Bravadin® (Bravadin)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
Read on
Active substanceIwabradineIwabradine
Similar drugsTo uncover
  • Bravadin®
    pills inwards 
    KRKA-PHARMA, doo, Zagreb, Croatia     Croatia
  • Coraxan®
    pills inwards 
    Servier Laboratories     France
    • Dosage form: & nbspfilm-coated tablets
    Composition:
    for 1 tablet of 5 mg:
    Core
    Active substance:
    Ivabradine hydrobromide 5.864 mg, which corresponds to ivabradine 5 mg
    Excipients: lactose monohydrate 64.636 mg, microcrystalline cellulose 20,000 mg, povidone 6,000 mg, croscarmellose sodium 2,000 mg, silicon dioxide colloid 0.500 mg, magnesium stearate 1,000 mg
    Film sheath: Fold orange 03H32599 3,000 mg
    for 1 tablet of 7.5 mg:
    Core
    Active substance:
    Ivabradine hydrobromide 8.796 mg, which corresponds to ivabradine 7.5 mg
    Excipients: lactose monohydrate 96.954 mg, microcrystalline cellulose 30,000 mg, povidone 9,000 mg, croscarmellose sodium 3,000 mg, silica colloidal dioxide 0.750 mg, magnesium stearate 1,500 mg
    Film sheath: Fold orange 03H325991 4,500 mg
    Composition Odorous orange 03H32599: hypromellose 71.714%, titanium dioxide (E171) 15.936%, talc 6.972%, propylene glycol 4.980%, iron dye oxide yellow (E 172) 0.332%, ferric oxide red oxide (E 172) 0.066%.
    Description:
    Tablets 5 mg. Oval, biconvex tablets, covered with a film shell of pale orange color, with a risk on one side. View of the fracture: a white rough mass with a film shell of a pale orange color.
    Tablets 7.5 mg. Round, slightly biconcave tablets covered with a film shell of a pale orange color, with a bevel. View of the fracture: a white rough mass with a film shell of a pale orange color.

    Pharmacotherapeutic group:Antianginal remedy
    ATX: & nbsp

    C.01.E.B.17   Iwabradine

    Pharmacodynamics:
    Ivabradin is a drug that slows the heart rhythm, the mechanism of its action is the selective and specific inhibition of sinus node channels, which controls spontaneous diastolic depolarization of the sinus node and regulates the heart rate (HR). Iwabradine has a selective effect on the sinus node, without affecting the timing of impulses for atrial, atrioventricular and intragastric conducting paths, as well as contractility of the myocardium and repolarization of the ventricles. Iwabradine can also interact with Ih canals of the retina, similar to If channels of the heart, involved in the onset of a temporary change in the system of visual perception due to a change in the reaction of the retina to bright light stimuli.In provoking conditions (sharp changes in the brightness of the illumination), partial inhibition of the Ihabradine of 1h channels occurs, which causes a transient change in brightness in a limited area of ​​the visual field (photopsy). The main pharmacodynamic property of ivabradine is a dose-dependent decrease in heart rate. Analysis of the dependence of the heart rate on the dose of ivabradine was carried out with a gradual increase in the dose to 20 mg twice a day and revealed a tendency to achieve the "plateau" effect when there is no increase in the therapeutic effect with a further increase in dose, which reduces the risk of severe bradycardia 40 bpm).
    In recommended doses, the decrease in heart rate is about 10-15 beats / minute at rest and under physical exertion. This leads to a decrease in the load on the myocardium due to a decrease in myocardial oxygen demand. Iwabradine does not affect intracardiac conduction, contractility of the myocardium (absence of negative inotropic action), or ventricular repolarization:
    in electrophysiological studies ivabradine had no effect on the time of impulses on the atrioventricular or intraventricular ways,as well as the adjusted QT interval; - in patients with left ventricular dysfunction (left ventricular ejection fraction (LVEF) from 30 to 45%) ivabradine did not have a negative effect on LVEF.
    Pharmacokinetics:
    Ivabradine is an S-enantiomer that does not demonstrate biological transformation in in vivo studies. The N-desmethylated derivative of ivabradine is the main active metabolite.
