Drug Information |
Amoxicillin
(Amoxil, Larotid, Trimox,
Wymox)
|
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
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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.
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4 Committee on Drugs,
American Academy of Pediatrics. The transfer of drugs and other chemicals
into human milk. Pediatrics. 2001;108(3):776-789.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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15 Hirakawa T, Suzuki T,
Sano Y, et.al. Reproduction studies in rats. Chemotherapy
1983;31:263-272.
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16 James PA, Hardy TL,
and Koshima Y. Reproduction studies of BRL 25000. Teratology studies in
the pig. Chemotherapy 1983;31:274-279.
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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.
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18 Nau H. Clinical
pharmacokinetics in pregnancy and perinatology. II. Penicillins. Dev
Pharmacol Ther 1987;10(3):174-198.
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FDA/Center for Drug Evaluation and Research
Last Updated: November 20, 2001
Originator: OTCOM/DLIS
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