CORAXAN PILLS 5MG

Dosage form

Coated Tablets

Active ingredient

1 tab. contains ivabradine 5 mg; excipients: lactose monohydrate, Magnesium stearate, corn starch, maltodextrin, anhydrous colloidal silicon dioxide, hypromellose, titanium dioxide (E171), macrogol 6000, glycerol, magnesium stearate, ferric oxide yellow (E172), ferric oxide red (E172)

Packaging

56 pcs.

Mechanism of action

Coraxan has antianginal, anti-ischemic effects.

Indications and usage

Treatment of stable angina in patients with normal sinus rhythm with intolerance or contraindications to the use of beta-blockers.

Contraindications

• Hypersensitivity to ivabradine or any of the coraxan excipients;
• Heart rate at rest below 60 beats / min (before treatment);
• cardiogenic shock;
• acute myocardial infarction;
• severe hypotension (SBP is below 90 mm Hg and DAD is below 50 mm Hg);
• severe liver failure (more than 9 according to Child-Pugh classification);
• sick sinus syndrome;
• sinoatrial blockade;
• stage III – IV chronic heart failure according to the NYHA classification (due to the lack of sufficient clinical data);
• the presence of an artificial pacemaker;
• unstable angina;
• AV blockade of III degree;
• simultaneous use with such strong inhibitors of cytochrome P 4503А4, as antifungal agents of the azole group (ketoconazole, itraconazole), macrolide antibiotics (clarithromycin, Erythromycin for oral administration, josamycin, telithromycin), HIV protease inhibitors (nelfinavir, ritone), niophenvir, nirminavir, niolivavir, nirminavir, nirminavir, antibiotics, oral antimicrobials
• pregnancy;
• breastfeeding period;
• children's age (up to 18 years) (the effectiveness and safety of its use in this age group has not been studied).

Pregnancy and Breastfeeding

At the moment there are no data related to the use of Coraxan in pregnant women. In studies of the effect of the drug on reproductive function in animals, the embryotoxic and teratogenic effects of the drug were demonstrated. The potential risk of influencing the reproductive function in humans has not been established.Thus, Coraxan is contraindicated for use in pregnancy. In animal studies, it was found that ivabradine is excreted in breast milk. In this regard, the use of Coraxan during breastfeeding is contraindicated. Use in children and adolescents. Coraxan is not recommended for use in children and adolescents under 18 years of age, since its efficacy and safety have not been studied in this age group.

Dosage and administration

Coraxan is taken orally, with a double dosing regimen during the day, i.e. morning and evening with meals. The usual recommended starting dose of Coraxan is 10 mg / day (1 tab. 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 tab. 7.5 mg twice a day). If, during therapy, the heart rate decreases to less than 50 beats / min or the patient has symptoms associated with bradycardia (such as dizziness, fatigue, or arterial hypotension), a lower dose of the drug must be selected. If the decrease in the dose of Coraxan does not normalize the heart rate and remains at less than 50 beats / min, the drug should be withdrawn. Use in the elderly. The use of Coraxan in patients 75 years and older has been studied in a limited number of patients, therefore, for this age group, it is recommended to begin treatment with an initial dose of 2.5 mg (1/2 pills of 5 mg) 2 times a day; may increase the daily dose depending on the condition of the patient. Renal failure. With Cl creatinine above 15 ml / min, a normal dosing regimen is recommended.

Special notes

Cardiac arrhythmia

Coraxan is not effective in treating or preventing heart arrhythmias. Its effectiveness falls on the background of the development of tachyarrhythmias (for example, ventricular or supraventricular tachycardia). Also, Coraxan is not recommended for patients with atrial fibrillation (atrial fibrillation) or other types of arrhythmias associated with the function of the sinus node.

With Coraxan therapy, it is recommended to conduct regular monitoring for the development of atrial fibrillation (paroxysmal or permanent). In case of clinical indications (for example, in case of complicated stenocardia, marked heartbeat, irregular heart rhythm), an electrocardiogram (ECG) should be included in the current control.

AV blockade II degree.Coraxan is not recommended for treatment with AV block II.

Use in patients with low heart rate. Coraxan is not recommended for patients who have a heart rate below 60 beats / min before prescribing.

If, during therapy, the heart rate decreases to less than 50 beats / min, or the patient has symptoms associated with bradycardia (such as dizziness, fatigue, or hypotension), a lower dose of the drug should be selected. If the decrease in the dose of Coraxan does not normalize the heart rate and remains at less than 50 beats / min, the drug should be withdrawn.

Combined use as part of antianginal therapy.The use of Coraxan in conjunction with BCA, slowing heart rate, such as Verapamil or diltiazem, is not recommended.

With the combined use of Coraxan with nitrates, BPC derivatives of the dihydropyridine series (such as amlodipine), no effect on safety and efficacy has been identified.

Chronic heart failure. Before prescribing Coraxan, the patient should be examined for chronic heart failure. In the presence of chronic heart failure functional class III – IV (NYHA classification), Coraxan is contraindicated due to the lack of sufficient data on the efficacy and safety of the drug. Due to the insufficient number of patients examined, the drug should be prescribed with caution in asymptomatic dysfunction of the left ventricle and in chronic heart failure class II (according to the NYHA classification).

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

Functions of visual perception (Visual function). Coraxan acts on the function of the retina. Currently, there is no evidence of the toxic effect of ivabradine on the reticular membrane of the eye. The effects of Coraxan on the retina with long-term use are not known today. In case of occurrence of violations of visual functions not described in the instructions, it is necessary to consider the issue of discontinuing Coraxan. The drug should be taken with caution in patients with retinal pigment degeneration (retinitis pigmentosa).

