Coraxan is a drug with anti-ischemic, antianginal action.
Release form and composition
Coraxan is produced in the form of film-coated tablets: pink-orange color, with an engraving of the company logo on one side; 5 mg each - biconvex, oval, with notches on both sides, with the number “5” on the second side; 7.5 mg each - triangular, with the number "7.5" on the second side (14 pieces in blisters, 1, 2, 4 blisters in a carton box).
The composition of 1 tablet includes:
- Active ingredient: ivabradine - 5 or 7.5 mg (ivabradine hydrochloride (respectively) - 5.39 or 8.085 mg);
- Auxiliary components: lactose monohydrate - 63.91 / 61.215 mg; maltodextrin 10 mg; magnesium stearate - 0.5 mg; corn starch - 20 mg; anhydrous colloidal silicon dioxide - 0.2 mg.
The composition of the film shell: titanium dioxide (E171) - 0,26026 mg; iron dye yellow oxide (E172) - 0,01457 mg; iron dye red oxide (E172) - 0.00485 mg; glycerol - 0.0874 mg; magnesium stearate - 0.0874 mg; hypromellose - 1,45276 mg; macrogol 6000 - 0.09276 mg.
Indications for use
Coraxan is prescribed for the treatment of stable angina in patients with normal sinus rhythm with the following indications:
- Intolerance or the presence of contraindications to the use of beta-blockers;
- Simultaneously with beta-adrenergic blockers with inadequate control of stable angina with optimally selected dose of beta-adrenergic blocker.
The drug is also used in chronic heart failure in order to reduce the incidence of cardiovascular complications (mortality from cardiovascular diseases and hospitalization due to an increase in symptoms of chronic heart failure (CHF)) in patients with chronic heart failure, with sinus rhythm and heart rate cuts (HR) of at least 70 beats per minute.
- Bradycardia (with a heart rate at rest before the start of treatment is less than 60 beats per minute);
- Acute myocardial infarction;
- Sick sinus syndrome;
- Sinoatrial blockade;
- Unstable Angina;
- Cardiogenic shock;
- Severe liver failure (on the Child-Pugh scale - more than 9 points);
- Severe arterial hypotension (with systolic pressure below 90 mm Hg, diastolic - below 50 mm Hg);
- Heart failure (unstable or acute);
- The presence of an artificial pacemaker working in the mode of constant stimulation;
- AV block III;
- Lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome;
- Simultaneous use with strong inhibitors of isoenzymes of the cytochrome P450 3A4 system (antifungal agents of the azoles group (itraconazole, ketoconazole)), HIV protease inhibitors (ritonavir, nelfinavir), macrolide antibiotics (clarithromycin, erythromycin for oral administration, telithromycin, and thytrathyromycymia, and erythromycin).
- Pregnancy, breastfeeding period and use in women of reproductive age who do not comply with reliable contraceptive measures;
- Age up to 18 years (the safety and efficacy of the drug in this age group of patients has not been studied);
- Hypersensitivity to the drug.
Caution should be taken when taking Coraxan for the following diseases / conditions:
- Severe renal failure (creatinine clearance less than 15 ml per minute);
- Congenital prolongation of the QT interval;
- Moderately severe liver failure (on the Child-Pugh scale - less than 9 points);
- AV block II degree;
- Retinal pigment degeneration (retinitis pigmentosa);
- A recent stroke;
- Chronic heart failure IV functional class according to the classification of NYHA;
- Simultaneously with taking prolonged QT interval drugs, grapefruit juice, moderate inhibitors and inducers of CYP3A4 isoenzymes, slow calcium channel blockers, which reduce heart rate (diltiazem, verapamil), non-sparing diuretics.
Dosing and Administration
Coraxan is taken orally during a meal 2 times a day (morning and evening).
With stable angina, the drug is taken in an initial daily dose of 10 mg.
