Minimal breast milk transfer of rituximab, a monoclonal antibody used in neurological conditions

Abstract

Objective: To determine the transfer of rituximab, an anti-CD20 monoclonal antibody widely used for neurologic conditions, into mature breast milk.

Methods: Breast milk samples were collected from 9 women with MS who received rituximab 500 or 1,000 mg intravenous once or twice while breastfeeding from November 2017 to April 2019. Serial breast milk samples were collected before infusion and at 8 hours, 24 hours, 7 days, and 18-21 days after rituximab infusion in 4 patients. Five additional patients provided 1-2 samples at various times after rituximab infusion.

Results: The median average rituximab concentration in mature breast milk was low at 0.063 μg/mL (range 0.046-0.097) in the 4 patients with serial breast milk collection, with an estimated median absolute infant dose of 0.0094 mg/kg/d and a relative infant dose (RID) of 0.08% (range 0.06%-0.10%). Most patients had a maximum concentration at 1-7 days after infusion. The maximum concentration occurred in a woman with a single breast milk sample and was 0.29 μg/mL at 11 days postinfusion, which corresponds with an estimated RID of 0.33%. Rituximab concentration in milk was virtually undetectable by 90 days postinfusion.

Conclusions: We determined minimal transfer of rituximab into mature breast milk. The RID for rituximab was less than 0.4% and well below theoretically acceptable levels of less than 10%. Low oral bioavailability would probably also limit the absorption of rituximab by the newborn. In women with serious autoimmune neurologic conditions, monoclonal antibody therapy may afford an acceptable benefit to risk ratio, supporting both maternal treatment and breastfeeding.

Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

Figures

Figure 1. Rituximab concentrations in breast milk (n = 9)

Rituximab concentrations (μg/mL) in 9 patients up to 90 days from infusion of rituximab 1,000 or 500 mg intravenous once or twice. Lines connect samples provided from a given individual. There was 1 outlier with a concentration of 0.29 μg/mL at 11 days postinfusion, although this level is still low.

Figure 2. Pharmacokinetic curves for rituximab concentration in breast milk for patients who provided serial samples (n = 4)

Rituximab concentrations (μg/mL) in 4 patients up to 30 days after infusion of rituximab 1,000 mg IV once (A: patient 1; B: patient 2), 500 mg IV twice day 0 and 19 (C: patient 3), or 500 mg IV once (D: patient 4). IV = intravenous.