Article date: May 2009
Angiotensin converting enzyme (ACE) inhibitors and angiotensin II receptor antagonists are licensed for a range of conditions including hypertension and may be particularly suitable for young patients with high blood pressure (but not those of black ethnic origin) and those with some comorbidities such as diabetic nephropathy.
Methyldopa is recognised to be the antihypertensive of choice during pregnancy and breastfeeding, but will not be suitable for some women and other options may need to be explored.
Reminder: use in pregnancy
Angiotensin II is essential for normal kidney development, and the use of ACE inhibitors and angiotensin II receptor antagonists in late pregnancy has been associated with adverse effects on the kidney and other congenital anomalies. Some data have also suggested an increased risk of congenital anomaly after exposure during the first trimester of pregnancy. Therefore, ACE inhibitors and angiotensin II receptor antagonists should not be used at any stage of pregnancy unless absolutely necessary, and only then after the potential risks and benefits have been discussed with the patient.
Use during breastfeeding
In general, ACE inhibitors have a small molecular size and so their transfer to breast milk is possible. With the exception of captopril, the active metabolites of ACE inhibitors have long elimination half-lives; however, these metabolites are poorly absorbed orally. Data on the use of ACE inhibitors in breastfeeding are sparse and relate mostly to captopril, enalapril, and quinapril; findings indicate that drug is transferred to breast milk. Although the levels transferred to an infant via breastfeeding are unlikely to be clinically relevant, there are insufficient data to exclude a possible risk of profound neonatal hypotension, particularly in preterm babies.
Angiotensin II receptor antagonists
No data on the use of angiotensin II receptor antagonists are available. These agents are also small enough to pass into breast milk, and some unpublished studies have found them in the milk of lactating rats. However, most angiotensin II receptor antagonists are highly bound to maternal plasma proteins, which can substantially limit their transfer into breast milk. The effects of potential exposure on a nursing infant are unknown.
Advice for healthcare professionals for ACE inhibitors includes:
- captopril, enalapril, or quinapril: use in breastfeeding is not recommended in the first few weeks after delivery because of the possibility of profound neonatal hypotension; preterm babies may be at particular risk -use may be considered when the infant is older if an ACE inhibitor is necessary for the mother; careful follow-up of the infant for possible signs of hypotension is recommended
- ramipril, lisinopril, fosinopril, trandolapril, moexipril, or perindopril: use in breastfeeding is not recommended - alternative treatments with more established safety profiles during breastfeeding are preferable, especially while nursing a newborn or preterm baby
For all angiotensin II receptor antagonists, use in mothers breastfeeding is not recommended. Alternative antihypertensive treatments with more established safety profiles during breastfeeding are preferable, especially while nursing a newborn or preterm baby.
See also clarification published July 2010 for more information
Article citation: Drug Safety Update May 2009, vol 2 issue 10: 3.