毒理性
◉ 母乳喂养期间使用总结:卡比马唑未在美国获得食品药品监督管理局的市场批准,但在其他国家可用。在研究的少数母乳喂养婴儿中,每日30毫克或每周50毫克的卡比马唑剂量并未产生不利影响。卡比马唑是甲巯咪唑的前药,甲巯咪唑在母乳喂养期间已经进行了广泛研究;母亲使用甲巯咪唑治疗并未影响甲状腺功能或母乳喂养婴儿的智力发育,剂量高达每日20毫克。一些专家现在建议,在哺乳期母亲中应考虑将甲巯咪唑作为抗甲状腺药物的首选。
美国甲状腺协会建议只监测婴儿在常规儿科健康和福祉评估期间的适当生长和发育,并不建议常规评估儿童的血清甲状腺功能。罕见的特异质反应(例如,粒细胞缺乏症)可能会发生,应观察婴儿是否有感染的迹象。如果怀疑有药物引起的血液病,建议监测婴儿的完整血细胞计数和分类。
◉ 对母乳喂养婴儿的影响:11位母亲在怀孕期间口服卡比马唑,剂量为每日5至20毫克,在母乳喂养期间为每日5至15毫克(程度未说明)。12名婴儿(包括一对双胞胎)在出生后第4天的血清甲状腺素(T4)浓度均未低于正常下限。在出生后前21天内的不同时间测量时,所有婴儿的促甲状腺激素(TSH)浓度均正常。
4位妇女每日接受10至20毫克卡比马唑。在出生后第4、7、10、42天以及3个月和6个月时采集婴儿血样。3名婴儿的甲状腺功能正常。一名婴儿在前10天的TSH升高。
一位双胞胎母亲在分娩后2个月开始服用每日30毫克卡比马唑。随着她达到正常甲状腺状态,剂量降低。婴儿进行了母乳喂养(程度未说明),并在接下来的4个月内进行了临床和实验室检查。没有甲状腺功能改变的证据。
15位母亲在怀孕期间接受了12至40周的卡比马唑10至20毫克/日治疗,其中9位在2至26周的哺乳期间继续服用该药物。他们的婴儿被监测了长达18个月。在这段时间内,婴儿的甲状腺功能正常,单个婴儿的平均值范围如下:TSH 1.4至5.9毫单位/L,游离T3 6.2至9.3皮摩尔/L和T4 104至189纳米摩尔/L。在2至18个月的时间间隔内进行的身体检查显示,所有接受卡比马唑的婴儿均正常,6名在18个月时接受评估的婴儿的格里菲斯心理发展量表评分正常。
一位母亲在怀孕和产后期间每周一次服用卡比马唑50毫克。她的婴儿在前84天接受了纯母乳喂养,并在出生后前4个月进行了临床和实验室检查。尽管婴儿的肌张力和深腱反射略有增加,且容易烦躁,但血清甲状腺激素水平正常,生长也正常。没有观察到低甲状腺症状或体征。
◉ 对泌乳和母乳的影响:截至修订日期,没有找到相关的已发布信息。
◉ Summary of Use during Lactation:Carbimazole is not approved for marketing in the United States by the U.S. Food and Drug Administration, but is available in other countries. 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.
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. 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.
◉ Effects in Breastfed Infants:Eleven mothers were taking oral carbimazole in dosages ranging from 5 to 20 mg daily during pregnancy and 5 to 15 mg daily during breastfeeding (extent not stated). None of the 12 infants, including one set of twins, had a serum thyroxine (T4) concentration below the lower limit of normal on day 4 of life. Thyrotropin (TSH) concentrations were normal in all infants when measured at various times over the first 21 days postpartum.
Four women were receiving 10 to 20 mg of carbimazole daily. Infant blood samples were obtained on days 4, 7, 10, and 42 and at 3 and 6 months postpartum. Thyroid function was normal in 3 infants. In one infant, the TSH was elevated for the first 10 days of life.
A mother with twins began taking carbimazole 30 mg daily 2 months postpartum. The dosage was lowered as she became euthyroid. The infants were breastfed (extent not stated) and clinical and laboratory examinations were performed over the following 4 months. There was no evidence of alterations in thyroid function.
Fifteen mothers received carbimazole 10 to 20 mg daily for 12 to 40 weeks during pregnancy and 9 continued to take the drug during 2 to 26 weeks of lactation. Their infants were monitored for up to 18 months. Infant thyroid function was within nornml over this period, the range of mean values for individual infants being TSH 1.4 to 5.9 millliunits/L, free T3 6.2 to 9.3 pmol/L and T4 104 to 189 nmol/L. Physical examination at intervals for 2 to 18 months was normal in all infants who received carbimazole and Griffiths mental development scales were normal in all 6 infants who were assessed at 18 months.
A mother was taking carbimazole 50 mg once weekly during pregnancy and postpartum. Her infant was exclusively breastfed for the first 84 days of life and had clinical and laboratory examinations performed over the first 4 months of life. Although the infant's tone and deep tendon reflexes were slightly increased and she was easily irritable, serum thyroid hormone levels were normal as was her growth. No symptoms or signs of hypothyroidism were observed.
◉ Effects on Lactation and Breastmilk:Relevant published information was not found as of the revision date.
来源:Drugs and Lactation Database (LactMed)