Raenom, 5mg pills 56pcs

Composition

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

Auxiliary substances:

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:

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 bicarbonate-0.004 mg).

Pharmacological action

An antianginal drug.

Selective inhibitor of sinus node If channels

Indications

Stable angina Therapy for stable angina in patients with normal sinus rhythm: — in case of intolerance or 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 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

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

— cardiogenic shock;

acute myocardial infarction;

— severe hypotension (systolic BP less than 90 mm Hg. art., and diastolic blood pressure less than 50 mm Hg. calendar);

— liver failure severe (more than 9 points on a scale child-Pugh);

— SSSU;

— sinoatrial block;

— the presence of an artificial pacemaker;

unstable angina;

AV-block III degree;

— simultaneous use with potent inhibitors of CYP3A4, such as antifungal agents of the group of azoles (ketoconazole, Itraconazole), the macrolide antibiotics (clarithromycin, erythromycin for oral use, josamycin, telithromycin), an HIV protease inhibitors (nelfinavir, ritonavir) and nefazodone;

— the simultaneous use with blockers of slow calcium channels (bmkk), regalski heart rate, such as verapamil or diltiazem;

— pregnancy;

— lactation (breastfeeding);

— use in women of reproductive age not using reliable methods of contraception;

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

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

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

With caution should prescribe the drug for liver failure average degree (less than 9 points on a scale child-Pugh); renal failure severe (CC less than 15 ml/min); congenital QT prolongation; couse of drugs that lengthen the QT interval; concomitant use of moderate inhibitors and inducers of CYP3A4 and grapefruit juice; simultaneous use with diuretics clinesperpage; asymptomatic left ventricular dysfunction; AV blockade of II degree; recent stroke; CHF IV functional class NYHA classification; pigment degeneration of the retina (retinitis pigmentosa); arterial hypotension; patients older than 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.

Adverse reactions are classified by organ-system classification according to MedDRA and with the 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 (

Nervous system disorders: 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 side of the visual organ:  very often-changes in light perception (photopsia 1); often-blurred vision; frequency unknown-diplopia, visual disturbances.

From the cardiovascular system: often – bradycardia 2, AV block I degree, ventricular extrasystole, short-term increase in blood pressure; infrequently-palpitation, supraventricular extrasystole, prolongation of the QT interval on the ECG; very rarely-atrial fibrillation, AV block II-III degree, SSR; 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 ivabradine-treated group and the control group, which suggests 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 system disorders: infrequently-shortness of breath.

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

Musculoskeletal disorders: infrequently-muscle spasms.

Allergic reactions: frequency unknown-skin rash, pruritus, erythema, angioedema, urticaria.

From the side of laboratory and instrumental studies: infrequently – hyperuricemia, eosinophilia, increased serum creatinine.

Other services: the frequency is 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 a sharp 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 repetition. The severity of photopsia was usually mild or moderate. Photopsia disappeared during therapy or after it was completed.

2 Bradycardia was observed more frequently 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

Unwanted combinations

Drugs that lengthen the QT interval

– antiarrhythmic agents, lengthening of the QT interval (eg, quinidine, disopyramide, bepridil, sotalol, ibutilide, amiodarone);

– drugs, lengthening the QT interval is not related to antiarrhythmic drugs (eg, pimozide, ziprasidone, sertindole, mefloquine, halofantrine, pentamidine, cisapride, erythromycin intravenous).

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.

CYP3A4 isoenzyme

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 significantly affect the metabolism and plasma concentrations of other substrates (potent, 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 was found that inhibitors of the CYP3A4 isoenzyme increase, and inducers of the CYP3A4 isoenzyme reduce the concentration of ivabradine in blood plasma.

Increased plasma concentrations of ivabradine may increase the risk of severe bradycardia.

Contraindicated combinations

Potent inhibitors of the CYP3A4 isoenzyme

Concomitant use of ivabradine with potent inhibitors of the CYP3A4 isoenzyme, such as azole antifungal agents (ketoconazole, itraconazole); macrolide antibiotics (clarithromycin, oral erythromycin, josamycin, telithromycin); HIV protease inhibitors (nelfinavir, ritonavir) and nefazodone, is contraindicated. Powerful 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 blood plasma by 7-8 times.

