Treating Hypertension During Breastfeeding

Diuretics

The first drug introduced for hypertension is often a diuretic. In the few cases in which a diuretic was measured in human milk, the amounts have been low. Hydrochlorothiazide was undetectable in one breastfed infant of a mother taking the drug and no adverse effects have been reported among infants whose mothers were taking a diuretic. No controlled observations on the safety of furosemide in breastfed infants have been published, but adverse effects have not been reported.^1–4 Intense diuresis with high dosages of diuretics has been used to suppress postpartum lactation, such as with hydrochlorothiazide 100–150 mg/day, or chlorthalidone 200 mg/day, followed by 100 mg/day. In these old studies, the drugs were used with the intention of suppressing lactation and were often started immediately postpartum combined with other measures, such as fluid restriction and breast binding. No cases of suppression of lactation have been reported with typical antihypertensive doses such as hydrochlorothiazide 25–50 mg/day or chlorthalidone 12.5–25 mg/day.

The potassium-sparing diuretics, amiloride, spironolactone, and triamterene, are often used in combination with a thiazide diuretic. Only spironolactone has been studied during breastfeeding. It appears to be acceptable to use in nursing mothers.

Calcium Channel Blockers

These drugs are first-line therapy for many patients. Drug levels in milk have been very low for all of the drugs tested. In the few cases in which breastfed infants have had serum level measurements, the drugs were undetectable. Studied drugs include amlodipine, diltiazem, nicardipine, nifedipine, nimodipine, and verapamil. Other calcium channel blockers have not been studied during lactation. The most extensive safety information is on nifedipine, with no reports of adverse reactions among numerous infants exposed through breast milk, including infants whose mothers were being treated for Raynaud phenomenon of the nipple.^1–4

Renin–Angiotensin System Inhibitors

Drugs in this class are often one of the first drugs used. Included are angiotensin converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), and the direct renin inhibitor, aliskiren. The mention of these drugs may send a shiver up the spine because of their well-known teratogenicity when used during pregnancy, but this is not a concern postpartum. The main problem with these drugs is the lack of information during breastfeeding. Most ACEIs are inactive drugs and are metabolized to active metabolites, which are poorly absorbed orally. One exception is lisinopril, which is orally absorbable and active. Among the ACEIs, lactation information is available only on benazepril, captopril, enalapril, perindopril (very limited information), and quinapril. All of these drugs are excreted very sparingly into milk and are probably not absorbed well by the infant. No adverse infant effects of ACEIs in breast milk have been reported. There is no lactation information on the ARBs; however, all of the ARBs are very highly bound to plasma proteins (>98%) and incompletely absorbed orally, so are very unlikely to affect nursing infants. Aliskren has oral bioavailability of only 2.5% in adults, so might not reach the infant in clinically relevant amounts, but no safety information is available. All of the drugs lacking information should be avoided, if possible, in neonates and preterm infants pending further data.

Beta-Blockers

The beta blocking drugs are more diverse in their breast milk excretion and effects on nursing infants than other classes, primarily because the extent of protein binding in maternal plasma varies considerably from drug to drug. For example, atenolol is only about 10% plasma protein bound and propranolol is 90% bound. Resultantly, atenolol passes into milk in much greater amounts than propranolol. Acebutolol is another poorly bound beta-blocker. The poorly bound drugs are also more water soluble and rely more on renal excretion than the lipid-soluble drugs such as propranolol. Both atenolol and acebutolol have clear-cut cases of adverse reactions in breastfed infants, such as bradycardia, hypotension, tachypnea, cyanosis, and hypothermia. ² A small prospective study of mothers taking beta-blockers during nursing found a numerically, but not statistically, significant increased number of adverse reactions in those taking any beta-blocker. Although the ages of infants were matched to control infants, the ages of the affected infants were not stated in the abstract of this meeting presentation. ⁵

