Chronic stable angina pectoris in coronary artery disease patients with normal sinus rhythm
Adult: In patients with contraindication to or unable to tolerate beta-blockers; or combined with beta-blockers in patients who are inadequately controlled with optimal dose of beta-blockers and whose heart rate is >60 beats/min. Usual recommended initial dose: 5 mg bid. Increase if necessary to 7.5 mg bid after 3-4 weeks. Titrate downward to 2.5-5 mg bid if patient develops bradycardia symptoms (e.g. dizziness, fatigue) or resting heart rate is persistently <50 beats/min).
Elderly: ≥75 yr old: Initiate treatment at 2.5 mg bid. Titrate up if necessary.
Renal impairment: Caution in patients with CrCl <15 ml/min.
Pregnancy, lactation, resting heart rate <60 beats/min prior to treatment, cardiogenic shock, acute myocardial infarction, severe hypotension (<90/50 mmHg), severe hepatic insufficiency, sick sinus syndrome, sino-atrial block, heart failure patients with NYHA class III-IV, pacemaker dependent, unstable angina, 3rd degree AV-block, concurrent use with potent CYP3A4 inhibitors.
Warnings / Precautions
Reduce dose if resting heart rate is persistently <50 beats/min or patient develops bradycardia symptoms during treatment; discontinue if heart rate <50 beats/min and symptoms persist. Not recommended in patient with AF or other cardiac arrhythmias that interfere with sinus node rhythm; monitor regularly for AF occurrence. Not recommended for concomitant use with heart rate reducing calcium channel blockers (e.g. diltiazem or verapamil), immediate use after a stroke or in patients with 2nd degree AV-block. Moderate hepatic insufficiency. Stop treatment if visual field deteriorates unexpectedly. Patients with retinitis pigmentosa.
Adverse Reactions
Luminous phenomena (phosphena), blurred vision, bradycardia, 1st degree AV-block, ventricular extrasystole, supraventricular extrasystoles, palpitations, headache, dizziness, nausea, constipation, diarrhoea, vertigo, dyspnoea, muscle cramps, hyperuricaemia, eosinophilia, elevated blood-creatinine.
Overdose Reactions
Severe and prolonged bradycardia.
Drug Interactions
Concomitant use with QT-prolonging drugs (e.g. quinidine, disopyramide, bepridil, sotalol, ibutilide, amiodarone, pimozide, ziprasidone, sertinole, mefloquine, halofantrine, pentamide, cisapride, erythromycin IV) is not recommended as QT prolongation may be enhanced by heart rate reduction. Concentrations may increase when used with CYP3A4 inhibitors. Use with verapamil or diltiazem (moderate CYP3A4 inhibitors) is not recommended. If used with other moderate CYP3A4 inhibitors (e.g. fluconazole), may consider starting at lower dose and with heart rate monitoring if resting heart rate >60 beats/min. Concentration may be reduced with CYP3A4 inducers (e.g. rifampicin, barbiturates, phenytoin, St John's Wort) and may require Ivabradine dose adjustment.
Potentially Fatal: Concurrent use with potent CYP3A4 inhibitors is contraindicated; e.g. azole antifungals (ketoconazole, itraconazole), macrolides (clarithromycin, erythromycin PO, josamycin, telithromycin), HIV protease inhibitors (nelfinavir, ritonavir) and nefazodone.
See Below for More ivabradine Drug Interactions
Food Interactions
Food delays absorption but increase exposure by 20-30%. Increased exposure when taken with grapefruit juice.
Mechanism of Actions
Ivabradine is a heart rate lowering agent that works through selective and specific inhibition of the cardiac pacemaker If current. If current controls the spontaneous diastolic depolarisation in the sinus node and regulate heart rate.
Absorption: Almost completely absorbed (about 90%). Absolute bioavailability: About 40% due to 1st pass effect in the gut and liver. Steady state achieved within 1 day.
Distribution: Vd: About 100 L. Protein binding: Around 70%.
Metabolism: Extensively metabolised in the liver and gut by oxidation through CYP3A4 to form major active metabolite N-desmethylated derivative (S18982) which is also metabolised by CYP3A4.
Excretion: Elimination half-life: About 2 hr. About 4% of an oral dose is excreted unchanged in the urine; metabolites are excreted to a similar extent in the urine and faeces.
Should be taken with food. (Avoid excessive consumption of grapefruit juice.)
ATC Classification
C01EB17 - ivabradine ; Belongs to the class of other cardiac preparations.
Available As
  • Ivabradine 5 mg
  • Ivabradine 7.5 mg
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