Amlodipine (Norvasc®)

Selected References:

  • Ahn HK, et al. 2007. Exposure to amlodipine in the first trimester of pregnancy and during breastfeeding. Hypertension in pregnancy, 26(2):179–187.
  • Aoki H, et al. 2018. Low Levels of Amlodipine in Breast Milk and Plasma. Breastfeeding medicine,13(9):622–626.
  • Centers for Disease Control and Prevention. (2024). Health and economic benefits of high blood pressure interventions. Retrieved August 2024 from https://www.cdc.gov/nccdphp/priorities/high-blood-pressure.html.
  • Faham DE, et al. 2019. Can Amlodipine Improve the Pre-ovulatory Follicle Blood Flow in Women with Polycystic Ovarian Syndrome?. Journal of reproduction & infertility, 20(2):89–94.
  • Ishikawa T, et al. 2023. Risk of major congenital malformations associated with first-trimester antihypertensives, including amlodipine and methyldopa: A large claims database study 2010-2019. Pregnancy hypertension, 31:73–83.
  • Magee LA, et al. 1996. The safety of calcium channel blockers in human pregnancy: a prospective, multicenter cohort study. Am J Obstet Gynecol, 174(3):823-828.
  • Mito AA, et al. 2019. Safety of Amlodipine in Early Pregnancy. Journal of the American Heart Association, 8(15):1-7.
  • Morgan JL, et al. 2018. Pharmacokinetics of amlodipine besylate at delivery and during lactation. Pregnancy hypertension, 11:77–80.
  • Naito T, et al. 2015. Amlodipine passage into breast milk in lactating women with pregnancy-induced hypertension and its estimation of infant risk for breastfeeding. Journal of human lactation, 31(2):301–306.
  • Rosbotham JL, et al. 1998. Painful subcutaneous fat necrosis of the newborn associated with intra-partum use of a calcium channel blocker. Clinical and experimental dermatology. 23(1):19–21.
  • Szucs KA, et al. 2010. Maternal membranous glomerulonephritis and successful exclusive breastfeeding. Breastfeeding Medicine, 5(3):123–126.
  • S. Food and Drug Administration. (2011). Norvasc (Amlodipine besylate) tablets label. Retrieved August 2024 from https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/019787s047lbl.pdf.
  • Vigil-De Gracia P, et al. 2014. Management of chronic hypertension during pregnancy with furosemide, amlodipine or aspirin: a pilot clinical trial. The journal of maternal-fetal & neonatal medicine: the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians, 27(13): 1291–1294.
  • Yin J, et al. 2022. Nifedipine or amlodipine? The choice for hypertension during pregnancy: a systematic review and meta-analysis. Archives of Gynecology and Obstetrics, 306(6):1891–1900.


Amlodipine (Norvasc®)

Selected References:

