Is Nitrofurantoin Safe During Pregnancy?

JANUARY 18, 2016
Nitrofurantoin is commonly used to treat urinary tract infections (UTIs) in pregnant women. Comfort in selecting this antibiotic comes from its friendly FDA pregnancy category B rating and long history of safe and effective use.
 
However, the FDA pregnancy category ratings can be misleading because they are only meant to identify potential teratogens. In the case of nitrofurantoin oral suspension (Furadantin), the prescribing information does not state that its use is contraindicated in pregnant patients at term (38 to 42 weeks of gestation), during labor and delivery, or when onset of labor is imminent.1

This information comes from a population-based cohort study from Norway that was published in 2013.2 Using the national Medical Birth Registry and Prescription Database, data from more than 180,000 births were analyzed to estimate whether exposure to nitrofurantoin is associated with increased incidence of negative pregnancy outcomes. 
 
After comparing 1334 mothers who received nitrofurantoin during their pregnancy with 5800 mothers who received pivmecillinam and 130,889 mothers who received no antibiotics for UTIs, the researchers found that the incidence of any malformation—including cardiovascular, atrial septum, or ventricular septum defects—were no different among the groups. Moreover, the rates of negative pregnancy outcomes such as stillbirth and neonatal mortality, low birth weight, preterm delivery, transfer to NICU, or Apgar score lower than 7 at 5 minutes were no different among the study groups. 

However, neonates exposed to nitrofurantoin in the last 30 days before delivery had a significantly higher rate of neonatal jaundice requiring treatment compared with neonates exposed to pivmecillinam during the same stage of pregnancy (10.8% and 8.8%, respectively; p=0.023). This significant difference held up after multivariate analysis that adjusted for prematurity, neonatal sex, year of birth, use of oxytocin to induce labor, neonatal systemic antibiotic treatment, maternal age, parity, and smoking at the end of pregnancy. 
 
It is important to note that the difference in incidence of neonatal jaundice did not affect pregnancy outcomes in the study population. While no neonates in the registry were identified as having glucose-6-phosphate dehydrogenase deficiency, there was no difference in the incidence of hemolytic anemia.

In isolation, this study would suggest that nitrofurantoin should be avoided in the last 30 days of pregnancy. However, the American College of Obstetricians and Gynecologists Committee Opinion on sulfonamides, nitrofurantoin, and risk of birth defects state that if other treatment options are not able to be used (eg, cephalosporins, erythromycin), then sulfonamides and nitrofurantoin may be used as first-line agents for the treatment of UTI during the second and third trimesters.3
 
This statement was derived from the generally mixed evidence concerning an association between nitrofurantoin and birth defects.4-8

Contraindicated is a strong term. Drug experts seem to disagree with nitrofurantoin’s prescribing information, but as always, each patient scenario must be viewed independently, and all risks and benefits must be weighed.
 
References
  1. Furadantin (nitrofurantoin) oral suspension [prescribing information]. Atlanta, GA: Sciele Pharma, Inc; 2009. http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/009175s037lbl.pdf. Accessed January 14, 2016.
  2. Nordeng H, Lupattelli A, Romøren M, Koren G. Neonatal outcomes after gestational exposure to nitrofurantoin. Obstet Gynecol. 2013 Feb;121(2 Pt 1):306-313.
  3. American College of Obstetricians and Gynecologists. Sulfonamides, nitrofurantoin, and risk of birth defects. Committee Opinion No. 494. Obstet Gynecol. 2011;117:1484-1485.
  4. Prytherch JP, Sutton ML, Denine EP. General reproduction, perinatal-postnatal, and teratology studies of nitrofurantoin macrocrystals in rats and rabbits. J Toxicol Environ Health. 1984;13:811-823.
  5. Gait JE. Hemolytic reactions to nitrofurantoin in patients with glucose-6-phosphate dehydrogenase deficiency: theory and practice. DICP. 1990;24:1210-1213.
  6. Ben David S, Einarson T, Ben David Y, et al. The safety of nitrofurantoin during the first trimester of pregnancy: meta-analysis. Fundam Clin Pharmacol. 1995;9:503-507.
  7. Le J, Briggs GG, McKeown A, et al. Urinary tract infections during pregnancy. Ann Pharmacother. 2004;38:1692-1701.
  8. Mohamed A, Dresser GK, Mehta S. Acute respiratory failure during pregnancy: a case of nitrofurantoin-induced pneumonitis. CMAJ. 2007;176(3):319-320.


Craig Cocchio, PharmD
Craig Cocchio, PharmD
Craig Cocchio, PharmD, BCPS, is an Emergency Medicine Clinical Pharmacist at Trinity Mother Frances Hospital in Tyler, Texas. Follow on Twitter @iEMPharmD and on his blog at empharmd.blogspot.com
SHARE THIS
50