BYSTOLIC
Clinical safety rating: caution
Comprehensive clinical and safety monograph for BYSTOLIC (BYSTOLIC).
Bystolic (nebivolol) is a beta-1 selective adrenergic receptor antagonist with additional nitric oxide-mediated vasodilatory effects. It decreases heart rate, myocardial contractility, and blood pressure by blocking beta-1 receptors in the heart and kidney, and enhances nitric oxide release from vascular endothelium via beta-3 receptor activation.
| Metabolism | Extensively metabolized via CYP2D6 and glucuronidation. Active metabolites are formed, including desmethylnebivolol. Genetic polymorphisms in CYP2D6 affect drug levels. |
| Excretion | Renal: 38% unchanged; hepatic metabolism: extensive; fecal: minor; total renal clearance accounts for 30-50% of dose |
| Half-life | Terminal elimination half-life: 10-12 hours; allows once-daily dosing in most patients; steady-state achieved in 3-5 days |
| Protein binding | 25-30% bound to albumin (alpha-1-acid glycoprotein not significant) |
| Volume of Distribution | Vd: ~2.5 L/kg (extensive extravascular distribution, consistent with moderate lipophilicity) |
| Bioavailability | Oral: 33% (due to first-pass metabolism; food does not significantly affect AUC; low variability) |
| Onset of Action | Oral: 1-2 hours for beta-blockade (reduction in heart rate and blood pressure) |
| Duration of Action | 24 hours (sustained beta-blockade with once-daily dosing); clinical effect persists for the full dosing interval |
| Molecular Weight | 405.44 |
Oral: 5 mg once daily; may increase at 2-week intervals to 10 mg, 20 mg, 40 mg; maximum 40 mg/day.
| Dosage form | TABLET |
| Renal impairment | No adjustment for mild to moderate renal impairment (CrCl ≥30 mL/min). For severe renal impairment (CrCl <30 mL/min), initial dose 2.5 mg once daily; titrate cautiously; maximum 20 mg/day. |
| Liver impairment | Child-Pugh Class A: initial 2.5 mg once daily; increase cautiously; maximum 20 mg/day. Child-Pugh Class B: initial 2.5 mg once daily; increase cautiously; maximum 10 mg/day. Child-Pugh Class C: not recommended. |
| Pediatric use | Not established; safety and efficacy not evaluated in pediatric patients. |
| Geriatric use | Initial dose 2.5 mg once daily; titrate slowly; maximum 40 mg/day. Monitor heart rate and blood pressure closely. |
| 1st trimester | Nebivolol, the active ingredient, is a beta-blocker with potential to reduce placental perfusion, which could lead to fetal growth restriction. Use only if benefit outweighs risk. |
| 2nd trimester | Continued risk of reduced placental perfusion and fetal growth restriction. Monitor fetal growth if used. |
| 3rd trimester | Risk of neonatal bradycardia, hypoglycemia, and hypotension. Discontinue 48-72 hours before delivery if possible. |
Clinical note
Comprehensive clinical and safety monograph for BYSTOLIC (BYSTOLIC).
| Placental transfer | Nebivolol crosses the placenta; evidence from animal studies and human data suggests transfer occurs. |
| Breastfeeding | Nebivolol is excreted into human breast milk in small amounts. Although no adverse effects have been reported in infants, caution is advised due to potential for bradycardia and hypotension. Use lowest effective dose if necessary. |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
Severe bradycardiaHeart block greater than first degreeCardiogenic shockDecompensated heart failureSick sinus syndrome (unless permanent pacemaker in place)Severe hepatic impairmentHypersensitivity to nebivolol or any component
| Precautions | Abrupt discontinuation may exacerbate angina or myocardial infarction in coronary artery disease, May mask signs of hyperthyroidism, Caution in peripheral vascular disease and Raynaud's phenomenon, May cause bronchospasm in patients with asthma or COPD, Caution in patients with diabetes mellitus due to masking of hypoglycemia, May cause bradycardia or heart block, Caution in renal or hepatic impairment |
| Food/Dietary | Avoid alcohol as it may increase blood pressure-lowering effect. No significant food interactions; however, grapefruit juice may slightly increase nebivolol levels but not clinically relevant. |
Loading safety data…
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | First trimester: Limited human data; animal studies show no teratogenicity at clinically relevant doses. Second/third trimester: Beta-blockers may cause fetal bradycardia, intrauterine growth restriction, and neonatal hypoglycemia; risk is dose-dependent. |
| Fetal Monitoring | Monitor maternal blood pressure and heart rate; fetal heart rate and growth during third trimester; neonates for bradycardia, hypoglycemia, and respiratory depression for 48 hours postpartum. |
| Fertility Effects | No human data; animal studies showed no impairment of fertility at doses up to 25 mg/kg/day. |
| Clinical Pearls | Bystolic (nebivolol) is a beta-1 selective blocker with nitric oxide-mediated vasodilation, resulting in lower incidence of fatigue and sexual dysfunction compared to other beta-blockers. No dose adjustment needed in mild to moderate hepatic impairment but contraindicated in severe impairment. Maximum antihypertensive effect may take 2 weeks. Use caution in patients with asthma or COPD due to beta-1 selectivity may be lost at higher doses. Do not discontinue abruptly; taper over 1-2 weeks. |
| Patient Advice | Take once daily at the same time each day, with or without food. · Do not stop taking suddenly as this may cause chest pain or heart attack; consult your doctor for gradual dose reduction. · May cause dizziness or drowsiness; avoid driving or operating machinery until you know how you react. · Notify your doctor if you experience slow heartbeat, shortness of breath, swelling of feet or legs, or signs of allergic reaction. · Inform all healthcare providers that you take this medication, especially before surgery or any procedure involving anesthesia. |