Fluoxetine / olanzapine Pregnancy and Breastfeeding Warnings

Fluoxetine / olanzapine is also known as: Symbyax

Fluoxetine / olanzapine Pregnancy Warnings

Fluoxetine-olanzapine has been assigned to pregnancy category C by the FDA. Animal studies have revealed evidence of decreases in fetal weight and retarded skeletal ossification in conjunction with maternal toxicity. Animal studies have also reported marked elevation in offspring mortality and growth retardation in comparison to the same doses of fluoxetine or olanzapine administered alone. Testicular degeneration and atrophy, depletion of epididymal sperm, and infertility have been reported in male animal progeny. There are no controlled data in human pregnancy. Neonates exposed to antipsychotic drugs during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery. There have been reports of agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress and feeding disorder in these neonates. These complications have varied in severity; while in some cases symptoms have been self-limited, in other cases neonates have required intensive care unit support and prolonged hospitalization. Fluoxetine-olanzapine is only recommended for use during pregnancy when there are no alternatives and benefit outweighs risk.

Neonates exposed to fluoxetine and other SSRIs or SNRIs late in the third trimester have developed complications requiring hospitalization, respiratory support, and tube feeding. Animal studies on fluoxetine alone have failed to reveal evidence of teratogenicity. In a postmarketing report, outcome data were available for 723 pregnancies, 476 normal live births, 20 premature births, 105 therapeutic abortions, 81 spontaneous abortions, 14 twin pregnancies without malformations, three stillbirths, 14 perinatal major malformations, and 10 postperinatal malformations were reported. A prospective study of fluoxetine compared the outcome of 228 pregnant women taking fluoxetine to 254 pregnant control women. The rates of spontaneous pregnancy loss were 10.5% and 9.1% respectively. The rates of major structural abnormalities were 5.5% and 4.0%. The incidence of three or more minor anomalies was significantly higher in exposed infants (15.5% vs. 6.5%). Infants exposed during the third trimester had high rates of premature delivery, admission to special care nurseries, and poor neonatal adaptation (including respiratory difficulty, cyanosis on feeding and jitteriness). Infants exposed late in gestation had shorter birth lengths and lower birth weights. One author has pointed out that he feels a problem with the above study was the absence of a relevant control group. Higher rates of perinatal complications, including lower birth weight, neonatal distress and prematurity, have been described in the offspring of mothers with mood and anxiety disorders who did not take any psychotropic drug during pregnancy. Furthermore, he points out that women who continued to take fluoxetine into the third trimester probably had more severe psychiatric illnesses. Another prospective study of 128 pregnancy women exposed to a mean daily dose of 25.8 mg of fluoxetine during the first trimester reported no increase in the frequency of major malformations compared to two groups of control patients. One control group received tricyclic antidepressants. The other control group received nonteratogens. However, women exposed to fluoxetine and tricyclic antidepressants did demonstrate an increased frequency of miscarriage (13.5% and 12.2% compared to 6.8% in women exposed to nonteratogens). One last prospective study of fluoxetine compared rates of neonatal complications from 112 pregnant women taking fluoxetine and the 115 infants they delivered to the National Hospital Discharge Survey. The study concluded it was unlikely that maternal fluoxetine use during the third trimester results in significant postnatal complications. Animal studies on olanzapine alone have revealed evidence of fetotoxicity. A study analyzing 23 prospectively and 11 retrospectively olanzapine-exposed pregnancies found that the rates for spontaneous abortion, stillbirth, prematurity, and malformation fell within the control range. Several additional cases of healthy infants born to olanzapine-treated mothers have also been reported.

Fluoxetine / olanzapine Breastfeeding Warnings

Fluoxetine is described by the American Academy of Pediatrics as a drug whose "effect on nursing infants is unknown but may be of concern". A report of ten women nursing eleven infants found that less than 10% of the dose of fluoxetine (per kg of body weight) was delivered to the nursing infant during chronic maternal therapy. Other reports from two lactating women taking fluoxetine have described milk fluoxetine and norfluoxetine concentrations to be about one-fifth to one-quarter serum concentrations. No adverse effects were reported in any of the nursing infants above. Two cases exposure to olanzapine during lactation have been reported. One infant experienced adverse effects which continued after olanzapine was discontinued, suggesting an alternate cause. No problems were reported in the other infant. A study involving lactating, healthy women reported a mean infant dose at steady-state of approximately 1.8% of the maternal olanzapine dose.

There are no data on the excretion of the combination product fluoxetine-olanzapine into human milk. Both fluoxetine and olanzapine individually have been reported to be excreted into human milk. Fluoxetine-olanzapine is considered contraindicated during breast-feeding by the manufacturer.

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