Pharmacological properties of the drug Coraxan
Ivabradine is a cardiac drug that opens a new pharmacotherapeutic class. Ivabradine has an effect solely on heart rate. Ivabradine acts by selectively and specifically inhibiting sinus node f channels, controlling spontaneous diastolic depolarization of the sinus node and reducing heart rate. Ivabradine acts only at the level of the sinus node and does not affect intraatrial, atrioventricular and intraventricular conduction, myocardial contractility and ventricular repolarization. Ivabradine does not change the QT -corrected index. Ivabradine can also interact with retinal h-channels, which are structurally similar to the f-channels of the sinus node of the heart. This can lead to temporary impairment of light perception due to a decrease in the retinal response to bright light stimuli. Trigger factors (sharp changes in lighting), partial inhibition of h-channels determine the possibility of developing photopsia (unwanted transient visual impairment in a limited area of the visual field). The main pharmacodynamic feature of ivabradine in humans is a selective reduction exclusively in heart rate. When using the usual recommended dose (5 or 7.5 mg 2 times a day), there is a decrease in heart rate by approximately 10–15 beats/min (depending on the initial heart rate) at rest and during exercise. This reduces the work of the heart and reduces oxygen consumption by the myocardium. The antianginal and anti-ischemic effectiveness of Coraxan has been proven in four randomized, blind, placebo-controlled studies (2 compared with placebo and 1 each with atenolol and amlodipine). These studies included 3222 patients with stable angina, of whom 2168 received ivabradine. Already after 3–4 weeks of treatment with ivabradine at a dose of 5 mg 2 times a day, its effectiveness was proven (according to physical stress tests). Additional benefits of ivabradine at a dose of 7.5 mg 2 times a day were proven in a controlled comparative study with atenolol. After 1 month of treatment with ivabradine at a dose of 5 mg 2 times a day, the duration of the exercise test in the interdose period increased by 1 minute. The dose of ivabradine was increased to 7.5 mg 2 times a day, and after 3 months of use, a further increase in the duration of the load by approximately 25 s was noted. In this study, the antianginal and anti-ischemic benefits of ivabradine were confirmed in patients aged 65 years and older. The effectiveness of ivabradine in doses of 5 and 7.5 mg 2 times a day was constant in all studies in all parameters (total duration of exercise, time to the development of an angina attack, time to the development of ST by 1 mm) and was accompanied by a decrease in the number of attacks of stable angina pectoris by approximately 70%. The dosing regimen of ivabradine 2 times a day provided a stable effective effect for 24 hours. The effectiveness of ivabradine was confirmed in studies that lasted 3–4 months. During treatment, there were no cases of pharmacological tolerance (loss of effectiveness) or withdrawal effects after sudden cessation of treatment. The antianginal and anti-ischemic effects of ivabradine were accompanied by a dose-dependent decrease in heart rate and a possible decrease in double product (DP) at rest and during exercise (DP is an indicator reflecting the myocardial oxygen demand, DP = heart rate • systolic blood pressure). The effect of ivabradine on blood pressure and peripheral vascular resistance was minimal and not clinically significant. A 1-year study of ivabradine in 713 patients confirmed a reduction in heart rate and demonstrated no effect of ivabradine on glucose and lipid metabolism. Studies have proven the anti-ischemic and antianginal effectiveness of ivabradine in patients with diabetes mellitus. The safety profile of ivabradine in this population did not differ from the safety profile in the general population. Clinical studies have proven the antianginal effectiveness of ivabradine, due to a selective decrease in heart rate in the absence of a negative effect on myocardial contractility and conductivity. The 4-month ASSOCIATE study involving 880 patients with angina pectoris demonstrated additional anti-ischemic efficacy of ivabradine when administered together with a beta-adrenergic blocker (atenolol 50 mg). According to the treadmill test, the increase in the total duration of physical activity during treatment with ivabradine and a β-adrenergic receptor blocker was 3 times higher than the result obtained using a β-adrenergic blocker alone. The use of ivabradine together with a β-adrenergic receptor blocker significantly improves stress test parameters and is safe in patients with coronary artery disease. In the double-blind, placebo-controlled BEAUTIFUL trial involving 10,917 patients with coronary