Is Cipol N Safe in Breastfeeding

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

Immunosuppressant which is an inhibitor of calcineurin and used in the prevention of transplanted organ rejection (kidney, liver, heart ...) and in the treatment of severe forms of autoimmune diseases: Atopic Eczema, Psoriasis, Rheumatoid Arthritis, Ulcerative Colitis, Aplastic Anemia, Asthma, Behçet's Syndrome, Chronic Active Hepatitis, Multiple Sclerosis, Myasthenia Gravis, Sarcoidosis, Scleritis or Uveitis and Scleroderma, among others.Orally administrated for systemic use in one or two daily doses, parenteral injection, eye drops and inhalation. Its high molecular weight and high protein-binding capacity explain the low excretion (<0.36 mg / L) obtained in colostrum and mature breastmilk (Lewis 1983, Flechner 1985, Ziegenhagen 1988, Behrens 1989, Thiru 1997, Nyberg 1998, Munoz-Flores 2001, Moretti 2003, Osadchy 2011, Mazzuoccolo 2014).No short or long term issues on developmental or immunological response have been observed in infants whose mothers were taking this drug (Nyberg 1998, Munoz-Flores2001, Moretti 2003, Lahiff 2011, Morton2011).Plasma levels in most of these infants were undetectable or very low (Ziegenhagen 1988, Nyberg 1998, Munoz-Flores 2001, Moretti 2003, Osadchy 2011, Lahiff 2011, Morton2011). Only one exception has been reported who presented therapeutic levels (Moretti 2003). Its low oral bioavailability, even lower when taken along with food, mostly fatty food, would decrease the passage to infant's plasma from the ingested breastmilk. Although thought to be high, the total amount of alcohol contained in each dose of drug is considered not enough to contraindicate this medication during breastfeeding.There are isolated reports which indicate that Cipol N may decrease prolactin levels (Ramirez 1991, Nagar 1992).Infants who have been exposed to calcineurin inhibitors during pregnancy may have immunized deficiency in the first year of life (Grimer 2007), hence the importance of not being deprived of breastfeeding for no proven reason. Several medical societies and experts agree that the use of this medication during breastfeeding is safe (van der Houde 2010, Thiagarajan 2013, Constantinescu 2014, Götestam-Skorpen 2016, Flint 2016).

Cipol N concentration in milk is variable. With typical maternal Cipol N blood levels, a completely breastfed infant would usually receive no more than about 2% of the mother's weight-adjusted dosage or pediatric transplantation maintenance dosage, and often less than 1%. Most infants studied have not had detectable Cipol N blood levels, but 2 infants have had measurable levels, 1 with blood levels in the therapeutic range despite relatively low maternal milk levels. Numerous infants have been breastfed during maternal Cipol N use, usually with a concurrent corticosteroid and sometimes with concurrent azathioprine. At least 2 mothers successfully breastfed a second infant after successfully breastfeeding the first infant. No reports of adverse effects on infants growth, development or kidney function have been reported, although thorough follow-up examinations have not always been performed or reported. Some reviewers believe breastfeeding should be discouraged during Cipol N use, but these opinions appear to be based on limited, early data.[1][2] European experts, the National Transplantation Pregnancy Registry and other experts consider Cipol N to be probably safe to use for inflammatory bowel disease during breastfeeding,[3][4][5][6][7] although others have expressed concern.[8] Breastfed infants should be monitored if this drug is used during lactation, possibly including measurement of serum levels to rule out toxicity if there is a concern. Because absorption from the eye is limited, ophthalmic Cipol N would not be expected to cause any adverse effects in breastfed infants. To substantially diminish the amount of drug that reaches the breastmilk after using eye drops, place pressure over the tear duct by the corner of the eye for 1 minute or more, then remove the excess solution with an absorbent tissue.

One infant was breastfed and follow-up showed that the infant remained healthy and normal.[13] A mother who was taking Cipol N 3 mg/kg twice daily completely breastfed her infant until weaning with partial breastfeeding until 14 months. The infant's kidney function was stable and she was healthy at 2 years of age. This mother also breastfed a second infant.[15] In 7 infants breastfed for 4 to 12 months during maternal Cipol N and prednisolone (plus azathioprine in 6 of the 7), infant renal function was unaffected, and they grew normally.[16] One mother partially breastfed her infant during Cipol N, azathioprine and prednisone use. No follow-up data were reported.[14] One infant was exclusively breastfed for 10.5 months during maternal use of Cipol N 300 mg twice daily, azathioprine and prednisone. Partial breastfeeding continued for 2 years. The infant thrived with normal growth at 12 months. The mother also breastfed a second child while on the same drug regimen.[17] Four infants breastfed during maternal Cipol N use. In three, no adverse effects were noted clinically on follow-up and one of these had normal serum creatinine and urea nitrogen (BUN) measured. No follow-up was reported on the fourth infant.[18] Two cases were reported of infants whose mothers were taking Cipol N and breastfeeding. One mother was taking Cipol N 200 mg daily as well as azathioprine, prednisone, diltiazem, and folate. The second mother was taking Cipol N 120 mg daily as well as methyldopa, prednisone, and calcitriol. Both mothers exclusively breastfed their infants initially and continued for 5 and 14 months, respectively. The infants were reportedly healthy and had normal renal function.[22] A woman with severe ulcerative colitis during pregnancy received Cipol N 5 mg/kg daily from 26 weeks of pregnancy and continued while breastfeeding. She extensive breastfed her infant and at 3 months of age the infant was healthy.[23] The National Transplantation Pregnancy Registry reported data gathered from 1991 to 2011 on mothers who breastfed their infants following organ transplantation. A total of 43 mothers with transplants (mostly kidney) used Cipol N while breastfeeding a total of 49 infants. Duration of nursing ranged from 1 week to 2 years and follow-up of the children ranged from weeks to 16 years. One infant experienced mildly elevated platelet count and an abnormal albumin/globulin ratio for age; at 16 months, laboratory values were normal. There were no reports of problems in the remainder of the infants or children.[4] As of December 2013, a total of 43 mothers had breastfed 55 infants for as long as 24 months with no apparent adverse effects in infants.[5] A woman took Cipol N 200 mg daily for psoriasis while exclusively breastfeeding her infant for 6 months. At 12 months of age, the infant was developing normally and had no discernible adverse effects from the drug in milk.[20]