When the Heart Is Not in It: Breastfeeding with Cardiovascular Disease

Antiarrhythmics

Antiarrhythmics are usually classified by the Vaughan-Williams classification system based on their electrophysiological properties. It is useful to look at the alternatives for nursing mothers within these classes because pharmacological and toxicological effects as well as the amount of available information can be different between drugs. However, drugs within each class are not necessarily interchangeable, so check with a cardiologist.

Little information exists on most of these drugs with respect to breastfeeding; therefore, the full range of milk levels are possibly not represented by the reported cases (i.e., higher milk levels and infant dosages might occur). The general admonition that neonates and preterm infants may be more susceptible to adverse drug effects than older infants also applies. Furthermore, infants of mothers who were receiving a drug during pregnancy might exhibit adverse effects in the neonatal period from transplacental drug passage. Drug assays are available for most of these drugs, so if an infant displays possible signs of toxicity, infant serum concentrations can usually be measured.

Class Ia includes disopyramide, procainamide, and quinidine. Disopyramide has been measured in the milk of five mothers and in the serum of four breastfed infants. It was found in the serum of nursing infants at levels ranging from undetectable to 12.5% of the mother's serum levels. However, in the cases reported, there were no adverse infant effects. The drug's metabolite is more anticholinergic than disopyramide itself and appears in breast milk in levels higher than the parent drug. Disopyramide may be used cautiously while breastfeeding with observation of the infant for anticholinergic symptoms. Theoretically, disopyramide might decrease the milk supply because of its anticholinergic activity.

Maternal doses of procainamide 2 g daily produced low levels of the drug and its active metabolite in the milk of one mother. Although it would not be expected to cause adverse effects in older breastfed infants, the relative lack of data concerning breastfeeding during maternal procainamide therapy would argue for careful monitoring if this drug is used while breastfeeding a neonate.

Maternal doses of quinidine up to 1.8 g daily produced low levels in the milk of one mother. A breastfed infant might receive up to 4% of the maternal weight-adjusted dosage.

Class Ib includes lidocaine and mexiletine. Lidocaine is used only acutely by intravenous (IV) injection or infusion, so is primarily of concern during acute maternal arrhythmia treatment. Lidocaine concentrations in milk during continuous IV infusion are low, and the lidocaine in milk is poorly absorbed by the infant. Maternal lidocaine is not expected to cause any adverse effects in breastfed infants. No special precautions are required for lidocaine use per se, although other maternal factors might dissuade an acutely ill mother from breastfeeding.

Maternal doses of mexiletine up to 600 mg daily produced low levels in the milk of two mothers. It is predicted that a breastfed infant would receive <2% of the maternal weight-adjusted dosage. One of the breastfed infants had undetectable serum levels at 2 and 6 weeks of age. Mexiletine is not expected to cause any adverse effects in breastfed infants.

Class Ic includes flecainide and propafenone. Maternal doses of flecainide up to 200 mg daily in 12 women produced low levels in milk that ranged from 0.7% to 6.9% of the maternal weight-adjusted dosage. Maternal doses of propafenone up to 900 mg daily produced low levels in the milk of two women, amounting to 0.1% of the maternal dose or less.

Class II is the beta-adrenergic blocking drugs, with the most commonly used for arrhythmias being esmolol, metoprolol, and propranolol. Esmolol has not been studied during breastfeeding, but based on its physicochemical properties and extremely short half-life, maternal esmolol would not be expected to cause adverse effects in breastfed infants. Metoprolol and especially propranolol have been well studied and are considered safe to use during breastfeeding.

Class III includes amiodarone, dofetilide, dronedarone, ibutilide, and sotalol. Only two of these agents have any information on breastfeeding: amiodarone and sotalol. The others are generally considered to be incompatible with breastfeeding because of lack of information and potential infant toxicity.

Amiodarone is an iodine-containing compound that is active and is metabolized to the active metabolite, desethylamiodarone. Metabolism also releases 6 mg of free iodine for each 100 mg of amiodarone. The drug has an exceptionally long half-life of 100 days in adults because of extensive storage in body fat. It requires weeks to months to attain steady state and to be cleared from the body. Breast milk and infant serum levels of amiodarone and its active metabolite are unpredictable but can be high during breastfeeding. From data in nine women, a breastfed infant would receive an estimated dose of amiodarone plus desethylamiodarone ranging from 0.6% to 45% of the mother's weight-adjusted amiodarone dose, with a median of about 11%. Serum levels of the drug plus metabolite in six infants ranged from 14% to 74% of simultaneous maternal serum levels, with the higher values partially reflecting transplacental passage of the drug. Even if a mother taking the drug during pregnancy had the drug discontinued at birth, she would continue to excrete amiodarone and its metabolite (and possibly large amounts of iodine) into breast milk for days to weeks.