artery disease and left ventricular dysfunction, treatment with ivabradine, given in addition to optimal preventive treatment (acetylsalicylic acid, beta-blocker, statin, ACE inhibitor) reduced the risk of myocardial infarction by 36 % and the need for revascularization by 30% in patients with coronary artery disease and heart rate 70 beats/min. High clinical efficacy and tolerability make the use of ivabradine particularly advisable in patients with restrictions or contraindications to the use of beta-blockers or for co-administration with beta-adrenergic blockers. After oral administration, ivabradine is rapidly released and dissolves well (10 mg/ml). Ivabradine is rapidly and almost completely absorbed. The maximum plasma concentration is reached after approximately 1 hour. The bioavailability of ivabradine is approximately 40%. Eating food does not affect the rate of absorption and concentration of ivabradine. Approximately 70% of ivabradine is bound to plasma proteins. The maximum plasma concentration with long-term use of the drug at the recommended initial dose of 5 mg 2 times a day is approximately 22 ng/ml. The average concentration in blood plasma at the stable concentration stage is 10 ng/ml. Ivabradine is extensively metabolized in the liver and intestines by oxidation by the cytochrome P450 3A4 (CYP 3A4) system. The main active metabolite of ivabradine is its N-desmethylated derivative (S18 982), its concentration is 40% that of ivabradine hydrochloride, and it has the same pharmacokinetic and pharmacodynamic properties. The main active metabolite is also metabolized by the CYP3A4 cytochrome system. Ivabradine has low affinity for CYP 3A4 and does not activate or inhibit it, thus it will not significantly alter the metabolism of CYP 3A4 or its plasma concentration. Conversely, CYP3A4 inhibitors and stimulants may significantly affect the plasma concentrations of ivabradine. The half-life of ivabradine is 2 hours, the effective half-life is 11 hours. The total clearance of ivabradine is 400 ml/min. Renal clearance of ivabradine is 70 ml/min. Excretion of metabolites and a small amount of unchanged active substance occurs equally in urine and feces. Approximately 4% of the active substance is excreted unchanged in the urine. The kinetics of ivabradine for doses of 0.5–24 mg is linear. Analysis of the pharmacokinetics/pharmacodynamics ratio demonstrated a linear dependence of the decrease in heart rate on the increase in the concentration of ivabradine and its active metabolite in the blood plasma for doses of 15–20 mg. High plasma concentrations of ivabradine may be due to its use in combination with strong CYP3A4 inhibitors, which can lead to a significant decrease in heart rate; the risk is reduced when used with moderate CYP3A4 inhibitors.
How to take Coraxan for VSD?
VSD sufferers often feel helpless in the face of their pseudo-illness. And if medications famous among dystonics suddenly turned out to be useless or worsened the condition, then the matter could end in global depression. Thus, some patients cannot tolerate beta-blockers, and drugs to restore normal heart rate, unfortunately, change blood pressure. But what if the heart rate goes off scale, preventing you from living and breathing freely?
Less panic, gentlemen! Modern medications are unlikely to allow the heart to take precedence over other problems. Some patients are prescribed Coraxan for VSD, which literally saves their fate.
Use of the drug Coraxan
Orally. Prescribed for adults 2 times a day, morning and evening during meals. Coraxan 5 mg tablet can be divided; 7.5 mg tablets are not split. The recommended starting dose of ivabradine is 5 mg 2 times a day (1 tablet of Coraxan 5 mg 2 times a day). After 3–4 weeks of treatment, if further reduction in heart rate is necessary, the dose can be increased to 7.5 mg 2 times a day (1 tablet of Coraxan 7.5 mg 2 times a day). If during the treatment period the heart rate becomes less than 50 beats/min or the patient experiences symptoms resulting from bradycardia, it is necessary to reduce the dose of the drug by titration, including the possibility of using ivabradine at a dose of 2.5 mg 2 times a day (1/2 t of Coraxan tablets 5 mg 2 times a day). The maximum recommended therapeutic daily dose of ivabradine is 15 mg. If the heart rate remains less than 50 beats per minute, stop using the drug. The use of Coraxan 5 mg in elderly patients, patients with heart failure, mild to moderate chronic renal and liver failure, diabetes mellitus, and asthma does not require dose adjustment.
Composition of the medicine
In pharmacies you can find Coraxan 5 and 7.5 milligrams. 1 tablet of five milligrams of the drug contains: ivabradine (5.39 mg), lactose monohydrate, magnesium stearate, corn starch, glycerol and other additional substances.
