Carbimazole and Breastfeeding

Carbimazole and Breastfeeding

Reference	Description
New Zealand Data Sheet. Carbimazole 5 mg Tablet. Available at: https://www.medsafe.govt.nz/Profs/Datasheet/n/Neo-Mercazoletab.pdf   Chapter 4 - Feline Hyperthyroidism, Editor(s): Edward C. Feldman, Richard W. Nelson, Claudia E. Reusch, J. Catharine R. Scott-Moncrieff, Canine and Feline Endocrinology (Fourth Edition),W.B. Saunders, 2015, Pages 136-195, Available at: https://doi.org/10.1016/B978-1-4557-4456-5.00004-3	Carbimazole is a prodrug which is converted to it’s active metabolite methimazole in the blood by hydrolysis and enzymatic decarboxylation.  10 mg of carbimazole is equivalent to 6 mg of methimazole. Carbimazole:Methimazole = 5:3
Sabah Obstetrics Shared Care Guidelines (2018)	ü  Carbimazole in doses up to 20-30mg/d is safe for lactating mothers and infants. ü  2nd line: PTU at 300mg/d (concerns of hepatotoxicity.) ü  To administer ATDs (antithyroid) following a feeding, in divided doses. ü  Refer all babies born to mothers with hyperthyroidism to Paediatric team. ü  Type 1 DM, Grave’s disease in remission and chronic viral hepatitis: ➢   at risk of developing post-partum thyroiditis ➢   To measure TSH level at 6-12 weeks gestation and 6 months postpartum ü  Women known to be thyroid antibody positive:        ➢    To measure TSH level at 6-12 weeks gestation and 6 months                 postpartum, or as clinically indicated.
https://www.drugs.com/breastfeeding/carbimazole.html	Doses of carbimazole of 30 mg daily or 50 mg weekly have not adversely affected the few breastfed infants studied. Carbimazole is a prodrug for methimazole which has been studied extensively during breastfeeding; maternal methimazole therapy does not affect thyroid function or intellectual development in breastfed infants with doses up to 20 mg daily. Some experts now recommend that methimazole should be considered the antithyroid drug of choice in nursing mothers.[1-3]   The American Thyroid Association recommends only monitoring infants for appropriate growth and development during routine pediatric health and wellness evaluations and routine assessment of serum thyroid function in the child is not recommended.[4] Rare idiosyncratic reactions (e.g., agranulocytosis) might occur, and the infant should be watched for signs of infection. Monitoring of the infant's complete blood count and differential is advisable if there is a suspicion of a drug-induced blood dyscrasia.
UptoDate: Methimazole (Drug Information)	·   Methimazole is present in breast milk. ·   Information related to the presence of methimazole in breast milk is available from 6 lactating women with Graves disease following a single dose of methimazole 15 mg. Peak methimazole concentrations were 0.32 ± 0.10 mcg/mL (breast milk) and 0.31 ± 0.09 mcg/mL (maternal plasma) 2 hours after administration. The half-life of methimazole was calculated to be 4.2 ± 0.8 hours in breast milk. Twelve hours after the dose, breast milk concentrations of methimazole had decreased to 0.03 ± 0.01 mcg/mL (Abe 1995). ·   Based on available data, thyroid function is normal in infants exposed to lower doses of methimazole via breast milk. In addition, IQ and physical development up to 74 months of age were not impaired in a long-term study of breastfed infants whose mothers were receiving treatment with methimazole. ·   The treatment of hyperthyroidism in breastfeeding patients is the same as non-breastfeeding females. ·   The lowest effective dose should be used; maternal doses of methimazole ≤20 mg/day are advised in breastfeeding patients. ·   Infants exposed to antithyroid medications via breast milk should be monitored for adequate growth and development; routine tests of thyroid function are not recommended (ATA [Alexander 2017]). ·   Taking the dose of methimazole after breastfeeding may help decrease potential infant exposure by providing a 3- to 4-hour interval before the next feed (Amino 2020).
Uptodate Hyperthyroidism during pregnancy: Treatment	o   Given the concerns about potential propylthiouracil (PTU)-associated hepatotoxicity, we suggest methimazole rather than PTU for nursing mothers. o   Methimazole should be administered following a feeding in divided doses. When the maternal dose of methimazole is >20 mg daily, infants should have thyroid function tests assessed after one and three months. o   PTU is less soluble than methimazole and is more bound to plasma proteins, whereas methimazole is free in serum, so that relatively more methimazole reaches the infant via breast milk [54]. Nonetheless, there is little difference in serum thyroid hormone concentrations or thyroid function in infants of mothers given moderate doses of either drug. As an example, in a study of 139 mothers taking up to 20 mg methimazole daily, thyroid function, growth, and development of their breastfed infants were normal [55]. Similar results were seen in a study of mothers taking PTU [56]. o   There has yet to be a report of agranulocytosis or liver disease in an infant who was nursed by a woman taking PTU or methimazole.
