Olanzapine

Drug Levels and Effects:




Summary of Use during Lactation:


Limited information indicates that maternal doses of olanzapine up to 20 mg daily produce low levels in milk and undetectectable levels in the serum of breastfed infants. In most cases, short-term side effects have not been reported, but sedation has occurred. Very limited long-term follow-up of infants exposed to olanzapine indicates that infants generally developed normally, but combinations of antipsychotic agents can negatively affect development. Monitor the infant for drowsiness and developmental milestones, especially if other antipsychotics are used concurrently.


Drug Levels:


Maternal Levels.

A nursing mother was started on olanzapine 20 mg daily on day 9 postpartum. Numerous milk olanzapine levels collected over the subsequent 8 days ranged from 7.6 to 27.5 mcg/L. The authors calculated that an exclusively breastfed infant would receive 0.011 mg/kg daily or about 4% of the maternal weight-adjusted dosage.[1]

Nine paired serum and milk levels were obtained from 5 mothers who were taking olanzapine. In 2 women taking 10 mg daily, one had a milk level of 21 mcg/L 11 hours after the dose and the other had a milk level of 16 mcg/L 23 hours after the dose. In 3 women taking 2.5 mg daily, milk levels ranged from <1 to="" 8="" mcg/l="" 11="" to="" 12="" hours="" after="" the="" dose,="" 4="" mcg/l="" at="" 16="" hours="" after="" the="" dose="" and="" 2="" to="" 7="" mcg/l="" at="" 22="" to="" 23="" hours="" after="" the="" dose.="" using="" these="" data,="" an="" exclusively="" breastfed="" infant="" would="" consume="" an="" average="" of="" 1.6%="" of="" the="" maternal="" weight-adjusted="" dosage="" (range="" 0="" to="">

Seven mother-infant pairs were studied during maternal olanzapine use. The mean dose was 7.5 mg daily (range 5 to 20 mg daily) and serum levels were at steady state. A median peak serum level of 16 mcg/L occurred 5.2 hours (range 0.7 to 13.2 hours) after the dose. The median infant dosage was 1.12% (range 0.22 to 1.19%) of the maternal weight-adjusted dosage in 6 of the mothers and 1.13% in the seventh.[3]

A woman was taking olanzapine 5 mg orally 3 times daily, amounting to 270 mcg/kg daily. After 11 days on olanzapine, a milk sample was taken just before nursing (time after dose not reported). The concentration of olanzapine was 12 ng per gram of breastmilk. The authors estimated that was 0.3% of the maternal weight-adjusted dosage.[4]

A woman was started on oral olanzapine 5 mg in the morning and 10 mg in the evening daily 3 months postpartum. Two weeks later, the milk concentration (time after dose not stated) was 5 mcg/L. Over a period of 5 months, milk olanzapine concentrations decreased somewhat with time and a reduction in dosage to a concentration of 3 mcg/L with a dosage of 10 mg daily.[5]

Infant Levels.

At birth, the infant of one mother who was taking olanzapine 10 mg daily orally had an olanzapine serum level of about one-third that of the mother. The infant was breastfed (extent not stated) and had undetectable serum levels (<2 mcg/L) at 2 and 6 weeks of age.[6]

In one 4-month-old infant, olanzapine was undetectable (<1 mcg/L) in serum 15 hours after the mother's dose (dose unstated).[2]

Olanzapine was undetectable (<0.1 to 0.5 mcg/L) in the serum of 5 breastfed infants with an average age 2.4 months (range 0.1 to 4.3 months) whose mothers were taking a mean dose of 7.5 mg daily (range 2.5 to 20 mg daily).[3]

A 5-month-old infant was breastfed (extent not stated) by a mother who had been taking olanzapine 5 mg 3 times daily for 11 days. After an overnight fast, the infant's serum olanzapine concentration was <5>