Coraxan 7.5 mg per tablet contains: ivabradine hydrochloride (8.085 milligrams), corresponding to pure ivabradine (7.5 mg). The medication also contains other additional components (lactose monohydrate, magnesium stearate, macrogol 6 thousand, hypromellose and others).
Contraindications to the use of the drug Coraxan
Hypersensitivity to ivabradine or other components of the drug; bradycardia (heart rate at rest less than 60 beats/min); cardiogenic shock; severe liver failure; sick sinus syndrome; sinoatrial block; the patient has an artificial pacemaker; AV block of the third degree; combination with strong and moderate CYP 3A4 inhibitors (antifungal drugs - azole derivatives (ketoconazole, etc.), macrolide antibiotics (clarithromycin, erythromycin for oral use, josamycin, telithromycin), antiviral drugs (nelfinavir, ritonavir and nefazodone); pregnancy and breastfeeding; acute myocardial infarction and unstable angina (due to lack of clinical data); severe hypotension - blood pressure less than 90/50 mmHg (due to insufficient clinical data); heart failure of functional classes III-IV according to NYHA (due to lack of clinical data).
In what cases is the drug prescribed?
Taking the medication Coraxan is advisable for persistent chronic angina and heart failure. Coraxan copes well with the symptoms of angina pectoris in people with coronary heart disease, sinus rhythm and a pulse of more than 70 beats per minute.
The drug is prescribed primarily to patients with the following indications: angina pectoris and heart failure. It reduces the risk of heart and vascular diseases. It is recommended to take the tablets for patients with chronic heart failure, with sinus rhythm and pulse more than 70 beats/min.
Side effects of the drug Coraxan
Side effects of ivabradine are dose-dependent and due to its pharmacological mechanism of action. Visual impairment (1/10)
Photopsia (light flashes appearing before the eyes - increased brightness in the visual field) are observed in approximately 14.5% of patients and are transient in nature. Photopsia are usually initiated by sudden changes in light intensity and occur during the first 2 months of treatment. Typically, photopsia is mild or moderate and resolves spontaneously during treatment in 77.5% of patients or upon cessation of treatment. In less than 1% of patients, the development of ophthalmological symptoms requires discontinuation of treatment. Blurred vision (1/100, ≤1/10). From the cardiovascular system (1/100, ≤1/10)
- Bradycardia . In 3.3% of patients, bradycardia may occur in the first 2–3 months of treatment. 0.5% of patients have a severe form of bradycardia (heart rate less than 40 beats/min);
- AV block of the first degree;
- Ventricular extrasystole. Very rarely (1/1000, ≤ 1/100) increased heart rate and supraventricular extrasystole may occur.
From the gastrointestinal tract Rarely (1/1000, ≤1/100), nausea, constipation or diarrhea may occur. From the side of the central nervous system : Possible occurrence (1/100, ≤1/10) of headache (in the first months of use), dizziness (reliably associated with bradycardia). Laboratory parameters rarely (1/1000, ≤1/100) may increase the level of creatinine and uric acid in the blood plasma, eosinophilia. Other manifestations (1/1000, ≤ 1/100) - convulsions, dyspnea.
Why is this drug needed?
Coraxan belongs to the group of drugs specifically for the heart and blood vessels and has an antianginal effect. The active substance is ivabradine, which is supplied in tablets in different dosages: 5 or 7.5 mg.
Note to the VSD person: the antianginal effect (in Greek “angi” means “against”, and “angina” means “angina pectoris”) is a special therapeutic effect. It does not consist in eliminating pain symptoms, but in influencing the heart in such a way as to reduce the need for oxygen (increasing its delivery to the heart muscle) - and therefore make the heart work calmer, slower.
Coraxan is essentially not intended for patients with VSD, but still often ends up in their first aid kits. Tachycardia is one of the most common symptoms of vegetative-vascular dystonia, which, while not deadly, still carries a hidden threat. Dystonics are not always able to calm their pounding hearts with sedative drops or the power of thought. After all, the work of the heart is regulated by the body’s autonomous systems, which do not obey only our “wants”. Anything can trigger tachycardia: from a banal temperature change outside the window to some kind of outburst of memories from the depths of the subconscious. But most often our heart plays with our restless central nervous system, which with dystonia every now and then breaks down, like an operating system infected with viruses.
