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Nitrofurantoin, sold under the trade name Macrobid among others, is an antibiotic used to treat bladder infections.
Common side effects include nausea, loss of appetite, diarrhea, and headaches.
Nitrofurantoin was first sold in 1953.
1 Medical uses
1.1 Antibacterial activity
2 Adverse effects
2.1 Pulmonary toxicity
4 Mechanism of action
6 Animal feed
7 Society and culture
7.2 Trade names
9 External links
100 mg Macrobid, Canada
Current uses include the treatment of uncomplicated urinary tract infections (UTIs) and prophylaxis against UTIs in people prone to recurrent UTIs.
Increasing bacterial antibiotic resistance to other commonly used agents, such as fluoroquinolones and trimethoprim/sulfamethoxazole, has led to increased interest in using nitrofurantoin.
Nitrofurantoin is not recommended for the treatment of pyelonephritis, because of extremely poor tissue penetration and low blood levels.
Nitrofurantoin has been shown to have good activity against:
Coagulase negative staphylococci
Bacillus subtilis species
It is used in the treatment of infections caused by these organisms.
Many or all strains of the following genera are resistant to nitrofurantoin:
Antibiotic susceptibility testing should always be performed to further elucidate the resistance profile of the particular strain of bacteria causing infection.
Nitrofurantoin is pregnancy category B.
Several trials on the safety and teratogenicity of nitrofurantoin in pregnancy have shown mixed results. A retrospective study in 2009 claimed that several birth defects, such as hypoplastic left heart syndrome, ophthalmic malformations, cleft lip and cleft palate, and atrial septal defect, were more common in neonates exposed to nitrofurantoin during pregnancy.
The most common side effects with nitrofurantoin are nausea, headache, and flatulence. Less common adverse events (occurring in less than 1% of those taking the drug) include:
Gastrointestinal: diarrhea, dyspepsia, abdominal pain, constipation, emesis
Neurologic: dizziness, drowsiness, amblyopia
Respiratory: acute pulmonary hypersensitivity reaction
Allergic: pruritus, urticaria
Dermatologic: hair loss
Miscellaneous: fever, chills, malaise
Patients should be informed that nitrofurantoin colours urine brown; this is completely harmless.
Some of the more serious but rare side effects of nitrofurantoin have been a cause of concern. These include pulmonary reactions, hepatotoxicity, and neuropathy.
The pulmonary toxicity caused by nitrofurantoin can be categorized into acute, subacute, and chronic pulmonary reactions. The acute and subacute reactions are thought to be due to a hypersensitivity reaction and often resolve when the drug is discontinued. Acute reactions have been estimated to occur in about one in 5000 women who take the drug.
Chronic pulmonary reactions caused by nitrofurantoin include diffuse interstitial pneumonitis, pulmonary fibrosis, or both.
Hepatic reactions, including hepatitis, cholestatic jaundice, chronic active hepatitis, and hepatic necrosis, occur rarely. The onset of chronic active hepatitis may be insidious, and patients should be monitored periodically for changes in biochemical tests that would indicate liver injury.
Neuropathy is a rare side effect of taking nitrofurantoin. Patients may experience numbness and tingling in a stocking-glove pattern, which may or may not improve upon discontinuation of the drug.
Nitrofurantoin is contraindicated in patients with decreased renal function (CrCl 100 μg/ml), nitrofurantoin is a bactericide. It is bacteriostatic against most susceptible organisms at concentrations less than 32 μg/ml.
Nitrofurantoin and the quinolone antibiotics are mutually antagonistic in vitro. It is not known whether this is of clinical significance, but the combination should be avoided.
Resistance to nitrofurantoin may be chromosomal or plasmid-mediated and involves inhibition of nitrofuran reductase. Acquired resistance in E. coli continues to be rare.
Nitrofurantoin and its metabolites are excreted mainly by the kidneys. In renal impairment, the concentration achieved in urine may be subtherapeutic. Nitrofurantoin should not be used in patients with a creatinine clearance of 60 ml/min or less. However, a retrospective chart review may suggest nitrofurantoin is not contraindicated in this population.
There are two formulations of nitrofurantoin.
Macrocrystals – (Macrodantin, Furadantin) – 25, 50, or 100 mg capsules – taken once every 6 hours
Monohydrate/macrocrystals – (Macrobid) – 100 mg capsules – taken once every 12 hours or 2 times a day
Mechanism of action
Nitrofurantoin is concentrated in the urine, leading to higher and more effective levels in the urinary tract than in other tissues or compartments.
The mechanism of action is unique and complex. The drug works by damaging bacterial DNA, since its reduced form is highly reactive.
Nitrofurantoin has been available for the treatment of lower urinary tract infections (UTIs) since 1953.
Residues from the breakdown of nitrofuran veterinary antibiotics, including nitrofurantoin, have been found in chicken in Vietnam, China, Brazil, and Thailand.
Society and culture
It is available as a generic medication.
The cost of the liquid formulation of nitrofurantoin in the U.S. became controversial after a 400% price increase. There are two manufacturers of the liquid formulation in the U.S., Casper Pharma and Nostrum Laboratories. In 2018, Casper increased their price to $2,800. In response to Casper, Nostrum increased their price from $474.75 to $2,392. In the U.K., a slightly larger bottle costs £446.95. In an interview with the Financial Times, Nirmal Mulye, Nostrum chief executive, said that there was a “moral requirement to sell the product at the highest price.” He defended Martin Shkreli, and said, “This is a capitalist economy and if you can’t make money you can’t stay in business.” Mulye also attacked the U.S. Food and Drug Administration as “incompetent and corrupt.” There is a shortage of liquid nitrofurantoin, because the FDA implemented new rules on impurities, he said. Mulye dismissed the new rules on impurities as a “piece of nonsense.”
FDA commissioner Scott Gottlieb tweeted a response: “[T]here’s no moral imperative to price gouge and take advantage of patients. FDA will continue to promote competition so speculators and those with no regard to public health consequences can’t take advantage of patients who need medicine.”
Nitrofurantoin is marketed under many names in countries worldwide.
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