Composition, form of production and packaging
The tablets covered with a film cover of light orange color, oval, biconcave, with two V-shaped risks for division on lateral sides, with engraving "SK3" on one side;on the cross section the core of the tablet is white.
1 tab.
ivabradine hydrobromide 5.863 mg,
which corresponds to the content of ivabradine 5 mg
[PRING] lactose - 44.607 mg, mannitol - 44.53 mg, maltodextrin - 3 mg, croscarmellose sodium - 1 mg, silicon dioxide colloid - 0.5 mg, magnesium stearate - 0.5 mg.
The composition of the shell: Opadrai 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 oxide yellow - 0.038 mg, iron oxide red oxide - 0.007 mg, sodium hydrogen carbonate - 0.004 mg).
14 pcs. - packings of cellular contour (1) - packs cardboard.
14 pcs. - packings cellular planimetric (2) - packs cardboard.
14 pcs. - packings cellular planimetric (4) - packs cardboard.
The tablets covered with a film cover of light orange color, round, biconcave, with engraving "SK4" on one side; on the cross section the core of the tablet is white.
1 tab.
ivabradine hydrobromide 8.795 mg,
which corresponds to the content of ivabradine 7.5 mg
[PRING] lactose - 41.675 mg, mannitol - 44.53 mg, maltodextrin - 3 mg, croscarmellose sodium - 1 mg, silicon dioxide colloid - 0.5 mg, magnesium stearate - 0.5 mg.
The composition of the shell: Opadrai 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 oxide yellow - 0.038 mg, iron oxide red oxide - 0.007 mg, sodium hydrogen carbonate - 0.004 mg).
14 pcs. - packings of cellular contour (1) - packs cardboard.
14 pcs. - packings cellular planimetric (2) - packs cardboard.
14 pcs. - packings cellular planimetric (4) - packs cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2017.
PHARMACHOLOGIC EFFECT
An antianginal drug that slows the heart rate. The mechanism of action of ivabradine consists in the selective and specific inhibition of If channels of the sinus node controlling spontaneous diastolic depolarization in the sinus node and regulating heart rate.
Ivabradine has a selective effect on the sinus node, without affecting the timing of impulses for atrial, atrioventricular and intraventricular conduction pathways, as well as contractility of the myocardium and repolarization of the ventricles.
Ivabradine can also interact with Ih retinal canals, similar in structure to If channels of the heart, involved in the mechanisms of temporary adaptation of the visual perception system by changing the retina response to bright light stimuli.
Under provocative circumstances (for example, a sharp change in the intensity of illumination in the visual field), the partial inhibition of Ih channels by ivabradine leads to a phenomenon of change in light perception (photopsy). Photopsy is characterized by a transient change in brightness in a limited area of ​​the visual field.
The main pharmacological effect of ivabradine is the dose-dependent decrease in heart rate. Analysis of the dependence of the reduction in heart rate on the dose of the drug was carried out with a gradual increase in the dose of ivabradine up to 20 mg 2 times / day and revealed a tendency to achieve a plateau effect (no increase in the therapeutic effect with a further increase in the dose), which reduces the risk of severe bradycardia (heart rate less than 40 bpm).
When the drug is used at recommended doses, the degree of heart rate reduction depends on its initial value and is approximately 10-15 bpm at rest as well as during physical exertion, as a result of which cardiac function and myocardial oxygen demand decrease.
Ivabradin does not affect intracardiac conduction, contractility of the myocardium (does not have a negative inotropic effect) and the process of repolarization of the ventricles. In clinical electrophysiological studies, ivabradine had no effect on the timing of pulses from the atrioventricular or intraventricular conduction pathways, as well as to the corrected QT intervals. In studies in patients with left ventricular dysfunction (LVEF 30-45%), it was shown that ivabradine does not affect the contractile ability of the myocardium.