The mother of a 3 month-old breastfed (extent not stated) infant was started on olanzapine 5 mg in the morning and 10 mg in the evening daily by mouth. Two weeks later, the infant's olanzapine serum concentration (time stated) was 11 mcg/L. At 5 and 6 months of age, the serum concentration was 0 and 0.8 mcg/L, respectively. At 7 months of age, the serum concentration was 1.3 mcg/L with a maternal dose of 10 mg daily. At 8 months of age, the serum concentration was 0.02 mcg/L with a maternal dose of 5 mg daily. At 9 months of age, the serum concentration was 0.8 mcg/L with a maternal dose of 10 mg daily. Whether the variability in infant concentrations was caused by variable sampling times or by changes in maternal dosage, infant metabolism, or extent of breastfeeding cannot be determined from the report.[5]


Effects in Breastfed Infants:


The manufacturer has reported 26 infants who were exposed to olanzapine in breastmilk.[7] Four of the infants had adverse reactions; however, 2 of these were judged to not be related to olanzapine in breastmilk. One was exposed for a few days during the first week postpartum and experienced jaundice and sedation; however, changing to bottle feeding made no difference in the infant's condition. Another infant had a protruding tongue. Two cases were judged to be possibly related: somnolence, diarrhea and diaper rash in 1 infant; and lethargy, poor sucking and shaking in a postmature infant.[8] Details of the exposures were not provided. Some of the 26 infants might be the same as those reported below.

One infant was breastfed for 2 months during maternal intake of 10 mg daily. No abnormalities were found in growth and development during 11 months of follow-up.[6]

Five infants aged 3 weeks to 6 months were breastfed during maternal olanzapine 2.5 to 10 mg daily. No adverse health or developmental effects were noted during the observation period of 5 days to 8 weeks.[2]

One infant was breastfed from birth during maternal use of olanzapine 5 mg daily orally. The infant was healthy at 6 months of age.[9]

Six breastfed infants with an average age 2.4 months (range 0.1 to 4.3 months) whose mothers were taking olanzapine 2.5 to 20 mg daily had no adverse effects reported by their mothers or found on detailed medical testing. Development was deemed normal in 4 infants after extensive testing. A fifth had a somewhat decreased intellectual development on testing, but her mother had also taken clonazepam, droperidol, sertraline, thioridazine and valproic acid while breastfeeding. Four of the infants' body weight were maintained, one fell slightly and one dropped from the 97th percentile at birth to the 50th percentile upon later measurement. One of the infants reportedly had drowsiness during maternal intake of 10 mg daily, but it was not evident 3 weeks after reducing the dose to 5 mg daily. The drowsiness was possibly related to olanzapine in milk.[3]

A 5-month-old infant was breastfed (extent not stated) by a mother who took olanzapine 5 mg 3 times daily for 13 days, then 5 mg twice daily. The infant was followed up after 2 months. The infant gained weight steadily and no jaundice or motor function impairment were noted.[4]

A case-control study compared mothers who took olanzapine 2.5 to 10 mg daily during breastfeeding to those who took the drug and did not breastfeed, and nursing mothers who tookacetaminophenwhich is thought to be safe during breastfeeding. Mothers filled out a questionnaire regarding adverse infant outcomes at 1 to 2 years postpartum. The percentage of adverse outcomes in the breastfed infants who were exposed to olanzapine in breastmilk (n = 22) was greater (14%), than those in the nonbreastfed (n = 15; 7%) and breastfed infants without olanzapine exposure (n = 51; 8%), but these differences were not statistically significant.[10]


Possible Effects on Lactation:


Unlike the phenothiazines, olanzapine has a minimal effect on serum prolactin levels.[11][12][13][14][15] However, olanzapine-induced hyperprolactinemia and galactorrhea have been reported rarely. One patient was also taking venlafaxine and interferon beta-1b which can increase serum prolactin; however, galactorrhea began only after olanzapine was started.[16]

In 2 studies, some patients who were taking a conventional antipsychotic agent or risperidone had their medication changed to olanzapine. Previously elevated prolactin levels normalized and galactorrhea diminished or stopped.[15][17]

The maternal prolactin level in a mother with established lactation may not affect her ability to breastfeed.


