Clavulanate Potassium in pregnancy and breastfeeding

Clavulanate Potassium]]>

Risk Factor: BM
Class: Anti-infectives/ Antibiotics/anti-infectives

Contents of this page:
Fetal Risk Summary
Breast Feeding Summary

Fetal Risk Summary

Clavulanic acid is a b-lactamase inhibitor produced by Streptomyces clavuligerus that is combined, as the potassium salt, with the penicillin antibiotics, amoxicillin or ticarcillin, to broaden their antibacterial spectrum of activity. No adverse fetal effects were observed in mice, rats, and pigs administered potassium clavulanate in combination with amoxicillin or ticarcillin during gestation (1,2,3,4 and 5).

Following a single oral dose of amoxicillin (250 mg) and potassium clavulanate (125 mg) in humans, both agents crossed the placenta to the fetus (6,7). Cord blood levels were found 1 hour after the dose with peak levels occurring at 23 hours. In one study, the mean peak maternal serum and umbilical cord blood levels occurred at 2 hours with values of 2.20 and 1.23 g/mL, respectively (fetal:maternal ratio 0.56) (7). Both amoxicillin and potassium clavulanate have been demonstrated in the amniotic fluid (6,7 and 8), with peak concentrations of clavulanate (0.44 g/mL) measured 5.5 hours after administration (7). A study using in vitro perfused human placentas demonstrated the transfer of potassium clavulanate when concentrations on the maternal side were 1013 g/mL, but not at 26 g/mL (8). A fetal/maternal gradient of 1:1 was obtained at the higher concentrations.

Several studies have described the use of amoxicillin and potassium clavulanate for various infections in pregnant women (7, 9,10 and 11). No adverse effects in the fetus or newborn attributable to the combination were observed (see also Amoxicillin and Ticarcillin).

In a surveillance study of Michigan Medicaid recipients involving 229,101 completed pregnancies conducted between 1985 and 1992, 556 newborns had been exposed to clavulanic acid (presumably in combination with penicillins) during the 1st trimester (F. Rosa, personal communication, FDA, 1993). A total of 24 (4.3%) major birth defects were observed (24 expected). Specific data were available for six defect categories, including (observed/expected) 5/6 cardiovascular defects, 2/1 oral clefts, 1/2 polydactyly, 0/1 limb reduction defects, 1/1 hypospadias, and 2/0.3 spina bifida. Only with the latter defect is there a suggestion of a possible association, but other factors, including the mother’s disease, concurrent drug use, and chance may be involved.

Breast Feeding Summary

Both amoxicillin and ticarcillin are excreted into breast milk (see Amoxicillin and Ticarcillin), but data pertaining to potassium clavulanate have not been located. Excretion probably occurs because of the low molecular weight (about 237). The effects of the b-lactamase inhibitor on the nursing infant are unknown.



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