  • Auffret M, et al. 2016. Misoprostol exposure during the first trimester of pregnancy: Is the malformation risk varying depending on the indication? Eur J Obstet Gynecol Reprod Biol, 207:188-192.
  • Baev OR, et al. 2017. Outcomes of mifepristone usage for cervical ripening and induction of labour in full-term pregnancy. Randomized controlled trial. Eur J Obstet Gynecol Reprod Biol, 217:144-149.
  • Brown A, et al. 2002. Daily low dose mifepristone has contraceptive potential by suppressing ovulation and menstruation: a double-blind randomised controlled trial of 2 and 5 mg per day for 120 days. J Clin Endocrinol Metab, 87:63-70.
  • Bos-Thompson MA, et al. 2008. Mobius syndrome in a neonate after mifepristone and misoprostol elective abortion failure. Ann Pharmacother, 42(6):888-892.
  • Chen A, et al. 2004. Mifepristone-induced early abortion and outcome of subsequent wanted pregnancy. Am J Epidemiol, 160(2):110-117.
  • Gary MM, Harrison DJ. 2006. Analysis of severe adverse events related to the use of mifepristone as an abortifacient. Ann Pharmacother, 40:191-197.
  • Glasier A, et al. 1992. Mifepristone (RU 486) compared with high-dose estrogen and progestogen for emergency postcoital contraception. N Engl J Med, 327:1041-1044.
  • Juneja SC, Dodson MG. 1990. In vitro effect of RU 486 on sperm-egg interaction in mice. Am J Obstet Gynecol, 163:216-221.
  • Lakha F, et al. 2007. A novel estrogen-free oral contraceptive pill for women: multicentre, double-blind, randomized controlled trial of mifepristone and progestogen-only pill (levonorgestrel). Hum Reprod, 22(9):2428-2436.
  • Liao H, et al. 2011. Repeated medical abortions and the risk of preterm birth in the subsequent pregnancy. Arch Gynecol Obstet, 284(3):579-586.
  • Lim BH, et al. 1990. Normal development after exposure to mifepristone in early pregnancy. Lancet, 336:257-258.
  • Mifepristone Drug Label. 2023. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b63fad9b-7f12-4400-9019-b0586054e534.
  • Peyron R, et al. 1993. Early termination of pregnancy with mifepristone (RU 486) and the orally active prostaglandin misoprostol. N Engl J Med, 328:1509-1513.
  • Pons JC, et al. 1991. Development after exposure to mifepristone in early pregnancy. Lancet; 338:763.
  • Saav I, et al. 2010. Medical abortion in lactating women–low levels of mifepristone in breast milk. Acta Obstet Gynecol Scand, 89(5):618-622.
  • Sanchez-Criado JE, et al. 1990. A possible dual mechanism of the anovulatory action of antiprogesterone RU486 in the rat. Biol Reprod, 42:877-886.
  • Shoupe D, et al. 1987. Effects of the antiprogesterone RU 486 in normal women. II. Administration in the late follicular phase. Am J Obstet Gynecol, 157:1421-1426.
  • Sitruk-Ware R, Davey A, Sakiz E. 1998. Fetal malformations and failed medical termination of pregnancy. Lancet, 352:323.
  • Swahn ML, et al. 1996. Contraception with anti-progesterone. Baillieres Clin Obstet Gynaecol, 10(1):43-53.
  • Task force on postovulatory methods of fertility regulation. 1999. Comparison of three single doses of mifepristone as emergency contraception: a randomised trial. Lancet 353:607-702.
  • van der Schoot P, et al.1987. Effects of the progesterone antagonist RU486 on ovarian activity in the rat. Endocrinology, 121:1375-1382.
  • Wolf JP. et al. 1990. Tolerance of perinidatory primate embryos to RU 486 exposure in vitro and in vivo. Contraception, 41:85-92.
  • Yang YQ, Wu JT. 1990. RU 486 interferes with egg transport and retards the in vivo and in vitro development of mouse embryos. Contraception, 41:551-556.
  • Zhu QX, et al. 2009. Mifepristone-induced abortion and placental complications in subsequent pregnancy. Hum Reprod, 24(2):315-319.


Amlodipine (Norvasc®)

Selected References:

  • American College of Obstetricians and Gynecologists (ACOG). 2022/Apr. Preeclampsia and High Blood Pressure during Pregnancy. https://www.acog.org/womens-health/faqs/preeclampsia-and-high-blood-pressure-during-pregnancy
  • Anderson PO, et al 2020. Drug treatment of Raynaud’s phenomenon of the nipple. Breastfeed Med 15:686-8.
  • Benoff S, et al. 1994. The effect of calcium ion channel blockers on sperm fertilization potential. Fertil Steril 62:606-17.
  • Bortolus R, et al. 2000. Nifedipine administered in pregnancy: Effect on the development of children at 18 months. BJOG 107:792-794.
  • Davis RL, et al 2011. Risks of congenital malformations and perinatal events among infants exposed to calcium channel and beta-blockers during pregnancy. Pharmocoepidemiol Drug Saf 20:13-145.
  • Dublin S, et al. 2022. Maternal and neonatal outcomes of antihypertensive treatment in pregnancy: a retrospective cohort study. PLoS One 17(5):e0268284
  • George R, et. 2022. Comparative efficacy and safety of oral nifedipine with other antihypertensive medications in the management of hypertensive disorders of pregnancy: a systematic review and meta-analysis of randomized controlled trials. J Hypertens 40(10):1876-1886.
  • Houtzager BA, et al. 2006. Long-term follow up of children exposed in utero to nifedipine or ritodrine for the management of preterm labour. BJOG. 2006 Mar; 113(3):324-31.
  • Magee LA, et al. 1996. The safety of calcium channel blockers in human pregnancy: A prospective, multicenter cohort study. Am J Obstet Gynecol 174:823-828.
  • Malfará BN, et al. 2019. ABCG2 c.421C>A polymorphism alters nifedipine transport to breast milk in hypertensive breastfeeding women. Reprod Toxicol 85:1-5.
  • Penny WJ, Lewis MJ. 1989. Nifedipine is excreted in human milk. Eur J Clin Pharmacol. 36(4):427-8.
  • Tabacova SA, et al. 2002. Developmental abnormalities reported to FDA in association with nifedipine treatment in pregnancy. Teratology; 65:368.
  • Taddio A, et al 1996. Is nifedipine use during labor and breast-feeding safe for the neonate? Clin Investig Med 19:S11. Abstract.
  • Weber-Schoendorfer C, et al. 2008. The safety of calcium channel blockers during pregnancy: a prospective, multicenter, observational study. Reprod Toxicol 26(1): 24-30.
  • Wu M, et al 2012. Raynaud’s phenomenon of the nipple. Obstet Gynecol. 119(2 Pt 2):447-9.