It was found that ivabradine in a dose of 5 mg 2 times / day improved the parameters of exercise tests after 3-4 weeks of treatment. Efficiency was confirmed for a dose of 7.5 mg 2 times / day. An additional effect with increasing the dose from 5 mg to 7.5 mg 2 times / day was established in a comparative study with atenolol.Exercise time increased by approximately 1 min after 1 month of ivabradine administration at a dose of 5 mg 2 times / day, while after an additional 3-month course of ivabradine administration, at a dose of 7.5 mg 2 times / day, a further increase in this index was observed for 25 seconds . Antianginal and antiischemic activity of ivabradine has also been confirmed in patients aged 65 years and older. The efficacy of ivabradine when used at doses of 5 mg and 7.5 mg 2 times / day was noted for all parameters of stress tests (total duration of exercise, time to the limiting angina attack, time to onset of angina attack, and time to development of ST-segment depression by 1 mm ) and was accompanied by a decrease in the incidence of angina attacks by about 70%. The use of ivabradine 2 times / day provided constant therapeutic efficacy within 24 hours.
In patients taking ivabradine, additional efficacy was shown for all load test parameters when added to the maximum dose of atenolol (50 mg) at a drop in its therapeutic activity (12 hours after ingestion).
There was no improvement in the efficacy of ivabradin when added to the maximum dose of amlodipine at a decrease in its therapeutic activity (12 hours after ingestion), while at the maximum of amlodipine activity (3-4 hours after ingestion) the additional efficacy of ivabradine was demonstrated.
In studies of the clinical efficacy of ivabradine, its therapeutic effect was completely preserved within 3-4 months of therapy. During treatment, there were no signs of a decrease in efficacy, and after the cessation of treatment, withdrawal syndrome was not observed. Antianginal and antiischemic effects of ivabradine were associated with both a dose-dependent decrease in heart rate and a significant decrease in the work product (heart rate and systolic blood pressure) both at rest and under physical exertion. Influence on indices of blood pressure and OPSS was insignificant and clinically insignificant.
A steady decrease in heart rate was noted in patients who took ivabradine for at least 1 year. Influences on carbohydrate metabolism and lipid profile were not observed.
In patients with diabetes mellitus, the efficacy and safety of ivabradine were similar to those in the general population.
There was no difference between the groups of patients taking ivabradine against standard therapy, and in patients with stable angina and left ventricular dysfunction (LVEF less than 40%), 86.9% of whom received beta-blockers and placebo, according to the combined frequency of deaths from cardiovascular diseases, hospitalization for acute myocardial infarction, hospitalization for new cases of heart failure or worsening of the course of chronic heart failure (CHF) and in a subgroup of patients with ES at least 70 u. / min.
Against the backdrop of ivabradine in patients with heart rate of at least 70 bpm, the incidence of hospitalizations for fatal and non-fatal myocardial infarction by 36% and the revascularization rate by 30% are shown.
In patients with angina pectoris, the relative risk of complications (mortality from cardiovascular diseases, hospitalization for acute myocardial infarction, hospitalization for new cases of heart failure or worsening of the course of CHF) was reduced by 24% in patients with angina pectoris. The noted therapeutic advantage is achieved, first of all, by reducing the frequency of hospitalizations for acute myocardial infarction by 42%.
Reducing the frequency of hospitalization for fatal and nonfatal myocardial infarction in patients with heart rate more than 70 beats / min is even more significant and reaches 73%. In general, good tolerability and safety of the drug was noted.
Against the backdrop of the use of ivabradin in patients with CHF II-IV FC with a LVEF less than 35%, a clinically and statistically significant reduction in the relative risk of complications (the rate of death from cardiovascular disease and the reduction in the frequency of hospitalizations due to worsening of the course of CHF) on 18%. Absolute risk reduction was 4.2%. The pronounced therapeutic effect was observed 3 months after the initiation of ivabradine therapy.
Reduction of mortality from cardiovascular diseases and hospitalizations due to worsening of CHF flow was observed irrespective of age, sex, functional class of CHF, use of beta-blockers, ischemic or non-ischemic etiology of CHF, presence of diabetes or history of arterial hypertension.
