Koraxan - instructions for use, reviews, analogs and formulations (5 mg and 7.5 mg tablets) of the drug for the treatment of angina and chronic heart failure in adults, children and pregnancy

In this article, you can read the instructions for using the drug Koraksan. Presented are reviews of visitors to the site - consumers of this medication, as well as opinions of doctors of specialists on the use of Coraxan in their practice. A big request is to actively add their feedback on the drug: the medicine helped or did not help get rid of the disease, which were observed complications and side effects, possibly not declared by the manufacturer in the annotation. Analogues of Koraksan in the presence of existing structural analogues. Use for the treatment of angina pectoris and chronic heart failure in adults, children, as well as in pregnancy and lactation.

Koraksan - a drug that slows the rhythm of the heart.

Coraxan has a selective effect on the sinus node, without affecting the timing of impulses at the intracardiac, atrioventricular and intraventricular conduction pathways, as well as the contractility of the myocardium and the repolarization of the ventricles.

The main pharmacological feature of ivabradine (active ingredient of the drug Coraxan) is its ability to dose-dependent decrease in heart rate. Analysis of the dependence of the decrease in heart rate on the dose of the drug was carried out with a gradual increase in the dose of ivabradine to 20 mg 2 and revealed a tendency to achieve a plateau effect (no increase in the therapeutic effect with a further increase in dose), which reduces the risk of severe bradycardia (heart rate less than 40 beats per minute) .

When the drug is prescribed in recommended doses, the degree of reduction in heart rate depends on its initial value and is approximately 10-15 beats / minute at rest and under physical exertion. As a result, the work of the heart decreases and myocardial oxygen demand decreases.

Coraxan does not affect intracardiac conduction, contractility of the myocardium (does not cause a negative inotropic effect), or the process of repolarization of the ventricles of the heart.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 adjusted QT intervals.

A sustained decrease in heart rate was demonstrated in patients taking ivabradine for at least 1 year. Influences on carbohydrate metabolism and lipid profile were not observed.

In patients with diabetes mellitus, the performance and safety of Coraxan were similar to those in the general population of patients.

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.

Patients with angina pectoris with ivabradine received a decrease in the relative risk of complications (mortality from cardiovascular disease, hospitalization for acute myocardial infarction, hospitalization for new cases of heart failure or increased symptoms of chronic heart failure) at 24 %.The noted therapeutic advantage is achieved, first of all, by reducing the frequency of hospitalization for acute myocardial infarction by 42%.

Reduction of mortality from cardiovascular diseases and a decrease in the frequency of hospitalizations due to increased symptoms of CHF flow were observed irrespective of age, sex, functional class of CHF, beta-blockers, ischemic or non-ischemic etiology of CHF, presence of diabetes or history of arterial hypertension.

In patients with a heart rate of 80 bpm, a decrease in heart rate was observed at an average of 15 bpm.

Composition

Ivabradine hydrochloride + excipients.

Pharmacokinetics

Koraksan quickly and almost completely absorbed into the digestive tract after ingestion. Bioavailability is approximately 40%, which is due to the effect of "first passage" through the liver. Food 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.

Ivabradine is largely metabolized in the liver and intestines by oxidation involving only cytochromeP450 3A4 (isoenzyme CYP3A4). Excretion of metabolites occurs at the same rate through the kidneys and intestines. About 4% of the dose is excreted by the kidneys unchanged.

Indications

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-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 CHF symptoms) in patients with chronic heart failure, with sinus rhythm and heart rate of at least 70 beats per minute.

Forms of release

Tablets coated with 5 mg and 7.5 mg.

Instructions for use and dosage

Koraksan should be taken orally 2 times a day, morning and evening during meals.

With stable angina, the recommended initial dose of the drug is 10 mg per day (1 tablet 5 mg 2 times a day). Depending on the therapeutic effect, after 3-4 weeks of use, the dose of the drug can be increased to 15 mg (1 tablet 7.5 mg twice a day).If, on the background of therapy with Koraxan, the heart rate at rest drops to less than 50 beats / min, or the patient has symptoms associated with bradycardia (such as dizziness, fatigue or a pronounced decrease in blood pressure), it is necessary to reduce the dose of Coraxan (eg, up to 2.5 mg (1/2 tablet 5 mg twice a day) If, with a decrease in the dose of Koraxan, the heart rate remains below 50 bpm, or the symptoms of severe bradycardia persist, the drug should be discontinued.

