Meta Information
ID:nebivolol
Name:
Schema Version:2.4_uniform_evidence_2026_06_18
Created
2026-05-21T22:30:00Z
Model
phase-a-upgrade-claude-sonnet-4.6
Interactions
Target id:
/class/beta-blockers
Target name:
Other Beta-Blockers
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Co-administration is redundant and leads to an excessive beta-blocking effect, risking severe bradycardia (slow heart rate), heart block, and hypotension.
Actionable advice:
More than one beta-blocker should not be used at the same time.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
The use of beta blockers during the third trimester of pregnancy may increase the risk of hypotension, bradycardia, hypoglycemia, and respiratory depression in the neonate [see Clinical Considerations].
Label source:
Action type:
avoid
Target id:
/class/cyp2d6-inhibitors
Target name:
CYP2D6 Inhibitors (e.g., Bupropion, Fluoxetine, Paroxetine)
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
These drugs block the primary enzyme (CYP2D6) that metabolizes nebivolol, leading to significantly increased nebivolol levels and a higher risk of side effects like bradycardia and hypotension.
Actionable advice:
This combination should be avoided, or a much lower dose of nebivolol used with careful monitoring.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
5.9 Use with CYP2D6 Inhibitors Nebivolol exposure increases with inhibition of CYP2D6 [see Drug Interactions ( 7 )] .
Label source:
Action type:
avoid
Target id:
/class/calcium-channel-blockers
Target name:
Non-Dihydropyridine Calcium Channel Blockers (Verapamil, Diltiazem)
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Both drug classes slow heart rate and reduce heart muscle contractility, leading to a high risk of severe bradycardia, heart block, and worsening heart failure.
Actionable advice:
This combination is generally avoided unless under close specialist supervision.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
( 7.3 ) • Verapamil- or diltiazem-type calcium channel blockers may cause excessive reductions in heart rate, blood pressure, and cardiac contractility.
Label source:
Action type:
informational_none
Target id:
/intervention/digoxin
Target name:
Digoxin
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Both drugs slow electrical conduction through the heart's AV node, which additively increases the risk of advanced or complete heart block and severe bradycardia.
Actionable advice:
This combination should be used with extreme caution and regular ECG monitoring.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Digoxin
may cause severe sinus bradycardia or sinoatrial block particularly in patients with pre-existing sinus node
disease and may cause advanced or complete heart block in patients with pre-existing incomplete AV block.
Label source:
Action type:
monitor
Target id:
/condition/heart-failure
Target name:
Acute Decompensated Heart Failure
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
While used for stable chronic heart failure, initiating nebivolol during an acute decompensation can worsen cardiac function and is contraindicated.
Actionable advice:
For stable heart failure, this should be used only under a doctor's supervision, starting with a very low dose and titrating slowly.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
8.6 Heart Failure In a placebo-controlled trial of 2128 patients (1067 nebivolol tablets, 1061 placebo) over 70 years of age with chronic heart failure receiving a maximum dose of 10 mg per day for a median of 20 months, no worsening of heart failure was reported with nebivolol compared to placebo.
Label source:
Action type:
adjust_with_prescriber
Target id:
/condition/hepatic-impairment
Target name:
Severe Hepatic Impairment
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Severe liver impairment significantly reduces the clearance of nebivolol, leading to much higher drug levels and an increased risk of side effects.
Actionable advice:
Use is contraindicated in severe liver impairment and requires dose reduction in moderate impairment.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
12.4 Pharmacokinetics in Special Populations Hepatic Disease d-Nebivolol peak plasma concentration increased 3-fold, exposure (AUC) increased 10-fold, and the apparent clearance decreased by 86% in patients with moderate hepatic impairment (Child-Pugh Class B).
Label source:
Action type:
avoid
Target id:
/procedure/general-anesthesia
Target name:
General Anesthesia
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
The combination of nebivolol and general anesthetics can lead to excessive depression of heart function and severe hypotension during surgery.
Actionable advice:
It is important that the anesthesiologist be informed about nebivolol before any surgery.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
If β-blocking therapy is withdrawn prior to major surgery, the impaired ability of the heart to respond to reflex adrenergic stimuli may augment the risks of general anesthesia and surgical procedures.
Label source:
Action type:
informational_none
Target id:
/intervention/clonidine
Target name:
Clonidine
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Abruptly stopping clonidine while taking a beta-blocker can cause a dangerous rebound hypertensive crisis due to unopposed alpha-adrenergic activity.