Patients with symptoms of heart failure with sinus rhythm and heart rate of at least 70 beats / minute received standard therapy, which included beta-blockers (89%), ACE inhibitors 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 the use of ivabradine, the functional class of CHF according to the NYHA classification is shown to improve.
Patients with a heart rate of 80 bpm noted a decrease in heart rate by an average of 15 bpm.
PHARMACOKINETICS
Ivabradine is an S-enantiomer with no bioconversion traits (according to in vivo studies). The main active metabolite is the N-desmethylated ivabradine derivative.
Suction
After oral administration, ivabradine is rapidly and almost completely absorbed from the digestive tract. C max in blood plasma is achieved within 1 hour after oral administration on an empty stomach. Bioavailability is approximately 40% due to the effect of "first passage" through the liver. The intake increases the absorption time by approximately 1 hour and increases the concentration in the blood plasma from 20% to 30%. To reduce variability in the concentration of the drug should be taken simultaneously with food intake.
Distribution
Binding to plasma proteins is approximately 70%. V d in the equilibrium state is about 100 liters. With max in blood plasma for long-term use in the recommended dose of 5 mg 2 times / day is approximately 22 ng / ml (coefficient of variation = 29%). The average C ss in blood plasma is 10 ng / ml (coefficient of variation = 38%).
The pharmacokinetics of ivabradine are linear in the dosage range of 0.5 to 24 mg.
Metabolism
Ivabradine is predominantly metabolized in the liver and intestines by oxidation with the participation of the CYP3A4 isoenzyme. The main active metabolite is the N-desmethylated derivative (S 18982), which accounts for 40% of ivabradine. Metabolism of the active metabolite of ivabradine also occurs with the involvement of the CYP3A4 isoenzyme. Ivabradine has a small affinity for the isoenzyme CYP3A4, does not induce or inhibit it. In this regard, it is unlikely that ivabradine affects the metabolism or concentration of substrates of the CYP3A4 isoenzyme in blood plasma. At the same time, the simultaneous use of ivabradine with potent inhibitors or inducers of cytochrome P450 can significantly affect the concentration of ivabradine in blood plasma.
Excretion
T 1/2 ivabradine is an average of 2 hours (70-75% AUC), effective T 1/2 is 11 hours. The total clearance is approximately 400 ml / min, the renal clearance is about 70 ml / min. Excretion of metabolites occurs at the same rate through the kidneys and intestines. About 4% of the dose is excreted by the kidneys unchanged.
Pharmacokinetics in specific patient groups
The pharmacokinetic parameters (AUC and C max ) do not differ significantly in the groups of patients aged 65 years and older, 75 years and older, and the general population of patients.
The effect of renal failure (QC 15 to 60 ml / min) on the kinetics of ivabradine is minimal, because Only about 20% of ivabradine and its active metabolite S 18982 is excreted by the kidneys.
In patients with mild liver failure (up to 7 on the Child-Pugh scale), the AUC of free ivabradine and its active metabolite is 20% greater than in patients with normal liver function. Data on the use of ivabradin in patients with moderate hepatic insufficiency (7-9 points on the Child-Pugh scale) are limited and do not allow estimating pharmacokinetics of the drug in this group of patients. Data on the use of ivabradin in patients with severe hepatic insufficiency (more than 9 on the Child-Pugh scale) are not available at the moment.
The relationship between pharmacokinetic and pharmacodynamic properties
Analysis of the relationship between the pharmacokinetic and pharmacodynamic properties of ivabradin allowed us to establish that the decrease in heart rate is in direct proportion to the increase in the concentration of ivabradine and the active metabolite S18982 in blood plasma when administered at doses up to 15-20 mg 2 times / day. At higher doses of the drug, the slowing of the heart rate does not have a proportional dependence on the concentration of ivabradine in the blood plasma and is characterized by a tendency to reach the plateau. The high concentrations of ivabradine that can be achieved with simultaneous use with potent inhibitors of the CYP3A4 isoenzyme may lead to a marked decrease in heart rate, but this risk is lower when combined with moderate inhibitors of the CYP3A4 isoenzyme.