    Absorption and bioavailability
    Ivabradine is rapidly and almost completely absorbed in the gastrointestinal tract after ingestion in the empty stomach, reaching a maximum concentration (Cmax) in the blood plasma after approximately 1 hour. Absolute bioavailability is about 40% and is due to the effect of "primary passage" through the liver.
    Food intake increases the time of absorption of ivabradine by approximately 1 hour and increases the concentration in the blood plasma from 20 to 30%. It is recommended to take tablets at the time of food intake in order to reduce the variability of the concentration.
    Distribution
    Iwabradine binds to blood plasma proteins by approximately 70%, the volume of distribution in patients in an equilibrium state is about 100 liters.Cmax ivabradine in blood plasma after a long oral dose of 5 mg twice a day is 22 ng / ml (coefficient of variation (CV) = 29%). The average equilibrium concentration in the blood plasma is 10 ng / ml (KB = 38%).
    Metabolism
    Ivabradine is largely metabolized in the liver and intestines by oxidation with cytochrome P450-ZA4 (isoenzyme CYP3A4). The main active metabolite is the N-desmethylated derivative (S 18982) with a concentration of about 40% with respect to the concentration of the starting material. The metabolism of this active metabolite also occurs with the participation of the CYP3A4 isoenzyme. Iwabradine has a low degree of affinity for the CYP3A4 isoenzyme, does not demonstrate clinically significant induction or inhibition of the CYP3A4 isoenzyme, therefore, the change in the metabolism or substrate concentration of the CYP3A4 isoenzyme in plasma under the action of ivabradine is unlikely. Conversely, strong inhibitors and inducers of cytochrome P450 can significantly affect the concentration of ivabradine in blood plasma.
    Excretion
    The half-life period (T1 / 2) of ivabradine is, on average, 2 hours (70-75% relative to the area under the concentration-time curve (AUC) in blood plasma), the effective T1 / 2 is 11 hours.The total clearance is about 400 ml / min, the renal clearance is about 70 ml / min. Excretion of metabolites occurs to the same extent through the intestines and kidneys. About 4% of the dose taken internally is excreted unchanged by the kidneys.
    Linearity / nonlinearity
    The pharmacokinetics of ivabradine is linear in the dose range of 0.5-24 mg.

    Special patient groups
    Patients of elderly and senile age
    Pharmacokinetic parameters (AUC and Cmax) are not significantly different in patients 65 years and older, 75 years and older and the general population of patients.
    Impaired renal function
    The change in the kinetics of ivabradin in patients with renal insufficiency (creatinine clearance 15-60 ml / min) is minimal, since only about 20% of ivabradine and its active metabolite S 18982 is excreted by the kidneys.
    Impaired liver function
    In patients with mild hepatic insufficiency (up to 7 on the Child-Pugh scale), AUC of ivabradine and its 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 to draw a conclusion about the specific pharmacokinetics of ivabradine in this group of patients,and in patients with severe hepatic insufficiency (more than 9 on the Child-Pugh scale) are absent.

    The relationship between pharmacokinetic and pharmacodynamic properties
    Decrease in heart rate is directly proportional to the increase in plasma concentrations of ivabradine and the active metabolite S 18982 when taken in doses of 15-20 mg twice a day. At higher doses of the drug, the decrease in cardiac rhythm does not have a proportional dependence on the concentration of ivabradine in blood plasma and is characterized by a tendency to achieve the "plateau" effect. The high concentrations of ivabradine in blood plasma that can be achieved with the simultaneous use of ivabradine with strong inhibitors of the CYP3A4 isoenzyme may lead to a marked decrease in heart rate, but this risk decreases with simultaneous use with moderate inhibitors of the CYP3A4 isoenzyme.
    Indications:
    Stable angina
    Therapy of stable angina in adult patients with normal sinus rhythm:
    - with intolerance or the presence of contraindications to the use of beta-blockers;
    - in combination with beta-blockers with inadequate control 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 increased symptoms of chronic heart failure (CHF)) in patients with CHF, with sinus rhythm and heart rate not less than 70 beats / min.