Amlodipine (Norvasc®)

Selected References:

  • Aselton P, et al. 1985. First-trimester drug use and congenital disorders. Obstet Gynecol, 65(4):451-455.
  • Cao Y, et al. 2021. Maternal use of cough medications during early pregnancy and selected birth defects: a US multisite, case–control study. BMJ Open, 11:e053604.
  • Einarson A, et al. 2001. The safety of dextromethorphan in pregnancy: Results of a controlled study. Chest, 119(2):466-469.
  • Heinonen OP, et al. 1977. Birth Defects and Drugs in Pregnancy. Littleton, Mass.: John Wright-PSG, page 382.
  • Martinez-Frias ML, et al. 2001. Epidemiologic analysis of prenatal exposure to cough medicines containing dextromethorphan: no evidence of human teratogenicity. Teratology, 63(1):38-41.
  • Shum S, et al. 2022. Infant dextromethorphanand dextrorphan exposure via breast milk from mothers who are CYP2D6 extensive metabolizers. J Clin Pharmacol, 62(6):747-755.
  • Ward KE. 2005. Can Robitussin DM be used to treat cough during pregnancy? Med Health R I, 88(3):99-100.


Amlodipine (Norvasc®)

Selected References

  • Anderson PO, McGuire GG. 1989. Neonatal alprazolam withdrawal – possible effects of breastfeeding. DICP. 23:614. Letter.
  • Andrade C. 2019. Gestational Exposure to Benzodiazepines, 1: The Risk of Spontaneous Abortion Examined Through the Prism of Research Design. J Clin Psychiatry.;80(5):19f13076
  • Barry WS, St. Clair SM. 1987. Exposure to benzodiazepines in utero. Lancet. 1:1436-7.
  • Browne JL, Hauge KJ. 1986. A review of alprazolam withdrawal. Drug Intell Clin Pharm; 20(11):837-41.
  • Eros E, et al. 2002. A population-based case-control teratologic study of nitrazepam, medazepam, tofisopam, alprazolum and clonazepam treatment during pregnancy. Eur J Obstet Gynecol Reprod Biol. 101:147-54.
  • Freeman MP, et al. 2018. Obstetrical and neonatal outcomes after benzodiazepine exposure during pregnancy: Results from a prospective registry of women with psychiatric disorders. Gen Hosp Psychiatry. 53:73-79.
  • Furugen A, et al. 2019. Quantification of eight benzodiazepines in human breastmilk and plasma by liquid-liquid extraction and liquid-chromatography tandem mass spectrometry: Application to evaluation of alprazolam transfer into breastmilk. J Pharm Biomed Anal. 168:83-93.
  • García-Algar O, et al. 2007. Confirmation of gestational exposure to alprazolam by analysis of biological matrices in a newborn with neonatal sepsis. Clin Toxicol (Phila). 45(3):295-8.
  • Grigoriadis S, er al. 2019. Benzodiazepine Use During Pregnancy Alone or in Combination With an Antidepressant and Congenital Malformations: Systematic Review and Meta-Analysis. J Clin Psychiatry. 80(4):18r12412
  • Ito S, et al. 1993. Prospective follow-up of adverse reactions in breastfed infants exposed to maternal medication. Am J Obstet Gynecol. 168:1393-9.
  • Källén B, et al. 2013. The use of central nervous system active drugs during pregnancy. Pharmaceuticals (Basel). 6(10):1221-86.
  • Kelty E, et al. 2023. Safety of alprazolam use in pregnancy in Western Australia: A retrospective cohort study using linked health data. J of Psychoactive Drugs. 1-7.
