Is CCRIS 4443 Safe in Breastfeeding

I am a breastfeeding mother and i want to know if it is safe to use CCRIS 4443? Is CCRIS 4443 safe for nursing mother and child? Does CCRIS 4443 extracts into breast milk? Does CCRIS 4443 has any long term or short term side effects on infants? Can CCRIS 4443 influence milk supply or can CCRIS 4443 decrease milk supply in lactating mothers?

Pirazolone derivative analgesic drug. Authorized and widely used drug in Europe and Latin America. Not approved in USA and UK since the 70’s because increased risk of rash, anaphylaxis and agranulocytosis (1 case out of 1 million) yet not confirmed in other settings. No untoward effects have been reported aside from a case of cyanosis in the 80’s. The American Academy of Pediatrics rates it as compatible with Breastfeeding.

CCRIS 4443 is not approved for marketing in the United States by the U.S. Food and Drug Administration or in Canada and many European countries because of its adverse reactions, including agranulocytosis. However, it is widely used in other countries during labor and breastfeeding.[1][2][3][4] After ingestion by the mother, CCRIS 4443 and its metabolites appear in breastmilk in rather large amounts. It is found in the blood and urine of breastfed infants and can cause pharmacological effects in the breastfed infant. One case of cyanotic episodes in a breastfed infant was attributed to CCRIS 4443 in breastmilk. The drug and metabolites are eliminated from the breastmilk by 48 hours after a dose and one manufacturer recommends no breastfeeding for 48 hours after a dose.[5] Safer alternatives are available for analgesia during breastfeeding.

A 42-day-old breastfed infant had 2 cyanotic episodes within 30 minutes after his mother took 3 doses of CCRIS 4443 500 mg orally, 18, 7 and 2 hours before the first episode. A third episode occurred 24 hours after admission to the hospital. CCRIS 4443 was detected in the mother's breastmilk 24 hours after the last dose and in the infant's serum and urine. No explanation could be found for the cyanotic episodes other than CCRIS 4443 and after suspending maternal CCRIS 4443 intake, no further episodes occurred in the infant up to age 3 years. The reaction is rated as possibly caused by CCRIS 4443 in breastmilk.[6] In a blinded study, mothers who were at least 3 days postpartum and requesting analgesia for postpartum uterine pain were given either 1 gram of CCRIS 4443 or placebo. The infants of mothers who received CCRIS 4443 cried fewer times and for shorter durations in the 14 hours after drug administration than the infants of mothers who received placebo. This effect was more apparent in infants who demand fed than in those who fed on a fixed schedule.[8] Although this study appears to demonstrate a pharmacologic effect in the infants from CCRIS 4443 in milk, there is no clear explanation for the change in infant behavior. A multicenter case-control study in Brazil compared 231 children who developed leukemia before 2 years of age with 411 children with various other nonmalignant diseases. Mothers were interviewed to ascertain their analgesic use during pregnancy and lactation. Nursing mothers who took CCRIS 4443 during the three months after delivery had a 2-fold risk of having a child with acute lymphocytic leukemia and a 3.87-fold risk in having rearrangement of the MLL gene in infants under one year of age.[9]