    Contraindications:
    - Hypersensitivity to ivabradine or any of the auxiliary components of the drug.
    - Bradycardia (heart rate at rest less than 60 beats / min (before treatment)).
    - Cardiogenic shock.
    - Acute myocardial infarction.
    - Severe arterial hypotension (systolic blood pressure (BP) is less than 90 mmHg and diastolic blood pressure is less than 50 mmHg).
    - Severe hepatic failure (more than 9 on the Child-Pugh scale).
    - Syndrome of weakness of the sinus node.
    - Sinoatrial blockade.
    - Unstable or acute heart failure.
    - The presence of an artificial pacemaker, working in a constant stimulation mode.
    - Unstable angina.
    - Atrioventricular blockade (AV) of the third degree.
    - Simultaneous use with strong inhibitors of cytochrome P450 ZA4 isoenzymes, such as antifungal agents of the azole group (ketoconazole, itraconazole), antibiotics from the macrolide group (clarithromycin, erythromycin for oral administration, josamycin, telithromycin), HIV protease inhibitors (nelfinavir, ritonavir) and nefazodone.
    - Pregnancy and the period of breastfeeding.
    - Age under 18 years (efficacy and safety of the drug in this age group has not been studied).
    - Deficiency of lactase, lactose intolerance, glucose-galactose malabsorption syndrome.
    Carefully:moderate hepatic insufficiency (less than 9 on the Child-Pugh scale), severe renal failure (QC less than 15 mL / min), congenital prolongation of the QT interval, simultaneous use of drugs that extend the QT interval, simultaneous use of moderate inhibitors and inducers isoenzyme CYP3A4 and grapefruit juice, asymptomatic left ventricular dysfunction, AV blockade II degree, recent stroke, retinitis pigmentosa retinitis, arterial hypotension, functional class IV CHF of NYHA classification, the simultaneous use of blockers "slow" calcium channel (BCCI) slows heart rate (verapamil or diltiazem), simultaneous use with non-potassium-sparing diuretics.
    Pregnancy and lactation:
    Pregnancy
    Studies in animals have demonstrated the presence of reproductive toxicity, embryotoxicity and teratogenic effects.
    The drug Bravadin® is contraindicated for use in pregnancy due to insufficient amount of safety data. Breastfeeding period
    The use of the drug Bravadin ® during breastfeeding is contraindicated. It is not known whether ivabradine in breast milk.
    If you need to use the drug Bravadin® during lactation, breastfeeding should be discontinued.
    Dosing and Administration:
    Inside, twice a day (morning and evening) during meals.
    Stable angina
    The recommended initial dose is 10 mg per day (1 tablet 5 mg twice a day).
    After 3-4 weeks of therapy, the dose may be increased to 15 mg per day (1 tablet 7.5 mg twice daily) depending on the therapeutic effect. If, during the application of Bravadine, the heart rate at rest is less than 50 beats / min, or the patient has symptoms associated with bradycardia (dizziness,increased fatigue or a pronounced decrease in blood pressure), the dose of Bravadin® should be reduced to 2.5 mg (5 mg tablet) twice a day. Therapy with Bravadin should be discontinued if, with a decrease in the dose of Bravadin®, the heart rate remains below 50 beats / min or the symptoms persist
    bradycardia.
    Chronic heart failure
    The recommended initial dose is 10 mg per day (1 tablet 5 mg twice a day).
    After 2 weeks of therapy, the dose can be increased to 15 mg per day (1 tablet 7.5 mg twice a day) if the heart rate at rest stably exceeds 60 beats / min, or reduced to 2.5 mg (4 tablets) 5 mg) twice a day if the heart rate is stably less than 50 beats / min or the patient has symptoms associated with bradycardia (dizziness, fatigue or a pronounced decrease in blood pressure).
    If the heart rate is in the range of 50-60 beats / min, it is recommended to use Bravadin® at a dose of 5 mg twice a day.