  • Lee H, et al. 2022. Pregnancy and Neonatal Outcomes After Exposure to Alprazolam in Pregnancy. Front Pharmacol. 25: 13:854562.
  • Mazzilli R, et al. 2021. Psychotropic Drugs Levels in Seminal Fluid: A New Therapeutic Drug Monitoring Analysis?. Front Endocrinol (Lausanne). 12:620936.
  • Meng LC, et al. 2024. Benzodiazepine Use During Pregnancy and Risk of Miscarriage. JAMA Psychiatry. 81(4):366-373.
  • Munjack DJ, Crocker B. 1986. Alprazolam-induced ejaculatory inhibition. J Clin Psychopharmacol 6:57-8.
  • Ogawa Y, et al. 2018. Maternal exposure to benzodiazepine and risk of preterm birth and low birth weight: A case-control study using a claims database in Japan. Asia Pac Psychiatry. 2018 Sep;10(3):e12309
  • Nishimura A, et al. 2021. Benzodiazepine Concentrations in the Breast Milk and Plasma of Nursing Mothers: Estimation of Relative Infant Dose. Breastfeed Med. 16(5): 424-432.
  • Noh Y, et al. 2022. First-trimester exposure to benzodiazepines and risk of congenital malformations in offspring: A population-based cohort study in South Korea. PLoS Med. 2022;19(3):e1003945
  • Nonacs R. 2020. “Benzodiazepines and Risk of Ectopic Pregnancy”. MGH Center for Women’s Mental Health. https://womensmentalhealth.org/posts/benzodiazepine-ectopic/. Psychiatric Disorder during Pregnancy
  • Nonacs R. 2019. “Benzodiazepines During Early Pregnancy and risk of Miscarriage”. MGH Center for Women’s Mental Health. https://womensmentalhealth.org/posts/benzodiazepine-during-early-pregnancy-and-risk-of-miscarriage-2/. Anxiety Disorder, June. Pregnancy Loss, Pregnancy Outcome.
  • Nonacs R. 2019. “Interpreting New Data on the Use of Benzodiazepines During Pregnancy. MGH Center for Women’s Mental Health. https://womensmentalhealth.org/posts/interpreting-new-data-on-the-use-of-benzodiazepines-during-pregnancy/. December. Psychiatric Disorders during Pregnancy
  • Oo CY, et al. 1995. Pharmacokinetics in lactating women: prediction of alprazolam transfer into milk. Br J Clin Pharmacol. 40:231-6.
  • Petric D, et al. 2011. High doses alprazolam induced amenorrhoea and galactorrhoea. Psychiatr Danub. 23(1):123-4.
  • Sheehy O, et al. 2019. Association Between Incident Exposure to Benzodiazepines in Early Pregnancy and Risk of Spontaneous Abortion. JAMA Psychiatry. 76(9): 948–957.
  • Shyken JM, et. Al. 2019. Benzodiazepines in Pregnancy. Clin Obstet Gynecol.;62(1):156-167
  • St Clair SM, Schnirmer RG. 1992. First-trimester exposure to alprazolam. Obstet Gynecol. 80:843-846.
  • Tinker SC, et al; National Birth Defects Prevention Study. 2019. Use of benzodiazepine medications during pregnancy and potential risk for birth defects, National Birth Defects Prevention Study, 1997-2011. Birth Defects Res; 111(10):613-620.
  • Wall-Wieler et al. 2020. Benzodiazepine use before conception and risk of ectopic pregnancy. Human Reproduction, Vol.35, No.7, pp. 1685–1692.
  • Wisner KL, Yonkers KA. 2019. Are Adverse Reproductive Outcomes Associated With the Illness or Its Treatment (or Both)?. JAMA Psychiatry. 2019;76(12):1317-1318
  • Yamamoto K, et al. 2019. Pharmacokinetic assessment of alprazolam-induced neonatal abstinence syndrome using physiologically based pharmacokinetic model. Drug Metab Pharmacokinet. 34(6):400-402.