Ivabradine

When ATH:
C01EB17

Pharmacological action.
Antianginalnoe.

Application.

Stable angina pectoris in patients with normal sinus rhythm in case of intolerance or contraindication to the use of beta-blockers.

Contraindications.

Hypersensitivity, Resting heart rate below 60 u. / min (before treatment), cardiogenic shock, acute myocardial infarction, severe hypotension (Sad below 90 mm Hg. Article. and DBP below 50 mm Hg. Art.), severe liver failure (more 9 points on the Child-Pugh classification), sick sinus syndrome, blue-atrialьnaя blockade, chronic heart failure III-IV Article. NYHA classification (due to the lack of sufficient clinical experience), the pacemaker, unstable angina, AV blockade II–III century., acute ischemic stroke, concomitant use of potent inhibitors of CYP3A4 (incl. ketoconazole, itraconazole, clarithromycin, Erythromycin, dzhozamitsin, telithromycin, Nelfinavir, ritonavir, nefazodon), galactose intolerance, lactase deficiency, glucose-galaktoznaya nedostatochnosty (for LF, containing lactose), pregnancy, lactation, Age to 18 years (efficacy and safety have not been established).

Restrictions apply.

Asymptomatic left ventricular dysfunction, Chronic heart failure Article II. (NYHA classification), pigmentnaya degeneration setchatki, mild to moderate hypotension, -moderate hepatic insufficiency, severe chronic renal failure (Cl creatinine <15 ml / min).

Pregnancy and breast-feeding.

There are no data on the use of ivabradine in pregnancy in humans.

Animal studies have shown embryotoxic and teratogenic effects.

Ivabradine is excreted in breast milk.

Side effects.

Often (>1/10): mild or moderate photopsia (14,5%) mainly in the first 2 months of treatment followed by a repetition. Manifestation photopsias stopped after the completion of therapy, So, In most cases (77,5%), and during its implementation. In 1% patients photopsias appearance caused the refusal of treatment or change the normal daily routine. Often (>1/100 and <1/10): blurred vision; bradycardia (3,3%), especially during the first 2-3 months of treatment, incl. heavy with HR 40 u. / min or lower (0,5%), AV blockade of the 1st century., ventricular premature beats; headache, particularly in the first month of treatment, dizziness (possibly related to bradycardia). Sometimes (>1/1000 and <1/100): heartbeat, supraventricular arrhythmias; nausea, constipation, diarrhea; dizziness, breathlessness, muscle cramps; hyperuricemia, eozinofilija, giperkreatininemiя. Communication with the reception of ivabradine is not installed: sinus arrhythmia, unstable angina, worsening of angina, atrial fibrillation, myocardial ischemia, myocardial infarction, ventricular tachycardia.

Cooperation.

The combined use of drugs, prolonging the QT interval (incl. quinidine, disopyramide, bepridil, sotalol, iʙutilid, Amiodarone, pimozid, ziprasidon, sertindole, mefloxin, galofantrin, pentamidine, cisapride, Erythromycin in /) can enhance the slowing of the heart rate, so simultaneous use is not recommended (if necessary, joint appointment should be careful cardiac monitoring). In a joint application with drugs, slows heart rate (diltiazem, verapamil) there was an increase in the concentration of ivabradine 2-3, thus further slowing of the heart rate was 5 u. / min. No significant effect on the metabolism and plasma concentrations of other drugs, metabolized with the participation of the CYP3A4 isoenzyme of cytochrome P450. Inhibitors of CYP3A4 increase (the risk of bradycardia), and inductors — reduce plasma concentrations of ivabradina. Contraindicated in combination: potent inhibitors of the cytochrome P450, incl. azole antifungals (ketoconazole, itraconazole), macrolide antibiotics (clarithromycin, oral erythromycin, dzhozamitsin, telithromycin), HIV protease inhibitors (Nelfinavir, ritonavir) and nefazodone. Ketoconazole (200 mg / day) or josamycin (1 g 2 once a day) increases the average concentration in the blood plasma of ivabradine 7-8 times. The use of ivabradine with moderate CYP3A4 inhibitors (incl. fluconazole) It must begin with a dose 2,5 mg 2 once a day. When the heart rate less 60 u. / min should be closely monitored heart rate. Grapefruit juice increases the concentration of ivabradine in blood 2 times. CYP3A4 inductors (rifampicin, barbiturates, phenytoin, and herbal preparations, containing St. John's wort) -decreased concentration and activity ivabradina (the need for a higher dose of ivabradine). Do not have a clinically meaningful effect on the pharmacokinetics and pharmacodynamics of ivabradine: proton pump inhibitors (omeprazole, lansoprazole), PDE5 inhibitors (sildenafil citrate), HMG-CoA reductase (simvastatin), BAC-derived digidropiridina (amlodipine, lacidipine), digoxin and warfarin. Ivabradine no clinically significant effect on the pharmacokinetics and pharmacodynamics of simvastatin, amlodipina, lacidipine, digoksina, varfarina, acetylsalicylic acid. It may be administered in combination with an ACE inhibitor, angiotensin II receptor antagonists, Diuretics, nitrates short and prolonged action, HMG-CoA reductase, fiʙratami, proton pump inhibitors, oral hypoglycemic drugs, acetylsalicylic acid, and other antiplatelet agents.

Overdose.

Symptoms: vыrazhennaya bradycardia.

Treatment: symptomatic, in specialized units: in / with the introduction of beta-agonists (Isoprenaline), If necessary, temporary installation of artificial driver rhythm.

Dosing and Administration.

Inside, 2 once a day (in the morning and in the evening), while eating. The recommended initial dose is 10 mg / day (by 5 mg 2 once a day). Depending on the therapeutic effect after 3-4 weeks the daily dose may be increased to 15 mg (by 7,5 mg 2 once a day). If the therapy reduced heart rate of less than 50 u. / min or symptoms occur, associated with bradycardia (dizziness, fatigue or decreased blood pressure), necessary to use a lower dose. If the dose is lowered heart rate returns to normal and remains less 50 u. / min, drug overturned. In elderly patients treatment should be started with a dose of 2,5 mg (1/2 for tablets 5 mg) 2 once a day, possible to increase the daily dose depending on the patient.

Precautions.

Not effective for the treatment or prophylaxis of cardiac arrhythmias. Efficiency is reduced to background tachyarrhythmias (incl. ventricular or supraventricular tachycardia). Not recommended for patients with atrial fibrillation or other types of arrhythmias, associated with sinus node dysfunction. During treatment, regular monitoring is recommended to detect paroxysmal or persistent atrial fibrillation. When complicated by angina, expressed heartbeat, arrhythmia monitoring should include an electrocardiogram. Before assigning the patient should be examined for the presence of chronic heart failure.

There is currently no data on the toxic effect of ivabradine on the retina, incl. prolonged use. If you have not described above impairment is necessary to consider the abolition of the drug. There is no evidence of risk of bradycardia in patients receiving the drug in restoring sinus rhythm during pharmacological cardioversion. Nonetheless, due to lack of sufficient data should, if possible delay cardioversion DC, and the drug should be discontinued 24 hours before the event. It should appoint a congenital long QT syndrome, as well as in combination with PM, slowing down the QT interval. If it is impossible to avoid ivabradine therapy must be carefully cardio.

In the period of treatment should be kept to a minimum consumption of grapefruit juice and taking drugs Hypericum perforatum. In connection with the possibility of visiting photopsias, caution should be exercised when driving and / or engage in other activities, require high concentration and speed of psychomotor reactions.

Cooperation