Kommersiellt obunden läkemedelsinformation riktad till läkare och sjukvårdspersonal

Drugline nr 21800

Publicerat 2005-02-08

Query Text

What is known about use of nefazodone during pregnancy and breast-feeding?

The question concerns a pregnant woman (first trimester) that is treated with nefazodone (dose unknown) for depression. She has been treated with the drug for a long time and has previously delivered a healthy child during nefazodone treatment.

Answer Text

Nefazodone is an antidepressant only prescribed on a licence today due to severe adverse effects on the liver. It exerts pharmacological action both as a SSRI and an antagonist at the 5-HT2A receptor site (1).

A total of 91 women treated with nefazodone and 58 with trazodone, which is similar to nefazodone, during pregnancy have been found in the literature (1,2,3). Only two major malformations were observed among the live born children. However, no increased risk of malformation compared with the normal population was detected. In two of the pregnancies the mothers dose was known to be 400 mg and 200 mg daily, respectively (3). In the Swedish Medical Birth Registry there are 43 exposures for nefazodone and only one child with a malformation (4).

No reports of neonatal withdrawal symptoms have been found in the literature for nefazodone. However, it is a well-known phenomenon for SSRIs (5). There are also several case reports of substance withdrawal syndrome in adults (6,7,8,9). Therefore, neonatal withdrawal symptoms might also be expected for nefazodone.

Nefazodone and its metabolites are excreted to a low extent into breastmilk (10,11,12,13). Through plasma and breast milk concentrations of nefazodone and its metabolites were measured at three different occasions. In one patient, treated with 200 mg two times daily, plasma concentration was 617 ng/ml and concentration in breast milk was 57 ng/ml. The second patient was treated with 50 mg two times daily at the first occasion and 50 mg mornings and 100 mg evenings at the second occasion. Plasma levels were <50 ng/ml and breast milk concentrations were 687 ng/ml for the lower dosage regimes and <50 ng/ml and 213 ng/ml, respectively, for the higher dosage regimen. The active metabolites were only detected in the second patient at <50 ng/ml for the lower dosage regimen and 104 for the higher dosage regimen (11). The highest estimated weight adjusted infant dose of nefazodone, based on these cases, was about 6%.

In two other mothers nefazodone but not the metabolites was excreted to a low extent into breast milk . The first mother was treated with nefazodone 150 mg daily and the second mother with 400 mg daily. The maximal weight adjusted infant dose of nefazondone in these infants were 2.2% of the maternal dose (12).

A premature infant was delivered at 27 weeks of gestation and breast-fed by her mother. When the infant was seven weeks of age the mother was prescribed nefazodone (200+100 mg) due to depression. The infant was admitted at nine weeks of age to hospital since she was drowsy, lethargic, unable to maintain normal body temperature and was feeding poorly. The mother breastmilk concentration was 358 ng/ml for nefazodone rendering in a weight adjusted infant dose of about 1%. The symptoms resolved within 72 hours in the infant after nefazodone treatment was stopped in the mother. It was speculated that the adverse effects in this infant might have resulted from a reduced clearance of the drug due to immature metabolic capacity (13).

No long-term effects on neurobehavior and developmental in the child after exposure of nefazodone during pregnancy or breast-feeding have been studied.

Answer Conclusion

Data does not indicate that nefazodone treatment during pregnancy increase the risk for malformations. So far, there are no neonatal withdrawal symptoms reported. Nefazodone passes over to breastmilk to a low extent and the weight adjusted infant dose of the maternal dose has been calculated to be at most about 6%. However, no long-term studies investigating neurodevelopment in infant exposed for nefazodone, in utero or through breastmilk, exists.

Kimland E
Böttiger Y


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Senast ändrad 2018-09-20