Moderate inhibitors of the CYP3A4 isoenzyme

The concomitant 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.

Combinations that require caution

Ivabradine can be used in combination with other moderate inhibitors of the CYP3A4 isoenzyme (for example, fluconazole), provided that the resting heart rate is more than 60 beats / min. The recommended initial dose of ivabradine is 2.5 mg twice daily. Heart rate monitoring is required.

Concomitant use with inducers of the CYP3A4 isoenzyme, such as rifampicin, barbiturates, phenytoin and herbal products containing St. John’s wort (Hypericum perforatum), may lead to a decrease in the plasma concentration and activity of ivabradine and require 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 Raenom®, the use of drugs and products containing St. John’s wort should be avoided as much as possible.

Caution should be exercised when using the drug concomitantly with potassium-sparing diuretics (thiazide diuretics and loop diuretics), as hypokalemia may increase the risk of arrhythmia. Since ivabradine can cause bradycardia, the combination of hypokalemia and bradycardia is a predisposing factor for the development of severe arrhythmia, especially in patients with QT prolongation syndrome, both congenital and caused by exposure to any substances.

Combined use with other medicinal products

No clinically significant effect on the pharmacodynamics and pharmacokinetics of ivabradine has been shown with concomitant use of the following drugs: proton pump inhibitors (omeprazole, lansoprazole), PDE5 inhibitors (for example, sildenafil), HMG-CoA reductase inhibitors (for example, simvastatin), BMCC derivatives of the dihydropyridine series (for example, amlodipine, lacidipine), digoxin and warfarin. Ivabradine has not been shown to 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 was used in combination with ACE inhibitors, angiotensin II receptor antagonists, beta-blockers, diuretics, aldosterone antagonists, short-and long-acting nitrates, HMG-CoA reductase inhibitors, fibrates, proton pump inhibitors, hypoglycemic agents for oral use, acetylsalicylic acid and other antiplatelet agents. The use of the above-mentioned drugs was not accompanied by a change in the safety profile of the therapy.

Other interactions that require caution when used together

While taking grapefruit juice, there was a twofold increase in the concentration of ivabradine in blood plasma. During therapy with Raenom®, if possible, avoid the use of grapefruit juice.

How to take, course of use and dosage

The drug is taken orally 2 times a day, in the morning and in the evening, during meals.

The decision to start therapy and titrate doses should be made with regular monitoring of heart rate, ECG.

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

If the patient’s resting heart rate is reduced to less than 50 beats / min during therapy with Raenom®, or if the patient has symptoms associated with bradycardia (such as dizziness, fatigue, or a marked decrease in blood pressure), the dose of Raenom® should be reduced (for example, to 2.5 mg (1/2 tab. 5 mg) 2 times/day). If the heart rate is reduced to less than 50 beats/min or if symptoms of severe bradycardia persist, Raenom® should be discontinued.

If the symptoms of angina persist for 3 months during therapy, treatment with the drug should be discontinued.

In patients with chronic heart failure, the recommended initial dose of Raenom®is indicated. it is 10 mg / day (1 tab. 5 mg 2 times/day) for patients under 75 years of age. Treatment should be initiated only in patients with stable CHF. After 2 weeks of use, the daily dose of Raenom® can be increased to 15 mg (1 tab. 7.5 mg 2 times / day), if the resting heart rate is stable more than 60 beats/min.

If the heart rate is stable no more than 50 beats / min or in case of symptoms of bradycardia, such as dizziness, fatigue or hypotension, the dose can be reduced to 2.5 mg (1/2 tab. 5 mg) 2 times/day.

If the heart rate is in the range of 50 to 60 beats / min, it is recommended to use Raenom® at a dose of 5 mg 2 times / day.

If the resting heart rate is consistently less than 50 beats / min during therapy, or if the patient has symptoms of severe bradycardia, the dose of the drug should be reduced for patients taking the drug at a dose of 5 mg 2 times / day or 7.5 mg 2 times/day.