Excipients. The composition of the excipients of the drug includes lactose, so patients with intolerance to galactose, Lapp lactase deficiency or glucogalactose absorption taking the drug Coraxan is not recommended.

Hypotension. Because of the insufficient amount of clinical data, Coraxan should be used with caution in patients with mild and moderate arterial hypotension.

Coraxan is contraindicated in severe hypotension (DAD below 90 mm Hg and SBP below 50 mm Hg);

Atrial fibrillation (atrial fibrillation) - cardiac arrhythmias

There is no evidence of the risk of developing bradycardia in patients receiving Coraxan when sinus rhythm is restored during pharmacological cardioversion. However, due to the lack of sufficient data, if it is possible to postpone DC-cardioversion, Coraxan should be stopped 24 hours before it is carried out.

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

Coraxan should not be prescribed for congenital long QT syndrome, as well as when combined with drugs that slow the QT interval. If it is impossible to avoid therapy with Coraxan, a careful cardiocontrol should be performed.

Mild liver failure. In moderate liver failure, coraxan therapy should be carried out with caution.

Severe renal failure. In severe renal failure (Cl creatinine

Influence on ability to drive vehicles and to perform the works demanding high speed of psychomotor reactions.It was shown that the use of Coraxan mainly does not affect the ability to drive a car, but due to the possibility of photopsia, caution should be exercised when driving and / or performing work that requires a high speed of psychomotor reactions.

Pharmacodynamic interaction

Not recommended combinations

Drugs that prolong the QT interval (eg, quinidine, disopyramide, bepridil, sotalol, ibutilide, amiodarone).

Drugs that prolong the QT interval, not related to cardiovascular agents (for example, pimozide, ziprasidone, sertindol, mefloquine, halofantrine, pentamidine, cisapride, erythromycin i / v).

Combined use with drugs that extend the QT interval, can increase the decrease in heart rate, therefore, if necessary, a joint appointment should be carried out by careful cardiac monitoring.

Pharmacokinetic interaction

Cytochrome P4503A4 (CYP3A4).Ivabradine is metabolized in the liver by enzymes of the cytochrome P450 system (CYP3A4) and is a very weak inhibitor of this cytochrome. Ivabradine has no significant effect on the metabolism and plasma concentration of other cytochrome CYP3A4 substrates. At the same time, inhibitors and inducers of CYP3A4 interact with ivabradine and affect its metabolism and pharmacokinetic properties. Cytochrome CYP3A4 inhibitors have been found to increase, while cytochrome CYP3A4 inducers reduce plasma concentrations of ivabradine. Increasing the plasma concentration of ivabradine increases the risk of developing bradycardia.

Contraindications

The simultaneous use of potent inhibitors of cytochrome P450, such as antifungals group azoles (ketoconazole, itraconazole), macrolide antibiotics (clarithromycin, erythromycin, oral, josamycin, telithromycin), HIV protease inhibitors (nelfinavir, ritonavir) and nefazodone, Ketoconazole (in a dose of 200 mg 1 time per day) or josamycin (at a dose of 1 g 2 times a day), increase the average concentration of ivabradine in the blood plasma by 7–8 times.

Not recommended combinations

Moderate CYP3A4 inhibitors. The combined use of ivabradine and hearth-reducing agents, diltiazem or verapamil, was well tolerated by patients and was accompanied by an increase in the concentration of ivabradine by 2–3 times, with an additional decrease in heart rate of about 5 beats / min.

This combination is not recommended.

Combinations that require caution when applying

Moderate CYP3A4 inhibitors. Simultaneous use of ivabradine with other CYP3A4 inhibitors (for example, fluconazole) should begin with an initial dose of 2.5 mg 2 times a day. With heart rate less than 60 beats./min, careful monitoring of heart rate is necessary.

Grapefruit juice. While taking grapefruit juice, there was a 2-fold increase in the concentration of ivabradine in the blood. During the period of therapy with ivabradine, the intake of grapefruit juice should be minimized.

Inductors CYP3A4, such as rifampicin, barbiturates, phenytoin and herbal preparations containing St. John's wort Hypericum perforatum, when used together, can lead to a decrease in blood concentration and activity of ivabradine and require the selection of a higher dose of ivabradine.During therapy with ivabradine, the use of drugs and products containing St. John's wort should be kept to a minimum.

Combined use with other drugs

It has been demonstrated no clinically significant effect on the pharmacodynamics and pharmacokinetics of ivabradine following drugs: inhibitors of proton pump (omeprazole, lansoprazole), inhibitors of phosphodiesterase-5 (sildenafil), inhibitors of HMG-CoA reductase inhibitor (simvastatin), BPC-derivatives of dihydropyridine (amlodipine, lacidipine ) Digoxin and Warfarin .

Ivabradine has not been shown to have a clinically pronounced effect on the pharmacokinetics of Simvastatin , Amlodipine , lacidipine, the pharmacokinetics and pharmacodynamics of digoxin, warfarin and the pharmacodynamics of Acetylsalicylic acid .

In a pilot phase III study, the use of the following medicines had no special restrictions, and therefore they can be administered in combination with ivabradine without special precautions: ACE inhibitors, angiotensin II receptor antagonists, diuretics, short and long-acting nitrates, HMG- inhibitors CoA reductase, fibrates, proton pump inhibitors, oral hypoglycemic agents, acetylsalicylic acid and other antithrombotic agents.

Symptoms: development of severe prolonged bradycardia poorly tolerated by patients.

Treatment: symptomatic, is carried out in specialized departments. In the case of the development of bradycardia in combination with adverse changes in hemodynamic parameters, symptomatic treatment is shown with intravenous administration of beta-adrenomimetics, such as isoprenaline. If necessary, consider the possibility of temporary installation of an artificial pacemaker.

In the dark place at a temperature of no higher than 15 ° C.

3 years.