Each nitrofurantoin capsules (monohydrate/macrocrystals) contains two forms of nitrofurantoin. Twenty-five percent is macrocrystalline nitrofurantoin, which has slower dissolution and absorption than nitrofurantoin monohydrate. The remaining 75% is nitrofurantoin monohydrate contained in a powder blend which, upon exposure to gastric and intestinal fluids, forms a gel matrix that releases nitrofurantoin over time. Based on urinary pharmacokinetic data, the extent and rate of urinary excretion of nitrofurantoin from the 100 mg nitrofurantoin capsules (monohydrate/macrocrystals) are similar to those of 50 mg or 100 mg Macrodantin® (nitrofurantoin macrocrystals) capsule. Approximately 20% to 25% of a single dose of nitrofurantoin is recovered from the urine unchanged over 24 hours.

Plasma nitrofurantoin concentrations after a single oral dose of the 100 mg nitrofurantoin capsules (monohydrate/macrocrystals) are low, with peak levels usually less than 1 mcg/mL. Nitrofurantoin is highly soluble in urine, to which it may impart a brown color. When nitrofurantoin (monohydrate/macrocrystals) is administered with food, the bioavailability of nitrofurantoin is increased by approximately 40%.

MICROBIOLOGY

Nitrofurantoin is a nitrofuran antimicrobial agent with activity against certain Gram-positive and Gram-negative bacteria.

Mechanism of Action

The mechanism of the antimicrobial action of nitrofurantoin is unusual among antibacterials. Nitrofurantoin is reduced by bacterial flavoproteins to reactive intermediates which inactivate or alter bacterial ribosomal proteins and other macromolecules. As a result of such inactivations, the vital biochemical processes of protein synthesis, aerobic energy metabolism, DNA synthesis, RNA synthesis, and cell wall synthesis are inhibited. Nitrofurantoin is bactericidal in urine at therapeutic doses. The broad-based nature of this mode of action may explain the lack of acquired bacterial resistance to nitrofurantoin, as the necessary multiple and simultaneous mutations of the target macromolecules would likely be lethal to the bacteria.

Interactions with Other Antibiotics

Antagonism has been demonstrated in-vitro between nitrofurantoin and quinolone antimicrobials. The clinical significance of this finding is unknown.

Development of Resistance

Development of resistance to nitrofurantoin has not been a significant problem since its introduction in 1953. Cross-resistance with antibiotics and sulfonamides has not been observed, and transferable resistance is, at most, a very rare phenomenon.

Nitrofurantoin has been shown to be active against most strains of the following bacteria both in-vitro and in clinical infections (see INDICATIONS AND USAGE):

Aerobic and facultative Gram-positive microorganisms:

Staphylococcus saprophyticus

Aerobic and facultative Gram-negative microorganisms:

Escherichia coli

At least 90 percent of the following microorganisms exhibit an in-vitro minimum inhibitory concentration (MIC) less than or equal to the susceptible breakpoint for nitrofurantoin. However, the efficacy of nitrofurantoin in treating clinical infections due to these microorganisms has not been established in adequate and well-controlled trials.

Aerobic and facultative Gram-positive microorganisms

Coagulase-negative staphylococci (including Staphylococcus epidermidis)

Enterococcus faecalis

Staphylococcus aureus

Streptococcus agalactiae

Group D streptococci

Viridans group streptococci

Aerobic and facultative Gram-negative microorganisms

Citrobacter amalonaticus

Citrobacter diversus

Citrobacter freundii

Klebsiella oxytoca

Klebsiella ozaenae

Nitrofurantoin is not active against most strains of Proteus species or Serratia species. It has no activity against Pseudomonas species.

Susceptibility Testing

For specific information regarding susceptibility test interpretive criteria and associated test methods and quality control standards recognized by FDA for this drug, please see: https://www.fda.gov/STIC.