From the Guidelines
Lisinopril should be avoided during the first trimester of pregnancy and throughout the entire pregnancy due to its potential to cause harm to the developing fetus. If you are taking lisinopril and discover you are pregnant, contact your healthcare provider immediately to switch to a safer alternative. Lisinopril belongs to a class of medications called ACE inhibitors, which are known to cause serious harm to the developing fetus, including birth defects, kidney problems, and even fetal death, particularly when used in the second and third trimesters 1. While first trimester exposure carries less documented risk than later exposure, the safest approach is to avoid lisinopril completely during pregnancy.
Alternative Medications
Alternative medications that are considered safer during pregnancy include:
- Certain beta-blockers (like labetalol)
- Methyldopa
- Nifedipine, which is available in multiple formulations, with the long-acting formulation recommended for maintenance and the short-acting formulation for rapid treatment of severe hypertension 1.
Management of Hypertension in Pregnancy
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. BP management during pregnancy is complicated by the fact that many commonly used antihypertensive agents, including ACE inhibitors and ARBs, are contraindicated during pregnancy because of potential harm to the fetus 1.
Key Considerations
Key considerations for the management of hypertension in pregnancy include:
- Regular blood pressure monitoring
- Careful weighing of the benefits of treating high blood pressure against potential risks to determine the most appropriate medication
- Use of reliable contraception and discussion of pregnancy plans with the healthcare provider before conceiving for women of childbearing age who take lisinopril 1.
Recommendations
The American College of Cardiology and American Heart Association recommend that women with hypertension who become pregnant, or are planning to become pregnant, should be transitioned to methyldopa, nifedipine, and/or labetalol during pregnancy 1. ACE inhibitors, ARBs, and direct renin inhibitors are contraindicated in pregnancy due to their associations with fetal teratogenicity and oligohydramnios 1.
From the FDA Drug Label
USE IN SPECIFIC POPULATIONS 8. 1 Pregnancy Pregnancy Category D ... Most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive use in the first trimester have not distinguished drugs affecting the renin-angiotensin system from other antihypertensive agents.
In the unusual case that there is no appropriate alternative to therapy with drugs affecting the renin-angiotensin system for a particular patient, apprise the mother of the potential risk to the fetus.
The use of lisinopril in the first trimester of pregnancy is not directly addressed in terms of specific risks. However, it is mentioned that most epidemiologic studies have not distinguished between drugs affecting the renin-angiotensin system and other antihypertensive agents.
- The drug label advises that if there is no alternative to therapy with drugs affecting the renin-angiotensin system, the mother should be informed of the potential risk to the fetus.
- It is recommended to discontinue lisinopril as soon as possible when pregnancy is detected, based on the information provided for the second and third trimesters.
- Appropriate management of maternal hypertension is important to optimize outcomes for both mother and fetus 2.
From the Research
Lisinopril and First Trimester of Pregnancy
- The use of lisinopril, an angiotensin-converting enzyme inhibitor (ACEI), during the first trimester of pregnancy has been associated with an increased risk of adverse pregnancy outcomes, including overall and specific congenital malformations, low birth weight, miscarriage, elective termination of pregnancy, stillbirth, and preterm delivery 3.
- A systematic review and meta-analysis found that first-trimester exposure to ACEIs or angiotensin II receptor blockers (ARBs) was significantly associated with an increased risk of overall congenital malformations (OR = 1.94,95% CI = 1.71-2.21, P < .0001) 3.
- There is no direct evidence from the provided studies on the safety of lisinopril during the first trimester of pregnancy, but the available data suggest that ACEIs and ARBs should be used with caution during this period.
- Other antihypertensive drugs, such as methyldopa, labetalol, and nifedipine, have been found to be effective and relatively safe for use during pregnancy, including the first trimester 4, 5, 6.
- However, the pharmacokinetics of these drugs during pregnancy are not well understood, and further studies are needed to determine the optimal dosing and potential risks associated with their use during this period 6.