    If, during the application of Bravadin®, the heart rate at rest is less than 50 beats / min, or the patient has symptoms associated with bradycardia, for patients receiving the drug 5 mg twice daily or 7.5 mg twice daily, the dose of the drug should be reduced.
    If patients receiving Bravadin 2.5 mg (5 mg tablet) twice a day or 5 mg twice daily, heart rate at rest stably more than 60 beats / min, the dose of Bravadin® can be increased.
    If the heart rate stays below 50 bpm, or if the patient has symptoms associated with bradycardia, therapy with Bravadin® should be discontinued.
    Patients older than 75 years
    Patients aged 75 years and older should be treated with a lower dose. The recommended initial dose is 2.5 mg (for Ug tablets 5 mg) twice daily. In the future, the dose may be increased.
    Impaired renal function
    Patients with impaired renal function (QC more than 15 ml / min) do not need dose adjustment.
    The recommended initial dose is 10 mg per day (1 tablet 5 mg twice a day). After 3-4 weeks of therapy, the dose can be increased to 15 mg per day (1 tablet 7.5 mg twice daily).
    Due to the lack of clinical data, the drug Bravadin® should be used with caution in patients with SC less than 15 mL / min.
    Impaired liver function
    Dose adjustment is not required in patients with mild liver failure (up to 7 on the Child-Pugh scale).Care should be taken when using Bravadin® in patients with moderate hepatic impairment (7-9 on the Child-Pugh scale).
    Patients with severe hepatic insufficiency (more than 9 points on the Child-Pugh scale) use of the drug Bravadin® is contraindicated.
    Children and teens
    The safety and effectiveness of ivabradine in children and adolescents under the age of 18 years have not been established.
    Side effects:
    The use of ivabradine has been studied in clinical trials involving almost 14,000 patients. The most common side effects were dose-dependent and were associated with the mechanism of action of ivabradine.
    Classification of the frequency of development of side effects of the World Health Organization (WHO):

    Often >1/10
    often from> 1/100 to <1/10
    infrequently from> 1/1000 to <1/100
    rarely from> 1/10000 to <1/1000
    rarely from <1/10000
    frequency unknown can not be estimated from the available data.

    In each group, undesirable effects are presented in order of decreasing severity.
    Disorders from the side of the organ of vision:
    very often: a change in light perception (photopsy) *;
    often: blurred vision.
    Hearing disorders and labyrinthine disturbances: infrequently: vertigo.
    Violations from the heart and blood vessels:
    often: uncontrolled blood pressure, bradycardia **, AV block of degree I (prolonged PQ interval on electrocardiogram (ECG)), ventricular extrasystole; infrequent: sensation of heartbeat, nadzhelud ochkovaya extrasystole, marked decrease in blood pressure, possibly associated with bradycardia;
    very rarely: atrial fibrillation, AV blockade of II and III degree, syndrome of sinus node weakness.
    Impaired nervous system:
    often: headache (especially in the first month of therapy), dizziness, possibly associated with bradycardia;
    frequency unknown: syncope, possibly associated with bradycardia.
    Disturbances from the respiratory system, chest and mediastinal organs:
    infrequently: shortness of breath.
    Disturbances from the skin and subcutaneous tissues:
    infrequently: angioedema, skin rash; rarely: itching, erythema, urticaria.
    Disorders from the gastrointestinal tract: infrequently: nausea, constipation, diarrhea.
    Disturbances from the musculoskeletal and connective tissue: infrequently: muscle spasms.
    General disorders and disorders at the site of administration:
    infrequently: asthenia, increased fatigue, possibly associated with bradycardia; rarely: malaise, possibly associated with bradycardia.
    Laboratory and instrumental data:
    infrequently: hyperuricemia, eosinophilia, increased creatinine concentration in the blood plasma, prolongation of the QT interval on the ECG.
    * Change in light perception (photopsy) was noted in 14.5% of patients and was described as a transient change in brightness in a limited area of ​​the visual field. As a rule, similar phenomena were provoked by a sharp change in the intensity of illumination in the zone of the visual field. Basically, a photopsy occurred in the first two months of therapy followed by a repetition. The severity of the photopsy, as a rule, was mild or moderate. The photopsy stopped with the continuation of therapy (77.5% of cases) or after its completion. In less than 1% of patients, the onset of photopsy led to the rejection of therapy.