Thyroid dysfunction was reported in one breastfed infant, presumably from the iodine released during amiodarone metabolism. If hypothyroidism develops, therapy should be promptly initiated. Some investigators believe that breastfeeding can be undertaken during maternal amiodarone use with monitoring of infant cardiac and thyroid function status, especially if only a single dose of amiodarone is given. Infant serum levels of amiodarone and desethylamiodarone may be useful for ruling out adverse effects of the drug.

Sotalol, which has beta-blocking activity, showed extensive excretion into breast milk in seven mothers. It is extensively excreted by the kidneys and has minimal safety data in breastfed infants. Some authors recommend using sotalol during breastfeeding only while monitoring the infant closely for signs of beta-blockade. Infants over 2 months of age have more mature kidney function and are less likely to be affected by sotalol in milk.

Class IV consists of the calcium-channel blockers diltiazem and verapamil. Based on a report in only one patient, amounts of diltiazem ingested by the infant are small and would not be expected to cause any adverse effects in breastfed infants. Maternal doses of verapamil up to 360 mg/day produced low levels in the milk of seven women. One newborn had detectable verapamil serum levels, but levels were low and might have been obtained transplacentally. Two older breastfed infants had undetectable serum levels at 2 and 6 weeks of age, respectively.

Other Cardiac Agents

Digitalis glycosides fall outside the Vaughan-Williams classification system. Digoxin is the most commonly used digitalis glycoside and is the only one with information on use in breastfeeding. Published evidence shows that the amount of digoxin in breast milk is very low in mothers being treated orally. Measurements of digoxin in the serum of two breastfed infants whose mothers were taking digoxin during pregnancy and postpartum found that the infants' serum levels had dropped by two-thirds in the 7 days after birth to undetectable in one infant and very low in another, indicating little contribution from the drug in breast milk.

Eleven mothers had digoxin measured in breast milk after an IV bolus dose of 0.5 mg. These mothers had elevated milk digoxin levels for only the first 2 hours after the dose before attaining the usual low levels in milk. If the mother is to receive IV digoxin, avoidance of breastfeeding for 2 hours after the dose will lessen the dose the infant receives. However, the amount of digoxin in milk during the first 2 hours would not be of concern if only a single dose is given.

Adenosine is usually given as a rapid IV bolus. No information is available on its use during breastfeeding, but with a half-life of less than 10 seconds and typical single dose use, there is no chance that it will pass into breast milk. Maternal adenosine is not considered to be of concern to her breastfed infant.

Drugs for Pulmonary Arterial Hypertension

A number of drugs that dilate the pulmonary vasculature are indicated for pulmonary hypertension. However, only a few of these drugs have even a single case report in nursing mothers. A 23-year-old woman with congenital heart disease and pulmonary hypertension was treated during pregnancy with sildenafil (yes, that sildenafil) and bosentan. Her infant was delivered at 30 weeks by cesarean section and weighed 1.41 kg at birth. These drugs and warfarin were continued postpartum. Amounts of sildenafil and its active metabolite in milk were small at 8 and 11 hours after the dose; bosentan was not measured. She nursed her infant in the neonatal intensive care unit for 11 weeks “with good outcome” according to the authors, but the infant died at 26 weeks of age from an unrelated respiratory syncytial virus infection. Tadalafil is similar to sildenafil pharmacologically, but longer acting and therefore might be less desirable while nursing a newborn.

Several prostanoid drugs are used for pulmonary hypertension. One mother taking treprostinil breastfed her infant for 1 year without any complications. The related prostanoid, epoprostenol, has a half-life of only 6 minutes and thus is not likely to affect a breastfed infant. Iloprost is used by inhalation and is not detectable in serum 30 minutes to 1 hour after inhalation, so timing of breastfeeding could be employed to avoid infant exposure.

Other drugs for pulmonary hypertension include macitentan, riociguat, and selexipag. No information is available on breastfeeding with these drugs, and their use during lactation is discouraged.

Nitrates

Nitrates such as nitroglycerin, isosorbide mononitrate (ISMN), and isosorbide dinitrate (ISDN) are used for angina and pulmonary hypertension. Sublingual and IV nitroglycerin have not been studied during breastfeeding, but topical use of the ointment for anal fissures by nursing mothers caused no adverse effects in their breastfed infants. Larger topical amounts used for angina and sublingual or IV use might cause effects in breastfed infants. The adverse effect in a breastfed infant would probably be limited to headache pain and hypotension, so clinically monitoring the infant should be an adequate precaution. No information is available on ISDN or ISMN, but concerns would be similar.