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 about three times 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.
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:
|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!
- 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.