Table 18-4. Drugs and substances that require a careful assessment of risk before they are prescribed for breast-feeding women

Category	Specific Drugs or Compounds	Management Plan and Rationale
Analgesic drugs	Meperidine, oxycodone	Use alternatives to meperidine and oxycodone. Breast-fed infants whose mothers were receiving meperidine had a higher risk of neurobehavioral depression than breast-fed infants whose mothers were receiving morphine. In breast-fed infants, the level of exposure to oxycodone may reach 10% of the therapeutic dose. For potent analgesia, morphine may be given cautiously. Acetaminophen and nonsteroidal anti-inflammatory drugs are safe.
Antiarthritis drugs	Gold salts, methotrexate, high-dose aspirin	Consider alternatives to gold therapy. Although the bioavailability of elemental gold is unknown, a small amount is excreted in breast milk for a prolonged period. Therefore, the total amount of elemental gold that an infant could ingest may be substantial. No toxicity has been reported. Consider alternatives to methotrexate therapy, although low-dose methotrexate therapy for breast-feeding women with rheumatic diseases had lower risks of adverse effects in their infants than did anticancer chemotherapy. High-dose aspirin should be used with caution, since there is a case report of metabolic acidosis in a breast-fed infant whose mother was receiving high-dose therapy. Although the risk seems small, the infant's condition should be monitored clinically if the mother is receiving long-term therapy with high-dose aspirin.
Anticoagulant drugs	Phenindione ²	Use alternatives to phenindione. Currently available vitamin K antagonists such as warfarin and acenocoumarol are considered safe, as is heparin.
Antidepressant drugs and lithium	Fluoxetine, doxepin, lithium ²	Use fluoxetine, doxepin, and lithium with caution. Although the concentrations of these drugs in breast milk are low, colic (with fluoxetine) and sedation (with doxepin) have been reported in exposed infants. Near-therapeutic plasma concentrations of lithium were reported in an infant exposed to the drug in utero and through breast-feeding. The incidence of these adverse events is unknown.
Antiepileptic drugs	Phenobarbital, ethosuximide, primidone	In breast-fed infants, the level of exposure to phenobarbital, ethosuximide, and primidone may exceed 10% of the weight-adjusted therapeutic dose. Consider alternatives such as carbamazepine, phenytoin, and valproic acid.
Antimicrobial drugs	Chloramphenicol, tetracycline	Use alternatives to chloramphenicol and tetracycline. Idiosyncratic aplastic anemia is a possibility among breast-fed infants whose mothers are receiving chloramphenicol. Although tetracycline-induced discoloration of the teeth of breast-fed infants has not been reported, the potential risk of this event needs to be clearly communicated to lactating women.
Anticancer drugs	All (eg, cyclophosphamide,² methotrexate,² doxorubicin²)	Because of their potent pharmacologic effects, cytotoxic drugs should not be given to breast-feeding women.
Anxiolytic drugs	Diazepam, alprazolam	Avoid long-term use of diazepam and alprazolam in breast-feeding women. Intermittent use poses little risk to their infants, but regular use may result in the accumulation of the drug and its metabolites in the infants. Lethargy and poor weight gain have been reported in an infant exposed to diazepam in breast milk, and the withdrawal syndrome was reported in a breast-fed infant after the mother discontinued alprazolam.
Cardiovascular and antihypertensive drugs	Acebutolol, amiodarone, atenolol, nadolol, sotalol	The use of acebutolol, amiodarone, atenolol, nadolol, and sotalol by breast-feeding women may cause relatively high levels of exposure among their infants, and these agents should therefore be used with caution. The two ß-adrenergic antagonists propranolol and labetalol are considered safe.
Endocrine drugs and hormones	Estrogens, bromocriptine ²	Estrogens and bromocriptine may suppress milk production. Oral contraceptives containing little or no estrogen have smaller risk than formulations with higher concentrations of estrogen. Nevertheless, caution should be exercised in their use.
Immunosuppressive drugs	Cyclosporine, ² azathioprine	Maternal plasma concentrations of cyclosporine and azathioprine should be monitored. In nine reported cases in breast-fed infants who were exposed to azathioprine in breast milk, no obvious adverse effects were noted.
Respiratory drugs	Theophylline	Theophylline should be used with caution. When the mother's doses are high, the levels of exposure in the infant may be substantial (ie, 20% of the therapeutic dose).
Radioactive compounds	All	Breast feeding should be stopped until the level of radioactivity in milk has returned to the background level.
Drugs of abuse	All	The use of drugs of abuse precludes breast feeding; cocaine-induced toxicity has been reported among breast-fed infants whose mothers abused cocaine. Methadone, used for the treatment of addiction, is safe for infants of breast-feeding women, at doses of up to 80 mg per day. Buprenorphine may be a safer alternative to methadone.
Nonmedicinal substances	Ethanol, caffeine, nicotine	In order to avoid exposure of the infant to ethanol, the mother should not consume alcohol or should consume no more than one drink 2 to 3 hours before breast feeding. The ingestion of moderate amounts of caffeine should be safe. Because of the effects of second-hand smoke and the fact that nicotine is excreted in breast milk, smoking is contraindicated in breast-feeding women.
Miscellaneous compounds	Iodides and iodine, ergotamine, ² ergonovine	Use alternatives to iodine-containing antiseptic agents. Ergotamine and ergonovine may suppress prolactin secretion in breast-feeding women. However, the use of methylergonovine to stimulate uterine involution is considered safe in breast-feeding women.

