The Basics
What is Tocilizumab?
Can be prescribed for rheumatoid arthritis, juvenile idiopathic arthritis (JIA) or giant cell arteritis. Tocilizumab works by blocking the effects of IL-6, a protein that can cause inflammation.
Brand names for Tocilizumab
Actemra
How Tocilizumab is classified
Antibodies – Monoclonal (Humanized), Antirheumatic Agents
Tocilizumab During Pregnancy
Tocilizumab pregnancy category
Category N/ANote that the FDA has deprecated the use of pregnancy categories, so for some medications, this information isn’t available. We still think it’s useful to list historical info, however, given what a common proxy this has been in the past.
What we know about taking Tocilizumab while pregnant
Information on pregnancy outcomes in women exposed to tocilizumab during pregnancy is limited, but it posed no demonstrable risk to the fetus in animal reproduction studies.* There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to ACTEMRA during pregnancy. Physicians are encouraged to register patients and pregnant women are encouraged to register themselves by calling 1-877-311-8972. Risk Summary The limited available data with ACTEMRA in pregnant women are not sufficient to determine whether there is a drug-associated risk for major birth defects and miscarriage. Monoclonal antibodies, such as tocilizumab, are actively transported across the placenta during the third trimester of pregnancy and may affect immune response in the in utero exposed infant [see Clinical Considerations]. In animal reproduction studies, intravenous administration of tocilizumab to Cynomolgus monkeys during organogenesis caused abortion/embryo-fetal death at doses 1.25 times and higher than the maximum recommended human dose by the intravenous route of 8 mg per kg every 2 to 4 weeks. The literature in animals suggests that inhibition of IL-6 signaling may interfere with cervical ripening and dilatation and myometrial contractile activity leading to potential delays of parturition . Based on the animal data, there may be a potential risk to the fetus. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.
Taking Tocilizumab While Breastfeeding
What are recommendations for lactation if you're taking Tocilizumab?
Little information is available on the clinical use of tocilizumab during breastfeeding. Only small amounts of tocilizumab were detected in breastmilk after intravenous doses in several mothers, and a few mothers have breastfed their infants with undetectable infant serum levels and no reported adverse effects. If tocilizumab is required by the mother, it is not a reason to discontinue breastfeeding.[1] Until more data become available, tocilizumab should be used with caution during breastfeeding, especially while nursing a newborn or preterm infant. Tocilizumab is a human immunoglobulin G1 (IgG1) kappa antibody. Holder pasteurization (62.5 degrees C for 30 minutes) decreases the concentration of endogenous immunoglobulin G by up to 79%.[2][3] A study of 67 colostrum samples that underwent Holder pasteurization found that IgG amounts decreased by 34 to 40%. Specific IgG subclasses decreased by different amounts, with IgG1 activity decreasing by about 37%.[4] None of the studies measured IgG activity.
Maternal / infant drug levels
Little information is available on the clinical use of tocilizumab during breastfeeding. Only small amounts of tocilizumab were detected in breastmilk after intravenous doses in several mothers, and a few mothers have breastfed their infants with undetectable infant serum levels and no reported adverse effects. If tocilizumab is required by the mother, it is not a reason to discontinue breastfeeding.[1] Until more data become available, tocilizumab should be used with caution during breastfeeding, especially while nursing a newborn or preterm infant. Tocilizumab is a human immunoglobulin G1 (IgG1) kappa antibody. Holder pasteurization (62.5 degrees C for 30 minutes) decreases the concentration of endogenous immunoglobulin G by up to 79%.[2][3] A study of 67 colostrum samples that underwent Holder pasteurization found that IgG amounts decreased by 34 to 40%. Specific IgG subclasses decreased by different amounts, with IgG1 activity decreasing by about 37%.[4] None of the studies measured IgG activity.
Possible effects of Tocilizumab on milk supply
Relevant published information was not found as of the revision date.
Possible alternatives to Tocilizumab
None listed
List of References
Lactation sources: Drugs and Lactation Database (LactMed) [Internet]. Bethesda (MD): National Library of Medicine (US); 2006-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK501922/*Hoeltzenbein M, Beck E, Rajwanshi R, et al. Tocilizumab use in pregnancy: Analysis of a global safety database including data from clinical trials and post-marketing data. Semin Arthritis Rheum. 2016;46(2):238-245. doi:10.1016/j.semarthrit.2016.05.004 1. Gotestam Skorpen C, Hoeltzenbein M, Tincani A et al. The EULAR points to consider for use of antirheumatic drugs before pregnancy, and during pregnancy and lactation. Ann Rheum Dis. 2016;75:795-810. PMID: 26888948
2. Koenig A, de Albuquerque Diniz EM, Barbosa SF et al. Immunologic factors in human milk: The effects of gestational age and pasteurization. J Hum Lact. 2005;21:439-43. PMID: 16280560
3. Adhisivam B, Vishnu Bhat B, Rao K et al. Effect of Holder pasteurization on macronutrients and immunoglobulin profile of pooled donor human milk. J Matern Fetal Neonatal Med. 2018;1-4. PMID: 29587541
4. Rodriguez-Camejo C, Puyol A, Fazio L et al. Antibody profile of colostrum and the effect of processing in human milk banks: Implications in immunoregulatory properties. J Hum Lact. 2018;34:137-47. PMID: 28586632
5. Saito J, Yakuwa N, Takai C et al. Tocilizumab concentrations in maternal serum and breast milk during breastfeeding and a safety assessment in infants: A case study. Rheumatology (Oxford). 2018;57:1499-501. PMID: 29635528
6. Saito J, Yakuwa N, Kaneko K et al. Tocilizumab during pregnancy and lactation: drug levels in maternal serum, cord blood, breast milk and infant serum. Rheumatology (Oxford). 2019. PMID: 30945743
7. Saito J, Yakuwa N, Kaneko K et al. Clinical application of the dried milk spot method for measuring tocilizumab concentrations in the breast milk of patients with rheumatoid arthritis. Int J Rheum Dis. 2019;22:1130-7. PMID: 30968569
8. Nakajima K, Watanabe O, Mochizuki M et al. Pregnancy outcomes after exposure to tocilizumab: A retrospective analysis of 61 patients in Japan. Mod Rheumatol. 2016;26:667-71. PMID: 26873562
9. Salonga A, Chay J, Nicholls D. A case series of patients with rheumatoid arthritis exposed to tocilizumab during pregnancy. Intern Med J. 2018;48:26-7. Abstract P50.
Disclaimer: This material is provided for educational purposes only and is not intended for medical advice, diagnosis, or treatment. Consult your healthcare provider with any questions.
