Kommersiellt obunden läkemedelsinformation riktad till läkare och sjukvårdspersonal

Drugline nr 20197

Publicerat 2003-07-28

Question

If treatment with a neuroleptic has been decided upon for a woman who breast-feed her child and wishes to continue doing so, is Truxal (chlorprothixene), Zyprexa (olanzapine) or Trilafon (perphenazine) safe?

A woman with a severe mental illness is in need of medical treatment. She has decided to breast-feed her child.

Answer

Many women with a mental illness would like to breast-feed their children (1). The incidence of psychiatric illness is also higher in the post-partum period than at any other time in a woman´s life. Patients treated with neuroleptics are generally advised not to breast-feed their children. However, if breast-feeding is considered necessary when taking neuroleptics there are a few recommendations that could be of help (1):

1. A drug that is excreted minimal into breast milk should be chosen and the dose should be kept at minimum.

2. Since the pharmacokinetics can vary, therapeutic drug monitoring can be used to keep the maternal dose as low as possible.

3. If possible, the drug administration can be given once daily and breast-feeding can be avoided up to 6 hours after the given dose.

4. The risk is always greater the younger the infant is since metabolic enzymes are not fully developed.

5. If adverse effects are seen, discontinue breast-feeding.

CHLORPROTHIXENE. The use of chlorprothixene during breast-feeding has previously been dealt with in Drugline (2). Chlorprothixene is excreted into breast milk. Only two cases have been reported when chlorprothixene was administered during breast-feeding (2,3).

Two women took daily doses of 200 mg and 200-400 mg respectively and the milk to plasma concentration ratio of chlorprothixene varied between 1.2 to 2.6 and 0.5 to 0.8 for the metabolite (3). The infants received about 0.1 to 0.3 percent of the maternal weight adjusted dose. The authors concluded that a daily dose of 200 mg would not likely give an immediate pharmacological effect on the infant. Long-term effects on the children have however not been investigated.

In FASS (the Swedish Catalogue of Approved Medical Products) chlorprothixene is classified into class II, which means that negative effects to the child when exposed to therapeutic doses seem unlikely. The infant dose is approximately 2 percent of the maternal dose (4). The manufacturer says that chlorprothixene therapy can be continued during breast-feeding if considered necessary. Observation of the infant is recommended, particularly during the first four weeks (5).

OLANZAPINE. Whether olanzapine is compatible with breast-feeding has been dealt with in Drugline (6,7). Olanzapine is excreted into breast milk. A few published case reports have been found where olanzapine has been administered to mothers who were breast-feeding.

Goldstein et al report two cases and they indicate that there is no risk of adverse effects for the infants (6,7,8). However, one of the infants, that had been exposed to olanzapine during the whole pregnancy and six days of breast-feeding, suffered from cardiomegaly, jaundice, somnolence and heart murmur. Bottle-feeding was initiated on day seven, but the jaundice and somnolence continued, suggesting lack of relationship to the exposure of olanzapine.

Kirchheiner et al report a case where olanzapine was given from the 18th gestational week and during breast-feeding (6,7,9). After delivery, the plasma level of olanzapine in the infant was one third of the maternal plasma level and during breast-feeding it decreased to an undetectable level.

Croke et al has studied five nursing mothers taking olanzapine (10). The infants were between 3 weeks and 6 months old and a relative infant dose for each child was calculated. The weight adjusted dose varied between zero and 2.5 percent (median value 1.6 percent). Plasma was taken from one of the infants 15 hours after the maternal dose was taken, and olanzapine was not detected in the sample. None of the infants experienced any adverse effects from the exposure to olanzapine.

The manufacturer has a total of 26 cases reported (11). The dose of olanzapine in these cases ranged from 2.5 to 20 mg and the exposure ranged from one day to eight months. The majority of the cases either did not comment the infant´s outcome or noted no adverse events. However, four out of these noted adverse effects. The first one is Goldstein´s case described above. The second infant experienced shaking, poor sucking, and lethargy during breast-feeding and these symptoms disappeared after discontinuation of breast-feeding. The third case is a child with a protruding tongue; this case was evaluated and considered unrelated to olanzapine exposure. The last case involved a nine-month old infant that experienced rash, diarrhea, and sleeping disorder one day after breast-feeding. The manufacturer made no definitive conclusions whether olanzapine contributed to these adverse events. They recommend that patients taking olanzapine should not breast feed.

PERPHENAZINE. The use of perphenazine during breast-feeding has previously been dealt with in Drugline (12).

Like the other two substances, perphenazine is excreted into breast milk. Only one case with an infant that has been exposed to perphenazine during breast-feeding has been found in the literature. The mother of a one-month-old infant was taking 24 mg perphenazine per day, which was later reduced to a daily dose of 16 mg (13). The dose passed over to the child was about 0.1 percent of the maternal weight adjusted dose. Perphenazine was given for three and a half months while breast-feeding and no adverse effects in the child were seen.

In FASS perphenazine is classified into class II (3). However, new unpublished information from the manufacturer implies that there is a potential risk of serious reactions in children that has been exposed to perphenazine through breast milk and the potential benefits of breast-feeding should be weighed against this risk (14).

These data indicate that there is a low risk when using chlorprothixene, olanzapine and perphenazine during breast-feeding. However, published information is sparse and no long-term effects have been studied.

Conclusion

Chlorprothixene, olanzapine and perphenazine are all excreted into breast-milk. The infant dose passed over from the mother varies between zero and 2.5 percent for all substances. Published cases are however limited in the literature and long-term data is not available. The risk of adverse events for the infants seem to be low, but the material is sparse.

Ståhle L
Jansson Å

References

  1. Spigset O, Hägg S. Excretion of psychotropic drugs into breast milk. Pharmacokinetic overview and therapeutic implications. CNS Drugs 1998;2:111-34.
  2. Drugline no 06695 (year 1989)
  3. Matheson I, Evang A, Overo KF, Syversen G. Presence of chlorprothixene and its metabolites in breast milk. Eur J Clin Pharmacol 1984;27:611-3.
  4. FASS 2003 (The Swedish catalogue of approved medical products)
  5. Personal communication with Anna-Greta Nylander, Productmanager CNS, Lundbeck
  6. Drugline no 19306 (year 2002)
  7. Drugline no 18925 (year 2002)
  8. Goldstein DJ, Corbin LA, Fung MC. Olanzapine-exposed pregnancies and lactation: early experience. J Clin Psychopharmacol 2000;20(4):399-403.
  9. Kirchheiner J, Berghöfer A, Bolk-Weischedel D. Healthy outcome under olanzapine treatment in a pregnant woman. Pharmacopsychiatry 2000;33(2):78-80.
  10. Croke S, Buist A; Hackett LP, Ilett KF, Norman TR, Burrows GD. Olanzapine excretion in human breast milk: estimation of infant exposure. Int J Neuropsychopharmacol 2002;5:243-7.
  11. Personal communication with Jonas Hjorth, Medical information, Lilly
  12. Drugline no 18885 (year 2002)
  13. Olesen OV, Bartels U, Poulsen JH. Perphenazine in breast milk and serum. Am J Psychiatry 1990;147(10):1378-9.
  14. Personal communication with Claes Nordenson, Medical information, Schering Plough

Senast ändrad 2018-09-20