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Drugs and Lactation Database (LactMed) [Internet]. Bethesda (MD): National Library of Medicine (US); 2006-.

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Drugs and Lactation Database (LactMed) [Internet].

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Rituximab

Last Revision: July 18, 2022.

Estimated reading time: 5 minutes

CASRN: 174722-31-7

Drug Levels and Effects

Summary of Use during Lactation

Rituximab is a genetically engineered chimeric murine/human monoclonal antibody that targets CD20, a B-cell-specific surface antigen. The amount in milk is very low and absorption is unlikely because it is a protein with a molecular weight of 143,860 Da. It is likely to be partially destroyed in the infant's gastrointestinal tract and absorption by the infant is probably minimal.[1,2] Although several breastfed infants apparently experienced no adverse effects during maternal use of rituximab, the manufacturer recommends that breastfeeding be discontinued during rituximab therapy and for 6 months after the last dose. However, the American College of Rheumatology and others consider rituximab to be acceptable for use during breastfeeding.[3,4] Until more data become available, rituximab should be used with caution during breastfeeding, especially while nursing a newborn or preterm infant.[5-7]

Drug Levels

Maternal Levels. A patient who had granulomatosis with polyangiitis received rituximab 1000 mg intravenously while exclusively breastfeeding her infant. Milk samples were collected daily for 4 days starting 7 days after the infusion. Milk rituximab concentrations averaged 0.5 mcg/L (range 0.4 to 0.6 mcg/L).[2]

A woman with ANCA-associated vasculitis was treated with rituximab 500 mg intravenously at week 19 postpartum. The median concentration of rituximab in milk samples collected on 4 consecutive days was 3 mcg/L (range 0 to 4 mcg/L). The relative infant dose to the infant was estimated to be 0.007%.[8]

Breastmilk samples were collected from 9 women with multiple sclerosis who received either 500 or 1000 mg of infliximab once or twice while breastfeeding. Four patients provided samples before infusion and at 8 hour, 24 hours, 7 days, and 18 to 21 days after a dose. Five additional patients provided 1 or 2 samples at various times after rituximab infusion. The median average rituximab concentration in mature breast milk was 63 mcg/L (range 46 to 97 mcg/L) in the 4 patients with serial breast milk collection, with an estimated median absolute infant dose of 9.4 mcg/kg daily. Most patients had a peak milk concentration at 1 to 7 days after infusion. The highest milk concentration was 290 mcg/L, which occurred in a woman with a single breast milk sample 11 days after a 1000 mg dose at 9 months postpartum. Rituximab concentration in milk was virtually undetectable by 90 days postinfusion in all women.[9]

Six mothers with relapsing-remitting multiple sclerosis received 500 or 1,000 mg of rituximab postpartum. Breastmilk was collected at six time points: pre infusion, two days after infusion, after one week, and after one, three and five half-lives of rituximab. The median average concentration in breastmilk was 41 mcg/L. The median relative infant dose based on the individual average concentrations was 0.07%.[10]

Infant Levels. A woman received rituximab 375 mg/square meter once weekly for 4 weeks beginning at week 30 of gestation. Her infant was born at 40 weeks of gestation and was exclusively breastfed with no major health issues. At 4 months of age, trace amounts of rituximab heavy and light chains were detected, but not quantified, in the infant's serum. Whether the drug was acquired transplacentally or during breastfeeding was not determined.[11]

A woman with ANCA-associated vasculitis was treated with rituximab 500 mg intravenously at week 19 postpartum. She continued to breastfeed her infant (extent not stated). There was no detectable rituximab in the serum of the infant (assay limit not stated) at 4 and 24 hours after the maternal dose.[8]

Six nursing (extent not stated) mothers with relapsing-remitting multiple sclerosis received 500 or 1,000 mg of rituximab postpartum. Infant serum was collected at six time points: pre infusion, two days after infusion, after one week, and after one, three and five half-lives of rituximab. All of the measurements of rituximab concentration in the infants’ serum were below 0.01 mcg/L, and most of them below the lower limit of quantification (<0.005 mcg/L).[10]

Effects in Breastfed Infants

A woman received rituximab 375 mg/square meter once weekly for 4 weeks beginning at week 30 of gestation. Her infant was born at 40 weeks of gestation and was exclusively breastfed with no major health issues. At 4 months of age, the infant's B-cell population and immunoglobulin levels did not appear to be affected.[11]

A woman received an IV infusion of 1000 mg of rituximab at about 3 months postpartum. Her infant who was fully breastfed had no serious infections during the lactation period and developed normally during a 1.5 year follow-up period.[2]

Four infants who were breastfed by mothers who received either 500 mg or 1000 mg of rituximab were followed for 8 to 12 months. One of the infants’ mothers receive 2 doses of rituximab at 0.5 and 7 months postpartum. All infants had typical childhood infections, but none were serious. Growth and development was normal in all 4 infants for up to 8 to 12 months of age.[9]

A retrospective cohort study from the German Multiple Sclerosis and Pregnancy Registry database identified 5 mothers who received rituximab during breastfeeding. Three mothers receive one dose of rituximab while nursing, one received 500 mg and two received 1000 mg. The infants breastfed for 1.6, 1.8 and 0.3 months, respectively. Infant blood counts were normal at 1 to 1.5 months after the mothers’ doses. A blood count was not performed in the third infant. One infant developed omphalitis, but all had normal development. The fourth woman received rituximab 250 mg on day 55 postpartum and ocrelizumab 300 mg on day 333 postpartum. She breastfed for 22.9 months after the rituximab dose. Her infant had normal blood counts at 45 and 213 days after the rituximab dose, but had conjunctivitis and otitis media during this time.[12]

