Is haloperidol (Haldol) compatible with breast-feeding? If not, is olanzapine (Zyprexa) a better ch

Fråga: Is haloperidol (Haldol) compatible with breast-feeding? If not, is olanzapine (Zyprexa) a better choice? A woman previously treated with olanzapine switched her medication to haloperidol during her pregnancy, as the latter drug is better documented. She is now going to breast-feed her child.

Sammanfattning: Haloperidol is excreted into breast-milk. A total of 18 reports have been found in the literature and the weight adjusted infant dose passed over from the mother varied from 0.2 percent up to around 10 percent. Extra pyramidal symptoms in the infants have been observed. Olanzapine is also excreted into breast-milk and a total of 26 cases have been reported. The infant dose varies between zero and 2.5 percent. Long-term effects on the infants have not been studied for either of the substances. Based on the existing data, olanzapine seems to be excreted to the breast milk to a lower extent than does haloperidol and might therefore be a better choice.

Svar: Generally, mothers treated with neuroleptics are advised against breast-feeding, since these drugs have a pharmacological action on dopamine receptors and long-term effects on the children are insufficiently studied (1). However, if breast-feeding is considered necessary, the recommendation is to choose a drug, which is minimally excreted to the breast milk, and to monitor drug concentrations to keep the mother´s dose as low as possible (2).

The question concerning haloperidol and breast-feeding has previously been dealt with in Drugline (1, 3, 4). Haloperidol is excreted into breast milk. Extrapyramidal symptoms have been observed in breast-fed children whose mothers were treated with haloperidol, and the benefits of breast-feeding should therefore be weighed against the possible risk (5).

Drug concentrations in milk were studied in three patients taking haloperidol (6). Based on an approximate milk intake of 150 ml per kilo and day and women weighing 60 kg, a relative weight adjusted infant dose could be calculated. One of the patients did not comply with treatment and the relative dose in that case could therefore not be calculated. The weight-adjusted dose for the other two was calculated to be 3.8 and 9.6 percent. However, no mention of any effects on nursing infants was made. Based on the same study, the relative dose received by the infant was calculated to be between 0.8 and 11.2 percent (including all three patients) (7).

In twelve women who received between one and 40 mg of haloperidol per day the relative infant dose was at most three percent of the maternal dose. The children whose mothers were prescribed monotherapy developed normally. Three children had mothers who were also treated with chlorpromazine, and were observed to have mental or psychomotor development delays during their second year of life (8). In a case report, small amounts of haloperidol could be detected in the urine of a child exposed to the drug through breast-milk. The child was followed for one year and developed normally (4). In two other case reports, the patients took 10 and 12 mg of haloperidol respectively and the weight-adjusted dose was 0.2 and 2.1 percent of the maternal dose (4, 8). Doses used in these studies are higher than doses recommended in Sweden. Usually, doses above 8 mg per day are not considered necessary (5).

Studies in rabbits have, however, shown behavioural and neurochemical changes after exposure to haloperidol during lactation. In rats, altered dopamine sensitivity has also been seen (7). An important thing to remember is that the rat nervous system is at an earlier stage of development than the human during the first postnatal weeks. Another concern is, that both rabbit and rat milk has a much higher fat content than human milk leading to higher concentrations of haloperidol in rabbit and rat milk. Therefore, its not clear if these results from animal studies can be extrapolated to human use.

Concerning olanzapine, this question has recently been answered (2). The manufacturer had a total of 26 case reports and the weight-adjusted dose varied between zero and 2.5 percent. Four of the infants were reported to have adverse effects, however only one of these had symptoms that could have been caused by olanzapine exposure. The manufacturer does however not recommend breast-feeding during olanzapine treatment.