RESEARCH - Enbrel (etanercept) in breast milk

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Etanercept in Breast Milk

To the Editor:

Etanercept (Enbrel®) is a soluble tumor necrosis factor (TNF) receptor

fusion protein that binds and inactivates TNF. Its metabolites are

excreted in bile and urine and are not bioactive. Clinical studies have

shown that etanercept effectively suppresses arthritis not only in

patients with rheumatoid arthritis (RA), but also in juvenile idiopathic

arthritis, ankylosing spondylitis, and psoriatic arthritis1. The main

side effect of etanercept in children and adults is infections,

particularly upper respiratory tract infections. However, serious events

like sepsis or aseptic meningitis occur in less than 1% of treated

patients1. In women with child-bearing potential, treatment with

etanercept can interfere with pregnancy or lactation. It is not known

whether etanercept is secreted into human breast milk. We measured

etanercept in breast milk of a patient with RA.

A 30-year-old woman with rheumatoid factor positive RA had active

disease throughout pregnancy. Four weeks after delivery, treatment with

etanercept injections 25 mg twice weekly was started because of acute

flares of arthritis. She did not breastfeed her child, but had milk flow

throughout the duration of the study. The first injection of 25 mg

etanercept was given 30 days after delivery, and thereafter twice weekly

subcutaneously. A blood sample of the mother was taken one day after the

fifth etanercept injection, and thereafter milk samples were collected.

The maternal plasma and milk samples were kept frozen at -80°C until

analyzed by an ELISA test selective for etanercept3.

The results are summarized in Table 1. The measured concentrations of

etanercept in maternal serum corresponds to 2 mg/ml levels reported

previously2. The maximal etanercept level measured in breast milk was 75

ng/ml on the day after injection and decreasing during the following

days (Figure 1). The lack of an increase of etanercept after the second

injection was presumably due to the spontaneous cessation of milk

secretion in this lactating, but not nursing mother.

To our knowledge this is the first report showing that etanercept is

secreted in human breast milk. It is not known whether etanercept can be

absorbed orally. Since it is a large protein, bioavailability by oral

ingestion can be assumed to be small. However, the nursing infant

absorbs immunoglobulins and thus the possibility exists for a fusion

protein3. The amount of a drug secreted into breast milk varies

depending on the frequency of nursing and the composition of milk

proteins and lipids. Thus no precise calculation of the amount ingested

by a nursing infant can be made in this lactating mother who was not

nursing her child. Further, the volume of milk secreted during the day

was not recorded. If one assumes that a nursing infant is breastfed 6

times a day with about 200 ml of milk at each feeding, the amount of

etanercept ingested by the child is 50 to 90 µg per day. Therefore, the

maximum exposure by oral ingestion can be calculated to be 0.1 to 0.05

mg/kg body weight. In comparison, the recommended dose of etanercept for

the treatment of children aged 4 years or older is 0.4 mg/kg

subcutaneously twice a week. At present, any risk possibly exerted by

these small amounts of etanercept, which theoretically could be ingested

by a nursing infant, remains speculative and not very likely. Should the

necessity arise to treat a nursing patient who wants to continue

breast-feeding during treatment with etanercept, measurement of serum

concentrations in the suckling child could solve the question whether

orally ingested etanercept is absorbed.

MONIKA OSTENSEN, MD, Department of Rheumatology and Clinical Immunology

and Allergy, University Hospital, CH-3010 Bern; GABRIELLA OBRIST

EIGENMANN, DrPharm, Wyeth-AHP (Schweiz) AG, Zug, Switzerland. E-mail:

monika.oestensen@...

REFERENCES

1. Culy CR, Keating GM. Etanercept: An updated review of its use in

rheumatoid arthritis, psoriatic arthritis and juvenile rheumatoid

arthritis. Drugs 2002;62:2493-537.

2. Korth-Bradley JM, Rubin AS, Hanna RK, Simcoe DK, Lebsack ME. The

pharmacokinetics of etanercept in healthy volunteers. Ann Pharmacother

2000;34:161-4.

3. Lohse AW, Gerken G, Altes U, Mayet WJ, Meyer zum Büschenfelde KH.

Transmission of maternal IgG autoantibodies via cord blood and

breastmilk without transmission of hepatitis. Lancet 1993;341:1216-7.

Journal of Rheumatology

May 2004

Letter

" Etanercept in Breast Milk " :

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