And, if Anaprilin aggravates the situation (besides, this is a rather harmless drug, it is not suitable for regular use), Coraxan comes to the rescue: for VSD, it is good because it does not affect blood pressure in any way. But this drug is prescribed to dystonics only if all other remedies do not have the desired effect or are simply not suitable for the patient.
Special instructions for the use of the drug Coraxan
Patients with diabetes mellitus and asthma should adhere to the same recommendations regarding route of administration and dosage as other patients. Taking into account the limited number of patients aged 75 years and older who took part in studies of ivabradine, treatment of such patients begins with a dose of 2.5 mg (1/2 t of Coraxan 5 mg tablets) 2 times a day. If it is necessary to further reduce heart rate, the dose can be increased by titration. Ivabradine should not be prescribed to prevent or treat arrhythmias. If a patient experiences tachyarrhythmia (ventricular or supraventricular) during treatment with ivabradine, treatment with ivabradine is not advisable. Ivabradine is not recommended for use in patients with atrial fibrillation and other types of arrhythmias that impair sinus node function. When treating with ivabradine, it is necessary to regularly monitor the patient’s condition in order to exclude the possibility of developing atrial fibrillation (paroxysmal or permanent) and, if necessary, conduct an ECG study. Ivabradine is not recommended for patients with second degree AV block. It is not recommended to prescribe ivabradine to patients with a heart rate ≤60 beats/min at rest. If during treatment the heart rate becomes less than 50 beats/min or the patient experiences symptoms that are a consequence of bradycardia (dizziness, weakness, hypotension), it is necessary to reduce the dose by titration, including the possibility of using ivabradine at a dose of 2.5 mg (1/2 t tablet drug Coraxan 5 mg) 2 times a day. If the heart rate remains below 50 beats/min, the use of ivabradine should be discontinued. A study in patients with heart failure (left ventricular ejection fraction 30–45%) demonstrated that ivabradine did not have a negative effect on ejection fraction in these patients. Use with caution in patients with asymptomatic left ventricular dysfunction and in patients with NYHA functional class II heart failure (due to the lack of sufficient data). The mechanism of action of ivabradine determines its effect on retinal function. To date, there is no data regarding the toxic effect of ivabradine on the retina when ivabradine is used for a year. There are no data regarding longer-term use of ivabradine at this time. If unexpected (see SIDE EFFECTS) retinal abnormalities occur, treatment should be discontinued. Use with caution in patients with retinitis pigmentosa. Ivabradine is not recommended for use in patients immediately after a stroke (due to the lack of clinical data). Ivabradine is not recommended for use in children and adolescents, as studies have not been conducted in this group of patients. The drug contains lactose, so it should not be prescribed to patients with congenital galactose intolerance, glucose-galactose malabsorption syndrome, or Lapp lactase deficiency. Ivabradine is not recommended for use with calcium channel blockers that reduce heart rate (verapamil or diltiazem). There are no data regarding the safety of ivabradine in studies of short- and long-acting nitrates and dihydropyridine calcium channel blockers (amlodipine). Ivabradine should be used with caution in patients with mild to moderate hypotension (due to insufficient data). There have been no reports regarding the risk of severe bradycardia during restoration of sinus rhythm following pharmacological cardioversion in patients treated with ivabradine. Despite this, due to the lack of sufficient data, DC cardioversion is not recommended earlier than 24 hours after the last dose of ivabradine. Ivabradine is not recommended for use in patients with congenital long QT and in patients taking drugs that prolong the QT . If it is necessary to prescribe ivabradine to such patients, it is necessary to periodically monitor heart rate and QT . Patients with mild hepatic impairment do not require dose adjustment. Ivabradine should be prescribed with caution to patients with moderately severe liver failure. Patients with a creatinine clearance of 15 ml/min do not require dose adjustment. Ivabradine should be administered with caution to patients with creatinine clearance ≤15 ml/min (due to insufficient data). There has been no negative effect of ivabradine on the ability to drive vehicles or operate machinery, however, the use of ivabradine may cause transient visual impairment (the appearance of flashes of light in front of the eyes or blurred vision), which is usually initiated by sudden changes in light intensity. This must be taken into account when driving vehicles and operating machinery. There is no drug withdrawal syndrome observed.
