Ciprofloxacin Pregnancy and Breastfeeding Warnings
Ciprofloxacin Pregnancy Warnings
Animal studies have failed to reveal evidence of embryotoxicity or teratogenicity. In rabbits, gastrointestinal toxicity was observed with oral doses and resulted in maternal weight loss and increased incidence of abortion, intrauterine deaths, and fetal retardation (but no teratogenicity); no maternal toxicity (and no embryotoxicity or teratogenicity) observed with IV doses. There are no controlled data in human pregnancy. This drug distributes into amniotic fluid. Levels reported were 57% (at 2 to 4 hours postdose) to 1000% (at 10 to 12 hours postdose) of that found in maternal serum. An expert review by the Teratogen Information System concluded that substantial teratogenic risk is unlikely using therapeutic doses; data insufficient to state there is no risk. In a controlled prospective observational study, 200 women exposed to fluoroquinolones (52.5% to ciprofloxacin and 68% during the first trimester) during gestation were followed. No increased risk of major malformations associated with in utero fluoroquinolone exposure during embryogenesis. Major congenital malformation rates were 2.2% for the fluoroquinolone group and 2.6% for the control group; background rate of major malformations was 1% to 5%. Rates of spontaneous abortions, prematurity, and low birth weight were not different between the groups; no clinically significant musculoskeletal dysfunctions observed in infants (up to 1 year of age) exposed to this drug. A prospective follow-up study by the European Network of Teratology Information Services reported on 549 pregnancies with fluoroquinolone exposure; 93% were first-trimester exposures and included all 70 exposures to ciprofloxacin. Malformation rates among live-born babies exposed to this drug and fluoroquinolones overall were within background rates in the general population. No specific patterns of congenital abnormalities were found. The study did not expose any clear side effects due to in utero ciprofloxacin exposure. In the US Michigan Medicaid surveillance study of 229,101 pregnancies, major birth defects were reported in 3 of 132 exposed neonates. An association between this drug and congenital defects is not supported by these data. Berkovitch and colleagues reviewed 35 pregnancies in women who received norfloxacin or ciprofloxacin during the first trimester for urinary tract infection. No malformations were observed among the infants of these women. There were no joint problems or walking delays, and when compared to nonexposed infants, there was no apparent difference in the acquisition of milestones. No differences in rates of prematurity, spontaneous abortions, or birth weight observed in women exposed to this drug during pregnancy; however, most data was from short-term, first-trimester exposure during small postmarketing epidemiology studies, which were not sufficient to assess risk for less common defects or to enable reliable, definitive conclusions regarding the safety of this drug in pregnant women and their developing fetuses. In mass casualty settings after release of biological weapons, the US CDC and Working Group on Civilian Biodefense have recommended ciprofloxacin as the drug of choice for postexposure prophylaxis and treatment of anthrax, and as an alternative for tularemia and plague. The risk of drug use during pregnancy is outweighed by the high fatality rates from these infections. Cartilage damage and arthropathy have been reported in immature animals of various species giving rise to concern over possible toxic effects on human fetal bone formation. Because safer alternatives are generally available, some experts consider ciprofloxacin contraindicated during pregnancy, especially during the first trimester. AU TGA pregnancy category B3: 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 shown evidence of an increased occurrence of fetal damage, the significance of which is considered uncertain in humans. US FDA pregnancy category C: Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.
This drug should not be used during pregnancy unless the benefit outweighs the risk to both fetus and mother. -UK: As a precaution, avoiding use during pregnancy is preferred. AU TGA pregnancy category: B3 US FDA pregnancy category: C
Ciprofloxacin Breastfeeding Warnings
A decision should be made to discontinue breastfeeding or discontinue the drug, taking into account the importance of the drug to the mother. Excreted into human milk: Yes Comments: -The effects in the nursing infant are unknown; potential risk of serious side effects (including articular damage) in the nursing infant. -This drug is considered compatible with breastfeeding by the American Academy of Pediatrics.
Cartilage erosion and arthropathy have been reported in immature animals giving rise to concern over toxic effects in the developing joints of nursing infants; however, some studies suggest risk is low. Absorption of the small amounts of fluoroquinolones in milk may be blocked by the calcium in milk; data insufficient to prove or disprove. Levels found in breast milk have ranged from 85% (at 24 hours postdose) to 214% (at 4 hours postdose) of maternal serum level. Postpartum (time not specified), 10 lactating women received 750 mg orally every 12 hours for 3 doses. At 2 hours after the third dose, milk drug levels were highest and averaged 3.79 mg/L. Milk levels then declined and averaged 2.26 mg/L at 4 hours, 0.86 mg/L at 6 hours, 0.51 mg/L at 9 hours, 0.2 mg/L at 12 hours, and 0.02 mg/L at 24 hours after the dose. Based on peak milk levels in this study, an exclusively breastfed infant would receive up to 0.57 mg/kg daily (estimated) with this maternal dose regimen, which is much lower than the dose used to treat neonates. A single 500 mg oral dose was given to a mother recovering from acute renal failure; this dose was administered with a prenatal vitamin and ferrous sulfate, which would be expected to decrease ciprofloxacin bioavailability. Milk levels were 3.5 mg/L at 4, 8, and 12 hours after the dose and 2.3 mg/L at 16 hours after the dose. Levels were probably elevated and elimination prolonged due to the renal dysfunction. A woman took 500 mg orally daily for 10 days. Drug level in breast milk was 0.98 mg/L at 10 hours and 40 minutes after the last dose. After breastfeeding once (8 hours after the dose), this drug was not detectable (less than 30 mcg/L) in the infant's serum 2.7 hours after nursing. In 1 case report, a 2-month-old girl with history of necrotizing enterocolitis developed perforated pseudomembranous colitis, most likely due to ingestion of this drug via her mother's milk, and subsequently required a bowel resection. The mother admitted self-treatment while breastfeeding her infant. This drug was used as part of multi-drug regimens to treat 3 pregnant women with multidrug-resistant tuberculosis throughout pregnancy and postpartum. Their 3 infants were breastfed (extent and duration not specified). At age 1.25, 1.8, and 3.9 years, 2 of the children were developing normally while the other child had failure to thrive, possibly due to contracting tuberculosis after birth. This drug is recommended by the US CDC as a preferred agent for postexposure prophylaxis and treatment of anthrax in lactating women. The Working Group on Civilian Biodefense has recommended this drug as an alternative for plague.
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