INDICATIONS
Stable angina
Stable angina therapy in patients with normal sinus rhythm:
- with intolerance or the presence of contraindications to the use of beta-blockers;
- in combination with beta-adrenoblockers with inadequate control of symptoms of stable angina pectoris against the background of the optimal dose of beta-adrenoblocker.
Chronic heart failure
- to reduce the incidence of cardiovascular complications (mortality from cardiovascular diseases and hospitalization due to worsening of CHF flow) in patients with chronic heart failure, with sinus rhythm and heart rate not less than 70 beats per minute.
DOSING MODE
The drug is taken orally 2 times / day, morning and evening, during meals.
The decision to initiate therapy and titration of doses should be taken with regular monitoring of heart rate, ECG.
With stable angina, the recommended initial dose of the drug is 10 mg / day (1 table 5 mg 2 times / day) for patients aged less than 75 years. After 3-4 weeks of the drug, depending on the therapeutic effect, the daily dose can be increased to 15 mg (1 tablet 7.5 mg 2 times / day).
If, on the background of therapy with Raen В®, the heart rate at rest is reduced to less than 50 bpm, or the patient has symptoms associated with bradycardia (such as dizziness, fatigue or a pronounced decrease in blood pressure), the dose of Raen В® should be reduced (for example, up to 2.5 mg (1/2 tablet 5 mg) 2 times / day). If, with a decrease in the dose of the drug, the heart rate remains below 50 bpm, or if the symptoms of severe bradycardia persist, the drug should be discontinued.
If, on the background of the therapy, the symptoms of angina persist for 3 months, the drug should be discontinued.
For chronic heart failure, the recommended initial dose of the drug is 10 mg / day (1 table 5 mg 2 times / day) for patients less than 75 years old. Treatment should be started only in patients with stable CHF. After 2 weeks of application, the daily dose of the drug Raen В® can be increased to 15 mg (1 table 7.5 mg 2 times / day) if the resting heart rate is stably more than 60 beats per minute.
If the heart rate is stable no more than 50 bpm, or if there are bradycardia symptoms such as dizziness, fatigue or hypotension, the dose can be reduced to 2.5 mg (1/2 tablet, 5 mg) 2 times / day .
If the heart rate is in the range from 50 to 60 beats / min, it is recommended to use the drug Raen В® in a dose of 5 mg 2 times / day.
If during the therapy heart rate at rest is stably less than 50 beats per minute or if the patient has symptoms of severe bradycardia, for patients taking the drug at a dose of 5 mg 2 times / day or 7.5 mg 2 times / day, the dose should be reduced.
If patients receiving a preparation of Ryan В® at a dose of 2.5 mg (1/2 table 5 mg) 2 times / day or 5 mg 2 times / day, heart rate at rest stably more than 60 beats / min, the dose of the drug may be increased.
If the heart rate is not more than 50 bpm, or the patient retains the symptoms of bradycardia, the use of Ranom В® should be discontinued.
For patients aged 75 years and older, the recommended initial dose of the drug is 2.5 mg (1/2 tablet 5 mg) 2 times / day. In the future, it is possible to increase the dose.
In patients with QC more than 15 ml / min the recommended initial dose of the drug is 10 mg / day (1 table 5 mg 2 times / day). After 3-4 weeks of the drug, depending on the therapeutic effect, the daily dose can be increased to 15 mg (1 tablet 7.5 mg 2 times / day). In patients with CC less than 15 ml / min, the drug should be used with caution (due to lack of clinical data).
Patients with mild hepatic impairment (7 points on the scale of Child-Pugh) appoint a drug RANS В® in normal dose. The recommended starting dose is 10 mg / day (1 tab. 5 mg, 2 times / day). After 3-4 weeks of the drug, depending on the therapeutic effect, the daily dose may be increased to 15 mg (1 tablet. 7.5 mg of 2 times / day). Caution must be exercised when using the drug RANS В® y with moderate hepatic insufficiency patients (7-9 points on the Child-Pugh) . Preparation RANS В®contraindicated in patients with hepatic impairment, severe (more than 9 points on a scale Child-Pugh) , since there is no data on the use of ivabradine in this group of patients (one can expect a substantial increase ivabradine plasma concentrations).