Treatment and exact dosage
Coraxan is prescribed to adults and is available in tablet form. Take tablets 2 times a day, preferably with meals. A dose of 5 milligrams can be divided into equal parts, but a dose of 7.5 milligrams cannot be divided in half.
Treatment of chronic angina should be carried out after measuring the pulse and obtaining the results of the electrocardiogram. Patients under the age of 75 years take an initial dose orally not exceeding 5 mg twice every 24 hours. Then you need to drink 2.5 or 5 milligrams of ivabradine twice a day for a month.
If the symptoms do not go away, the doctor increases the daily dose (it should not be more than 7.5 milligrams twice a day). If therapy does not help within three months, the medication should be changed. Therapy should also be discontinued if side effects occur. When your heart rate drops to 50 beats per minute, you need to drink only half a tablet twice a day and monitor your heart rate.
Chronic heart failure is treated as follows: take 5 mg tablets twice a day. Then, after 2 weeks, you need to take 7.5 milligram tablets, also twice a day. During therapy, the pulse should remain at least 60 beats per minute in a calm state of the body. If the heart rate is lower, then the dose is reduced (half a tablet twice a day).
The appointment of Corexan should be considered and careful for patients with liver and kidney diseases. If necessary, the dose is adjusted and effective therapy is carried out.
Children under 18 years of age are not prescribed pills, since their positive and negative effects on the body have not been studied. Pregnant women should not take the medication, as it can adversely affect the reproduction and vital functions of the fetus. You should also not take medicine while breastfeeding, because the active substances and excipients, if released into breast milk, can harm the baby.
Interactions of the drug Coraxan
Pharmacodynamic interactions Ivabradine is not recommended for use in combination with drugs that prolong the QT interval, namely:
- cardiac drugs (quinidine, disopyramide, bepridil, sotalol, ibutilide, amiodarone);
- other drugs that prolong the QT (pimozide, ziprasidone, sertindole, mefloquine, halofantrine, pentamidine, cisapride, erythromycin IV).
Prolongation of the QT resulting from the use of the above drugs may increase due to a decrease in heart rate. Should be used with caution. Pharmacokinetic interactions Inhibitors or stimulators of cytochrome P450 3A4 (CYP 3A4). Not recommended for use in combination with moderate CYP3A4 inhibitors. Concomitant use of ivabradine and diltiazem or verapamil is not recommended. Use with caution Other moderate CYP3A4 inhibitors (fluconazole and others). Treatment with ivabradine can be started with a dose of 2.5 mg 2 times a day. Heart rate monitoring is necessary. Drinking grapefruit juice is not recommended during treatment with ivabradine. Grapefruit juice can cause an increase in the concentration of ivabradine in the blood plasma and an increase in the effect relative to the decrease in heart rate. CYP3A4 stimulants such as rifampicin, barbiturates, phenytoin, St. John's wort (Hypericum perforatum). The simultaneous use of these drugs with ivabradine may lead to a decrease in the concentration of ivabradine and therefore there may be a need to adjust the dose of ivabradine. Other drugs Targeted drug interaction studies have demonstrated the absence of any clinically significant pharmacokinetic or pharmacodynamic interactions between ivabradine and the following drugs: HMG Co-A reductase inhibitors (simvastatin), proton pump inhibitors (omeprazole, lansoprazole), dihydropyridine calcium channel blockers (amlodipine). , lacidipine), digoxin and warfarin. Clinical studies have shown the possibility of using ivabradine with ACE inhibitors, angiotensin II antagonists, diuretics, short- and long-acting nitrates, fibrates, oral antidiabetic agents, acetylsalicylic acid and other antithrombotic drugs.
Analogs
Coraxan has several analogues. List of the most common:
- Bravadin – contains the same active substance and is taken as an antianginal agent. An effective medicine for angina, congestive and chronic heart failure.
- Metocard is a medicine that copes well with diseases: angina pectoris, primary and secondary hypertension, supraventricular tachycardia, cardiac arrhythmias and others. The active substance of the drug is metoprolol tartrate and auxiliary agents (lactose, rice starch, magnesium stearate and others).
- Advocard is a combined medication that has anti-ischemic, antioxidant, anti-hypoxic and anti-sclerotic effects. Advocard will help cure chronic heart disease, improve health and will be an excellent analogue of the drug Coraxan.
