Excretion of Psychoactive Drugs into Breast Milk

Abstract

The postpartum period is a time of great physical and emotional changes. The incidence of psychiatric illness is higher in this period than at any other time in a women's life. Therefore, the question of whether women receiving psychotropic drugs should continue breast feeding is an important one. Drug excretion in breast milk depends mostly on passive diffusion of the unionised unbound drug. Passive diffusion is affected mainly by the drug disposition in lactating mothers, by the physicochemical properties of the molecule and by the protein and lipid contents of breast milk. Indeed, breast milk can be considered as a compartment with bidirectional transfer rather than a reservoir into which drug accumulates. Benzodiazepines are the most prescribed psychotropic drugs. Generally there does not seem to be any contraindication to breast feeding after a single dose, provided the dose administered is relatively low. If higher doses are to be used or long term administration is required, then breast feeding should probably be discontinued, particularly with drugs with a long elimination half-life. On the basis of the average concentration of phenobarbital (phenobarbitone) in milk, breast feeding is not recommended. For glutethimide, breast feeding would appear to be safe for the infant when a single dose is taken occasionally. Zopiclone may also be prescribed on a short term basis to breast feeding mothers. Due to limited available data or to the large amount transferred to milk, administration of phenothiazines and nonphenothiazine tricyclic, butyrophenone, and benzamide antipsychotics to breast feeding mothers cannot be recommended. Breast feeding is not always considered an absolute contraindication to lithium therapy, but the mother should watch for signs of toxicity in her baby. Whether clomipramine should be contraindicated during breast feeding depends on the concentration of active metabolites in breast milk, and this has not yet been determined. It is probably safe for mothers to breast feed while receiving amitriptyline, but before more conclusive recommendations are made more infants should be studied. The available data suggest that the amount of doxepin and its metabolite in breast milk is small. However, the metabolite of doxepin may accumulate in the infant with risk of sedation and respiratory depression: therefore, an alternative antidepressant should be selected for breast feeding mothers.(ABSTRACT TRUNCATED AT 400 WORDS)

Transfer of Aciclovir from Plasma to Human Breast Milk

“…The same is valid for some other drugs showing a milk/ plasma ratio greater than 1 (i.e. sumatriptan, lithium, nitrofurantoin, phencyclidine, doxorubicin, prazepam, metoclopramide, thiouracil, propylthiouracil, erythromycin) [3,8,9]. The results presented here clearly demonstrate that passive diffusion of aciclovir through a semipermeable membrane not only leads to equal levels of aciclovir in both compartments, but also to an increased aciclovir concentration in breast milk.…”

Stereoselective disposition of fluoxetine and norfluoxetine during pregnancy and breast‐feeding

“…where C milk is the analyte concentration in milk, V milk is the estimated volume of the milk ingested by the nursing infant (150 ml kg − 1 day − 1 ) [17] and F BF is the percentage of breast-feeding reported by mother. The relative infant dose was calculated from the expression:…”

Clinical Lactation Studies of Lithium: A Systematic Review

“…First 4 to 10 days postpartum, lithium can pass between alveolar cells because large gaps exist. By the end 1st week postpartum, alveolar cells swell under influence of prolactin, closing the intracellular gaps, and limiting access to the milk (Pons et al, 1994) ( Figure 1 ). Factors that affect the passage of a drug into breast milk include route of administration, absorption rate, half-life, peak serum time, dissociation constant, volume of distribution, molecular size, protein binding, degree of ionization, pH, and solubility (Lawrence, 1994; Tanaka et al, 2008).…”

“…Because of its very low molecular weight and lack of protein binding, lithium is readily transferred into breast milk. The amount of drug received by the infant also depends on multiple factors: milk yield and composition (i.e., colostrum versus mature milk), concentration of the drug in the milk, which breast is being suckled (as the yield from each breast is not equal), and how well the breast was emptied during the previous feeding (Lawrence, 1994; Pons et al, 1994). However, the mean volume of milk transferred to the infants is lower during the first 2 days after delivery and increases rapidly on days 3 and 4, and then more slowly to a maximum of approximately 800ml/day at 6 months of age (Neville et al, 1988).…”