Should I administer Amlodipine (amlodipine) 5mg to a patient with newly diagnosed hypertension tonight and another dose in the morning, or start treatment with one dose tomorrow morning?

Timing of Amlodipine Administration for Newly Diagnosed Hypertension

Start amlodipine 5 mg tomorrow morning as a single dose, rather than giving one dose tonight and another in the morning. There is no clinical benefit to administering two doses within 12-24 hours, and doing so could increase the risk of hypotension without improving blood pressure control.

Rationale for Once-Daily Morning Dosing

Pharmacokinetic Properties Support Single Daily Dosing

• Amlodipine has an exceptionally long half-life of 40-60 hours, which means it accumulates gradually in the body and reaches steady-state over 1-1.5 weeks 1
• The drug demonstrates only 20-25% fluctuation in plasma concentration between doses when given once daily, providing consistent 24-hour blood pressure control 1
• Peak plasma concentrations occur 6-8 hours after administration, with gradual onset of antihypertensive effect over 4-8 hours after a single dose 1

Standard Dosing Guidelines

• The FDA-approved initial dose for adults is 5 mg once daily, with a maximum of 10 mg once daily 2
• The American College of Cardiology recommends amlodipine as a once-daily medication at doses of 2.5-10 mg for adults 3
• Dose adjustments should occur after 7-14 days, not within the first 24 hours 2

Why Not Give Two Doses in 12-24 Hours?

No Clinical Benefit

• Blood pressure reduction with amlodipine occurs gradually over days to weeks, not hours 1
• After single doses, blood pressure decreases gradually over 4-8 hours and may slowly return to baseline over 24-72 hours 1
• There is no evidence that loading doses or rapid dose escalation improves outcomes in newly diagnosed hypertension 4

Potential Risks

• Giving two doses within 24 hours effectively doubles the initial dose to 10 mg, which exceeds standard initiation protocols 2
• This could lead to excessive hypotension, dizziness, or peripheral edema, particularly in treatment-naive patients 3
• Small, fragile, or elderly patients should actually start at 2.5 mg once daily, not higher doses 2

Optimal Timing: Morning vs. Evening

Either Time is Acceptable

• Both morning and evening administration of amlodipine provide equivalent 24-hour blood pressure control in essential hypertension 5, 6
• A randomized controlled trial found no difference in nighttime systolic BP reduction between nighttime dosing (-9.9 mmHg) and daytime dosing (-11.5 mmHg) 6
• The drug can be administered at the most convenient time of day for the patient to improve adherence 7

Morning Dosing is Conventional

• Most clinical trials and guidelines reference morning administration as standard practice 2, 8
• Morning dosing allows for monitoring of initial response during waking hours when medical support is more readily available
• Recent evidence does not support preferential bedtime dosing for cardiovascular benefit, contrary to older recommendations 9

Follow-Up and Dose Titration

Assessment Timeline

• Reassess blood pressure after at least 2 weeks of treatment at 5 mg once daily 9, 7
• The American Heart Association recommends increasing from 5 mg to 10 mg once daily if blood pressure remains above target (≥130/80 mmHg) after 2-6 weeks 7
• Do not consider dose escalation before 6 weeks unless clinically warranted, as studies show no advantage to early dose titration 4

Blood Pressure Targets

• Target blood pressure is less than 130/80 mmHg for most adults with hypertension 7
• Confirm inadequate control with home blood pressure monitoring (≥135/85 mmHg) before escalating therapy 7

When to Add Second Agent

• Consider adding a second agent rather than maximizing amlodipine if blood pressure control is inadequate after 4-6 weeks at 5 mg 7
• Preferred combinations include amlodipine + ACE inhibitor/ARB, or amlodipine + thiazide-type diuretic 9, 7
• For patients with blood pressure ≥160/100 mmHg, initial treatment with two antihypertensive medications is recommended 9

Common Pitfalls to Avoid

• Do not give "stat" or loading doses of amlodipine—the drug's pharmacokinetics do not support this approach 1
• Check medication adherence before escalating dose, as non-adherence is a common cause of apparent treatment failure 7
• Avoid combining ACE inhibitors with ARBs, as this increases risk of end-stage renal disease and stroke 9
• Monitor for peripheral edema, the most common side effect, which may require dose reduction or addition of an ACE inhibitor/ARB 3, 7