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
| 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:
| 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!
References
- 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.
Like most drugs, amlodipine oral tablet may cause mild or serious side effects. The lists below describe some of the more common side effects. These lists don’t include all possible side effects.
Keep in mind that side effects of a drug can depend on:
- your age
- the dosage you’re prescribed
- other health conditions you have
- other medications you may be taking
Your doctor or pharmacist can tell you more about the potential side effects of amlodipine oral tablet. They can also suggest ways to help reduce side effects.
Mild side effects
Here’s a short list of some of the mild side effects that amlodipine oral tablet can cause. To learn about other mild side effects, talk with your doctor or pharmacist, or read amlodipine oral tablet’s prescribing information.
Mild side effects of amlodipine oral tablet that have been reported include:
Mild side effects of many drugs may go away within a few days or a couple of weeks. But if they become bothersome, talk with your doctor or pharmacist.
* For more information on this side effect, see the “Side effect focus” section below.
Serious side effects
Serious side effects from amlodipine oral tablet can occur, but they aren’t common. If you have serious side effects, call your doctor right away. However, if you think you’re having a medical emergency, you should call 911 or your local emergency number.
Serious side effects of amlodipine oral tablet that have been reported include:
* For more information on this side effect, see the “Side effect focus” section below.
Side effect focus
Learn more about some of the side effects amlodipine oral tablet may cause.
Weight gain
You may have weight gain while you’re taking amlodipine oral tablets. But this wasn’t a common side effect in studies of the drug.
You may also gain weight if you have edema (swelling), which is a possible side effect of amlodipine oral tablet. For more information about this, see the “Edema, such as leg swelling” section just below.
What might help
If you’re concerned about weight gain while taking amlodipine, talk with your doctor. They can recommend healthy ways to manage your weight.
Edema, such as leg swelling
You may have edema (swelling) while you’re taking amlodipine oral tablets. This was the most common side effect reported in studies of the drug.
Swelling from amlodipine oral tablets typically happens in your arms, feet, hands, or legs. Your risk for swelling with amlodipine may increase with higher doses of the drug.
What might help
Tell your doctor about any swelling you have while you’re taking amlodipine oral tablets. They may lower the dosage you’re prescribed. Or they may switch you to a different drug to treat your condition.
If your swelling is mild and isn’t bothersome, your doctor may tell you it’s safe to keep taking amlodipine oral tablets. To help lessen swelling while taking this drug, you can try the following remedies:
- wear compression stockings or wraps on the swollen area
- keep the swollen area elevated
If your swelling is severe or bothersome, your doctor may have you stop taking amlodipine oral tablets. If so, your swelling will likely go down within several days after stopping the drug.
Constipation
You may have constipation while you’re taking amlodipine oral tablets. But this wasn’t a common side effect in studies of the drug.
Constipation can cause symptoms such as:
- having fewer bowel movements than usual
- passing hard stools
- taking a longer time than usual to pass stools
What might help
Tell your doctor if you have constipation while taking amlodipine oral tablets.
If you have constipation, it’s important to keep your body hydrated by drinking plenty of water. You can also try eating certain foods to help stay hydrated.
Eating foods rich in fiber can help relieve your constipation. These foods include whole grains, vegetables, and raw fruits.
Over-the-counter medications, such as laxatives and stool softeners, are also effective for relieving constipation. But make sure you check with your doctor or pharmacist before taking any new medications with amlodipine oral tablet.
Allergic reactionSome people may have an allergic reaction to amlodipine oral tablet.
Symptoms of a mild allergic reaction can include:
- skin rash
- itchiness
- flushing (temporary warmth, redness, or deepening of skin color)
A more severe allergic reaction is rare but possible. Symptoms of a severe allergic reaction can include swelling under your skin, typically in your eyelids, lips, hands, or feet. They can also include swelling of your tongue, mouth, or throat, which can cause trouble breathing.
Call your doctor right away if you have an allergic reaction to amlodipine oral tablet. But if you think you’re having a medical emergency, call 911 or your local emergency number.
Most people who begin amlodipine will see their blood pressure go down (and stay down!) within about 1 week of starting the medicine. After about a week of taking amlodipine daily, your blood pressure should reach a lower level.
This tells you how long amlodipine takes to lower your blood pressure in the long run. But how long does it take for each amlodipine dose to take effect on a daily basis?
Although each dose of amlodipine begins working as soon as it enters the blood, it takes 6-12 hours for amlodipine to reach its greatest effect. This means your blood pressure should begin to go down within 12 hours of taking amlodipine. So if you take amlodipine at 8:00 am with your breakfast, when you check your pressure at 4:00 pm (6-12 hours later), it should have gone down. However, each person is different. You may see your blood pressure go down more quickly or more slowly than this. Once you are taking amlodipine at the same time every day, your blood pressure should stay down throughout the day.
Amlodipine is like a sprinter. As soon as the race starts, the runner starts sprinting, but it takes the sprinter a few strides to reach their fastest pace.
Amlodipine takes about a week to reach its peak!