Selective If-channel inhibitor in the sinus nodeREQUIRES MONITORING

Ivabradine

Procoralan · Ivabradine Accord

The only drug that reduces heart rate without affecting contractility, blood pressure, or conduction — it inhibits the funny current (If) that drives spontaneous depolarisation of the sinus node and does nothing else. It therefore works only in sinus rhythm: in atrial fibrillation the rate control sits in the AV node and ivabradine is ineffective. Its place in treatment is the symptomatic patient with HFrEF who remains above 70 beats per minute despite maximally tolerated beta-blockade, where SHIFT demonstrated reduced risk of heart failure hospitalisation.

BOXED WARNING

Combination with strong CYP3A4 inhibitors (azole antifungals, macrolides, HIV protease inhibitors, verapamil, diltiazem) is contraindicated — plasma concentration can be multiplied several-fold and produce marked bradycardia. The drug is contraindicated in atrial fibrillation and in a resting rate below 60 beats per minute before initiation.

Dosing in adults

By indicationuppdaterad 2026-08-22

Indication	Regimen	Comment
Chronic heart failure with reduced EF (NYHA II–IV)	5 mg × 2 orally for 2 weeks, then titration to 7,5 mg × 2	sinus rhythm and resting rate ≥ 70 per minute despite maximal beta-blockade
Dose adjustment after 2 weeks	Pulse > 60 per minute: increase one step. Pulse 50–60 per minute: maintain. Pulse < 50 per minute or bradycardia symptoms: reduce one step	stop if 2,5 mg × 2 is not tolerated
Patient aged ≥ 75 years	Starting dose 2,5 mg × 2, titrate slowly	higher risk of bradycardia
Chronic stable angina pectoris	5 mg × 2, if insufficient effect 7,5 mg × 2	when beta-blockade is contraindicated or insufficient
Administration	Morning and evening with a meal	grapefruit juice should be avoided

Renal impairment

No dose adjustment at creatinine clearance above 15 ml/min. Insufficient documentation below 15 ml/min.

Hepatic impairment

No adjustment in mild impairment; caution in moderate. Contraindicated in severe hepatic insufficiency.

Children

Insufficient documentation for heart failure in children below 18 years outside specialised paediatric cardiology.

Pitfall

Do not use for rate control in atrial fibrillation — the If current is in the sinus node and is irrelevant when ventricular rate is governed by AV nodal conduction. Also avoid as a replacement for beta-blockade: ivabradine has no mortality benefit on its own and should be added to a maximally titrated beta-blocker, not instead of it.

Pharmacokinetics

BIOAVAIL.: approximately 40 % (extensive first-pass metabolism)
t½: 2 hours effective, 11 hours terminal
PROTEIN BINDING: 70 %
METABOLISM: CYP3A4 (both substrate and weak inhibitor)
ACTIVE METABOLITE: N-desmethylivabradine
EXCRETION: Equal parts renal and faecal as metabolites
ONSET: rate reduction within 1–2 hours
EFFECT: approximately 10 beats per minute lower resting rate at target dose

Adverse effects by frequency

≥ 10 %

Phosphenes — transient visual phenomena at changing light intensity, most common in the first months

1–10 %

Bradycardia, atrial fibrillation, AV block I, headache, dizziness, blurred vision

< 1 %

Marked symptomatic bradycardia, supraventricular ectopics, angioedema, urticaria

Monitoring schedule

Resting pulse and ECG: before initiation, after 2 weeks, and at every dose change
Atrial fibrillation (new onset): clinically at every visit; ECG with irregular pulse
Symptoms of bradycardia and visual phenomena: at every follow-up
Review of CYP3A4 inhibitors in the medication list: at every medication change

Interaction burden

22clinically significant

6 contraindicated · 8 major · 8 moderate. Strong CYP3A4 inhibitors are contraindicated, as are rate-lowering calcium antagonists (verapamil, diltiazem). Moderate inhibitors such as fluconazole require a starting dose of 2,5 mg × 2. CYP3A4 inducers — rifampicin, phenytoin, St John's wort — can render the treatment ineffective.

Formulation & cost

Film-coated tablet 5 mg: divisible, dosing morning and evening
Film-coated tablet 7,5 mg: target dose with good tolerability
Restriction: the approved Swedish indication requires resting rate ≥ 75 per minute; ESC recommends ≥ 70 per minute