SIDE EFFECT
The most common side effects of ivabradine, bradycardia and photopsia, were dose dependent and were due to its mechanism of pharmacological action.
Undesirable side reactions are presented by system-organ class according to the classification MedDRA and a frequency of occurrence: very often (1/10?); often (? 1/100, <1/10); infrequently (? 1/1000, <1/100); rarely (? 1/10 000, <1/1000); very rarely (<1/10 000); frequency is unknown (not enough data to estimate the incidence).
From the nervous system: often - headache (especially in the first month of treatment), dizziness, possibly related to bradycardia; rare - vertigo, muscle cramps; the frequency is unknown - a faint, possibly related to bradycardia.
From a sight organ: very often - changes photoreception (photopsia 1 ); often - blurred vision; the frequency is unknown - diplopia, blurred vision.
Cardio-vascular system: often - bradycardia 2, AV-block I degree, ventricular arrythmia, transient increase in blood pressure; rarely - palpitations, supraventricular arrhythmias, prolonged QT interval on an electrocardiogram; very rarely - atrial fibrillation, AV-block II-III degree CCCU; the frequency is unknown - an excessive fall in blood pressure, possibly related to bradycardia.
The following are the adverse effects identified in clinical trials, that met with equal frequency in patients treated with ivabradine, and in the control group, which suggests their association with the disease as such, rather than with taking ivabradine: sinus arrhythmia, angina, in including unstable angina, atrial fibrillation, myocardial ischemia, myocardial infarction and ventricular tachycardia.
On the part of the respiratory system: infrequently - shortness of breath.
From the digestive system: rarely - nausea, constipation, diarrhea.
On the part of the musculoskeletal system: rarely - muscle spasms.
Allergic reactions: frequency not known - skin rash, pruritus, erythema, angioedema, urticaria.
From the laboratory and instrumental studies: infrequently - hyperuricemia, eosinophilia, elevated serum creatinine concentration in the serum.
Other: the frequency is unknown - asthenia, fatigue, malaise, possibly related to bradycardia.
1Photopsia - transient change in brightness in a limited area of the visual field. Typically, these phenomena are provoked by a sharp change in light intensity in the area of the visual field. In most photopsia appeared in the first 2 months of therapy, followed by repetition. Intensity photopsias tend to be weak 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 develop severe bradycardia with a heart rate less than 40 beats. / Min.
CONTRAINDICATIONS
- bradycardia (heart rate at rest less than 60 beats / min (before treatment).);
- cardiogenic shock;
acute myocardial infarction;
- severe hypotension (systolic blood pressure less than 90 mmHg and diastolic blood pressure less than 50 mmHg....);
- hepatic insufficiency of severe degree (more than 9 points on the Child-Pugh scale);
- SSSU;
- sinoatrial block;
- the presence of an artificial pacemaker;
- unstable angina;
- AV-block III degree;
- simultaneous application of potent inhibitors isoenzyme CYP3A4, such as the group of azoles antifungals (ketoconazole, itraconazole), macrolide antibiotics (clarithromycin, erythromycin for oral, josamycin, telithromycin), HIV protease inhibitors (nelfinavir, ritonavir) and nefazodone;
- simultaneous application of calcium channel blockers slow (BCCI) slows heart rate, such as verapamil or diltiazem;
- Pregnancy;
- the period of lactation (breastfeeding);
- the use in women of reproductive age who are not using reliable methods of contraception;
- the age of 18 years (effectiveness and safety of the drug in this age group has not been studied);
- lactase deficiency, lactose intolerance, malabsorption syndrome glucose / galactose;
- Hypersensitivity to ivabradine or any of the auxiliary components of the preparation.
