From the Guidelines
Amlodipine is not the preferred first-line treatment for hypertension during pregnancy, and its use should be carefully considered due to limited human studies and potential fetal risks. According to the 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults 1, women with hypertension who become pregnant should be transitioned to methyldopa, nifedipine, and/or labetalol during pregnancy. While calcium channel blockers as a class are considered relatively safe in pregnancy, other medications have more established safety profiles in pregnant women.
Some key points to consider when evaluating the use of amlodipine in pregnant women with hypertension include:
- Amlodipine is FDA pregnancy category C, meaning animal studies have shown adverse effects on the fetus, but there are insufficient well-controlled studies in humans.
- The main concern with calcium channel blockers in pregnancy is the theoretical risk of reducing uterine blood flow, though this appears to be less significant with dihydropyridines like amlodipine compared to non-dihydropyridine calcium channel blockers.
- If amlodipine must be used during pregnancy, it should be at the lowest effective dose and under close medical supervision with regular monitoring of maternal blood pressure and fetal well-being.
The goal of antihypertensive treatment during pregnancy includes prevention of severe hypertension and the possibility of prolonging gestation to allow the fetus more time to mature before delivery, as stated in the guideline 1. Management of hypertension during pregnancy requires balancing the risks of uncontrolled maternal hypertension against potential medication effects on the developing fetus.
In terms of treatment options, the guideline recommends that women with hypertension who become pregnant should not be treated with ACE inhibitors, ARBs, or direct renin inhibitors due to potential harm to the fetus 1. Instead, medications like methyldopa, labetalol, and nifedipine are preferred first-line agents with more established safety profiles in pregnant women. The use of amlodipine during pregnancy should be carefully weighed against the potential benefits and risks, and alternative treatments should be considered whenever possible.
From the FDA Drug Label
The limited available data based on post-marketing reports with amlodipine use in pregnant women are not sufficient to inform a drug-associated risk for major birth defects and miscarriage. There are risks to the mother and fetus associated with poorly controlled hypertension in pregnancy [see Clinical Considerations] In animal reproduction studies, there was no evidence of adverse developmental effects when pregnant rats and rabbits were treated orally with amlodipine maleate during organogenesis at doses approximately 10 and 20-times the maximum recommended human dose (MRHD), respectively However for rats, litter size was significantly decreased (by about 50%) and the number of intrauterine deaths was significantly increased (about 5-fold). Amlodipine has been shown to prolong both the gestation period and the duration of labor in rats at this dose [ see Data].
The safety of amlodipine in pregnant women with hypertension is not well established due to limited available data.
- Key points:
- Limited human data on amlodipine use in pregnancy
- Animal studies show no adverse developmental effects at high doses, but decreased litter size and increased intrauterine deaths in rats
- Poorly controlled hypertension in pregnancy poses risks to the mother and fetus
- Clinical decision: Amlodipine should be used with caution in pregnant women with hypertension, as the benefits and risks are not well established 2.
From the Research
Amlodipine Safety in Pregnancy with Hypertension
- Amlodipine is a calcium channel blocker that can be used to treat hypertension during pregnancy, according to a systematic review and meta-analysis published in 2022 3.
- The study found that amlodipine has slightly superior efficacy to nifedipine in treating hypertension during pregnancy, with a decreased risk of maternal side effects.
- Amlodipine was also found to have no difference in pregnancy outcomes, including caesarean section, premature labor, placental abruption, fetal growth restriction, fetal distress, and neonatal asphyxia, compared to nifedipine 3.
- Another study published in 2022 found that several antihypertensive drugs, including nifedipine, labetalol, and methyldopa, can be used to treat severe hypertension in pregnancy, but did not specifically mention amlodipine 4.
- A pharmacokinetic study published in 2018 found that amlodipine crosses the placenta in measurable quantities, but is not detected in breast milk or infant plasma, indicating that it is likely safe to use during the peripartum period 5.
- A review article published in 2011 discussed the principles of treatment for hypertension in pregnancy and mentioned that methyldopa, labetalol, and nifedipine are safe for use in pregnancy, but did not specifically mention amlodipine 6.
- A pilot clinical trial published in 2014 found that amlodipine may have the same effect as furosemide during pregnancy, but a large clinical trial is necessary to prove this 7.
Key Findings
- Amlodipine can be effectively and safely used for hypertension during pregnancy 3.
- Amlodipine has slightly superior efficacy to nifedipine in treating hypertension during pregnancy 3.
- Amlodipine is not detected in breast milk or infant plasma, indicating that it is likely safe to use during the peripartum period 5.
Antihypertensive Drugs in Pregnancy
- Several antihypertensive drugs, including nifedipine, labetalol, and methyldopa, can be used to treat severe hypertension in pregnancy 4.
- Methyldopa, labetalol, and nifedipine are safe for use in pregnancy, whereas angiotensin converting enzyme inhibitors and angiotensin receptor blockers should be avoided 6.