If patients receiving Raenom® at a dose of 2.5 mg (1/2 tab. 5 mg) 2 times/day or 5 mg 2 times/day have a stable resting heart rate of more than 60 beats / min, the dose of the drug may be increased.

If the heart rate does not exceed 50 beats/min or the patient continues to have symptoms of bradycardia, the use of Raenom® should be discontinued.

For patients aged 75 years and older, the recommended initial dose of the drug is 2.5 mg (1/2 tab. 5 mg) 2 times / day. In the future, it is possible to increase the dose of the drug.

In patients with creatinine clearance greater than 15 ml / min, the recommended initial dose of the drug is 10 mg / day (1 tab. 5 mg 2 times / day). After 3-4 weeks of using the drug, depending on the therapeutic effect, the daily dose can be increased to 15 mg (1 tab. 7.5 mg 2 times / day). In patients with creatinine clearance less than 15 ml / min, the drug should be used with caution (due to insufficient clinical data).

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

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

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

Overdose

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

Treatment: treatment of severe bradycardia is symptomatic, performed in specialized departments.

If bradycardia develops in combination with impaired hemodynamic parameters, symptomatic treatment with intravenous use of beta-adrenomimetics, such as isoprenaline, is indicated.

If necessary, an artificial pacemaker can be installed.

Special instructions

Heart rhythm disorder

Ivabradine is ineffective for the treatment or prevention of arrhythmias. Its effectiveness decreases with the development of tachyarrhythmias (for example, ventricular or supraventricular tachycardia). Raenom®preparation It is not recommended for patients with atrial fibrillation (atrial fibrillation). or other types of arrhythmias related to sinus node function.

Patients should be clinically monitored for atrial fibrillation (paroxysmal or persistent) during Raen therapy. For clinical indications (e. g. worsening of angina, palpitation, irregular heart rate), an ECG should be included in the current monitoring.

The risk of 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 simultaneously 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 the resting heart rate is less than 60 beats/min before starting therapy. If the patient’s resting heart rate is reduced to less than 50 beats/min during therapy, or if the patient experiences symptoms associated with bradycardia (such as dizziness, fatigue, or hypotension), the dose of the drug should be reduced. If the heart rate is reduced to less than 50 beats/min or symptoms associated with bradycardia persist, then Raenom® should be discontinued.

Combined use in antianginal therapy

The use of Raenom® in combination with BMCC that reduce heart rate, such as verapamil or diltiazem, is contraindicated. When ivabradine was used in combination with nitrates and BMCC, dihydropyridine derivatives, such as amlodipine, no changes in the safety profile of the therapy were observed. Combined use with BMCC has not been shown to increase the efficacy 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.

Visual perception functions

Ivabradine affects the function of the retina of the eye. 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 of the eye with prolonged use (over 1 year).If visual impairment occurs that is not described in these instructions, discontinuation of Raenom should be considered. Patients with retinitis pigmentosa should be treated with caution.

Arterial hypotension

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

Raenom® is contraindicated in patients with 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 increased risk of developing 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 delay elective electrical cardioversion, Raenom® should be discontinued 24 hours before it is performed.

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

Raenom®preparation it should not be used in patients with congenital long QT syndrome, or in combination with drugs that can prolong the QT interval. If the simultaneous use of such drugs is necessary, strict ECG monitoring is necessary. A decrease in heart rate due to the use of Raenom®can exacerbate 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 arterial hypertension who need to switch to another antihypertensive drug

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

Chronic heart failure

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

Moderate hepatic insufficiency

In patients with moderate hepatic insufficiency (less than 9 points on the Child-Pugh scale), therapy with Raen® should be carried out with caution.

Severe renal failure

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

Auxiliary substances

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

Influence on the ability to drive motor vehicles and manage mechanisms

Ivabradine does not affect the ability to drive vehicles and perform work that requires a high rate of psychomotor reactions. However, you should be aware of the possibility of photopsia when the light intensity changes dramatically, especially when driving vehicles at night.

Active ingredient

Ivabradin

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

For adults as directed by your doctor

Indications

Heart Failure, Arrhythmia, Angina