With cautionIt should be prescribed with moderate hepatic failure (less than 9 points on the Child-Pugh); severe renal failure (creatinine clearance less than 15 mL / min); congenital long QT interval; simultaneous application of drugs, prolonging the interval QT; simultaneous application of moderate inhibitors and inducers of CYP3A4 and grapefruit juice; kaliynesberegayuschimi applied simultaneously with diuretic; asymptomatic left ventricular dysfunction; AV-II blockade degree; recent stroke; IV heart failure NYHA functional class classification; pigmentary degeneration of the retina (retinitis pigmentosa); hypotension; Patients over the age of 75 years.
PREGNANCY AND LACTATION
Use of the drug RANS В® is contraindicated in pregnancy. At present, there is insufficient data on the use of ivabradine in pregnancy. In preclinical studies, ivabradine showed embryotoxic and teratogenic effects.
Women of childbearing age should use reliable methods of contraception during treatment with the drug RANS В® .
Use of the drug RANS В® is contraindicated during lactation. Information on the allocation of ivabradine in breast milk are not available. In animal studies it has been shown that ivabradine is excreted in breast milk.
APPLICATION FOR FUNCTIONS OF THE LIVER
Precautions should be prescribed with severe renal failure (CC less than 15 ml / min).
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Do not use this drug in severe liver failure (more than 9 points on the Child-Pugh).
Precautions should be prescribed with moderate hepatic failure (less than 9 points on the Child-Pugh).
APPLICATION FOR CHILDREN
Do not use this drug before the age of 18 years (effectiveness and safety have not been studied in this age group).
APPLICATION IN ELDERLY PATIENTS
With care should be prescribed to patients over the age of 75 years.
SPECIAL INSTRUCTIONS
Cardiac arrhythmias
Ivabradine is not effective in the treatment or prophylaxis of arrhythmias. Its effectiveness decreases against the background of tachyarrhythmias (e.g., ventricular or supraventricular tachycardias). Preparation RANS В® not recommended for patients with atrial fibrillation (atrial fibrillation) or other types of arrhythmias associated with the function of the sinus node.
During therapy with RANS В® should conduct the clinical monitoring of patients in order to identify atrial fibrillation (paroxysmal or persistent). According to clinical indications (e.g., worsening of angina, palpitations appearance, irregular heart rhythm) in the current control should include an electrocardiogram.
The risk of developing atrial fibrillation may be higher in patients with CHF, taking the drug RANS В® . Atrial fibrillation is more common among patients who received both ivabradine with amiodarone or antiarrhythmics class I. Patients with CHF and intraventricular conduction disturbances (blockade of the left or right bundle branch) and ventricular dyssynchrony should be controlled.
Use in patients with bradycardia
Ivabradine is contraindicated if the heart rate before the beginning of therapy alone is less than 60 u. / Min. If background therapy in heart rate at rest slows to less than 50 u. / Min or the patient has symptoms associated with bradycardia (such as dizziness, fatigue or hypotension), the dose should be reduced. If the heart rate at lower doses of the drug is less than 50 u. / Min or stored symptoms associated with bradycardia, then the drug RANS В® should be discontinued.
Combined use of a composition antianginal therapy
Use of the drug RANS В®together with BCCI, slows heart rate, such as verapamil or diltiazem, contraindicated. The combined use of ivabradine with nitrates and BCCI, dihydropyridine derivatives such as amlodipine, changing the profile of the safety of the therapy were observed. It is determined that the combined use with BCCI ivabradine improves efficiency.
Stroke
is not recommended to assign the drug RANS В® immediately after stroke, as Data on the use of the drug during this period are not available.
The visual function
Ivabradine influences on retinal function of the eye. So far, it showed no toxic effect of ivabradine on the retina. However, data on the effect of ivabradine on the retina of the eye is not long-term use (over 1 year). In the event of violation of visual functions that are not described in this manual should consider discontinuation of the drug RANS В® . Patients with pigmentary degeneration of the retina (retinitis pigmentosa) preparation RANS В® should be taken with caution.