    ** Bradycardia was noted in 3.3% of patients, especially in the first 2-3 months of therapy, 0.5% of patients developed severe bradycardia with a heart rate less than or equal to 40 beats / min.
    Overdose:
    Symptoms
    Overdose of the drug Bravadin® can lead to severe and prolonged bradycardia.
    Treatment
    Treatment of severe bradycardia is symptomatic and should be carried out in the conditions of specialized departments of the hospital.In the case of a combination of bradycardia with a violation of the parameters of hemodynamics, the use of beta-adrenomimetics (isoprenaline) is necessary. If necessary - the installation of an artificial pacemaker.

    Interaction:
    Pharmacodynamic interaction
    Simultaneous use is not recommended
    LS, extending the interval QT:
    - anti-arrhythmic agents, QT interval prolongation (for example, quinidine,
    disopyramide, beprideal, sotalol, ibutilide, amiodarone);
    - LC, QT prolonging interval, not related to antiarrhythmics
    (e.g., pimozide, ziprasidone, sertindole, mefloquine, halofantrine, pentamidine, cisapride, erythromycin for intravenous administration). The simultaneous use of ivabradine and LS prolonging the QT interval is not recommended, since a decrease in heart rate may cause an additional prolongation of the QT interval. When simultaneous application is required, careful ECG monitoring is required.
    Concurrent use requiring caution
    Non-potassium-sparing diuretics (thiazide and "loop")
    Hypokalemia may increase the risk of arrhythmia. Since the use of ivabradine can cause bradycardia,the combination of hypokalemia and bradycardia is a predisposing factor for the development of severe arrhythmia, especially in patients with the QT prolonged interval syndrome, both congenital and induced use of LC.
    Pharmacokinetic interaction
    Cytochrome P450 ZA4 (isoenzyme CYP3A4)
    Ivabradin is metabolized in the liver with only the CYP3A4 isoenzyme and is a very weak inhibitor of this cytochrome. It does not affect the metabolism and concentration in the blood plasma of other substrates (strong, moderate and weak inhibitors) of the CYP3A4 isoenzyme. Inhibitors and inducers of the CYP3A4 isoenzyme can interact with ivabradine and have a clinically significant effect on its metabolism and pharmacokinetic properties. Inhibitors of the CYP3A4 isoenzyme are increased, and inducers of the CYP3A4 isoenzyme decrease the concentration of ivabradine in the blood plasma. An increase in ivabradine concentration in the blood plasma can cause a risk of severe bradycardia (see section "Special instructions"). Simultaneous use is contraindicated
    Simultaneous application with strong inhibitors of the CYP3A4 isoenzyme, such as antifungal agents of the azole group (ketoconazole, itraconazole), antibiotics from the macrolide group (clarithromycin, erythromycin for oral administration, josamycin, telithromycin), HIV protease inhibitors (nelfinavir, ritonavir) and nefazodone is contraindicated (see section "Contraindications"). Strong inhibitors of the isoenzyme CYP3A4 - ketoconazole (200 mg once daily) or josamycin (1 g twice daily) increase the average concentration of ivabradine in blood plasma by 7-8 times. Simultaneous use is not recommended Moderate inhibitors of the isoenzyme CYP3A4
    Simultaneous application of ivabradine and diltiazem or verapamil (J1C, which cut heart rate) in healthy volunteers and patients was accompanied by an increase in AUC 2-3 times and an additional decrease in heart rate by 5 beats / min. Concurrent use requiring caution
    Moderate inhibitors of the isoenzyme CYP3A4
    The simultaneous use of ivabradine with other moderate inhibitors of the CYP3A4 isoenzyme (eg, fluconazole) is possible if the heart rate at rest is more than 60 beats / min. The recommended initial dose of ivabradine is 2.5 mg twice daily. Need control of heart rate. Grapefruit juice
    With simultaneous application with grapefruit juice, there was an increase in the concentration of ivabradine in blood plasma by a factor of two.During the application of ivabradine, the use of grapefruit juice is not recommended. Inductors of the isoenzyme CYP3A4
    Inductors of the isoenzyme CYP3A4 (for example, rifampicin, barbiturates, phenytoin and LC containing Hypericum perforated) may reduce plasma concentrations and activity of ivabradine and require a higher dose of ivabradine. Simultaneous application of ivabradine in a dose of 10 mg twice a day and LC containing St. John's wort penetrated, reduces the AUC of ivabradine by a factor of 2. The concomitant use of LS containing St. John's Wort is not recommended, and ivabradine is not recommended.
