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Tocilizumab use while Breastfeeding

Drugs containing Tocilizumab: Actemra

Medically reviewed by Drugs.com. Last updated on Apr 19, 2020.

Tocilizumab Levels and Effects while Breastfeeding

Summary of Use during Lactation

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.[1,2] 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%.[3-5] 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%.[6] None of the studies measured IgG activity.

Drug Levels

Maternal Levels. A woman with rheumatoid arthritis resumed tocilizumab at 5 weeks postpartum at a dose of 400 mg intravenously every month. Breastmilk concentration were determined at 13, 18 and 22 weeks postpartum. The highest tocilizumab concentrations in milk occurred 3 days after the injection and was 68.2 mcg/L. The lowest concentration was <0.2 mcg/L at 34 days after the dose. Another mother resumed monthly tocilizumab 400 mg intravenously 9 days postpartum. Breastmilk concentration were measured after the doses at 35 and 49 weeks postpartum. The highest concentrations occurred 3 days after the injection at 148.2 mcg/L and fell to 9 mcg/L after 28 days.[7]

A woman was treated for adult onset Still's disease with tocilizumab 400 mg every 4 weeks, prednisolone 5 mg daily and tacrolimus 2 mg daily throughout pregnancy. The tocilizumab concentration in milk at 5 days postpartum (32 days after the previous dose) was 3.4 mcg/L. Another dose was given at 6 days postpartum. At about 19 hours later the milk level was 55.4 mcg/L; at 2.8 days after the dose the milk level was 215 mcg/L; at 18 days after the dose, the milk level was 70.4 mcg/L; at 28 days after the dose and before the next dose, the level was 3.8 mcg/L. Another dose was given on day 28. At about an hour after this dose the milk level was 48 mcg/L; 3 days later, the milk level was 205 mcg/L; at 11 days after the dose, the milk level was 127 mcg/L; at 17 days after the dose it was 65 mcg/L, and at 28 days after the dose it was 4.9 mcg/L.[8] In addition to these two patients, the same authors measured trough tocilizumab concentrations in two other women with rheumatoid arthritis receiving the drug 400 mg every 4 weeks, using dried milk spots. One mother had a trough milk level of 12.2 mcg/L after 10 doses of tocilizumab and another had a trough milk level of 4.9 mcg/L after one dose.[9]

A woman with Takayasu arteritis was receiving tocilizumab 162 mg subcutaneously every 2 weeks. She collected breastmilk at 5 unspecified times during therapy. All milk samples contained between 3 and 6 mcg/L of tocilizumab.[10]

Infant Levels. A woman was treated for adult onset Still's disease with tocilizumab 400 mg every 4 weeks, prednisolone 5 mg daily and tacrolimus 2 mg daily throughout pregnancy. She breastfed almost exclusively postpartum while tocilizumab was continued. The concentration in the umbilical cord blood was 683 mcg/L at delivery 28 days after the previous tocilizumab dose. Even though the infant was almost completely breastfed, the tocilizumab concentration in the infant's serum 5 days after delivery decreased to 177 mcg/L. By 4 weeks after delivery, tocilizumab was not detectable in the infant's serum. Another dose of tocilizumab was give at 28 days postpartum. At 55 days postpartum, tocilizumab was not detected in the infant's serum.[7]

Effects in Breastfed Infants

A pregnancy registry in Japan reported that two mothers resumed tocilizumab therapy while nursing their infants. No adverse events were reported in the infants, but details regarding extent of nursing, infant age, etc. are lacking.[11]

Two women in Japan were treated with intravenous tocilizumab 400 mg monthly for rheumatoid arthritis while they reportedly breastfed their infants exclusively for 9 and 11 months, respectively. Neither infant experienced any adverse effects from the drugs and received all routine immunizations, including BCG without any adverse consequences.[7] It is possible that these two mothers are the same as those reported above.

Three women with rheumatoid arthritis became pregnant while taking tocilizumab. The drug was stopped for the remainder of the pregnancy, but resumed (dose not stated) postpartum. They breastfed their infants (extent not stated). No infants had any adverse effects during the first year.[11]

A woman was treated for adult onset Still's disease with tocilizumab 400 mg every 4 weeks, prednisolone 5 mg daily and tacrolimus 2 mg daily throughout pregnancy and postpartum. She breastfed almost exclusively postpartum while tocilizumab was continued every 4 weeks. Her infant developed no serious infections and demonstrated no developmental delay as of 6 months of age. The infant's routine childhood vaccinations included Haemophilus influenzae type b conjugate, hepatitis B, diphtheria, pertussis, tetanus, inactivated polio, and 13-valent pneumococcal polysaccharide vaccines. No live vaccines were given for the first 6 months postpartum. No adverse effects such as serious infections or immune reactions were seen.[8]

Effects on Lactation and Breastmilk

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

Alternate Drugs to Consider

(Rheumatoid Arthritis) Adalimumab, Certolizumab Pegol, Etanercept, Infliximab

References

1.
Götestam 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. [PubMed: 26888948]
2.
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]
3.
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. [PubMed: 16280560]
4.
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. 2019;32:3016–9. [PubMed: 29587541]
5.
Rodríguez-Camejo C, Puyol A, Fazio L, et al. Impact of Holder pasteurization on immunological properties of human breast milk over the first year of lactation. Pediatr Res. 2020;87:32–41. [PubMed: 31288249]
6.
Rodríguez-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. [PubMed: 28586632]
7.
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. [PubMed: 29635528]
8.
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;58:1505–7. [PubMed: 30945743]
9.
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. [PubMed: 30968569]
10.
Moriyama M, Wada Y, Minamoto T, et al. Unexpectedly lower proportion of placental transferred tocilizumab relative to whole immunoglobulin G: A case report. Scand J Rheumatol. 2020;49:165–6. [PubMed: 31436129]
11.
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. [PMC free article: PMC5020345] [PubMed: 26873562]

Substance Identification

Substance Name

Tocilizumab

CAS Registry Number

375823-41-9

Drug Class

Breast Feeding

Lactation

Antibodies, Monoclonal, Humanized

Antirheumatic Agents

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