Case Reports
should be accompanied by careful observation of the in-
fant. In the medium to long term, due consideration must
also be given to the possible effects of these drugs on the
infant during a period where there is significant brain
growth and neurodevelopment.
Discussion
This study shows a clear temporal relationship between
the cessation of exposure to nefazodone through breast
milk in a premature infant and the resolution of adverse
clinical symptoms. Oversedation and failure to thrive in
the neonate resolved after discontinuation of breast feed-
ing. Previous medical interventions had been ineffective. A
Naranjo probability scale7 assessment indicated that it was
probable that the adverse reaction was drug related. In
hindsight, it is regrettable that no infant blood sample was
taken for drug analysis.
Patrick Yapp B App Sci (Pharm), Deputy Chief Pharmacist, Phar-
macy Department, King Edward Memorial and Princess Margaret
Hospitals, Subiaco, Australia
Kenneth F Ilett B Pharm PhD, Associate Professor, Department
of Pharmacology, University of Western Australia, Nedlands, Aus-
tralia
Judith H Kristensen B Pharm, Senior Pharmacist, Pharmacy De-
partment, King Edward Memorial and Princess Margaret Hospitals
Nefazodone is known to have a sedative effect8; this can
be beneficial in the hyperarousal and sleep disturbance ex-
perienced by many women with postnatal depression.
However, our detailed study of the distribution of nefa-
zodone and its active metabolites in human milk showed
that the infant would be expected to receive an average
dose of only 0.45% of the maternal weight-adjusted nefa-
zodone dose. A recent article by Dodd et al.9 reported an
M/P ratio of 0.1 for nefazodone in a patient taking nefa-
zodone 200 mg twice daily. This is about one-third of the
M/P ratio (0.27) found in our study. The difference may be
attributed to the use of a single pair of milk and plasma
concentrations rather than using AUC data, as we did in
our study, for the calculation of the M/P ratio.
L Peter Hackett LRCS, Research Scientist, Clinical Pharmacolo-
gy and Toxicology Laboratory, The Western Australian Centre for
Pathology and Medical Research, Nedlands
Michael J Paech MBBS FANZCA, Anaesthetist, Department of
Anaesthesia, King Edward Memorial and Princess Margaret Hospi-
tals
Jonathon Rampono MB ChB FRANZCP, Psychiatrist, Depart-
ment of Psychological Medicine, King Edward Memorial and Princess
Margaret Hospitals
Reprints: Patrick Yapp B App Sci (Pharm), Pharmacy Department,
King Edward Memorial Hospital, Subiaco, 6008, Western Australia,
FAX +61 8 9340 2713, E-mail patrick.yapp@health.wa.gov.au
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However, our case highlights the importance of individ-
ualizing both the calculation and impact of drug exposure
on the neonate. In our case, the infant was born 13 weeks
preterm and was still only at a corrected gestational age of
36 weeks and weighed only 2.1 kg when the drowsiness
and poor feeding were noted. Infant exposure to antide-
pressants and other drugs is generally considered safe when
the relative infant dose is <10% of the maternal dose.6
However, plasma concentrations in the infant are not only
dependent on intake, but also on hepatic and renal clear-
ance mechanisms.10 In our case, we suggest that clearance
likely was low, considering the infant’s gestational age and
body weight. The adult elimination half-lives for nefazo-
done (2– 4 h), HO-nefazodone (1.5–4 h), m-chlorophenyl-
piperazine (4–8 h), and triazoledione (18 h) are likely to
be longer in the neonate. The case therefore illustrates the
importance of low neonatal clearance capacity in preterm
infants. Nefazodone was the preferred antidepressant drug
in this patient. For this reason, rechallenge by reintroduc-
ing breast feeding was not an option.
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Summary
While this report suggests a putative association be-
tween nefazodone and adverse effects in a breast-fed baby,
the calculated infant dose was very low, and the associa-
tion should be interpreted with caution. Our findings do
not necessarily mean that breast feeding should be avoided
in full-term or older infants whose mothers are taking ne-
fazodone. Finally, when maternal use of novel antidepres-
sants is necessary, decisions on breast feeding should be
made following an individual risk–benefit analysis and
EXTRACTO
OBJETIVO: Investigar si los efectos adversos presentados por un
neonato prematuro pudieran ser atribuídos a la nefazodona ingerida
a través de la lecha materna.
RESUMEN DEL CASO: Una infante alimentada con leche materna (2.1 kg,
36 semanas de edad gestacional), cuya madre de 36 años de edad (60
kg) estaba tomando nefazodona (300 mg/d), fue admitida al hospital en
estado de adormecimiento, letargo, falta de control de su temperatura
corporal, y pobremente alimentada. Después de excluir otros posibles
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The Annals of Pharmacotherapy
2000 November, Volume 34
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