IVABRADINE HYDROCHLORIDE
Clinical safety rating: safe
Animal studies have demonstrated safety
Selective and specific inhibitor of the If (funny) current in the sinoatrial node, reducing heart rate without affecting myocardial contractility, conduction, or blood pressure.
| Metabolism | Primarily metabolized by CYP3A4; metabolites active (N-desmethyl ivabradine). |
| Excretion | Renal: ~20% unchanged; Fecal: ~55% (unabsorbed drug and biliary excretion); Extensive metabolism via CYP3A4, with metabolites excreted renally. |
| Half-life | Terminal elimination half-life: ~2 hours (range 1.5–3 hours). In therapeutic use, due to offset of pharmacodynamic effect (heart rate reduction) and drug accumulation, the effective half-life is ~6 hours with multiple dosing. |
| Protein binding | ~70% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Volume of distribution: ~1.7 L/kg (range 1.2–2.0 L/kg); indicates extensive extravascular distribution. |
| Bioavailability | Oral bioavailability: ~40% (due to first-pass metabolism). |
| Onset of Action | Oral: Onset of heart rate reduction within 30–60 minutes; peak effect at 1–3 hours. |
| Duration of Action | Duration: Heart rate reduction persists for ~12 hours after a single dose; with steady-state (twice-daily dosing), effect is maintained over 24 hours. |
5 mg orally twice daily for patients <75 years; increase to 7.5 mg twice daily after 2 months if heart rate >60 bpm. Maximum dose 7.5 mg twice daily.
| Dosage form | TABLET |
| 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: not recommended. |
| Liver impairment | Child-Pugh A: 2.5 mg twice daily; Child-Pugh B: contraindicated; Child-Pugh C: contraindicated. |
| Pediatric use | Not approved for pediatric use; efficacy and safety not established. |
| Geriatric use | Start at 2.5 mg twice daily in patients ≥75 years; titrate based on heart rate and tolerability; maximum 7.5 mg twice daily. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Strong CYP3A4 inhibitors may increase levels Can cause bradycardia and phosphenes (visual brightness).
| Breastfeeding | Excretion into human milk unknown; M/P ratio not available. Animal studies show milk concentrations similar to maternal plasma. Due to potential for infant bradycardia, breastfeeding is not recommended during therapy. |
| Teratogenic Risk | First trimester: Animal studies show embryotoxicity and teratogenicity (cardiovascular and skeletal malformations) at clinically relevant exposures. Avoid use. Second and third trimesters: Risk of fetal bradycardia and reduced placental perfusion. Contraindicated unless no alternative, and only if potential benefit justifies fetal risk. |
■ FDA Black Box Warning
None.
| Common Effects | Slow heart rate Luminous phenomena Enhanced brightness High blood pressure Atrial fibrillation Dizziness Blurred vision E C G changes |
| Serious Effects |
["Severe hepatic impairment","Sick sinus syndrome or sinoatrial block without pacemaker","Resting heart rate < 60 bpm before treatment","Acute myocardial infarction","Severe hypotension (< 90/50 mmHg)","Cardiogenic shock","Concomitant use with strong CYP3A4 inhibitors"]
| Precautions | ["Risk of atrial fibrillation","Bradycardia and conduction disturbances","Use with caution in patients with hypotension, recent stroke, or hepatic impairment","Avoid use with strong CYP3A4 inhibitors","Photosensitivity reactions"] |
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| Fetal Monitoring | Maternal: Heart rate, blood pressure, ECG. Fetal: Heart rate monitoring, ultrasound for growth and amniotic fluid volume if used in second/third trimester. Monitor for signs of fetal bradycardia. |
| Fertility Effects | Animal studies show no impairment of fertility at doses up to 10 mg/kg/day. Human data lacking. |