Animal studies have failed to reveal evidence of adverse developmental outcomes, fetal harm, or impaired fertility. No adverse developmental outcomes were observed when pregnant mice and rats were administered the oral formulation during organogenesis at 14 and 9 times the maximum recommended human dose (MRHD) based on body surface area (BSA), respectively; no evidence of impaired fertility or fetal harm was observed when mice and rabbits were administered doses up to 6.3 and 2.1 times the MRHD based on BSA, respectively. This drug crosses the placental barrier into cord blood and amniotic fluid. There are no controlled data in human pregnancy. While published data from epidemiologic studies, case series, and case reports over several decades have not shown an association with cephalosporin use (including this drug) during pregnancy and major birth defects, miscarriage, or other adverse maternal/fetal outcomes, absence of risk has not been definitively established; available studies have methodologic limitations, including small sample size, retrospective data collection, and inconsistent comparator groups.

Clinical considerations: Maternal gonorrhea may be associated with preterm birth, low neonatal birth weight, chorioamnionitis, intrauterine growth restriction, small for gestational age, and premature rupture of membranes. Perinatal transmission of gonorrhea to the child can lead to infant blindness, joint infections, and bloodstream infections.

This drug reaches therapeutic levels in cord blood and amniotic fluid after IM or IV maternal dose.

In a study of 7 pregnant women, 750 mg IV dose 1 to 8 hours before delivery revealed passage of the drug across the placenta. The average maternal plasma, amniotic fluid, umbilical cord, and neonatal plasma drug levels ranged from 0 to 24, 1.2 to 18, less than 2 to 11, and less than 2 to 3.6 mcg/mL, respectively. No adverse effects on the fetus or neonates were observed.

The US Michigan Medicaid surveillance study showed no association between this drug and congenital defects. This report is a summary of information from a study in which 143 of 229,000 pregnant women from 1985 to 1992 received this drug. There were 3 defects observed relative to 6 expected. Neither cleft palate nor cardiovascular defects were observed. These data do not support an association between this drug and congenital defects.

In a study of 78 pregnant women between 15 to 35 weeks gestation who were given a 750 mg IV dose 8 to 138 minutes prior to delivery, the average fetal plasma levels were 7.4 mcg/mL (normal fetuses), 6.2 mcg/mL (hydropic fetuses), and 4.9 mcg/mL (oligohydramniotic fetuses). These data show that transplacental passage is significantly reduced in the presence of oligohydramnios.

Incidentally, the plasma clearance of this drug is significantly increased, and the elimination half-life significantly decreased during pregnancy.

Frequent urination (as occurs in many pregnancies) can lead to an increased rate of drug elimination; combined with a larger volume of distribution (and the likelihood of a consequential decreased serum level), dose adjustment may be needed to ensure adequate antimicrobial coverage is maintained.

AU TGA pregnancy category B1: Drugs which have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed. Studies in animals have not shown evidence of an increased occurrence of fetal damage.

US FDA pregnancy category Not Assigned: The US FDA has amended the pregnancy labeling rule for prescription drug products to require labeling that includes a summary of risk, a discussion of the data supporting that summary, and relevant information to help health care providers make prescribing decisions and counsel women about the use of drugs during pregnancy. Pregnancy categories A, B, C, D, and X are being phased out.

This drug should be used during pregnancy only if clearly needed and the benefit outweighs the risk.

AU TGA pregnancy category: B1
US FDA pregnancy category: Not assigned.

Risk summary: Available data (spanning over several decades) on use of cephalosporins (including this drug) in pregnant women have not established a drug-related risk.

Comments:
-Maternal and/or embryo/fetal risk due to the mother's underlying condition should be considered.

See references

After a single 750 mg IM injection in 8 women with endometritis, milk drug levels increased from 0.34 mg/L at 30 minutes after dosing to 1.45 mg/L at 8 hours after dosing.

After 750 mg IM 3 times a day, peak milk levels averaged 1.2 mg/L at 6 hours after dosing. This drug was detectable at 30 minutes after dosing (0.36 mg/L); by 8 hours after dosing, milk level decreased to 1.06 mg/L.

After a single 750 mg IV dose in 5 women, peak drug level in milk averaged 0.37 mg/L at 3 hours after dosing; at 2 to 4 hours after dosing, individual peak levels were 0.33 to 0.5 mg/L.

After 750 mg IV 3 times a day for 2 days after cesarean section, 2 women provided milk samples an hour after dosing. Milk drug levels were 0.34 and 0.39 mg/L.

A mother received 500 mg orally 3 times a day for acute mastitis of the left breast (after incision and drainage of the lesion); milk samples were collected from each breast 30 minutes after dosing on the first day of therapy. The drug concentration was 90 mcg/L in the unaffected breast and 590 mcg/L in the breast with mastitis. On the second day of therapy, milk samples collected 90 minutes after dosing contained 57 mcg/L in the right breast and 59 mcg/L in the left breast. On the third day, milk samples collected 90 minutes after dosing contained 27 mcg/L in the unaffected breast and 1.07 mg/L in the affected breast.

In a prospective controlled study (through an information service), mothers using this drug were asked about side effects in their breastfed infants. A case of diarrhea was reported, which was 2.6% of cefuroxime-exposed infants.

Use is considered acceptable; caution is recommended. Benefit to mother should outweigh risk to the infant.
-According to some authorities: A decision should be made to discontinue breastfeeding or discontinue the parenteral drug, taking into account the importance of the drug to the mother and the benefit of breastfeeding for the infant.

Excreted into human milk: Yes (in small amounts)

Comments:
-Developmental and health benefits of breastfeeding should be considered as well as the mother's clinical need for this drug; potential side effects in the breastfed child due to this drug or the mother's underlying condition should be considered.
-Limited information indicates the low levels produced in milk are not expected to cause severe adverse effects in the nursing infant.
-Disruption of infant's gastrointestinal flora (resulting in diarrhea or thrush) reported occasionally with cephalosporins, but such effects have not been adequately evaluated; possibility of sensitization should be considered.
-This drug is considered compatible with breastfeeding by some experts; other cephalosporins have been considered compatible with breastfeeding by the American Academy of Pediatrics.

See references