What is the initial dosing and titration for Nebevilol (nebivolol) in a patient with hypertension or heart failure, considering age, impaired renal function, and respiratory comorbidities like asthma or COPD?

Nebivolol Dosing and Titration

Initial Dosing for Hypertension

For most patients with hypertension, start nebivolol at 5 mg once daily, taken with or without food. 1

• The FDA-approved starting dose is 5 mg once daily for uncomplicated hypertension 1
• This can be used as monotherapy or combined with other antihypertensive agents 1
• Clinical trials demonstrate that 5 mg once daily effectively reduces diastolic blood pressure comparably to standard doses of atenolol, metoprolol, lisinopril, and nifedipine 2

Dose Titration Protocol

If blood pressure control is inadequate after 2 weeks, increase nebivolol by 2.5-5 mg increments every 2 weeks up to a maximum of 40 mg daily. 1

• Titrate at 2-week intervals based on blood pressure response 1
• More frequent dosing adjustments are unlikely to provide additional benefit 1
• Target blood pressure should be <130/80 mmHg per current hypertension guidelines 3

Initial Dosing for Heart Failure

For heart failure with reduced ejection fraction, start nebivolol at 1.25 mg once daily and titrate gradually to a target dose of 10 mg once daily. 3

• The European Society of Cardiology recommends initiating at 1.25 mg once daily 3
• Double the dose every 2-4 weeks if the preceding dose is well tolerated 3
• Target dose is 10 mg once daily, which has been shown to reduce mortality and hospitalizations 3
• Monitor for signs of worsening heart failure, symptomatic hypotension, or excessive bradycardia (pulse <50 bpm) at each visit 3

Dose Adjustments for Renal Impairment

In patients with severe renal impairment (creatinine clearance <30 mL/min), start with 2.5 mg once daily and titrate slowly as needed. 1

• Reduce initial dose by 50% in severe renal dysfunction 1
• Nebivolol has not been studied in dialysis patients 1
• Monitor renal function and blood pressure closely during titration 1

Dose Adjustments for Hepatic Impairment

In patients with moderate hepatic impairment, start with 2.5 mg once daily and titrate slowly as needed. 1

• Reduce initial dose by 50% in moderate hepatic dysfunction 1
• Nebivolol is not recommended in severe hepatic impairment due to lack of safety data 1

Special Considerations for Elderly Patients

No dose adjustment is necessary based on age alone in elderly patients. 1

• Standard dosing of 5 mg once daily can be used in geriatric populations 1
• However, elderly patients may have concurrent renal or hepatic impairment requiring dose reduction 1

Use in Patients with Respiratory Comorbidities

Nebivolol can be safely used in patients with asthma or COPD at standard doses, unlike non-selective beta-blockers. 3, 4

• Asthma is listed as an absolute contraindication for non-selective beta-blockers, but COPD is not a contraindication for cardioselective agents like nebivolol 3
• A controlled study in 24 patients with bronchial hyperreactivity (asthma, COPD) showed that nebivolol 5 mg did not significantly worsen airway obstruction or bronchial hyperreactivity compared to placebo 4
• Another study in 50 patients with coronary disease and COPD demonstrated that nebivolol 5 mg daily had no adverse effect on bronchial patency 5
• Nebivolol's high beta-1 selectivity minimizes beta-2 receptor blockade in the lungs, reducing bronchospasm risk 6

Absolute Contraindications

Do not initiate nebivolol in patients with second or third-degree heart block, sick sinus syndrome without a pacemaker, or sinus bradycardia <50 bpm. 3

• Severe bradycardia and high-grade AV block are absolute contraindications 3
• Unlike other beta-blockers, asthma is not an absolute contraindication for nebivolol due to its high beta-1 selectivity 3, 4
• Decompensated heart failure requires stabilization before initiating beta-blocker therapy 3

Monitoring During Titration

Check blood pressure and heart rate at each visit during dose titration, targeting a resting heart rate of 50-60 bpm unless limiting side effects occur. 3

• Monitor for symptomatic hypotension (dizziness), which often improves with time 3
• Assess for signs of worsening heart failure (increased dyspnea, edema, weight gain) 3
• Consider reducing diuretic or other vasodilator doses if symptomatic hypotension occurs, rather than stopping nebivolol 3

Common Pitfalls to Avoid

Do not discontinue nebivolol abruptly, as this can cause rebound hypertension or worsening angina. 7

• Gradual tapering is essential when discontinuing beta-blocker therapy 7
• In hospitalized patients with worsening heart failure, dose reduction rather than complete discontinuation is preferred 3
• Nebivolol can be cautiously initiated prior to hospital discharge in recently decompensated patients who have improved with other treatments 3