Is Amlodipine Safe While Trying to Get Pregnant?
Women with hypertension who are planning to become pregnant should be transitioned off amlodipine and switched to methyldopa, nifedipine (extended-release), or labetalol before attempting conception. 1
Why Amlodipine Should Be Discontinued
Guideline Recommendations Are Clear
The 2017 ACC/AHA guidelines explicitly state that women with hypertension who are planning to become pregnant should be transitioned to methyldopa, nifedipine, and/or labetalol during pregnancy. 1 While this recommendation specifically addresses pregnancy, the preconception period is the ideal time to make this medication switch.
The JNC 7 guidelines recommend that in hypertensive women planning to become pregnant, it may be prudent prior to conception to change to antihypertensive medications known to be safe during pregnancy, such as methyldopa or beta-blockers. 1
Limited Safety Data for Amlodipine
The FDA drug label for amlodipine states that "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." 2
Animal studies showed concerning findings: litter size decreased by approximately 50% and intrauterine deaths increased 5-fold in rats at doses equivalent to 10 times the maximum recommended human dose. 2
Amlodipine prolonged both gestation period and duration of labor in animal studies. 2
Preferred Alternatives for Preconception Planning
First-Line Agents
Labetalol is increasingly preferred over methyldopa due to:
- Superior prevention of disease progression (0% developed significant proteinuria vs. 18.5% on methyldopa) 3
- Better maternal tolerability with fewer side effects 3
- Lower rates of labor induction and cesarean section 3
- Main contraindication is reactive airway disease (asthma) 3
Extended-release nifedipine (a different calcium channel blocker than amlodipine):
- Recommended as first-line by ACC/AHA and ACOG 1, 4
- Has more extensive safety data in pregnancy compared to amlodipine 4
- Meta-analysis found it may be preferred as first-line agent for severe hypertension 5
Methyldopa:
- Has the longest safety record with long-term infant follow-up data 4
- Preferred by JNC 7 if delivery is likely more than 48 hours off 3
- Important caveat: Should be avoided in women at risk for depression and must be switched postpartum due to increased risk of postnatal depression 3, 4
Clinical Action Plan
Timing of Medication Switch
Switch medications before attempting conception, not after pregnancy is confirmed. 1 This avoids any first-trimester exposure to amlodipine when organogenesis occurs.
Allow time to establish blood pressure control on the new medication before conception. 1
Blood Pressure Targets
- Target blood pressure should be below 140/90 mmHg but not below 80 mmHg diastolic. 4
- Once pregnant, target becomes 110-135/85 mmHg to balance maternal safety with fetal perfusion. 1, 4
Important Caveats
What About Research Showing Amlodipine May Be Safe?
A 2022 meta-analysis found amlodipine "can be effectively and safely used for hypertension during pregnancy" with slightly superior efficacy to nifedipine. 6
A 2014 pilot trial showed amlodipine had similar maternal and neonatal outcomes to other agents. 7
A 2007 case series of three women exposed to amlodipine in first trimester found no apparent teratogenicity. 8
However, these research findings do not override guideline recommendations. The guidelines prioritize medications with more extensive safety data and longer track records (methyldopa, labetalol, nifedipine), and the FDA label confirms insufficient data for amlodipine. 1, 2 In clinical practice, we should not use patients trying to conceive as an opportunity to gather more safety data when proven alternatives exist.