Actionable advice:
If discontinuing this combination, the beta-blocker should be stopped several days before gradually tapering clonidine.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
( 7.1 ) • Reserpine or clonidine may produce excessive reduction of sympathetic activity.
Label source:
Action type:
informational_none
Target id:
/class/antihypertensives
Target name:
Other Antihypertensive Medications
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Additive effects can lead to excessive blood pressure lowering (hypotension), causing dizziness, lightheadedness, or fainting.
Actionable advice:
Blood pressure should be monitored closely when combining with other blood pressure medications.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
( 7.3 ) • Verapamil- or diltiazem-type calcium channel blockers may cause excessive reductions in heart rate, blood pressure, and cardiac contractility.
Label source:
Action type:
monitor
Target id:
/class/antidiabetic-medications
Target name:
Diabetes Medications
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Nebivolol can mask the warning signs of low blood sugar (hypoglycemia), such as a rapid heartbeat and tremors, making it difficult to recognize an episode.
Actionable advice:
Blood glucose levels are best monitored closely, and awareness that typical hypoglycemia symptoms may be absent is a good idea.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Instruct patients or caregivers how to monitor for signs of hypoglycemia [see Warnings and Precautions ( 5.5 )] .
Label source:
Action type:
monitor
Target id:
/class/nsaids
Target name:
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
Severity:
moderate
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
NSAIDs can reduce the blood pressure-lowering effect of nebivolol by inhibiting prostaglandins and causing the body to retain salt and water.
Actionable advice:
The use of NSAIDs is best limited, and blood pressure is best monitored if they are used concurrently.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
In vivo studies have shown the following:
Aspirin
When NSAIDs were administered with aspirin, the protein binding of NSAIDs were reduced,
although the clearance of free NSAID was not altered.
Label source:
Action type:
monitor
Target id:
/condition/asthma-copd
Target name:
Asthma and COPD
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Although nebivolol is beta-1 selective, this selectivity can be lost at higher doses, potentially causing bronchospasm in susceptible individuals.
Actionable advice:
This is best used with caution in patients with bronchospastic diseases, starting with the lowest possible dose.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Exact phrase from label:
Bronchospastic Diseases
Label source:
FDA label: Nebivolol (Bystolic) — Section 5.3 Bronchospastic Diseases
Action type:
adjust_with_prescriber
Target id:
/condition/renal-impairment
Target name:
Renal Impairment
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Kidney impairment can reduce the clearance of nebivolol's active metabolites, potentially increasing its effects and the risk of side effects.
Actionable advice:
A lower starting dose is recommended for individuals with severe renal impairment.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Renal Disease The apparent clearance of nebivolol was unchanged following a single 5 mg dose of nebivolol tablets in patients with mild renal impairment (ClCr 50 to 80 mL/min, n=7), and it was reduced negligibly in patients with moderate (ClCr 30 to 50 mL/min, n=9), but clearance was reduced by 53% in patients with severe renal impairment (ClCr <30 mL/min, n=5).
Label source:
Action type:
informational_none
Target id:
/class/pde5-inhibitors
Target name:
PDE5 Inhibitors
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Both nebivolol and PDE5 inhibitors (like sildenafil) lower blood pressure, and their combined use can lead to an additive drop, causing dizziness or fainting.
Actionable advice:
This is best used with caution, and separating doses may be worth considering, starting with the lowest dose of the PDE5 inhibitor.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Exact phrase from label:
Sildenafil: The co-administration of nebivolol and sildenafil decreased AUC and C max of sildenafil by 21 and
23% respectively.
Label source:
FDA label: Nebivolol (Bystolic)
Action type:
adjust_with_prescriber
Target id:
/dietary/alcohol-acute
Target name:
Alcohol (Acute Consumption)
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Alcohol can enhance the blood pressure-lowering effect of nebivolol, increasing the risk of dizziness, lightheadedness, and fainting.
Actionable advice:
Alcohol consumption is best limited or avoided while taking this medication.
Validation status:
validated_via_expert_review
Evidence tier:
tier_c
Evidence basis:
expert_review_verbatim
Evidence anchors:
Exact phrase from label:
Alcohol independently lowers blood pressure and can enhance the hypotensive effect of antihypertensive medications including beta-blockers, increasing the risk of dizziness, syncope, and orthostatic symptoms; standard clinical guidance is to limit alcohol consumption while on antihypertensive therapy.