After 21-28 days of use, depending on the therapeutic effect, the dose can be increased to 15 mg (2 times a day, 7.5 mg). If the heart rate at rest diminishes to less than 50 beats per minute during treatment, or the patient has symptoms associated with bradycardia (fatigue, dizziness, or marked reduction in blood pressure), reduce the dose of Coraxan (for example, to 5 mg per day). The drug is discontinued in cases where a dose reduction does not lead to an improvement in heart rate indicators or if the symptoms of severe bradycardia persist.
The recommended initial daily dose for chronic heart failure is 10 mg. If the heart rate at rest is steadily more than 60 beats per minute, after 2 weeks it can be increased to 15 mg (2 times a day, 7.5 mg). With a stable heart rate of no more than 50 beats per minute or when symptoms of bradycardia appear, the dose is reduced to 5 mg per day.
With a HR value in the range of 50-60 beats per minute, Coraxan is recommended to take 5 mg daily dose.
The dose of the drug depends on the heart rate:
- Less than 50 beats per minute (with a daily dose of 5 or 7.5 mg) - reduce the dose;
- More than 60 beats per minute (with a daily dose of 5 or 10 mg) - the dose is increased.
If the heart rate does not exceed 50 beats per minute or the patient has symptoms of bradycardia, use of Coraxan should be discontinued.
Patients over 75 are advised to prescribe Coraxan at an initial daily dose of 5 mg. In the future, you may increase the dose.
Patients with impaired renal function with creatinine clearance of more than 15 ml per minute, the drug is usually prescribed 10 mg per day. After 3-4 weeks of coraxan use, it is possible to increase the dose to 15 mg per day.
Due to the lack of data on the use of Coraxan in patients with creatinine clearance less than 15 ml per minute, the drug should be used with caution.
Patients with a mild degree of liver failure (on the Child-Pugh scale - up to 7 points) are recommended the usual dosing regimen in an initial daily dose of 10 mg with its subsequent increase to 15 mg.
Caution should be exercised when applying Coraxan to patients with moderate hepatic insufficiency (on a Child-Pugh scale - 7–9 points).
Coraxan should not be used in patients with severe liver failure (according to the Child-Pugh scale - more than 9 points), since its use in these patients has not been studied (a significant increase in the plasma concentration of the drug is not excluded).
During therapy may develop disorders of some body systems:
- Musculoskeletal System: Infrequently - muscle spasms;
- Digestive system: infrequently - constipation, nausea, diarrhea;
- Cardiovascular system: often - bradycardia, ventricular premature beats, AV-blockade I degree, short-term increase in blood pressure; infrequently - supraventricular premature beats, palpitations; very rarely - atrial fibrillation, AV-blockade II-III degree, sick sinus syndrome; with an unspecified frequency - marked reduction in blood pressure, possibly associated with bradycardia;
- Respiratory system: infrequently - shortness of breath;
- Central nervous system: often - dizziness, possibly associated with bradycardia, headache (especially in the first month of treatment); with unknown frequency - syncope, possibly associated with bradycardia;
- Skin and subcutaneous fat: with an unknown frequency - itching, skin rash, angioedema, erythema, urticaria;
- Sense organs: very often - changes in light perception (photopsia); often - blurred vision; infrequently - vertigo; with unknown frequency - visual impairment, diplopia;
- Laboratory and instrumental indicators: infrequently - prolongation of the QT interval on the ECG, eosinophilia, hyperuricemia, increase in plasma creatinine concentration;
- General disorders: with an unknown frequency - fatigue, asthenia, malaise.
Coraxan is not effective in treating or preventing arrhythmias. The effectiveness of the drug decreases with the development of tachyarrhythmias. The drug is not recommended for patients with atrial fibrillation or other types of arrhythmias associated with the function of the sinus node.
During treatment, it is necessary to conduct clinical observation of patients in order to identify paroxysmal or permanent atrial fibrillation. With clinical indications (for example, the appearance of a sensation of increased heartbeat, worsening of the course of angina, irregular heart rhythm), an ECG should be included in the process of current monitoring. The risk of atrial fibrillation is usually higher in patients with chronic heart failure taking Coraxan. More often, atrial fibrillation was found in patients who took anti-arrhythmic drugs of class I or amiodarone simultaneously with the drug.
