2. Excretion into Breast Milk:

Plasma pH 7.4

Breast Milk pH 6.4 - 7.3 (~ 6.8)

The excretion of drug from the plasma into breast milk is dependent almost entirely on the pH - partition behaviour, plasma protein binding and lipid solubility of the drug.

Generally the total amount of drug excreted is < 1% of dose, and is too small to achieve therapeutic or toxic levels in the infant’s plasma.

Exceptions:

(Usually due to infant’s insufficient hepatic and renal elimination accumulation).

Eg. Sulphonamides - Risk of neonatal hyperbilinbinaemia.

Tetracycline - Possible mottling of teeth and bone.

Diazepam (>30mg daily) - Accumulation of drug and metabolites.

General Rules:

Breast feeding is preferable to bottle feeding.

Use drugs only if necessary and for shortest possible period.

Avoid known “high risk” drugs.

Administer drug immediately after breast feeds, if possible.

 

3. Salivary Excretion:

Plasma pH 7.4

Saliva pH 6.4

Small contribution to total elimination.

Transfer again depends on pH partition plasma protein binding, and lipid solubility.

Drugs excreted in saliva include Phenytoin, Lithium, Paracetamol, Digoxin and Salicylate.

May be responsible for adverse localised effect, eg. Antibiotics, Phenytoin, Tricyclic antidepressants.

 

DRUGS AND BREAST FEEDING

• Anti-metabolites and radiopharmaceuticals.
• Cimetidine.
• Ergot alkaloids.
• Anti-thyroid drugs.
• Gold compounds.
• Amiodarone.

Table 1:Drugs which should be avoided in breast feeding, based on likely infant concentrations (see Appendix for references).

• Med J Aust 1987; 146: 308-313
• Postgrad Med 1988; 83(1): 211-218
• Clinical Pharmacokinetics 1988; 14: 217-240

The numerous advantages of breast feeding and breast milk to the mother - infant pair are recognised widely and breast feeding is encouraged. Some drugs administered to a nursing mother may pose a problem for the infant. It is understandable, therefore, that the question arises within the medical and pharmaceutical professions, as well as from the medicated mother and her partner, of the possible adverse effects of drugs on the lactating mother and her infant.

In reviewing the literature on drugs in breast milk with a view to providing guidelines on which drugs contraindicate breast feeding one is confronted with difficulties. Many of the literature reports are on isolated cases and often the documentation is less than complete so that meaningful interpretation of the data is difficult or impossible.

In spite of the problems involved in reviewing some of the case study reports in the literature, it is possible to provide information that is applicable generally on the excretion of a drug in breast milk and the transference of drug to the breast-fed infant, and also to summarise a number of practical considerations on drugs and breast feeding.

Determinants of Infant Exposure to Drugs in Breast Milk:

Virtually all drugs can be expected to be excreted in breast milk to some extent. There are a number of factors which determine the magnitude of the plasma drug concentration achieved in the breast-fed infant. These determinations are:-

(a) The maternal plasma drug concentration, which is determined by the dose or dosing rate of drug administered and the pharmacokinetics of the drug in the mother.

(b) The milk/plasma ratio, (the ratio of the drug’s concentration in milk to that in maternal plasma), which is largely determined by the drug’s physicochemical properties and/or differences in the degree of drug binding and pH between the two fluids.

(c) The time between drug intake by the mother and the next feed.

(d) The volume of milk taken by the infant at the time of feeding.

(e) The pharmacokinetics of the drug in the infant.

Undue emphasis is sometimes placed solely on the magnitude of the milk/plasma ratio. Consideration of the above points indicates that a number of other factors also need to be considered. For example, even for those drugs having a milk/plasma ratio considerably greater than unity the “dose” delivered to the breast-fed infant can still be relatively small if the maternal plasma drug concentration is low.

 

General Practical Considerations:

(a) Breast feeding offers numerous advantages for both the mother and her infant. In many cases, these advantages may outweigh the possible adverse effects of the mother’s medication on her breast-fed infant.

(b) Only those drugs that are considered essential for the treatment of a maternal condition should be prescribed. The mother should be encouraged to restrict the intake of over-the-counter medication and social drugs.

(c) Most drugs will be excreted in breast milk to some extent. In the majority of cases, the amount of drug delivered via the milk to a breast-fed infant will be small and adverse effects are unlikely. Theoretically, exposure to small amounts of some drugs (eg. Penicillins) may result in the induction of hypersensitivity.

(d) If drugs with a known or a serious theoretical risk are considered necessary, then breast feeding should be discontinued, temporarily if possible.

(e) Advice to discontinue breast feeding to express and discard the milk for a day or two during periods of medication should not be given lightly. Such a course of action firstly may unnecessarily deprive the mother and her infant of the benefits of breast feeding and secondly, for a mother to express milk may be difficult and inconvenient.

(f) While the mother is receiving medication, any unusual reaction in the infant should be discussed with the Doctor or Pharmacist.

(g) Methods of minimising drug transfer to the infant:-

(i) Consider alternative routes of drug administration and drug products, eg. an inhaled rather than an oral bronchodilator for asthma; nasal drops in preference to an oral decongestant; a poorly absorbed laxative such as a bulk forming agent (ie. fibre) instead of a stimulant cathartic.

(ii) The lowest appropriate drug dose to treat the mother should be used.

(iii) Maternal drug administration after the breast feed will generally minimise drug transfer to the infant.

 

Specific Drugs of Concern:

Reasons given for the avoidance of certain drugs in nursing mothers fall into two broad categories. The drug may have a detrimental effect on the production of milk or may have a direct adverse effect on the infant.

It appears that only a small number of drugs pose real concern for a nursing mother. However, in providing guidelines on drugs and breast feeding one must err on the side of safety.

Those drugs which are contraindicated when breast feeding are listed in Table 1, while drugs which require cautious use are to be found in Table 2. Some of the recommendations in the Tables are theoretical and, as such, are usually based on the relatively high level of toxicity of the drugs concerned.

Drug Information Services can provide additional information on drugs and breast feeding.

Table 1 - Contraindicated Drugs:

Table 2 - Contraindicated Drugs: