Tocilizumab concentrations in maternal serum and breast milk during breastfeeding and a safety assessment in infants: a case study

Saito, Jumpei; Yakuwa, Naho; Takai, Chinatsu; Nakajima, Ken; Kaneko, Kayoko; Goto, Mikako; Ishikawa, Yoichi; Murashima, Atsuko

doi:10.1093/rheumatology/key091

Cited by 41 publications

(45 citation statements)

References 6 publications

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“…a) The first issue is that breastfeeding in COVID-19 patients under pharmacological treatment is only acceptable if the parents are informed about the possible risks. The most extended treatments used to treat the COVID-19 infection such as azithromycin, hydroxychloroquine sulfate, lopinavir-ritonavir, tocilizumab and methylpredinosolone, are excreted in very small amounts in breast milk [35][36][37][38][39][40][41]. Although no specific studies have been conducted, it seems that most common medicines used for SARS-CoV-2 infection are safe and compatible with breastfeeding, so there are no contraindications or special recommendations to follow regarding the pharmacological treatment that breastfeeding mothers receive.…”

Section: Breastfeeding Advice During the Covid-19 Outbreakmentioning

confidence: 99%

Breastfeeding mothers with COVID-19 infection: a case series

et al. 2020

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Background: The first reports of the Chinese experience in the management of newborns of mothers with SARS-CoV 2 infection did not recommend mother-baby contact or breastfeeding. At present, the most important International Societies, such as WHO and UNICEF, promote breastfeeding and mother-baby contact as long as adequate measures to control COVID-19 infection are followed. In cases where maternal general health conditions impede direct breastfeeding or in cases of separation between mother and baby, health organizations encourage and support expressing milk and safely providing it to the infants. Methods: A series of 22 case studies of newborns to mothers with COVID-19 infection from March 14th to April 14th, 2020 was conducted. Mothers and newborns were followed for a median period of 1.8 consecutive months. Results: Out of 22 mothers, 20 (90.9%) chose to breastfeed their babies during hospital admission. Timely initiation and skin to skin contact at delivery room was performed in 54.5 and 59.1%, respectively. Eighty two percent of newborns to mothers with COVID-19 were fed with breast milk after 1 month, decreasing to 77% at 1.8 months. Six of 22 (37.5%) mothers with COVID-19 required transitory complementary feeding until exclusive breastfeeding was achieved. During follow-up period, there were no major complications, and no neonates were infected during breastfeeding. Conclusions: Our experience shows that breastfeeding in newborns of mothers with COVID-19 is safe with the adequate infection control measures to avoid mother-baby contagion. Supplementing feeding with pasteurized donor human milk or infant formula may be effective, until exclusive breastfeeding is achieved.

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Section: Breastfeeding Advice During the Covid-19 Outbreakmentioning

confidence: 99%

Breastfeeding mothers with COVID-19 infection: a case series

et al. 2020

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“…The present study showed that like adalimumab and infliximab, TCZ was excreted into human breast milk and reached peak concentrations within 3 to 5 days after injection . In addition, breast milk concentrations of TCZ were low compared to serum.…”

Section: Discussionmentioning

confidence: 57%

Clinical application of the dried milk spot method for measuring tocilizumab concentrations in the breast milk of patients with rheumatoid arthritis

et al. 2019

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Aims: Tocilizumab (TCZ), a humanized anti-interleukin-6 receptor monoclonal antibody, is used to treat rheumatic diseases. There is limited information about the administration of TCZ during lactation. The dried spot method, a simple technique for processing biological samples which involves placement of a drop of specimen onto filter paper, has been used in clinical pharmacology to determine various drug concentrations. This study examined the feasibility of sample collection using the dried milk spot (DMS) method for obtaining data about the transfer of TCZ into breast milk. Methods:Concentrations of TCZ determined using DMSs prepared by patients were compared with those using liquid breast milk. Results:In an enzyme-linked immunosorbent assay of TCZ in DMSs, the accuracy ranged from 93.0% to 113.8% and the precision ranged from 0.3% to 8.4%. All concentrations of TCZ were within 15% of the reference value when analyzed on separate days. TCZ in DMSs at room temperature, 4°C, and −20°C were stable for 28 days.Extracted TCZ concentrations from patient-prepared DMSs were strongly correlated with those of liquid samples (r = 0.996). In a pharmacokinetic study, the median (range) maximum and minimum concentrations were 113 ng/mL (68-205) and 8.5 ng/ mL (4.8-13.4), respectively. The milk-to-serum ratio at the trough TCZ concentration of 3 lactating mothers were 0.0015, 0.00082 and 0.0014. Conclusions:The DMS method for measuring TCZ transfer into breast milk may be reliable and feasible, and should contribute to evaluating the safety of breast-fed infants whose mothers receive TCZ during lactation.

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“…Studies on Tocilizumab suggest that there may be no increased risk of congenital malformations but a slightly increased risk of spontaneous miscarriage (25% vs. baseline risk of 12–15%) ( 68 – 72 ). Tocilizumab concentration in breast milk peaks on the third day after treatment administration, with a breast milk to maternal serum concentration ratio ranging from 1:500 to 1:1,000, and infants showing no signs of health problems, developmental delays or adverse events following routine vaccinations ( 73 ). Current phase-III clinical trials are ongoing on satralizumab ( 74 ) and inebilizumab ( 75 ), neither of which are expected to have teratogenic effects in humans, although pregnancy and lactation risks need to be further investigated.…”

Section: Discussionmentioning

confidence: 99%

Pregnancy and Neuromyelitis Optica Spectrum Disorder – Reciprocal Effects and Practical Recommendations: A Systematic Review

et al. 2020

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Introduction: Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory disorder of the central nervous system characterized by severe, antibody-mediated astrocyte loss with secondary demyelination and axonal damage, predominantly targeting optic nerves and the spinal cord. Recent publications have alluded to increased disease activity during pregnancy, and adverse maternal and fetal outcomes in patients with NMOSD. Our objective was to systematically review published literature to help counsel and manage women with NMOSD contemplating pregnancy. Methods: We searched five databases including MEDLINE and EMBASE, for English-language publications describing pregnancies in women with NMOSD. Article selection, data extraction, and risk-of-bias assessment using Joanna Briggs' critical appraisal tool for case reports and case series, were performed in duplicate. Pooled incidences were calculated where possible, and a narrative summary was provided. Results: Of 2,118 identified titles, 22 case reports and seven case series, representing 595 pregnancies in 389 women, were included. The mean maternal age was 28.12 ± 5.19 years. At least 20% of cases were first diagnosed during pregnancy. There were no maternal deaths. Pooled estimates for clinical outcomes could not be obtained due to inadequate reporting. NMOSD-related disability and relapses increased considerably during pregnancy and especially in the immediate postpartum period. Although a high proportion of early pregnancy losses were reported, an association with disease activity or therapeutic interventions could not be established. Apart from one publication which reported an increased risk of preeclampsia, there was no increase in adverse obstetric outcomes including preterm birth, fetal growth restriction or congenital malformations. Initial attacks and relapses were successfully managed with oral or intravenous D'Souza et al. NMOSD and Pregnancy: Systematic Review corticosteroids and immunosuppressants, and refractory cases with immunoglobulin, plasma exchange and immunoadsorption. Conclusion: Increased NMOSD-related disability and relapses during pregnancy the postpartum period may respond to aggressive management with corticosteroids and immunosuppressants such as azathioprine, which are safely administered during pregnancy and lactation. Emerging safety data on monoclonal antibodies during pregnancy, make these attractive options, while intravenous immunoglobulin, plasma exchange and immunoadsorption can be safely used to treat severe relapses. The complex interplay between NMOSD and pregnancy outcomes would be best understood through prospective analysis of data collected through an international registry. Disclosure: Dalia Rotstein has served as a consultant or speaker for Alexion and Roche. She has received research support from Roche Canada. Rohan D'Souza has served as a consultant and speaker for Ferring Canada Inc and Ferring Global Inc, on topics unrelated to this manuscript. The other authors have no relevant relationships to disclose.

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Tocilizumab concentrations in maternal serum and breast milk during breastfeeding and a safety assessment in infants: a case study

Cited by 41 publications

References 6 publications

Breastfeeding mothers with COVID-19 infection: a case series

Breastfeeding mothers with COVID-19 infection: a case series

Clinical application of the dried milk spot method for measuring tocilizumab concentrations in the breast milk of patients with rheumatoid arthritis

Pregnancy and Neuromyelitis Optica Spectrum Disorder – Reciprocal Effects and Practical Recommendations: A Systematic Review

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