    Simultaneous application with other LCs
    There is no clinically significant effect on the pharmacodynamics and pharmacokinetics of ivabradin when used concurrently with proton pump inhibitors (omeprazole, lansoprazole), inhibitors of phosphodiesterase-5 (sildenafil), inhibitors of HMG-CoA reductase (simvastatin), BCCC (amlodipine, lacidipine), digoxin and warfarin.
    Ivabradine has no clinically significant effect on the pharmacokinetics of simvastatin, amlodipine, lacidipine, pharmacokinetics and pharmacodynamics of digoxin, warfarin, and the pharmacodynamics of acetylsalicylic acid.
    Simultaneous use of ivabradine and angiotensin converting enzyme inhibitors, angiotensin II receptor antagonists, beta-blockers, diuretics, aldosterone antagonists, nitrates, short and long-acting HMG-CoA reductase inhibitors, fibrates, proton pump inhibitors, hypoglycemic agents for oral administration, acetylsalicylic acid and other antiplatelet agents was not accompanied by a change in the safety profile of the therapy.
    Special instructions:
    Heart rhythm disturbances
    The drug Bravadin® is ineffective in the treatment or prevention of arrhythmia, its effectiveness is reduced by the occurrence of tachyarrhythmias (eg, ventricular or supraventricular tachycardia). The use of Bravadin® is not recommended in patients with atrial fibrillation (atrial fibrillation) or other types of arrhythmias associated with sinus node function.
    When using the drug Bravadin®, it is recommended to conduct clinical observation of patients for atrial fibrillation (paroxysmal or permanent form), including an ECG study in the presence of clinical indications (for example,deterioration of the course of angina pectoris, the appearance of a palpitation, irregular heart rhythm).
    The risk of developing atrial fibrillation may increase in patients with CHF who are taking Bravadin®. Atrial fibrillation was more common among patients concomitantly taking ivabradine with amiodarone or antiarrhythmic drugs of the first class.
    Patients with CHF and intraventricular conduction disorders (left or right bundle bundle blockade) and ventricular dissynchrony should be closely monitored. A V blockade of the II degree
    The use of the drug Bravadin ® is not recommended in patients with AV blockade of the II degree.
    Use in patients with bradycardia
    The use of Bravadin® is contraindicated in patients with a heart rate of less than 60 beats per minute at rest before therapy.
    If the Bravadine heart rate is at rest less than 50 beats / min at rest, or the patient has symptoms associated with bradycardia (dizziness, fatigue or a pronounced decrease in blood pressure), the dose of the drug should be reduced.
    If Bravadin® heart rate is less than 50 beats per minute or the symptoms associated with bradycardia persist, Bravadin® therapy should be discontinued.
    Combined use as part of antianginal therapy
    Simultaneous use of the drug Bravadin® with BCCC, piercing the pulse (verapamil, diltiazem) Not recommended. When used simultaneously with nitrates or BCCC, derivatives of dihydropyridine (amlodipine), there was no change in the safety profile of the therapy. It has not been established that simultaneous use with BCCC derived dihydropyridine increases the efficacy of ivabradine.
    Chronic heart failure
    The possibility of using the drug Bravadin ® is considered only in patients with stable course of CHF. With the use of Bravadin ® in patients with NYHA class IV CHF functional class, care should be taken in connection with the limited amount of data on use in this group of patients. Stroke
    It is not recommended to use the drug Bravadin® immediately after a stroke, in view of the lack of data on efficacy and safety in this period.
