If channel inhibitor (heart rate lowering)
Ivabradine is a medicine that lowers heart rate, used in chronic heart failure in patients with sinus rhythm and elevated heart rate, and in angina in patients who cannot tolerate beta-blockers. It reduces the work of the heart.
Also known as: Ivabradina, Procoralan, Corlanor
Ivabradine + clarithromycin: clarithromycin increases ivabradine plasma concentration — QUADRO 2 recommends avoiding concomitant use (possible ventricular arrhythmia).
Ivabradine is metabolised predominantly by CYP3A4 and clarithromycin is a strong inhibitor of that enzyme: the combination significantly increases ivabradine plasma concentration, with marked bradycardia, atrioventricular block and risk of ventricular arrhythmias (including torsades de pointes in predisposed patients). QUADRO 2 of Annex 7 explicitly recommends avoiding concomitant use. The contraindication is also in the ivabradine label, which prohibits combination with strong CYP3A4 inhibitors. In respiratory infections where clarithromycin would be used, alternatives should be preferred (azithromycin has weaker CYP3A4 inhibition, or beta-lactams). If the combination is unavoidable (a non-recommended situation), heart rate and ECG should be monitored and the ivabradine dose adjusted — in practice, the contraindication makes this monitoring insufficient, so the antibiotic should be changed.
Ivabradine + clarithromycin: clarithromycin (strong CYP3A4 inhibitor) increases ivabradine concentration — extreme bradycardia and arrhythmias; avoid the combination.
Clarithromycin (macrolide) inhibits CYP3A4 which metabolises ivabradine — increased plasma concentration, marked bradycardia and possible ventricular arrhythmia (QUADRO 2, Ivabradine: "Increase ivabradine plasma concentration: Clarithromycin (avoid concomitant use)").
If unavoidable, monitor heart rate and ECG.
Severe bradycardia, syncope, ventricular arrhythmias in a patient on ivabradine + clarithromycin.
Avoid the combination (strong CYP3A4 inhibitor); choose an alternative antibiotic.
Prontuário Terapêutico do INFARMED (11th ed., 2012) — Annex 7, QUADRO 2 (Ivabradine)
FDA label (7.1): grapefruit juice is a moderate CYP3A4 inhibitor — avoid concomitant use (it increases ivabradine concentrations, exacerbating bradycardia and conduction disturbances).
Avoid grapefruit juice during treatment.
DailyMed/FDA (NIH/NLM) — Ivabradine (CORLANOR), 7.1: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=92018a65-38f6-45f7-91d4-a34921b81d0d
FDA label (CONTRAINDICATIONS): contraindicated in patients with sick sinus syndrome, sinoatrial block or third-degree AV block, unless a functioning demand pacemaker is present.
Contraindicated in conduction disorders without a pacemaker.
DailyMed/FDA (NIH/NLM) — Ivabradine (CORLANOR), CONTRAINDICATIONS: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=92018a65-38f6-45f7-91d4-a34921b81d0d
FDA label (CONTRAINDICATIONS): contraindicated in patients with clinically significant hypotension and clinically significant bradycardia.
Contraindicated in clinically significant hypotension and bradycardia.
DailyMed/FDA (NIH/NLM) — Ivabradine (CORLANOR), CONTRAINDICATIONS: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=92018a65-38f6-45f7-91d4-a34921b81d0d
FDA label (CONTRAINDICATIONS): contraindicated in severe hepatic impairment (extensive hepatic metabolism of the drug).
Contraindicated in severe hepatic impairment.
DailyMed/FDA (NIH/NLM) — Ivabradine (CORLANOR), CONTRAINDICATIONS: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=92018a65-38f6-45f7-91d4-a34921b81d0d
FDA label (5.1/8.1): ivabradine may cause fetal toxicity (animal data — embryo-fetal and cardiac teratogenic effects in rats at exposures 1-3× the maximum recommended human dose). No adequate data in pregnant women.
Risk of fetal toxicity (animal data); avoid in pregnancy.
No specific breastfeeding data in the label (section 8.2 not detailed in extraction).
Advise women of reproductive potential to use effective contraception during treatment (5.1).
DailyMed/FDA (NIH/NLM) — approved Ivabradine label (CORLANOR), sections 5.1/8.1: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=92018a65-38f6-45f7-91d4-a34921b81d0d
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Selective If channel inhibitor: dose-dependent heart rate reduction, without effects on intracardiac conduction, contractility or repolarisation (FDA label).
Selective inhibition of the sinus node If channel (pacemaker current) — pure negative chronotropy.
Rapid and almost complete oral absorption; bioavailability is approximately 40% due to first-pass metabolism (12.3).
Extensive CYP3A4 metabolism (substrate) — inhibitors increase exposure (bradycardia/conduction disturbances) and inducers decrease it (7.1).
Effective half-life of approximately 6 hours (2 hours for plasma activity) (12.3).