Drugs in Pregnancy and Lactation (Briggs & Freeman 2015)	Methimazole is excreted into breast milk (54–57). In a patient given 10 mg of radiolabeled carbimazole (converted in vivo to methimazole), the milk:plasma ratio was a fairly constant 1.05 over 24 hours (54). This represented about 0.47% of the given radioactive dose. In a second study, a patient was administered 2.5 mg of methimazole every 12 hours (55). The mean milk:plasma ratio was 1.16, representing 16–39 mcg of methimazole in the daily milk supply. Extrapolation of these results to a daily dose of 20 mg indicated that approximately 3 mg/day would be excreted into the milk.  Five lactating women were given 40 mg of carbimazole, producing a mean milk:plasma ratio at 1 hour of 0.72 (56). For the 8-hour period after dosing, the milk:plasma ratio was 0.98. A new radioimmunoassay was used to measure methimazole milk levels after a single 40-mg oral dose in four lactating women. The mean milk:plasma ratio during the first 8 hours was 0.97, with 70 mcg excreted in the milk (56).  A 1987 publication described the results of carbimazole therapy in a woman breastfeeding twins (57). Two months after delivery, the mother was started on carbimazole, 30 mg/day. The dose was decreased as she became euthyroid. Three paired milk:plasma levels revealed ratios of 0.30–0.70. The mean free methimazole concentration in milk, determined between 2 and 16 weeks of therapy, was 43 ng/mL (range 0–92 ng/mL). Peak milk levels occurred 2–4 hours after a dose. Mean plasma levels in the twins were 45 ng/mL (range 0–105 ng/mL) and 52 ng/mL (range 0–156 ng/mL), with the highest concentrations occurring while the mother was taking 30 mg/day. No evidence of thyroid suppression was found clinically or after thyroid function tests in the nursing twins (57).  Two other studies also found no effect on clinical status or thyroid function in nursing infants of mothers taking carbimazole or methimazole (58,59). In one report, no adverse effects were observed during a 3-week study of 11 infants whose mothers were taking carbimazole 5–15 mg/day (58). In the other study, normal thyroid function in 35 nursing infants, whose mothers were taking methimazole, was documented over periods ranging from 1 to 6 months (59). Most mothers were taking 5–10 mg/day, but six received 20 mg/day for 1 month and then tapered to 5 mg/day.  Because the amounts found in some studies may cause thyroid dysfunction in the nursing infant, methimazole and carbimazole have, in the past, been considered contraindicated during lactation. If antithyroid drug therapy was required, PTU was considered the treatment of choice, partially because PTU is ionized at physiologic pH and because 80% of the drug is protein bound (60). Methimazole is neither ionized nor protein bound, but small doses of methimazole (e.g., 10–20 mg/day or less) do not appear to pose a major risk to the nursing infant if thyroid function is monitored at frequent (e.g., weekly or biweekly) intervals (58–60). In 2000, a long-term study confirmed the lack of toxicity in infants of mothers being treated with methimazole (61). A total of 139 thyrotoxic lactating mothers and their nursing infants were studied, 51 of the mothers were treated with methimazole during pregnancy and continued their treatment during lactation. The other 88 women started methimazole therapy during lactation with 10–20 mg/day for 1 month, 10 mg/day during the second month, then 5–10 mg/day thereafter. Methimazole serum levels in six infants whose mothers were taking 20 mg/day were <0.03 mcg/mL, 2 hours after breastfeeding. No effects on infant thyroid function were detected at various times up to 12 months. In a blinded assessment, the total IQ scores, including verbal and performance IQ, of 14 children (age 48–74 months) exposed to methimazole in milk did not differ from 17 nonexposed controls (61). The American Academy of Pediatrics classifies methimazole and carbimazole as compatible with breastfeeding (62).

 All info accessed on 24/08/2021 (J Ho)