nitrofurantoin
Tradename
Macrodantin, Furadantin, Macrobid
Usage and Dosing
- Nitrofurantoin is used to treat uncomplicated lower urinary tract infections (UTI), e.g., cystitis, urethritis.
- Not effective for infections outside of the urinary tract.
- Because nitrofurantoin is a weak acid with a pKa of 7.2, absorption is enhanced in an acidic environment. Renal clearance is enhanced in an alkaline environment (Urology 1988;32:67).
- Increased activity in acidic urine.
- Original capsules contain microcrystals of nitrofurantoin, marketed in US as Furadantin. To decrease frequency of nausea, the drug was later formulated in macrocrystalline form (marketed as Macrodantin). Subsequently a slow release formulation was developed (25% macrocrystals, 75% monohydrate), marketed as Macrobid. As the name implies, administered bid.
- Long-standing admonition to not use in patients with CrCl <50-60 mL/min for fear of inadequate urine concentrations and/or increased adverse effects. However, in retrospective study, there was no difference in the safety and efficacy of nitrofurantoin in patients with CrCl ≤50 mL/min or CrCl >50 mL/min. Current American Geriatric Society recommendation is that nitrofurantoin can be used with relative safety and efficacy in patients with CrCl >30 mL/min (J Am Geriatr Soc 67:674, 2019). Not effective in end-stage renal disease.
- Pregnancy risk and lactation safety
- Contraindicated in pregnant patients at term (38 to 42 weeks gestation), during labor and delivery, or when the onset of labor is imminent (the drug can cause hemolytic anemia in the newborn). For the same reason, the drug is contraindicated in neonates under one month of age.
- Systematic Review: J Antimicrob Chemother 70:2456, 2015
Renal Adjustment
- CrCl >50 mL/min: Give usual dose
- CrCl <50 mL/min: See comment
Hepatic Adjustment
- None
Adverse Effects
- Rare but serious liver injury.
- Peripheral neuropathy can occur.
- May impart a brown color to the urine.
- Interstitial pneumonitis with progressive fibrosis can occur, usually after 6 months of therapy.
- Hemolytic anemia if G6PD-deficient.
- DRESS syndrome: Drug rash, eosinophilia, systemic symptoms hypersensitivity syndrome reported (Neth J Med 67:147, 2009).
- In retrospective study, Nitrofurantoin was associated with increased risk of birth defects (Arch Ped Adol Med 163:978, 2009); in contrast, subsequent study shows no risk of major malformations after exposure to Nitrofurantoin during the first trimester (J Clin Pharmacol 53:991, 2013).