Is taking Benazapril (Angiotensin-Converting Enzyme (ACE) inhibitor) twice a day an effective regimen for managing hypertension?

Benazepril Twice Daily for Hypertension Management

Benazepril can be administered twice daily for hypertension management when once-daily dosing does not provide adequate trough (pre-dosing) blood pressure control. 1

Dosing Recommendations for Benazapril

• The FDA-approved dosing for benazapril indicates that while once-daily dosing is common, a divided regimen (twice daily) is more effective in controlling trough blood pressure than the same total daily dose given once daily 1
• The recommended initial dose for adults not receiving a diuretic is 10 mg once daily, with a usual maintenance dosage range of 20-40 mg per day 1
• When once-daily dosing does not provide adequate trough response, either an increase in dosage or divided administration (twice daily) should be considered 1
• Dosage adjustment should be based on measurement of peak (2-6 hours after dosing) and trough responses 1

Evidence Supporting Twice-Daily Dosing

• Studies comparing the same daily dose of benazapril given as a single morning dose versus a twice-daily dose found that blood pressure reductions at the time of morning trough blood levels were greater with the divided regimen 1
• A 2021 review found that twice-daily administration of ACE inhibitors may promote added blood pressure-lowering effects compared to once-daily dosing 2
• Twice-daily dosing may help maintain consistent blood pressure control throughout the 24-hour period, especially for patients who experience early morning blood pressure elevations 2

Clinical Considerations

• The antihypertensive effect of a single dose of benazapril persists for 24 hours, but the maximum effect occurs at 2-4 hours after dosing 1
• For patients with inadequate blood pressure control on once-daily dosing, splitting the total daily dose into twice-daily administration can provide more consistent 24-hour coverage 1
• The total daily dose should not exceed 80 mg, regardless of whether administered once or twice daily 1

Special Populations

• For patients with renal impairment (creatinine clearance <30 mL/min), the recommended initial dose is 5 mg once daily, which can be titrated up to a maximum of 40 mg daily 1
• In elderly patients, treatment should be simplified with once-daily dosing when possible, but twice-daily dosing can be considered if blood pressure control is inadequate 3

Combination Therapy

• If blood pressure is not controlled with benazapril alone, a thiazide diuretic can be added 1
• The combination of an ACE inhibitor with a diuretic provides greater blood pressure reduction than either agent alone 4
• For non-Black patients with uncontrolled hypertension, the recommended approach is to optimize the ACE inhibitor dose before adding other agents 3

Monitoring and Follow-up

• Blood pressure should be monitored to assess both peak and trough responses to determine optimal dosing frequency 1
• The goal is to reduce blood pressure by at least 20/10 mmHg, ideally to <130/80 mmHg 3
• Maximum reduction in blood pressure with any dose is generally achieved after 1-2 weeks of therapy 1

Common Pitfalls and Caveats

• Symptomatic hypotension can occur in patients who are salt- and/or volume-depleted, particularly when initiating therapy 1
• For patients currently on diuretic therapy, the diuretic should be discontinued 2-3 days before starting benazapril if possible, or start with a lower dose (5 mg) of benazapril 1
• Concomitant administration of benazapril with potassium supplements, potassium salt substitutes, or potassium-sparing diuretics can lead to increases in serum potassium 1
• ACE inhibitors are contraindicated in pregnancy; women of childbearing age should use reliable contraception 3
• Cough is the most common adverse effect limiting ACE inhibitor therapy in clinical practice 5

In conclusion, benazapril twice daily is an effective regimen for managing hypertension, particularly when once-daily dosing does not provide adequate 24-hour blood pressure control. The divided regimen has been shown to provide better trough blood pressure control while maintaining the overall safety profile of the medication.