Labetalol is frequently used during the perinatal period to control blood pressure. Theoretically, it has desirable pharmacokinetic properties from the standpoint of breastfeeding: low oral bioavailability, moderate protein binding, and little excretion of unchanged drug through the kidney. Nevertheless, one possible adverse reaction was published only in a nonpeer-reviewed abstract. A 26-week premature infant weighing 640 g developed sinus bradycardia (80–90 bpm) and isolated atrial premature beats after nasogastric feeding with the mother's pumped breast milk was initiated on day 8 of life. Bradycardia and premature beats resolved within 24 hours of substitution of formula for breast milk. This case seems to illustrate the higher susceptibility of preterm infants to adverse drug reactions from drugs in breast milk.

Beta-blockers are not considered to be drugs of choice for hypertension in general, unless another indication exists simultaneously, such as migraine or angina prophylaxis. During breastfeeding, another problem is that the better tolerated beta-blockers such as atenolol have the greatest excretion into milk and the drugs that have less excretion into milk, such as propranolol, are poorly tolerated by the mother (e.g., sedation and depression). Labetalol and metoprolol appear to represent a balance between these extremes, with the caveat of caution in preterm infants.

Central Alpha-Adrenergic Agonists

Currently marketed drugs in this class include clonidine, guanfacine, and methyldopa. Of five literature reports of infants exposed to clonidine in breast milk, one infant experienced adverse effects. A 2-day-old infant whose mother took clonidine during pregnancy and postpartum presented with drowsiness, hypotonia, and suspected generalized seizures. At day 5, episodes of apnea were noted. On day 9 postpartum, breastfeeding was stopped and all symptoms were resolved within 24 hours. No adverse effects in breastfed infants have been reported with methyldopa, and no reports of infants receiving guanfacine in milk have been published.

The effect of these drugs on serum prolactin is complex. Guanfacine causes a decrease in serum prolactin among men and nonlactating women, but its effect on breastfeeding is not known. Both clonidine and methyldopa sometimes cause increases in serum prolactin and cases of nonpuerperal galactorrhea have been reported.

All of these drugs can cause sedation in the mother, so their use has generally fallen out of favor. Methyldopa is acceptable for nursing mothers if it is tolerated, but clonidine and guanfacine should be avoided.

Alpha-Adrenergic Blockers

The alpha-adrenergic blocking drugs are weak antihypertensives that are sometimes used as add-on drugs. This group includes doxazosin, prazosin, and terazosin. Milk excretion data are sparse, with two case reports for doxazosin, poorly documented manufacturer data for prazosin, and no information for terazosin. The amounts in milk appear to be quite low and the drugs appear not to affect serum prolactin, but they can cause stress incontinence in women, so are not ideal for nursing mothers.

Direct Vasodilators

Hydralazine and minoxidil are direct-acting vasodilators. Used alone, these vasodilators cause reflex tachycardia, so are usually given with a beta-blocker. A very limited amount of published information indicates that the amounts of these drugs in breast milk are small. Minoxidil is known for causing hypertrichosis, which did not occur in the short term in the one reported case of a breastfed infant whose mother was taking minoxidil. Only one infant safely breastfed with maternal hydralazine has been reported. These drugs are usually last-line agents for treating hypertension, but might be acceptable if a mother is nursing an older infant.

Summary

The good news for nursing mothers with hypertension is that some drugs in currently preferred categories are available with reasonably good safety information during breastfeeding. Diuretics, calcium channel blockers, and ACEIs are first-line drugs that can be used, although it might be best to limit use to drugs with breastfeeding safety information. In patients who do not tolerate an ACEI, ARBs are unlikely to adversely affect nursing infants, although no data are available. Some beta-blockers appear to be acceptable during breastfeeding, but acebutolol and atenolol should be used with caution, especially while nursing a neonate, because of the relatively large amounts excreted into milk and their excretion is predominantly renal. Most other antihypertensive drugs have scant information on use during breastfeeding, but data are sufficient to recommend avoiding clonidine and guanfacine.