Antihypertensive Therapy During Lactation The need for therapy is rising, but little is known of the effects on the infant

The recent dramatic increase in the number of women breast-feeding, combined with the increasing tendency to delay pregnancy until later years, may to some extent be responsible for the rise in the number of pregnant and lactating women who require treatment for chronic hypertension. The only published information concerning the effect of antihypertensive drugs on breast-feeding infants comes from case reports or small studies, most of which have ignored the pharmacokinetics of individual drugs.

An equilibrium is set up between the amount of a drug in plasma and the unionised portion that enters the milk ultrafiltrate. However, this is influenced strongly by the binding affinity of the drug to plasma and milk proteins and to a lesser extent by the lipid-solubility of the drug. Another factor involved is the ionisation of the drug, with weakly basic drugs having a higher milk (pH7) to plasma (pH7.4) ratio than those that are weakly acidic. The transfer of a drug into milk is dynamic and reversible with peak concentrations often lagging behind those in plasma and milk levels persisting longer than plasma levels because of slow diffusion of ionised forms. Although seldom measured, it is possible to estimate the drug intake in an infant if milk drug concentrations are known, and assuming an average 165 ml/kgjday intake of milk in a newborn infant.

Although levels of the diuretics chlorothiazide, hydrochlorothiazide, chlorthalidone and a spironolactone metabolite (canrenone) have been found to be very low in breast milk, the ability of thiazide diuretics to decrease total milk production is an important consideration when diuretics are prescribed to lactating women. The weakly basic nature of ~-blockers means they invariably have a high milk to plasma ratio. Although the ratio is > 3 for atenolol, metoprolol and nadolol there are, as yet, no reports of adverse effects or transfer into the infant. The ratio for propranolol on the other hand, is < 1 and once again no adverse effects have been reported in the infants. Methyldopa is an a-blocker widely used during pregnancy but little is known of its transfer into milk. Small, preliminary studies have found low levels in the milk at delivery and in breast-fed infants. Low levels of clonidine have also been found in milk. Other agents include hydralazine which is often used for severe hypertension late in pregnancy and during labour but rarely after delivery. However, levels of the drug have been measured in breast milk. Reserpine has been traced in breast milk and possibly causes nasal congestion and a rise in respiratory secretions in infants. Minimal levels of guanethidine have been found in breast milk. A selective restriction of captopril movement into breast milk appears to keep levels low despite a 300 mgjday dosage.

The risks of antihypertensive medication must be carefully weighed against the scientifically-proven, nutritional and immunological benefits of breast-feeding. There are however differences between the drugs, so that an agent found in very low concentrations in the milk should be recommended during the lactation period . Diuretics appear to be best avoided because of their reduction of milk production; propranolol would probably be the most appropriate of the i1-blockers although none have ever been reported to cause adverse effects in infants, while captopril appears to be safely administered in patients with severe hypertension. White. WB .. Hypertension 6' 297 (May·Jun 1984)

0156-2703/ 84/ 1006-0003/ 0$01.00/ 0 © ADIS Press INPHARMA® 6 Oct 1984 3