In chronic heart failure, the recommended initial dose is 10 mg per day (1 tablet 5 mg twice a day). After two weeks of application, the daily dose of Coraxan can be increased to 15 mg (1 tablet 7.5 mg twice a day) if the heart rate at rest is stably more than 60 beats per minute.

In case the heart rate is stable no more than 50 bpm, or in case of symptoms of bradycardia such as dizziness, fatigue or hypotension, the dose can be reduced to 2.5 mg (1/2 tablet 5 mg) twice a day.

If the value of the heart rate is in the range from 50 to 60 beats / min, it is recommended to apply Coraxan in a dose of 5 mg 2 times a day.

If during the application of the resting heart rate is stably less than 50 beats per minute or if the patient has bradycardia symptoms, for patients receiving Coraxan 5 mg twice daily or 7.5 mg twice a day, the dose should be reduced.

If patients receiving Koraxan in a dose of 2.5 mg (1/2 tablet 5 mg) twice a day or 5 mg twice a day, heart rate at rest is stable more than 60 beats / min, the dose of the drug can be increased.

If the heart rate is not more than 50 bpm, or the patient retains the symptoms of bradycardia, the drug should be discontinued.

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

Coraxan is contraindicated in patients with severe hepatic insufficiency (more than 9 on the Child-Pugh scale), since the use of the drug in such patients has not been studied (a significant increase in plasma concentration of the drug can be expected).

Side effect

• changes in light perception (photopsy);
• blurred vision;
• bradycardia;
• AV-blockade of 1 degree;
• ventricular extrasystole;
• a feeling of palpitations;
• supraventricular extrasystole;
• Arterial hypotension, possibly associated with bradycardia;
• sinus arrhythmia;
• atrial fibrillation;
• myocardial ischemia;
• myocardial infarction;
• ventricular tachycardia;
• nausea;
• constipation;
• diarrhea;
• headache (especially in the first month of therapy);
• dizziness, possibly associated with bradycardia;
• dyspnea;
• muscle spasms;
• syncope, possibly associated with bradycardia;
• eosinophilia;
• skin rash;
• itching;
• erythema;
• angioedema;
• hives;
• asthenia;
• increased fatigue;
• malaise, possibly associated with bradycardia.

Contraindications

• bradycardia (heart rate at rest less than 60 beats / min (before treatment));
• cardiogenic shock;
• acute myocardial infarction;
• severe arterial hypotension (systolic blood pressure below 90 mmHg and diastolic blood pressure below 50 mmHg);
• severe hepatic insufficiency (more than 9 on the Child-Pugh scale);
• syndrome of weakness of the sinus node (SSSU);
• sinoatrial blockade;
• presence of an artificial pacemaker;
• unstable angina;
• AV-blockade of the third degree;
• simultaneous application with strong inhibitors of the isoenzyme system of cytochrome P450 3A4,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;
• deficiency of lactase, lactose intolerance, glucose-galactose malabsorption syndrome;
• pregnancy;
• lactation period;
• age to 18 years (efficacy and safety of the drug in this age group has not been studied);
• hypersensitivity to ivabradine or any component of the drug.

Application in pregnancy and lactation

Coroxane is contraindicated in pregnancy. At the moment there is insufficient data on the use of the drug in pregnancy.

Pre-clinical studies of ivabradine revealed embryotoxic and teratogenic effects.

The use of Koraxan during the period of breastfeeding is contraindicated. There is no information on the penetration of ivabradine into breast milk.

Use in children

Contraindicated in children and adolescents under the age of 18 years (efficacy and safety of the drug in this age group has not been studied).

special instructions

Heart rhythm disturbances

Coraxan is ineffective for treating or preventing arrhythmias. Its effectiveness decreases with the development of tachyarrhythmias (eg, ventricular or supraventricular tachycardia). The drug is not recommended for patients with atrial fibrillation (atrial fibrillation) or other types of arrhythmias associated with sinus node function.

