Using Amlodipine Responsibly in Hospitalized Patients

Amlodipine (Norvasc) is a great drug — but it takes 8 hours for the drug to reach its peak drug concentration, and about a week to reach steady-state full antihypertensive effect.

Delayed Onset of First Dose

Most dihydropyridine calcium channel blockers (eg, not diltiazem or verapamil) can cause reflex tachycardia by causing vasodilation too quickly.  Amlodipine has an extremely prolonged absorption profile, where the time to peak concentrations can take more than 8 hours.  The following is a table from an oral dosing pharmacokinetic study (mean ± s.d.):1

Day 1 Day 14
Time of peak (hrs) 8.9 ± 3.7 8.7 ± 1.9
Peak (ng/mL) 6.9 ± 2.6 18.1 ± 7.1
Trough (ng/mL) 3.3 ± 1.2 11.8 ± 5.3

Unlike other agents, like oral hydralazine, clonidine, or nifedipine XL which work within 1 to 2 hours, amlodipine has a very, very delayed onset of effect.  This is particularly important when trying to convert from IV to PO antihypertensives in the inpatient setting — amlodipine just isn’t a good option for acute management.

Accumulating Antihypertensive Effect

In general, any drug reaches a steady state concentration with consistent dosing after 3 to 5 half-lives.  The half-life of amlodipine is about 30-50 hours, meaning that “steady state” occurs between 4 and 10 days after starting therapy.  As you can see in the table above, peak and trough concentrations at steady state are significantly higher than the first dose.

What’s the Risk?

The combination of a delayed onset of effect (8 hours) and a delayed time to steady state (4 to 10 days) means that amlodipine is not a good oral antihypertensive when you want an effect within the next few days.  For providers who are unaware of the “slow” effect of amlodipine, it becomes too easy to rapidly increase the dose or add additional antihypertensives before amlodipine’s full effect has been seen.

Don’t get me wrong — amlodipine is a great antihypertensive for outpatient use.  It lasts 24 hours, does not require laboratory monitoring, is well tolerated, and is generic.  Because of amlodipine’s tortoise-like speed, it should not be used to quickly convert patients from parenteral to oral antihypertensives in the inpatient setting.

Alternative Agents

The following agents offer faster onset, ability to titrate quickly, and a short half-life so steady-state is reached quickly.  These agents are particularly attractive for short-term, strict blood pressure parameters (eg, neurosurgical patients) and may facilitate quicker weaning of continuous IV vasoactive agents:

Drug Dose Onset Peak Duration
Nifedipine XL 60 mg PO daily (max 180 mg/day) 2 hrs 6 hrs 24 hrs
Clonidine 0.1-0.2 mg PO Q12hr or Q8hr (max 0.8 mg/day) 0.5-1 hrs 3-5 hrs 6-10 hrs
Hydralazine 25 mg PO Q8hr (max 100 mg Q8hr) 0.5 hrs 1-2 hrs 8 hrs

What are your favorite quick-acting oral antihypertensives?  How do you start your dosing?  Leave a comment below!


  1. Faulkner JK, McGibney D, Chasseaud LF, et al. The pharmacokinetics of amlodipine in healthy volunteers after single intravenous and oral doses and after 14 repeated oral doses given once daily. Br J Clin Pharmacol. 1986;22(1):21-5. PMID 2943308.

2 thoughts on “Using Amlodipine Responsibly in Hospitalized Patients

  1. Kanwar

    1) Our commonest clinical context is the asymptomatic hypertensive. Debate used to be between Felodipine & Amlo. The latter was considered favourable for the slow drop it achieves (but after reading your post, I’m not sure if the ‘drop’ we saw was just physiology from the patient getting more relaxed, versus actual antihypertensive effect)…

    2) Regarding hydralazine, you recommend a once dose to get high SBP numbers under control – followed by a discharge prescription of say, Amlo? Or, discharge with hydralazine as well?

    1. Sean P. Kane Post author

      1) I actually don’t have any experience with felodipine — it appears to have a quicker onset of action and a shorter duration than amlodipine, and may even be a bit quicker in onset than nifedipine XL. Although it has a favorable kinetic profile, you may run into formulary or availability issues as it’s one of the least commonly prescribed calcium channel blockers (about 1/70th the popularity of amlodipine per ClinCalc DrugStats).

      2) Definitely do not discharge with hydralazine unless the patient is maximized on other therapies. Hydralazine needs to be dosed TID, so patient compliance is quite poor.


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