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U.S. Department of Health and Human Services

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Amoxicillin (Amoxil, Larotid, Trimox, Wymox) Use by Pregnant and Lactating Women

According to the Centers for Disease Control and Prevention (CDC), ciprofloxacin (500 mg, orally, two times a day for 60 days) is the antibiotic of choice for initial prophylactic therapy among asymptomatic pregnant women exposed to Bacillus anthracis1. Amoxicillin does not have an approved indication for anthrax prophylaxis or treatment2, however, the CDC recommends in instances where the specific B. anthracis strain has been shown to be penicillin-sensitive, prophylactic therapy with amoxicillin (500 mg, orally, three times a day for 60 days) may be considered1.

While there are no controlled studies of amoxicillin use in pregnant women to show safety, an expert review of published data on experiences with amoxicillin use during pregnancy by TERIS - the Teratogen Information System - concluded that therapeutic doses during pregnancy are unlikely to pose a substantial teratogenic risk (quantity and quality of data = fair), but the data are insufficient to state that there is no risk3. There are no human data available to assess the effects of long-term therapy in pregnant women such as that proposed for treatment of anthrax exposure. Amoxicillin is excreted into breast milk but is considered as "usually compatible with breastfeeding" by the American Academy of Pediatrics.4

Background:

Penicillins as a class are generally considered safe for use in pregnancy and are widely used in the treatment of various infections in pregnant women. Amoxicillin, which is chemically and pharmacologically similar to ampicillin, is more rapidly and completely absorbed from the gastrointestinal tract5.

 

Teratogenic Effects

· A controlled clinical trial on the treatment of gonorrhea during pregnancy showed no significant increase in the frequency of major or minor anomalies among the children of 14 women treated during the first 14 weeks of gestation with amoxicillin and probenecid or among the children of 57 women so treated after the fourteenth week6.

· The frequency of congenital anomalies was not increased among the infants of 284 women who took either amoxicillin or ampicillin during the first trimester of pregnancy or among the infants of 1060 women who took one of these drugs anytime during pregnancy7.

· A population based case-control study of 538 infants with neural tube defects showed no association with maternal ampicillin or amoxicillin treatment during first trimester of pregnancy8.

· Controlled clinical trials for antibiotic treatment of preterm rupture of the membranes showed no adverse effects on newborn infants exposed to amoxicillin during the second and third trimester of pregnancy 9,10,11.

· A case-control study (6,935 mothers of infants with congenital anomalies and 10,238 mothers of infants with no congenital anomalies) did not show a higher use of Augmentin® (amoxicillin with clavulanate) in any congenital abnormality group12.

· A large case-control study of over 50,000 mother-child pairs showed no teratogenic effects in the 3,546 mothers exposed to penicillin derivatives during the first trimester of pregnancy. For the principal outcomes, the narrow confidence limits around the relative risks suggest that it is unlikely that penicillin is teratogenic13.

· No adverse fetal effects were seen in pregnant rats administered amoxicillin (with clavulanic acid) at maximum doses of 400 mg and 1,200 mg per day on days 6-15 and 15-21, respectively14.

· No adverse reproductive effects were seen in rats given amoxicillin (with clavulanic acid) at maximum doses of 400 mg and 1,200 mg per day prior to fertilization and during the first 7 days of gestation15.

· No adverse fetal effects were seen in pregnant pigs gavaged with amoxicillin (with clavulanic acid) at doses of 600 mg per kg on days 12-4216.

Changes in Pharmacokinetics

 

· Multiple pregnancy-associated physiologic changes have the potential to influence antimicrobial pharmacokinetic parameters, e.g., expanded intravascular volume, increased blood flow to the kidneys, skin, uterus, and mammary glands, increased glomerular filtration rate, decreased gastrointestinal motility, decreased plasma albumin concentration and changes in drug metabolizing enzymes17.

· Amoxicillin is suggested to give effective drug levels even after oral administration except during labor18.

Duration of Exposure · The vast majority of reported human experience with amoxicillin and pregnancy outcomes (as described above) is based on short-term exposure. Clinical studies for the treatment of infections in pregnancy involve all trimesters.

Prepared by the Pregnancy Team, Food and Drug Administration 11/19/01

 

 1 Notice to readers: Updated recommendations for antimicrobial prophylaxis among asymptomatic pregnant women after exposure to Bacillus anthracis. MMWR 2001;50(43):960.
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 2 Product information Amoxil®, 2001

 3 Friedman JM and Polifka JE. Teratogenic Effects of Drugs. A Resource for Clinicians (TERIS). Baltimore, MD: The Johns Hopkins University Press; 2000:149-195.

 4 Committee on Drugs, American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics. 2001;108(3):776-789.

 5 Hardman JG and Limbird LE (Eds). Goodman & Gilman's The Pharmacological Basis of Therapeutics. 10th ed. New York: McGraw-Hill Professional Publishing, 2001.
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 6 Cavenee MR, Farris JR, Spalding TR, et al.: Treatment of gonorrhea in pregnancy. Obstet Gynecol 1993;81:33-38.

 7 Colley DP, Kay J, and Gibson GT. Amoxycillin and ampicillin: A study of their use in pregnancy. Aust J Pharm 1983;64:207-111.

 8 Shaw GM, Todoroff K, Velie EM and Lammer EJ. Maternal illness, including fever, and medication use as risk factors for neural tube defects. Teratology 1998;57:1-7.

 9 Almeida L, Schmauch A, and Bergstrom S. A randomized study on the impact of peroral amoxicillin in women with pre-labour rupture of membranes preterm. Gynecol Obstet Invest 1996;41:82-84.
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 10 Lovett SM, Weiss JD, Diogo MJ, Williams PT, and Garite TJ. A prospective, double-blind, randomized, controlled clinical trial of ampicillin-sulbactam for preterm premature rupture of membranes in women receiving antenatal corticoid therapy. Am J Obstet Gynecol 1997;176:1030-1038.

 11 Mercer BM, Miodovnik M, Thurmau GR et al. Antibiotic therapy for reduction of infant morbidity after preterm premature rupture of the membranes. A randomized controlled trial. JAMA 1997;278:989-995.

 12 Czeizel AE, Rockenbauer M, Sorensen HT, and Olsen J. Augmentin treatment during pregnancy and the prevalence of congenital abnormalities: A population-based case-control teratologic study. Eur J Obstet Gynecol Reprod Biol 2001;97:188-192.

 13 Heinonen OP, Slone D, Shapiro S. Antimicrobial and antiparasitic agents. Birth defects and drugs in pregnancy. Littleton, Mass:Publishing Sciences Group 1977:296-313.
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 14 Baldwin JA, Schardein JL, and Koshima Y. Reproduction studies of BRL 14151K and BRL 25000. Teratology and peri-and postnatal studies in rats. Chemotherapy 1983;31:238-262.

 15 Hirakawa T, Suzuki T, Sano Y, et.al. Reproduction studies in rats. Chemotherapy 1983;31:263-272.

 16 James PA, Hardy TL, and Koshima Y. Reproduction studies of BRL 25000. Teratology studies in the pig. Chemotherapy 1983;31:274-279.

 17 Stika CS and Frederiksen MC. Drug therapy in pregnant and nursing women. In: Principles of Clinical Pharmacology, Atkinson AJ (Eds) New York:Academic Press, 2001.

 18 Nau H. Clinical pharmacokinetics in pregnancy and perinatology. II. Penicillins. Dev Pharmacol Ther 1987;10(3):174-198.
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