During therapy, patients should be clinically monitored for atrial fibrillation (paroxysmal or persistent). For clinical indications (eg, worsening of angina, the appearance of palpitations, irregular heart rhythms), ECG should be included in routine monitoring.

Use in patients with bradycardia

Coroxane is contraindicated if before the start of therapy, the heart rate at rest is less than 60 bpm. If, on the background of therapy, heart rate at rest is reduced to less than 50 beats / min, or the patient has symptoms associated with bradycardia (such as dizziness, fatigue or hypotension), it is necessary to reduce the dose of the drug. If, with a decrease in the dose of the medication, the heart rate remains below 50 bpm, or if the symptoms associated with bradycardia persist,then taking Koraxan should be stopped.

Combined use as part of antianginal therapy

The use of the preparation Coraxan together with blockers of "slow" calcium channels, lowering the heart rate, such as Verapamil or diltiazem, is not recommended.

With the combined use of ivabradine with nitrates and blockers of "slow" calcium channels - dihydropyridine derivatives such as amlodipine, there has been no change in the safety profile of the therapy. It is not established that a combined use with blockers of "slow" calcium channels increases the efficacy of ivabradine.

Stroke

It is not recommended to prescribe the drug immediately after a stroke, because there are no data on the use of the drug in this period.

Functions of visual perception

Coraxan affects the function of the retina. At present, toxic effects of ivabradine on the retina of the eye have not been identified, but the effect of the drug on the retina for prolonged use (over 1 year) is not known to date. If there are visual impairments not described in this manual, you should consider stopping the use of Koraxan.Patients with pigmented degeneration of the retina Corachsan should be taken with caution.

Excipients

The composition of the drug includes lactose, so Coraxan is not recommended for patients with lactase deficiency, lactose intolerance, glucose-galactose malabsorption syndrome.

Arterial hypotension

Due to the lack of clinical data, the drug should be administered with caution to patients with arterial hypotension.

Coraxan is contraindicated in 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 Coraxan during the restoration of sinus rhythm during pharmacological cardioversion. However, due to the lack of sufficient data, if possible to delay electrical cardioversion, taking Koraxan should be stopped 24 hours before the procedure.

Use in patients with congenital syndrome of an extended QT interval or patients taking drugs that extend the QT interval

Coraxan should not be prescribed in the congenital syndrome of the extended QT interval, and also in combination with drugs that extend the QT interval. If necessary, such therapy requires strict ECG monitoring.

Moderate hepatic impairment

With moderate hepatic insufficiency (less than 9 on the Child-Pugh scale), therapy with Koraxan should be done with caution.

Severe renal insufficiency

In severe renal failure (QC less than 15 ml / min), treatment with Coraxan should be done with caution.

Impact on the ability to drive vehicles and manage mechanisms

The use of Coraxan does not impair the quality of motor transport management. Coraxan does not affect the ability to drive vehicles and perform work that requires a high rate of psychomotor reactions. However, one should remember about the possibility of the appearance of a photopsy with a sudden change in the intensity of illumination, especially when driving at night.

Drug Interactions

Undesirable combinations of drugs

Avoid simultaneous use of ivabradine and drugs that extend the QT interval (antiarrhythmics: for example, quinidine, disopyramide, bepridil, sotalol, ibutilide, amiodarone, and not related to antiarrhythmics: for example, pimozide, ziprasidone, sertindole, mefloquine, halofantrine, pentamidine, cisapride , Erythromycin for intravenous administration) because a decrease in heart rate can cause an additional prolongation of the QT interval. If you need to co-prescribe these drugs, you should carefully monitor the ECG.

Ivabradine is metabolized in the liver with the participation of cytochrome P450 isozymes (isozyme CYP3A4) and is a very weak inhibitor of this isoenzyme. Ivabradin does not significantly affect the metabolism and concentration in the blood plasma of other substrates (potent, moderate and weak inhibitors) of cytochrome CYP3A4. 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 the inhibitors of the CYP3A4 isoenzyme increase, and the inducers of the CYP3A4 isoenzyme reduce the plasma concentrations of ivabradine.