Hypotension
RANS В® should be used with caution in patients with hypotension (due to lack of clinical data).
RANS В®is contraindicated in severe arterial hypotension (systolic blood pressure less than 90 mm Hg. v. and diastolic blood pressure less than 50 mm Hg. v.).
Atrial fibrillation (atrial fibrillation) - cardiac arrhythmias
Increased risk of bradycardia during treatment with ivabradine during pharmacological cardioversion to restore sinus rhythm has not been proven. However, due to insufficient data, when the possibility to delay the planned electrical cardioversion, reception Ryan preparation В® should be discontinued 24 hours prior to imaging.
The use in patients with congenital QT syndrome elongate slot or in patients taking drugs lengthening QT interval
drug RANS В®It should not be applied at elongate slot congenital syndrome QT, as well as in combination with drugs able to lengthen the interval QT. If necessary, the simultaneous use of these drugs requires strict control ECG. Due to slowing of the heart rate of the drug RANS В® may exacerbate lengthening the interval QT, which in turn can trigger the development of severe arrhythmias, in particular polymorphic ventricular tachycardia type "pirouette".
Patients with hypertension who need to transition to another antihypertensive
When changing antihypertensive therapy in patients with CHF, taking the drug RANS В® , blood pressure monitoring is required at appropriate intervals.
Chronic heart failure
prior to the application of solution preparation RANS В® for heart failure should be stable. Caution must be exercised when using the drug RANS В® in patients with CHF IV NYHA functional class classification because of limited data on the drug administration in this patient.
Moderate hepatic impairment
In patients with moderate hepatic failure (less than 9 points on the Child-Pugh) therapy with RANS В® should be done with caution.
Renal failure, severe
In renal failure, severe (CC less than 15 ml / min) therapy with RANS В® should be undertaken with caution.
Excipients
Preparation RANS В® contains lactose, so it is not recommended for patients with lactase deficiency, lactose intolerance and malabsorption syndrome glucose / galactose.
Impact on the ability to drive vehicles and manage mechanisms
Ivabradine does not influence the ability to drive vehicles and the performance of work requiring a high rate of psychomotor reactions. However, be aware of the possibility of photopsias the sudden change in light intensity, especially when driving at night.
OVERDOSE
Symptoms: an overdose of ivabradine may lead to severe and prolonged bradycardia.
Treatment: therapy bradycardia - symptomatic, conducted in specialized units. In the case of bradycardia in combination with impaired hemodynamics shown symptomatic treatment with / in a beta-agonists such as isoprenaline. If necessary, one can raise the pacemaker.
DRUG INTERACTION
Adverse combination
Medications, lengthening the interval QT
- antiarrhythmics, lengthening the interval QT (e.g., quinidine, disopyramide, bepridil, sotalol, ibutilide, amiodarone);
- drugs, lengthening the interval QT, non antiarrhythmic agents (e.g., pimozide, ziprasidone, sertindole, mefloquine, halofantrine, pentamidine, cisapride, erythromycin for / in the introduction).
It should avoid the simultaneous use of ivabradine and these drugs because slowing heart rate may cause additional lengthening of the interval QT. If necessary, the simultaneous use of these drugs should be closely monitored ECG.
CYP3A4 isoenzyme
Ivabradine is metabolized in the liver involving CYP3A4 isozyme and is a very weak inhibitor of the cytochrome. Ivabradine has no significant effect on the metabolism and blood plasma concentration of other substrates (strong, moderate and weak inhibitors) isoenzyme CYP3A4. At the same time, inhibitors and inducers of CYP3A4 isozyme can react with ivabradine and exert a clinically significant effect on its metabolism and pharmacokinetic properties. It has been found that inhibitors of CYP3A4 isoenzyme increased, and inducers of CYP3A4 isoenzyme ivabradine reduce the concentration in the blood plasma.
Increase ivabradine plasma concentrations may increase the risk of bradycardia.
counterindication
