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
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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
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Sabah Obstetrics
Shared Care Guidelines (2018)
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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.
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https://www.drugs.com/breastfeeding/carbimazole.html
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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.
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UptoDate: Methimazole
(Drug Information)
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·
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).
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Uptodate
Hyperthyroidism during pregnancy: Treatment
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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.
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Drugs in Pregnancy
and Lactation (Briggs & Freeman 2015)
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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).
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