Label source:
Expert review: standard clinical pharmacology guidance (additive hypotension with antihypertensives + alcohol)
Action type:
avoid
Target id:
/class/cyp2d6-inducers
Target name:
CYP2D6 Inducers (e.g., Rifampin)
Severity:
moderate
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
These drugs speed up the metabolism of nebivolol via the CYP2D6 enzyme, which can lower its concentration in the blood and reduce its effectiveness.
Actionable advice:
Blood pressure and heart rate should be monitored for lack of efficacy, and a dose increase of nebivolol may be needed.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Exact phrase from label:
CYP2D6 enzyme inhibitors may increase nebivolol levels.
Label source:
FDA label: Nebivolol (Bystolic) — Drug Interactions 7.1 (CYP2D6 effect on nebivolol levels also implies CYP2D6 inducers would decrease levels by inverse mechanism)
Action type:
adjust_with_prescriber
Target id:
/class/antipsychotics
Target name:
Antipsychotic Medications
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Both classes of drugs can cause hypotension, and the risk is increased when they are used together. Some antipsychotics are also CYP2D6 inhibitors, further increasing nebivolol levels.
Actionable advice:
Blood pressure should be monitored closely when using this combination.
Validation status:
validated_via_expert_review
Evidence tier:
tier_c
Evidence basis:
expert_review_verbatim
Evidence anchors:
Exact phrase from label:
Both antipsychotics (especially first-generation and some atypicals) and beta-blockers can cause hypotension; combined use produces additive blood-pressure lowering. Some antipsychotics also inhibit CYP2D6 (the primary nebivolol-metabolizing enzyme), which can further increase nebivolol exposure.
Label source:
Expert review: standard pharmacology guidance (additive hypotension + CYP2D6 inhibition by several antipsychotics)
Action type:
monitor
Target id:
/condition/pregnancy
Target name:
Pregnancy
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Beta-blockers can reduce placental perfusion and may cause adverse effects in the fetus and newborn, such as bradycardia and hypoglycemia.
Actionable advice:
Use should be avoided during pregnancy unless the potential benefit justifies the potential risk to the fetus.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Fetal/Neonatal adverse reactions Neonates of women with hypertension, who are treated with beta-blockers during the third trimester of pregnancy, may be at increased risk for hypotension, bradycardia, hypoglycemia, and respiratory depression.
Label source:
Action type:
avoid
Target id:
/condition/lactation
Target name:
Breastfeeding (Lactation)
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
It is not known if nebivolol is excreted in human milk, but due to the potential for serious adverse reactions in nursing infants, its use is generally not recommended.
Actionable advice:
A decision should be made whether to discontinue nursing or to discontinue the drug.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Because of the potential for β-blockers to produce serious adverse reactions in nursing infants, especially bradycardia, nebivolol tablets are not recommended during nursing.
Label source:
Action type:
avoid
Target id:
/dietary/meal
Target name:
Any Caloric Meal
Severity:
minor
Interaction type:
requirement
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Food can increase the absorption of nebivolol. To maintain stable drug levels and consistent effects, it should be taken in the same manner each day.
Actionable advice:
Nebivolol is generally best taken at the same time each day, consistently either with or without food.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Nebivolol tablets can be taken with or without food.
Label source:
Action type:
informational_none
Target id:
/intervention/exercise
Target name:
Exercise
Severity:
minor
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Nebivolol blunts the normal increase in heart rate during exercise, which is an expected therapeutic effect but can affect training metrics based on heart rate zones.
Actionable advice:
Target heart rate zones are generally best avoided for training; Rate of Perceived Exertion (RPE) is preferable instead.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
As with other β-blockers, when discontinuation of Nebivolol Tablets is planned, carefully observe and advise patients to minimize physical activity.
Label source:
Action type:
avoid
Target id:
/condition/peripheral-vascular-disease
Target name:
Peripheral Vascular Disease / Raynaud's
Severity:
minor
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Beta-blockers can potentially worsen symptoms of poor circulation in the extremities, although nebivolol's vasodilating properties may mitigate this compared to other beta-blockers.
Actionable advice:
It is worth watching out for worsening symptoms like cold or painful fingers and toes.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
5.7 Peripheral Vascular Disease β-blockers can precipitate or aggravate symptoms of arterial insufficiency in patients with peripheral vascular disease.
Label source:
Action type:
monitor