¹ Data modified from Ito S: Drug therapy for breast-feeding women. N Engl J Med 2000;343:120. Drugs for which there is no information are not included, though a careful risk assessment is necessary before such drugs are prescribed.

² The use of this drug or these drugs by breast-feeding women is contraindicated according to the American Academy of Pediatrics.

Category	Specific Drugs or Compounds	Management Plan and Rationale
Analgesic drugs	Meperidine, oxycodone	Use alternatives to meperidine and oxycodone. Breast-fed infants whose mothers were receiving meperidine had a higher risk of neurobehavioral depression than breast-fed infants whose mothers were receiving morphine. In breast-fed infants, the level of exposure to oxycodone may reach 10% of the therapeutic dose. For potent analgesia, morphine may be given cautiously. Acetaminophen and nonsteroidal anti-inflammatory drugs are safe.
Antiarthritis drugs	Gold salts, methotrexate, high-dose aspirin	Consider alternatives to gold therapy. Although the bioavailability of elemental gold is unknown, a small amount is excreted in breast milk for a prolonged period. Therefore, the total amount of elemental gold that an infant could ingest may be substantial. No toxicity has been reported. Consider alternatives to methotrexate therapy, although low-dose methotrexate therapy for breast-feeding women with rheumatic diseases had lower risks of adverse effects in their infants than did anticancer chemotherapy. High-dose aspirin should be used with caution, since there is a case report of metabolic acidosis in a breast-fed infant whose mother was receiving high-dose therapy. Although the risk seems small, the infant's condition should be monitored clinically if the mother is receiving long-term therapy with high-dose aspirin.
Anticoagulant drugs	Phenindione ²	Use alternatives to phenindione. Currently available vitamin K antagonists such as warfarin and acenocoumarol are considered safe, as is heparin.
Antidepressant drugs and lithium	Fluoxetine, doxepin, lithium ²	Use fluoxetine, doxepin, and lithium with caution. Although the concentrations of these drugs in breast milk are low, colic (with fluoxetine) and sedation (with doxepin) have been reported in exposed infants. Near-therapeutic plasma concentrations of lithium were reported in an infant exposed to the drug in utero and through breast-feeding. The incidence of these adverse events is unknown.
Antiepileptic drugs	Phenobarbital, ethosuximide, primidone	In breast-fed infants, the level of exposure to phenobarbital, ethosuximide, and primidone may exceed 10% of the weight-adjusted therapeutic dose. Consider alternatives such as carbamazepine, phenytoin, and valproic acid.
Antimicrobial drugs	Chloramphenicol, tetracycline	Use alternatives to chloramphenicol and tetracycline. Idiosyncratic aplastic anemia is a possibility among breast-fed infants whose mothers are receiving chloramphenicol. Although tetracycline-induced discoloration of the teeth of breast-fed infants has not been reported, the potential risk of this event needs to be clearly communicated to lactating women.
Anticancer drugs	All (eg, cyclophosphamide,² methotrexate,² doxorubicin²)	Because of their potent pharmacologic effects, cytotoxic drugs should not be given to breast-feeding women.
Anxiolytic drugs	Diazepam, alprazolam	Avoid long-term use of diazepam and alprazolam in breast-feeding women. Intermittent use poses little risk to their infants, but regular use may result in the accumulation of the drug and its metabolites in the infants. Lethargy and poor weight gain have been reported in an infant exposed to diazepam in breast milk, and the withdrawal syndrome was reported in a breast-fed infant after the mother discontinued alprazolam.
Cardiovascular and antihypertensive drugs	Acebutolol, amiodarone, atenolol, nadolol, sotalol	The use of acebutolol, amiodarone, atenolol, nadolol, and sotalol by breast-feeding women may cause relatively high levels of exposure among their infants, and these agents should therefore be used with caution. The two ß-adrenergic antagonists propranolol and labetalol are considered safe.
Endocrine drugs and hormones	Estrogens, bromocriptine ²	Estrogens and bromocriptine may suppress milk production. Oral contraceptives containing little or no estrogen have smaller risk than formulations with higher concentrations of estrogen. Nevertheless, caution should be exercised in their use.
Immunosuppressive drugs	Cyclosporine, ² azathioprine	Maternal plasma concentrations of cyclosporine and azathioprine should be monitored. In nine reported cases in breast-fed infants who were exposed to azathioprine in breast milk, no obvious adverse effects were noted.
Respiratory drugs	Theophylline	Theophylline should be used with caution. When the mother's doses are high, the levels of exposure in the infant may be substantial (ie, 20% of the therapeutic dose).
Radioactive compounds	All	Breast feeding should be stopped until the level of radioactivity in milk has returned to the background level.
Drugs of abuse	All	The use of drugs of abuse precludes breast feeding; cocaine-induced toxicity has been reported among breast-fed infants whose mothers abused cocaine. Methadone, used for the treatment of addiction, is safe for infants of breast-feeding women, at doses of up to 80 mg per day. Buprenorphine may be a safer alternative to methadone.
Nonmedicinal substances	Ethanol, caffeine, nicotine	In order to avoid exposure of the infant to ethanol, the mother should not consume alcohol or should consume no more than one drink 2 to 3 hours before breast feeding. The ingestion of moderate amounts of caffeine should be safe. Because of the effects of second-hand smoke and the fact that nicotine is excreted in breast milk, smoking is contraindicated in breast-feeding women.
Miscellaneous compounds	Iodides and iodine, ergotamine, ² ergonovine	Use alternatives to iodine-containing antiseptic agents. Ergotamine and ergonovine may suppress prolactin secretion in breast-feeding women. However, the use of methylergonovine to stimulate uterine involution is considered safe in breast-feeding women.