The condition of patients with impaired intraventricular conduction, chronic heart failure and ventricular dyssynchrony should be kept under close supervision.
The use of Coraxan simultaneously with slow calcium channel blockers that reduce heart rate (diltiazem, verapamil) is not recommended.
Before starting therapy, the course of heart failure must be stable. Due to limited data, it is necessary to use the drug with caution in patients with chronic heart failure of the IV functional class according to the NYHA classification.
It is not recommended to prescribe Coraxan immediately after a stroke.
Coraxan affects the function of the retina. Toxic effects of the drug were not identified, but its effect on the retina of the eye with prolonged use (longer than 1 year) is unknown. With the development of disorders of visual functions not described in this manual, it is necessary to consider the issue of discontinuing therapy. Patients with retinal pigment degeneration are advised to take Coraxan with caution.
Coraxan can cause a short-term change in light perception (usually in the form of a photopsia), which must be taken into account when driving vehicles or other mechanisms, especially at night with a sharp change in the intensity of light.
It is necessary to avoid the simultaneous use of ivabradine with drugs prolong the interval QT (antiarrhythmics example, disopyramide, quinidine, bepridil, ibutilide, sotalol, amiodarone and non antiaritmikam example, sertindole, cisapride, pimozide, ziprasidone, mefloquine, pentamidine, halofantrine , erythromycin for intravenous administration). This is due to the fact that a decrease in heart rate can lead to an additional lengthening of the QT interval. If necessary, the simultaneous appointment of these drugs should be carefully monitored ECG.
Coraxan needs to be used with caution with non-calcareous diuretics (“loop” and thiazide diuretics), since hypokalemia may increase the risk of arrhythmias. Ivabradine can cause bradycardia, which in combination with hypokalemia is a predisposing factor for the onset of severe arrhythmias, especially in patients with the syndrome of lengthening the QT interval (congenital or caused by exposure to any substances).
Simultaneous use of ivabradine with moderate inhibitors of CYP3A4 isoenzyme verapamil or diltiazem is not recommended.
Contraindicated for concomitant use of ivabradine with such strong inhibitors isoenzyme CYP3A4, both nefazodone, antifungals group azoles (itraconazole, ketoconazole), HIV protease inhibitors (ritonavir, nelfinavir), macrolide antibiotics (erythromycin for oral, clarithromycin, telithromycin, josamycin). Strong inhibitors of the isoenzyme CYP3A4 - ketoconazole (in a daily dose of 200 mg) or josamycin (2 times a day, 1 g) increase 7-8 times the average plasma concentrations of ivabradine.
It is possible to take ivabradine simultaneously with other moderate inhibitors of the CYP3A4 isoenzyme (for example, fluconazole), provided that the heart rate at rest is more than 60 beats per minute. In this case, the recommended initial daily dose of ivabradine 5 mg. During Coraxan administration, heart rate monitoring is necessary.
When used together, inducers of the CYP3A4 isoenzyme (phenytoin, barbiturates, rifampicin, and herbal remedies that contain Hypericum perforatum) can lead to a decrease in activity and blood concentration of Ivabradine, which may require higher doses. During treatment, it is recommended to avoid the use of medicines and products with the content of Hypericum perforatum.
Clinically significant effect on the pharmacokinetics and pharmacodynamics of Ivabradine with the combined use of the following drugs: PDE5 inhibitors (sildenafil), proton pump inhibitors (lansoprazole, omeprazole), HMG-CoA reductase inhibitors (simvastatin), blockers, slow-acting calcium channel blockers, simulastatin, I, I, I, I, I, I, I, I, I, I, IUvradine, inhibitors of proton pump inhibitors, simulastatin, blockers, proton pump inhibitors; , amlodipine), acetylsalicylic acid, warfarin and digoxin is absent.
Terms and conditions of storage
Keep out of the reach of children. Special storage conditions are not required.
Shelf life - 3 years.