▪ 약물의 분류: 항우울제(SSRI, selective serotonin reuptake inhibitor)
▪ 임신부 약물등급(US FDA): C
▪ 임신부 안전 및 기형발생정보:
Based on experimental animal studies and human experience, fluoxetine is not expected to increase the risk of major congenital anomalies. Human studies have inconsistently reported associations of fluoxetine use during pregnancy and heart defects in the offspring. Use of fluoxetine late in pregnancy can be associated with a mild transient neonatal syndrome of central nervous system, motor, respiratory, or gastrointestinal signs. Use of fluoxetine after 20 weeks gestation has been associated with an increased risk of neonatal pulmonary hypertension in some studies but not in others. Long-term neurodevelopmental studies suggest that antenatal fluoxetine exposure, unlike maternal depression, does not adversely affect outcome.
▪ 모유수유부 약물등급(Medication and Mother’s MilK): L2
▪ 모유수유 안전 및 유해성정보:
Fluoxetine exposure of rat pups via lactation prevented some of the behavioral and hippocampal effects seen in adolescence associated with maternal exposure to stress during gestation. Fluoxetine exposure of rats via lactation was associated with decreased anogenital distance in adult male but not female offspring and with impairment in sexual behavior in males. There were no differences in estradiol or testosterone concentrations in fluoxetine-exposed offspring independent of the prenatal stress condition. The volume of the sexually dimorphic nucleus of the preoptic area was reduced in males exposed to fluoxetine, with a larger effect if also exposed to prenatal stress. In contrast, no effect on sexual development was observed in male or female rats exposed during gestation and lactation by oral gavage of the mothers, although maternal and fetal toxicity was evident at the highest dose level.
Fluoxetine and its major active metabolite norfluoxetine are excreted in human milk. Most reports suggested low levels of exposure and a lack of apparent toxicity for the infant. There are isolated case reports of adverse outcome. One case involved colic in an exposed infant. This observation was supported by a daily diary of infant behavior kept by the mother before and after the infant was exposed to the drug in her milk. Maternal bias might have played a role in the report. In another case report, a pediatrician whose nursing wife began taking fluoxetine 3 months postpartum noted increased irritability in the infant during the first two weeks of therapy. Neither the wife nor the infant`s pediatrician noted this adverse effect. Serotonin syndrome was diagnosed in a late preterm male infant who had been exposed to fluoxetine 60 mg/day throughout gestation and breastfeeding. The infant presented on postpartum day 2 with jitteriness, hyperreflexia, rigidity, fever, and compensated metabolic acidosis.
These symptoms were still present on day 8 when the mother was readmitted for a wound infection.
The infant was fully breastfed with a serum fluoxetine concentation of 120 mcg/L, considered to be in the adult therapeutic range. The maternal serum concentration was not reported. Symptoms resolved gradually when breastfeeding was discontinued, and development was normal at age 3 months.
In another report, milk/plasma ratios for fluoxetine and norfluoxetine were estimated to be about 0.6, and the mean total infant exposure (in fluoxetine equivalents) was estimated to be 6.81% (range 2.15-12%) of the weight-adjusted maternal dose of fluoxetine. Two additional estimates of the milk:plasma ratio suggested a range of 0.2 to 0.25. One estimate of total fluoxetine intake by a nursing infant was 15 to 20 mcg/kg/day, which was a very low level of drug exposure. In another study, the total dose of fluoxetine and norfluoxetine, expressed as fluoxetine equivalents, was about 40 mcg/kg/day. No adverse effects were noted in 11 infants nursed by 10 mothers on fluoxetine in this study. A third study of four mother-infant pairs found fluoxetine in maternal plasma at 138 to 427 ng/mL and in milk at 39 to 177 ng/mL. In this study, serial behavioral testing using the Bayley scales of infant development showed no abnormalities associated with lactational exposure to fluoxetine. Based on measurement of fluoxetine and metabolites in infant serum, one group reported that if a nursing woman is taking 20 mg/day or less of fluoxetine, low infant serum concentrations would be expected.
One clinical study reported finding a reduced rate of weight gain among the infants of mothers who breastfed while taking fluoxetine. This effect was not great enough to be of general clinical significance, but the authors noted that such an effect might be of clinical importance in cases in which infant weight gain was critical. Concern about possible adverse effects on neonates has led to a labeling revision for fluoxetine to recommend that it not be used by nursing mothers. We have not seen controlled studies supporting this recommendation. An Australian midwife reported that an apparent reduction in milk supply associated with the use of sertraline was overcome in 2-3 days by increasing both oral fluids and the frequency of feeding. Eight women who took serotonin reuptake inhibitors at the end of pregnancy and following delivery (including 3 on fluoxetine) were reported to have a 1 day delay in the onset of copious milk secretion after delivery.
▪ 한국마더세이프전문상담센터 DB 정보 (모태독성학2016):
플루옥세틴에 노출된 후 추적된 임신부는 총 1010례이었으며 초기 노출 후 자연유산율은 8.9%(9/101)이었다. 임신 37주 이전의 조산률은 2.2%(2/89), 2,500 g 미만의 저체중증은 2.3%(2/88)
이었다. 주요기형발생은 3.4%(3/88): right renal cyst(1), right liver mass(1), choledochal cyst(1), PDA(1)가 있었다. 그리고 사산 1례가 있었다.
2) 모유 수유 시 독성 및 적합성 정보
수유부-수유아 2쌍 중 부작용 사례는 없었다.