowing due to administration of Raenom® may exacerbate QT interval prolongation, which in turn may provoke a severe form of arrhythmia, in particular, polymorphic ventricular tachycardia such as “pirouette”.

Patients with arterial hypertension who require switching to another antihypertensive medication

When changing hypotensive therapy in patients with CHF taking Raenom®, BP monitoring at appropriate intervals is required.

Chronic Heart Failure

The course of heart failure should be stable before deciding on the use of Raenom®. Caution should be exercised when using Raenom® in patients with NYHA functional class IV chronic heart failure due to limited data on its use in this patient population.

Moderate hepatic impairment

In moderately severe hepatic impairment (less than 9 points by Child-Pugh score), therapy with Raenom® should be used with caution.

Severe renal failure

In severe renal failure (CKR less than 15 ml/min), therapy with Raenom® should be used with caution.

Auxiliary substances

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

Influence on driving and operating ability

Ivabradine does not affect the ability to drive vehicles and perform work requiring high speed psychomotor reactions. However, one should be aware of the possibility of photopsia in case of sudden changes in lighting intensity, especially when driving vehicles at night.

Contraindications

– bradycardia (resting heart rate less than 60 beats.

– cardiogenic shock;

– acute myocardial infarction;

– severe arterial hypotension (systolic BP less than 90 mm Hg and diastolic BP less than 50 mm Hg).);

– severe hepatic insufficiency (more than 9 points by Child-Pugh score);

– CCSU;

– sinoatrial block;

– presence of an artificial pacemaker;

– unstable angina pectoris;

– grade III AV blockade;

– concomitant use with potent CYP3A4 isoenzyme inhibitors, such as azole antifungals (ketoconazole, itraconazole), macrolide antibiotics (clarithromycin, oral erythromycin, jozamycin, telithromycin), HIV protease inhibitors (nelfinavir, ritonavir) and nefazodone;

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

– pregnancy;

– lactation (breastfeeding) period;

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

– age less than 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;

– hypersensitivity to ivabradine or any of the excipients of the drug.

With cautiousness the drug should be prescribed in mild hepatic impairment (less than 9 points on the Child-Pugh scale); severe renal impairment (CK less than 15 ml/min); congenital prolongation of QT interval; concomitant use of QT interval prolonging drugs; concomitant use of moderate inhibitors and inducers of CYP3A4 and grapefruit juice; concomitant use with potassium-saving diuretics; asymptomatic left ventricular dysfunction; grade II AV-blockade; recent stroke; CHF class IV by NYHA classification; retinal pigment degeneration (retinitis pigmentosa); hypotension; patients aged 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.

Unwanted adverse reactions are presented by systemic organ class according to the MedDRA classification and with frequency of occurrence: very common (≥1/10); common (≥1/100, < 1/10); infrequent (≥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).

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

VIight:very common – changes in light perception (photopsia1); common – blurred vision; common unknown – diplopia, visual disturbances.

Cardiovascular system disorders: often – bradycardia2, AV-blockade of degree I, ventricular extrasystole, transient rise in BP; infrequently – palpitations, supraventricular extrasystole, prolongation of QT interval on ECG; very rarely – atrial fibrillation, AV-blockade of degree II-III, SSRI; frequency unknown – excessive BP decrease, possibly associated with bradycardia.

The following are the adverse events detected in clinical studies, which occurred with equal frequency in the group of patients receiving ivabradine and in the control group, which suggests their association with the disease itself and not with taking ivabradine: sinus arrhythmia, angina pectoris, including unstable angina.including unstable angina, atrial fibrillation, myocardial ischemia, myocardial infarction, and ventricular tachycardia.

Respiratory system disorders: infrequent – dyspnea.

Digestive system disorders: infrequent – nausea, constipation, diarrhea.

Muscular system disorders: infrequent – muscle spasms.

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

From laboratory and instrumental investigations: infrequent – hyperuricemia, eosinophilia, increased serum creatinine concentration.

Others: frequency unknown – asthenia, increased 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 an abrupt change in the intensity of illumination in the area of the visual field. Most often photopsia appeared in the first 2 months of therapy with subsequent recurrence. As a rule, the severity of photopsia was weak or moderate. Photopsia disappeared against the background of therapy or after its completion.

2 Bradycardia was observed more frequently in the first 2-3 months of therapy, and only some patients developed marked bradycardia with HRs of 40 bpm or less.

Overdose

Symptoms:Ivabradine overdose may lead to severe and prolonged bradycardia.

Treatment:The therapy of severe bradycardia is symptomatic and is carried out in specialized departments.

In case of bradycardia combined with hemodynamic abnormalities, symptomatic treatment with intravenous administration of beta-adrenomimetics such as isoprenaline is indicated.

If necessary, an artificial pacemaker may be inserted.

Similarities