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Drugline nr 23243

Publicerat 2007-03-13

Question

What is known about the use of quetiapine during breast-feeding?

The question relates to a pregnant patient suffering of schizophrenia who is treated with quetiapine (Seroquel) (500mg/day). During the pregnancy a dose reduction was tried, but the patient developed catatonia. The patient plans to breast-feed the infant during the ongoing treatment with quetipaine.

Answer

In an extensive search in relevant literature and databases only sparse data are available. Four published case reports and a small case report series of 6 patients was found.

In one case report, pharmacokinetic data from one lactating mother was presented (1). The woman received 200mg/day of quetiapine, and breast milk samples were collected at one occasion during a six-hour period three weeks postpartum. Average milk concentration of quetiapine was 13 ug/L, with a maximum concentration of 62 ug/L at one hour after ingestion of quetiapine. From available data it was calculated that an exclusively breast-fed infant would receive 0.09% of the weight-adjusted dosage on average, with a "worst-case" dosage of 0.43% of weight-adjusted maternal dose. Based on these results the woman started breast-feeding and a follow up at 4.5 months indicated that the infant was developing well, and no adverse effects of quetiapine were reported.

A 33-year-old woman suffering from severe postpartum psychotic depression after the birth of her first child planned a pregnancy without discontinuation of her medication, which was a combination of quetiapine (400 mg/day) and fluvoxamine (200 mg/day) (2). Due to insufficient milk production mixed feeding with supplemental formula and breast-feeding was required. No adverse effects were observed in the baby during the first three months.

In a third case report a 39-year-old woman suffering from bipolar disorder with post-partum onset started treatment with quetiapine (200 mg/day) at six months post-partum (3). She had at that time been treated with paroxetine for two months. Three months after initiation of quetiapine treatment she remained in full remission on the same dose. Throughout that period she had been breast-feeding regularly with no noticeable adverse effects on the baby.

A 26-year-old mother and her 3 month-old son were studied over a 24-hour quetiapine dose (400 mg/day) interval at steady-state (6). The average concentration in milk was 41 ug/L, and the relative infant dose was 0.09 % of the maternal weight adjusted dose. The infant plasma concentration of 1.4 ug/L was 6% of the corresponding maternal plasma concentration and no adverse effects were noted in the infant.

In the small case report series, six nursing mothers who were 6.5 to 18.5 weeks postpartum were taking quetiapine in doses of 25 mg to 400 mg daily in addition to an antidepressant for major depression (4). Milk samples obtained at various times after the dose had undetectable (< 11.5 ug/L) levels of quetiapine in the 4 mothers taking 75 mg daily or less. A mother taking 100 mg daily had a milk quetiapine level of 12.3 ug/L and another taking 400 mg daily had a level of 101 ug/L. The authors estimated that exclusively breastfed infants would receive less than 0.1 mg/kg daily with a maternal dose of 400 mg daily.

The breastfed infants´ development was tested at 9 to 18 months of age with the Bayley scales. Measurements were slightly low on the mental and psychomotor development scale in one infant and on the mental development scale in another. Both these infants were nursed by a mother with undetectable levels of quetiapine and paroxetine in the breast milk, and the authors concluded that the drugs received by the infants in breast milk did probably not cause the very mild development delays in these two infants. All other score were within normal limits.

The development of cytochrome activity after birth adds complexity in the evaluation of risks for the infant. CYP3A activity increases close to ten-fold during the first three months (5). If cytochrome activity at three months is comparable to the activity in adults you could in worst-case expect the exposition for the infant to be roughly 5 % of the maternal dose, if bioavailability is constant (10 times the excreted 0.5 % of the weight adjusted maternal dose).

All these reports have severe limitations and must be considered anecdotal. However, the available data regarding milk concentrations of quetiapine indicates that the amount of quetiapine the infant ingest is very small, and therefore the risk for side effects in the infant should be low. The long-term effects have not been studied and little is known about the infants´ later development.

Conclusion

A limited amount of data is available concerning treatment with quetiapine during breast-feeding, but considering the risk of relapse in the mother and the associated risk for the infant, it does appear that breastfeeding of the baby could be considered. The infant should be monitored for side effects.

Bäckström T
Böttiger Y

References

  1. Lee A, Giesbrecht E, Dunn E, Ito S. Excretion of quetiapine in breast milk. Am J Psychiatry 2004;161(9):1715-1716
  2. Gentile S. Quetiapine-fluvoxamine combination during pregnancy and while breastfeeding. Arch Womens Ment Health 2006;9(3):158-159
  3. Ritz S. Quetiapine monotherapy in post-partum onset bipolar disorder with a mixed affective state. Eur Neuropsychopharmacol 2005;15:S407
  4. Misri S, Corral M, Wardrop AA, Kendrick K. Quetiapine augmentation in lactation: a series of case reports. J Clin Psychopharmacol 2006;26(5):508-511
  5. Kearns GL, bdel-Rahman SM, Alander SW, Blowey DL, Leeder JS, Kauffman RE. Developmental pharmacology--drug disposition, action, and therapy in infants and children. N Engl J Med 2003;349(12):1157-1167
  6. Rampono J, Kristensen JH, Ilett KF, Hackett LP, Kohan R. Quetiapine and Breast Feeding (April). Ann Pharmacother 2007;41:711-4

Senast ändrad 2018-09-20