Amlodipine Should Not Be Dosed Twice Daily
Amlodipine is designed and FDA-approved for once-daily dosing only, and twice-daily administration is not supported by pharmacokinetic data, clinical evidence, or prescribing guidelines. 1
FDA-Approved Dosing
The FDA label explicitly states that amlodipine should be administered once daily, with the usual initial antihypertensive dose being 5 mg once daily and a maximum dose of 10 mg once daily. 1 The recommended dose range for all indications—hypertension, chronic stable angina, vasospastic angina, and coronary artery disease—is 5 to 10 mg once daily. 1
Pharmacokinetic Rationale Against Twice-Daily Dosing
Amlodipine's pharmacokinetic profile makes twice-daily dosing unnecessary and inappropriate:
- Elimination half-life of 40-60 hours allows for true once-daily dosing with minimal plasma concentration fluctuation (only 20-25% between doses). 2
- High oral bioavailability (60-80%) and accumulation to steady-state over 1-1.5 weeks with once-daily administration. 2
- Gradual onset of effect after oral administration, with peak plasma concentrations occurring 6-8 hours after dosing. 2
The long elimination half-life means that splitting the dose into twice-daily administration provides no pharmacodynamic advantage and only increases pill burden without improving efficacy. 2
Clinical Evidence Supports Once-Daily Dosing
Multiple studies confirm 24-hour blood pressure control with once-daily amlodipine:
- Continuous intra-arterial blood pressure monitoring demonstrated that amlodipine 5-10 mg once daily effectively reduced blood pressure throughout the entire 24-hour period without altering normal circadian patterns. 3
- Daytime blood pressure was reduced from 165/103 to 147/89 mmHg and nighttime blood pressure from 137/79 to 121/69 mmHg with once-daily dosing. 3
- Dose-response studies showed that 73% of patients achieved target blood pressure with 10 mg once daily, demonstrating adequate efficacy without need for divided dosing. 4
Comparison with Shorter-Acting Agents
When compared to felodipine extended-release (which has a shorter elimination half-life), amlodipine demonstrated superior nighttime blood pressure control precisely because of its longer duration of action, further supporting once-daily dosing. 5 Amlodipine was more effective than felodipine at controlling ambulatory blood pressure during the night (systolic P=0.026, diastolic P=0.019). 5
Common Pitfall to Avoid
Do not confuse amlodipine with diltiazem or other calcium channel blockers that may require divided dosing. Diltiazem immediate-release formulations require multiple daily doses (typically four times daily), but amlodipine's unique pharmacokinetic profile eliminates this need. 6
Proper Dose Titration
If blood pressure control is inadequate on amlodipine 5 mg once daily, the correct approach is to increase to 10 mg once daily, not to split the dose. 1 Wait 7 to 14 days between titration steps, though more rapid titration is acceptable if clinically warranted with frequent patient assessment. 1
Special Populations
Even in elderly, fragile, or hepatically impaired patients who may be started on 2.5 mg, the dosing frequency remains once daily. 1 The dose may be lower, but the frequency does not change.