Alternate Drugs to Consider:


Haloperidol,Risperidone


References:


1. Ambresin G, Berney P, Schulz P et al. Olanzapine excretion into breast milk: a case report. J Clin Psychopharmacol. 2004;24(1):93-5. Letter. PMID:14709955
2. Croke S, Buist, Hackett LP et al. Olanzapine excretion in human breast milk: estimation of infant exposure. Int J Neuropsychopharmacol. 2003;5:243-7. PMID:12366877
3. Gardiner SJ, Kristensen JH, Begg EJ et al. Transfer of olanzapine in to breast milk, calculation of infant drug dose, and effect on breast-fed infants. Am J Psychiatry. 2003;160:1428-31. PMID:12900304
4. Lutz UC, Wiatr G, Orlikowsky T et al. Olanzapine treatment during breast feeding: a case report. Ther Drug Monit. 2008;30:399-401. PMID:18520614
5. Whitworth A, Stuppaeck C, Yazdi K et al. Olanzapine and breast-feeding: changes of plasma concentrations of olanzapine in a breast-fed infant over a period of 5 months. J Psychopharmacol. 2008;99:379-83. PMID:18801835
6. Kirchheiner J , Berghofer A, Bolk-Weischedel D. Healthy outcome under olanzapine treatment in a pregnant woman. Pharmacopsychiatry. 2000;33:78-80. PMID:10761825
7. Gentile S. Infant safety with antipsychotic therapy in breast-feeding: a systematic review. J Clin Psychiatry. 2008;e1-e8. PMID:18370569
8. Goldstein DJ, Corbin LA, Wohlreich K, Kwong K. Olanzapine use during breast-feeding. Schizophr Res. 2002;53(3 Suppl 1):185. Abstract.
9. Friedman SH, Rosenthal MB. Treatment of perinatal delusional disorder: a case report. Int J Psychiatry Med. 2003;33(4):391-4. PMID:15152788
10. Gilad O, Merlob P, Stahl B, Klinger G. Outcome of infants exposed to olanzapine during breastfeeding. Breastfeed Med. 2011;6:55-8. PMID:21034242
11. Crawford AM, Beasley CM Jr, Tollefson GD. The acute and long-term effect of olanzapine compared with placebo and haloperidol on serum prolactin concentrations. Schizophr Res. 1997;26(1):41-54. PMID:9376336
12. Maguire GA. Prolactin elevation with antipsychotic medications: mechanisms of action and clinical consequences. J Clin Psychiatry. 2002;63(suppl 4):56-62. PMID:11913677
13. Bergemann N, Mundt C, Parzer P et al. Plasma concentrations of estradiol in women suffering from schizophrenia treated with conventional versus atypical antipsychotics. Schizophr Res. 2005;73:357-66. PMID:15653282
14. Weiden PJ, Daniel DG, Simpson G, Romano SJ. Improvement in indices of health status in outpatients with schizophrenia switched to ziprasidone. J Clin Psychopharmacol. 2003;23:595-600. PMID:14624190
15. Kim KS, Pae CU, Chae JH et al. Effects of olanzapine on prolactin levels of female patients with schizophrenia treated with risperidone. J Clin Psychiatry. 2002;63:408-13. PMID:12019665
16. Miller DE, Sebastian CS. Olanzapine-induced hyperprolactinemia and galactorrhea reversed with addition of bromocriptine: a case report. J Clin Psychiatry. 2005;66:269-70. PMID:15705020
17. Kinon BJ, Ahl J, Liu-Seifert H, Maguire GA. Improvement in hyperprolactinemia and reproductive comorbidities in patients with schizophrenia switched from conventional antipsychotics or risperidone to olanzapine. Psychoneuroendocrinology. 2006;31:577-88. PMID:16488084



Substance Identification:




Substance Name:

Olanzapine

CAS Registry Number:

132539-06-1

Drug Class:


  • Antipsychotic Agents


  • Administrative Information:




    LactMed Record Number:


    205


    Last Revision Date:


    Disclaimer:Information presented in this database is not meant as a substitute for professional judgment. You should consult your healthcare provider for breastfeeding advice related to your particular situation. The U.S. government does not warrant or assume any liability or responsibility for the accuracy or completeness of the information on this Site.