Can Bisoprolol (beta-blocker) be split to twice a day?

Bisoprolol Administration: Once Daily vs. Twice Daily

Bisoprolol should be administered once daily rather than split into twice-daily dosing, as all clinical evidence and guidelines support once-daily dosing to achieve optimal therapeutic outcomes and maintain 24-hour efficacy. 1, 2

Evidence for Once-Daily Dosing

The 2022 AHA/ACC/HFSA guideline for heart failure management clearly specifies bisoprolol as a once-daily medication:

• Bisoprolol is recommended at an initial dose of 1.25 mg once daily, with a target dose of 10 mg once daily 1
• The mean dose achieved in clinical trials was 8.6 mg total daily 1
• The pharmacokinetic profile of bisoprolol supports once-daily dosing:
  • Long elimination half-life of 9-12 hours 2
  • Steady state is attained within 5 days of once-daily dosing 2
  • Low plasma accumulation with accumulation factor of only 1.1-1.3 2

Pharmacokinetic Rationale

Bisoprolol has specific pharmacokinetic properties that make it suitable for once-daily administration:

• High oral bioavailability (approximately 80-90%) 2, 3
• Long plasma elimination half-life (9-12 hours) 2
• Predictable pharmacokinetics with less than twofold intersubject variation in peak plasma levels 2
• Equal elimination by renal and non-renal pathways 2

Clinical Evidence Supporting Once-Daily Dosing

Multiple clinical studies have confirmed the efficacy of once-daily bisoprolol dosing:

• Antihypertensive effects are sustained over the entire 24-hour dosing interval 4
• Near maximal antihypertensive effects are achieved within 1 week of therapy initiation 4
• In angina studies, once-daily bisoprolol (10 mg) maintained efficacy at 22-24 hours after the last dose 5
• Dose-ranging studies confirm that once-daily administration provides effective 24-hour blood pressure control 6

Practical Recommendations

When initiating bisoprolol therapy:

1. Start with a low dose (1.25-2.5 mg once daily) 1
2. Titrate gradually, doubling the dose at not less than 2-week intervals 1
3. Aim for the target dose of 10 mg once daily or the highest tolerated dose 1
4. Monitor heart rate, blood pressure, and clinical status during titration 1

Special Considerations

• In patients with hepatic impairment or renal dysfunction (creatinine clearance <40 mL/min), start with 2.5 mg once daily and use caution in dose titration 2
• For elderly patients, no dose adjustment is necessary unless there is significant renal or hepatic dysfunction 2
• If a patient experiences side effects, reducing the dose is preferable to splitting the dose 1

Potential Pitfalls

• Splitting bisoprolol to twice daily may:
  • Deviate from evidence-based dosing regimens used in clinical trials 1
  • Complicate the medication regimen, potentially reducing adherence
  • Alter the pharmacokinetic profile that has been optimized for once-daily dosing
  • Potentially increase the risk of dosing errors

Remember that the clinical benefits of beta-blockers in heart failure (34% reduction in all-cause mortality) were demonstrated with specific dosing regimens, including once-daily dosing for bisoprolol 1.