Can amlodipine be taken twice daily?

Amlodipine Dosing Schedule: Once vs. Twice Daily

Amlodipine should be administered once daily as per FDA labeling and clinical guidelines, and splitting the dose to twice daily is generally not recommended or necessary due to its long half-life of 36-45 hours.

Pharmacokinetic Properties Supporting Once-Daily Dosing

Amlodipine has distinct pharmacokinetic characteristics that make it ideal for once-daily administration:

• Long elimination half-life: 36-45 hours 1, with some sources reporting 40-60 hours 2
• Slow clearance rate: Results in minimal fluctuations (20-25%) in plasma concentration between doses 2
• Gradual onset of action: Peak plasma concentration occurs 6-8 hours after dosing 2, 3
• High bioavailability: 60-80% with once-daily administration 2
• Linear dose-related pharmacokinetics: Provides consistent blood pressure control throughout the 24-hour dosing interval 3

Official Dosing Recommendations

The FDA-approved labeling for amlodipine clearly states:

• "The usual initial antihypertensive oral dose of Amlodipine besylate tablets is 5 mg once daily, and the maximum dose is 10 mg once daily" 4
• "Take amlodipine besylate tablets, USP once a day, with or without food" 4

Clinical Evidence Supporting Once-Daily Dosing

Multiple clinical studies have confirmed amlodipine's effectiveness as a once-daily medication:

• Dose-ranging studies determined that 5 mg once daily is the most appropriate starting dose, with simple adjustment to 10 mg if necessary 5
• Clinical trials demonstrated effective 24-hour control of hypertension with once-daily administration 1
• During chronic, once-daily dosing, blood pressure remains decreased from baseline with minimal fluctuation over the 24-hour dose interval 2
• A dose-response study involving 205 patients confirmed amlodipine's suitability for once-daily dosing 6

Special Situations

While amlodipine is typically administered once daily, there are specific circumstances where dose adjustment (but not necessarily frequency change) might be considered:

• Hepatic insufficiency: Start with 2.5 mg once daily 4
• Elderly or fragile patients: Start with 2.5 mg once daily 4
• When adding to other antihypertensive therapy: May start with 2.5 mg once daily 4

Potential Pitfalls and Caveats

1. Confusion with other CCBs: Unlike amlodipine, some calcium channel blockers (such as immediate-release diltiazem or verapamil) do require multiple daily dosing 7

2. Administration challenges: For patients with swallowing difficulties, amlodipine tablets can be crushed and mixed with food or liquid while maintaining once-daily dosing 8

3. Misinterpreting side effects: Peripheral edema is a common side effect of amlodipine 4 and should not be confused with a need to split the dose

Conclusion

Based on amlodipine's pharmacokinetic profile and extensive clinical evidence, once-daily dosing provides optimal blood pressure control with minimal fluctuations. The long half-life of amlodipine (36-45 hours) ensures consistent plasma levels throughout the 24-hour period, making twice-daily dosing unnecessary and potentially complicating adherence without providing additional clinical benefit.