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

Contraindicated drug combinations

The simultaneous use of Coraxan with potent inhibitors of the isoenzyme CYP3A4, such as antifungal agents of the azole group (ketoconazole, itraconazole), macrolide antibiotics (clarithromycin, erythromycin for oral administration, josamycin, telithromycin), HIV protease inhibitors (nelfinavir, ritonavir) and nefazodone are contraindicated. Powerful inhibitors of the isoenzyme CYP3A4-ketoconazole (200 mg once a day) or Josamycin (1 g 2 times daily) increase the average concentration of ivabradine in blood plasma by 7-8 times.

Undesirable combinations of drugs

The combined use of ivabradine and moderate inhibitors of the CYP3A4 diltiazem isoenzyme or verapamil in healthy volunteers and patients was accompanied by a 2-3 fold increase in ivabradin AUC and an additional 5-minute / minute heart rate. This application is not recommended.

Combinations of medicines requiring caution

The use of Coraxan in combination with other mild inhibitors of the CYP3A4 isoenzyme (eg, fluconazole) is possible,that the heart rate at rest is more than 60 bpm. The recommended initial dose of ivabradine is 2.5 mg twice a day. Need control of heart rate.

Inductors of the CYP3A4 isoenzyme such as rifampicin, barbiturates, phenytoin and herbal preparations containing St. John's Wort, when administered together, may lead to a decrease in blood concentrations and activity of ivabradine and require a higher dose of ivabradine. With the combined use of ivabradine and preparations containing St. John's wort, a two-fold decrease in ivabradine AUC was noted. In the period of therapy with the drug Coraxan should whenever possible avoid the use of drugs and products containing St. John's wort.

Combined use with other drugs

The absence of a clinically significant effect on the pharmacodynamics and pharmacokinetics of ivabradine has been demonstrated with simultaneous use of the following drugs: proton pump inhibitors (omeprazole, lansoprazole), PDE5 inhibitors (eg sildenafil), HMG-CoA reductase inhibitors (eg simvastatin), slow calcium channel blockers - dihydropyridine derivatives (for example, amlodipine, lacidipine), Digoxin and warfarin.It has been shown that 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.

Coroxane was used in combination with ACE inhibitors, angiotensin 2 receptor antagonists, beta adrenoblockers, diuretics, aldosterone antagonists, short and prolonged-action nitrates, HMG-CoA reductase inhibitors, fibrates, proton pump inhibitors, oral hypoglycemic agents, Acetylsalicylic acid and other antiplatelet agents means. The use of the above medicines was not accompanied by a change in the safety profile of the therapy.

Other interactions that require caution when combined

Against the background of taking grapefruit juice there was an increase in the concentration of ivabradine in the blood 2 times. During the period of therapy with Corraxan, grapefruit juice should be avoided whenever possible

Analogues of the drug Coraxan

Structural analogs for the active substance:

• Ivabradin;
• Ivabradine hydrochloride.

Analogues on the curative effect (agents for the treatment of angina pectoris):

• Altiazem PP;
• Amiodarone;
• Amlodipine;
• Anaprilin;
• Asparks;
• Aspirin Cardio;
• Atenolol;
• Betalk;
• Biol;
• Validol;
• Verapamil;
• Hypoxen;
• Diltiazem;
• Isoket;
• Isolong;
• Isoptin;
• Inosie F;
• Kalchek;
• Carvedilol;
• Cocarboxylase;
• Concor;
• Corvitol;
• Cordaflex RD;
• Cordipine;
• Corinfar;
• Corinfar retard;
• Lokren;
• Metocard;
• Metoprolol;
• Mildronate;
• Monolong;
• Monosan;
• Monochinkwe;
• Monochinkwe retard;
• Nitroglycerine;
• Nitromint;
• Nitrogen;
• Nifedipine;
• Nifecard;
• Normodipine;
• Papaverine;
• Plavix;
• Preductal MB;
• Prestan;
• Propranolol;
• Stamlo;
• Sustak forte;
• Sustonite;
• Tenox;
• Trimetazidine;
• Egilok;
• Egilok Retard;
• Efoks long.

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