A woman was diagnosed with B-cell lymphoma at 27 weeks of pregnancy. Labor was induced at 34 4/7 weeks and treatment was begun with a standard regimen of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone in unspecified doses on a 21-day cycle, starting on day 2 postpartum. She pumped and discarded her milk and fed her infant donor milk for the first 10 days of each cycle and then breastfed her infant for the remaining 10 days before the next treatment cycle. The 10-day period of breastfeeding abstinence was determined by using about 3 half-lives of vincristine. After completion of 4 cycles of chemotherapy, her infant was reportedly healthy and developing without any complications.[13]

A woman with ANCA-associated vasculitis was treated with rituximab 500 mg intravenously at week 19 postpartum. She continued to breastfeed her infant (extent not stated) for another 4 months. The infant did not experience any serious infections or allergies, developed normally during the following 2 years and received all recommended vaccinations.[8]

Six nursing (extent not stated) mothers with relapsing-remitting multiple sclerosis received 500 or 1,000 mg of rituximab postpartum. Infants were followed for at least 5 half-lives of the drug. No apparent abnormalities in white blood cell count, lymphocytes or immunoglobulin levels were detected in the infants after rituximab infusion.[10]

Effects on Lactation and Breastmilk

Relevant published information was not found as of the revision date.

Alternate Drugs to Consider

(Multiple Sclerosis) Glatiramer, Immune Globulin, Interferon Beta (Rheumatoid Arthritis) Adalimumab, Certolizumab Pegol, Etanercept, Infliximab, Tocilizumab

References

1.
Pistilli B, Bellettini G, Giovannetti E, et al. Chemotherapy, targeted agents, antiemetics and growth-factors in human milk: How should we counsel cancer patients about breastfeeding? Cancer Treat Rev. 2013;39:207–11. [PubMed: 23199900]
2.
Bragnes Y, Boshuizen R, de Vries A, et al. Low level of rituximab in human breast milk in a patient treated during lactation. Rheumatology (Oxford). 2017;56:1047–8. [PubMed: 28339781]
3.
Sammaritano LR, Bermas BL, Chakravarty EE, et al. 2020 American College of Rheumatology Guideline for the Management of Reproductive Health in Rheumatic and Musculoskeletal Diseases. Arthritis Rheumatol. 2020;72:529–56. [PubMed: 32090480]
4.
Dobson R, Rog D, Ovadia C, et al. Anti-CD20 therapies in pregnancy and breast feeding: A review and ABN guidelines. Pract Neurol. 2022 [PubMed: 35803727]
5.
Almas S, Vance J, Baker T, et al. Management of multiple sclerosis in the breastfeeding mother. Mult Scler Int. 2016;2016:6527458. [PMC free article: PMC4757692] [PubMed: 26966579]
6.
Keeling SO, Oswald AE. Pregnancy and rheumatic disease: "by the book" or "by the doc". Clin Rheumatol. 2009;28:1–9. [PubMed: 18987777]
7.
Østensen M. Management of early aggressive rheumatoid arthritis during pregnancy and lactation. Expert Opin Pharmacother. 2009;10:1469–79. [PubMed: 19505214]
8.
Bosshard N, Zbinden A, Eriksson KK, et al. Rituximab and canakinumab use during lactation: No detectable serum levels in breastfed infants. Rheumatol Ther. 2021;8:1043–8. [PMC free article: PMC8217349] [PubMed: 33999372]
9.
Krysko KM, LaHue SC, Anderson A, et al. Minimal breast milk transfer of rituximab, a monoclonal antibody used in neurological conditions. Neurol Neuroimmunol Neuroinflamm. 2020;7:e637. [PMC free article: PMC6857908] [PubMed: 31719115]
10.
Rød B, Bø L, Myhr K, et al. Rituximab exposure from breastfeeding. A case series. Multiple Sclerosis Journal. 2022;28(1) Suppl:210–11. https://www​.abstractsonline​.com/pp8/#!/10495​/presentation/481
11.
Jin J, Mills J, Conboy E, et al. In utero rituximab: Detection of rituximab in an infant at 4 months of age. Ann Allergy Asthma Immunol. 2014;113:A14–Abstract 36. http://www​.sciencedirect​.com/science/journal​/10811206/113/5/supp/S
12.
Ciplea AI, Langer-Gould A, de Vries A, et al. Monoclonal antibody treatment during pregnancy and/or lactation in women with MS or neuromyelitis optica spectrum disorder. Neurol Neuroimmunol Neuroinflamm. 2020;7:e723. [PMC free article: PMC7188475] [PubMed: 32327455]
13.
Hersey AE, Giglio P, Kurt H, et al. Diffuse large B-cell lymphoma during third-trimester pregnancy and lactation. Obstet Gynecol. 2020;135:383–6. [PubMed: 31923071]

Substance Identification

Substance Name

Rituximab

CAS Registry Number

174722-31-7

Drug Class

Breast Feeding

Lactation

Milk, Human

Antibodies, Monoclonal

Antirheumatic Agents

Antineoplastic Agents

Disclaimer: Information presented in this database is not meant as a substitute for professional judgment. You should consult your healthcare provider for breastfeeding advice related to your particular situation. The U.S. government does not warrant or assume any liability or responsibility for the accuracy or completeness of the information on this Site.

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