    Spotting functions
    The drug Bravadin ® affects the function of the retina. At present, there has been no toxic effect on the retina of the eye,However, the effect of the drug Bravadin on the retina with prolonged use (over 1 year) is currently unknown.
    If you experience any visual impairment not described in this manual, the use of Bravadin® should be discontinued. Care should be taken when using Bravadine in patients with retinal pigmented degeneration.
    Arterial hypotension
    The drug Bravadin® should be used with caution in patients with arterial hypotension (insufficient amount of clinical data).
    The use of the drug Bravadin® is contraindicated in patients with severe arterial hypotension (systolic blood pressure less than 90 mmHg and diastolic blood pressure less than 50 mmHg).
    Atrial fibrillation (atrial fibrillation) - cardiac arrhythmias There is no evidence of an increased risk of developing severe bradycardia with the use of Bravadin® in restoring sinus rhythm during pharmacological cardioversion. Nevertheless, due to the lack of sufficient data, if possible to delay planned electrical cardioversion, the use of Bravadin® should be stopped 24 hours before the procedure.
    The use in patients with congenital syndrome of prolonged QT interval or in patients taking JIC, prolonging the QT interval
    The drug Bravadin® is not used in patients with congenital long QT syndrome, as well as in patients taking LS prolonging the QT interval. When simultaneous application is required, strict ECG monitoring is required. Decrease in heart rate due to the use of the drug Bravadin® can aggravate the prolongation of the QT interval and provoke the development of severe arrhythmia, in particular, polymorphic ventricular tachycardia such as pirouette.
    Patients with hypertension who require a change in antihypertensive therapy
    In a clinical study, cases of increased blood pressure were more common in the group of patients taking ivabradine (7.1%), compared with the placebo group (6.1%). Such cases were encountered especially often immediately after the change in antihypertensive therapy, were of a temporary nature and did not affect the efficacy
    therapy with ivabradine. When changing hypotensive therapy in patients with CHF, taking the drug Bravadin ®, you should monitor BP at certain intervals.
    Moderate hepatic impairment
    Care should be taken when using Bravadin® in patients with moderate hepatic impairment (less than 9 on the Child-Pugh scale).
    Severe renal insufficiency
    Care should be taken when using Bravadin ® in patients with severe renal insufficiency (CC less than 15 ml / min).
    Special information on excipients
    The drug Bravadin contains lactose, so the drug is contraindicated in patients with lactase deficiency, lactose intolerance, glucose-galactose malabsorption syndrome.
    Effect on the ability to drive transp. cf. and fur:A study was conducted to assess the possible impact of ivabradine on the ability to drive a car with healthy volunteers, which resulted in the ability to drive the car unchanged. However, in the postmarketing period, there have been reports of impairment of the ability to drive vehicles due to symptoms associated with visual impairment. The drug Bravadin ® can cause a temporary change in light perception (mainly in the form of a photopsy),which should be taken into account when driving vehicles or other mechanisms with a sudden change in light intensity, especially at night.
    Form release / dosage:
    Tablets, film-coated, 5 mg, 7.5 mg.
    Packaging:
    For 14 or 15 tablets in a contour mesh box made of a combined material of PVC / PE / PVDC and aluminum foil.
    1, 2, 4, 6, 7 contour cell packs according to (14 tablets) or 2, 4, 6 contour cell packs of (15 tablets) together with the instructions for use are placed in a pack of cardboard.
    Storage conditions:At a temperature of no higher than 25 ° C, in the original packaging. Keep out of the reach of children.
    Shelf life:
    3 years
    Do not use the drug after the expiration date.

    Terms of leave from pharmacies:On prescription
    Registration number:LP-002544
    Date of registration:25.07.2014
    The owner of the registration certificate:KRKA-PHARMA, doo, Zagreb, CroatiaKRKA-PHARMA, doo, Zagreb, Croatia Croatia
    Manufacturer: & nbsp
    Representation: & nbspKRKA KRKA Slovenia
    Information update date: & nbsp25.07.2014
    Illustrated instructions
      Instructions
      Up