Tofacitinib Appears in Breast Milk and is Contraindicated in Breast Feeding.

The JAK Inhibitor Tofacitinib Should be Avoided During Breastfeeding.

Many organizations recommend that women avoid breastfeeding if they are using JAK inhibitors. This recommendation comes about mainly based on studies in animals.  In lactating rats, for example, research showed that the concentration of tofacitinib in milk was actually two times higher than the concentrations in the blood. To date, there had been no really good human data.

For tofacitinib, the company that manufacturers the medication (Pfizer)  recommends that breastfeeding in humans should be avoided for at least 18 h after the last dose. The half life of the drug is 3 hours and so 18 hours means that about 6 half lives would take place by this 18 hour time point.  

Julsgaard M et al. 2023

In a new report in The Lancet Gastroenterology and Hepatology authors report data on tofacitinib concentrations in breast milk.

The patient studied was a 39 year old woman with inflammatory bowel disease who was started on tofacitinib 10 mg twice daily. After starting tofacitinib, she stopped breastfeeding her daughter. For the next 37 days, milk samples were taken. On three occasions, both plasma and milk samples were collected at the same time at 4, 5, and 8 h after intake of tofacitinib.

Results

 The drug tofacitinib was detected in all 37 milk samples and in three plasma samples. The highest plasma tofacitinib concentrations occurred at around 1 hour. The highest milk concentrations observed were within 1 h and 5·5 h after intake of tofacitinib 10 mg. The highest tofacitinib milk concentration was observed 4 h after intake. The lowest measured tofacitinib milk concentration was observed 14 h after intake.

After 4 hours of intake, tofacitinib concentrations were higher in the plasma than in milk. However, after 5 hours the opposite finding occurred- milk concentrations became higher than plasma concentrations. The same was true at 8 hours.

 The authors point out that tofacitinib accumulates well in breast milk and this is different than for other drugs like methotrexate and azathioprine where milk concetration generally are lower than for plasma.

Overall the authors concluded that babies consuming breast milk would receive about 3.4 % of the maternal dose of tofacitinib. The authors feel these  observations support the recommendation to avoid breastfeeding among people treated with tofacitinib due to the risk of infant exposure. A very low concentration was seen in the lactating woman 14 h after oral intake. The manufacturers recommend avoiding breastfeeding for at least 18 h after intake of tofacitinib. This recommendation is reasonable given that the mean tofacitinib half-life is approximately 3·2 h.

REFERENCE

Julsgaard M et al. Tofacitinib concentrations in plasma and breastmilk of a lactating woman with ulcerative colitis. The Lancet Gastroenterology and Hepatology. May 2023