The rather vexed question of how far the medication of a breast-feeding mother is likely to have adverse effects on her infant has been approached by Shinya Ito of Toronto in the New England Journal of Medicine for July 13. Although breast feeding is now agreed to be best for the first 12 months of life, there are some misgivings when a mother has to receive medication during this period. The key questions that demand an answer are how much of a drug is excreted in milk, and what is the risk of adverse effects to the infant of this quantity.
Excretion of a drug in milk depends on the plasma protein binding, ionisation, molecular weight and pharmacokinetics of the drug, and what it undergoes in the shape of passive diffusion and carrier-mediated transport. Most drugs have a milk-to-plasma ratio of 1:1 or less, while some 25 per cent of ratios lie between 1:1 and 2:1 and about 25 per cent exceed 2:1. Drugs with a low rate of clearance from the body are likely to expose an infant to higher and more variable concentrations. The rate of drug clearance in the infant is more important than its milk-to-plasma ratio. It is arbitrarily assumed that if the dose received in breast milk is less than 10 per cent of the infant therapeutic dose, exposure is clinically insignificant. The exception is for infants with an enzyme deficiency.
For antidepressant drugs, including tricyclic compounds and selective serotonin reuptake inhibitors, breast milk concentrations rarely reach 10 per cent of the therapeutic dose. However, some accumulation of fluoxetine, doxepin, sertraline and lithium has been reported in infants. Breast-feeding women should use lithium with caution. The antiepileptics carbamazepine, phenytoin and valproate are considered acceptable, but substantial amounts of phenobarbitone, ethosuximide or primidone have been found in milk. Drugs such as atenolol, nodolol and sotalol, which are mainly excreted by the kidneys, may accumulate in neonates because of their immature kidney function. Amiodarone needs careful monitoring.
Although cyclosporin has been suspect because of its immunosuppressive effects, concentrations in breast milk appear to be clinically unimportant. Among drugs of abuse, cocaine and cannabis may be dangerous, but methadone treatment of an addicted mother is considered justified. Caffeine, as coffee, taken by mothers in doses of 750mg daily, is not contraindicated, but may cause irritability in infants. Ethanol is hazardous, since the hepatic alcohol dehydrogenase activity in infants during the first year of life is less than half that in adults, and impairment of neurological development may occur. Smoking and other methods of taking nicotine cannot be justified in terms of infant welfare.
Among drugs of choice for treating breast-feeding women are paracetamol, ibuprofen, warfarin, tricyclic antidepressants, carbamazepine, loratadine, penicillins, cephalosporins and aminoglycosides, labetalol, propranolol, prednisone and prednisolone.