CORLANOR
Clinical safety rating: caution
Comprehensive clinical and safety monograph for CORLANOR (CORLANOR).
Ivabradine inhibits the If current in the sinoatrial node, reducing heart rate without affecting myocardial contractility or conduction.
| Metabolism | Primarily metabolized by CYP3A4; minor contribution from CYP3A5 and CYP2C9. |
| Excretion | Renal: ~75% (as metabolites), Fecal: ~20% (as parent drug and metabolites), Biliary: minimal |
| Half-life | Terminal elimination half-life: 6 hours (range 4.6–7.2 hours) in patients with normal renal function; prolonged to 19 hours in severe renal impairment |
| Protein binding | ~70% bound to plasma proteins (primarily albumin) |
| Volume of Distribution | Vd: 1.3–1.8 L/kg (indicating extensive tissue distribution) |
| Bioavailability | Oral: ~40% (extensive first-pass metabolism) |
| Onset of Action | Oral: Heart rate reduction begins within 1–2 hours; peak effect at 3–4 hours |
| Duration of Action | Oral: Heart rate reduction persists for up to 12 hours following a single dose; steady-state achieved within 2–3 days with twice-daily dosing |
Oral, 5 mg twice daily with food. Increase to 7.5 mg twice daily after 2 weeks if heart rate >60 bpm. Reduce to 2.5 mg twice daily if heart rate <50 bpm or symptoms of bradycardia.
| Dosage form | SOLUTION |
| Renal impairment | eGFR 30-59 mL/min: 2.5 mg twice daily. eGFR 15-29 mL/min: 1.25 mg twice daily. eGFR <15 mL/min or dialysis: not recommended. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: 2.5 mg twice daily. Child-Pugh C: contraindicated. |
| Pediatric use | Not approved for pediatric use. |
| Geriatric use | No specific dose adjustment; monitor heart rate and renal function due to age-related decline in GFR. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for CORLANOR (CORLANOR).
| Breastfeeding | Excreted in rat milk; unknown in human milk. M/P ratio not available. Not recommended during breastfeeding due to potential for adverse effects (bradycardia, hypotension) in the infant. |
| Teratogenic Risk | In animal studies, ivabradine was not teratogenic in rats or rabbits at exposures up to 40 times the maximum recommended human dose. No adequate well-controlled studies in pregnant women. Unknown fetal risk; use only if potential benefit justifies risk. First trimester: Limited data; avoid unless necessary. Second and third trimester: Same as first; no specific malformation signal. |
■ FDA Black Box Warning
None.
| Serious Effects |
["Severe hepatic impairment (Child-Pugh class C).","Resting heart rate <60 bpm before treatment.","Cardiogenic shock or acute decompensated heart failure.","Sick sinus syndrome, sinoatrial block, or third-degree AV block unless paced.","Concomitant use with strong CYP3A4 inhibitors (e.g., clarithromycin, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir).","Pregnancy and lactation."]
| Precautions | ["Concomitant use with strong CYP3A4 inhibitors (e.g., azole antifungals, macrolide antibiotics) is contraindicated due to increased ivabradine exposure.","Avoid use in patients with atrial fibrillation/flutter; increased risk of bradycardia and stroke when used with amiodarone or other rate-control drugs.","Monitor heart rate; reduce dose if resting heart rate <50 bpm or symptoms of bradycardia occur.","Use with caution in patients with electrolyte disturbances (hypokalemia, hypomagnesemia) due to increased risk of arrhythmias.","May cause visual disturbances (phosphenes); advise patients not to drive or operate machinery if affected."] |
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| Fetal Monitoring | Monitor maternal heart rate and blood pressure; fetal heart rate monitoring if used near term; assess for signs of fetal bradycardia. No specific fetal ultrasound required, but standard prenatal care applies. |
| Fertility Effects | In animal studies, ivabradine reduced fertility in male rats at high doses; no human data on fertility effects. |