Clinical data | |
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Trade names | Macrobid, others [1] |
AHFS/Drugs.com | Monograph |
MedlinePlus | a682291 |
License data | |
Pregnancy category | |
Routes of administration | By mouth |
ATC code | |
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Legal status | |
Pharmacokinetic data | |
Bioavailability | 40% |
Metabolism | Liver (75%) |
Elimination half-life | 20 minutes |
Excretion | Kidney and bile duct |
Identifiers | |
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CAS Number | |
PubChem CID | |
DrugBank | |
ChemSpider | |
UNII | |
KEGG | |
ChEBI | |
ChEMBL | |
CompTox Dashboard (EPA) | |
ECHA InfoCard | 100.000.587 |
Chemical and physical data | |
Formula | C8H6N4O5 |
Molar mass | 238.159 g·mol−1 |
3D model (JSmol) | |
Melting point | 270 to 272 °C (518 to 522 °F) (decomp.) |
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Nitrofurantoin is an antibacterial medication of the nitrofuran class used to treat urinary tract infections, although it is not as effective for kidney infections. [10] It is taken by mouth. [10]
Common side effects include nausea, loss of appetite, diarrhea, and headaches. [10] Rarely numbness, lung problems, or liver problems may occur. [10] While it appears to be generally safe during pregnancy its use is not recommended near time of delivery. [10] [2] While it usually works by slowing bacterial growth, it may result in bacterial death at the high concentrations found in urine, provided forced fluid dilution of urine is avoided. [10] [ failed verification ]
Nitrofurantoin was first sold in 1953. [11] It is on the World Health Organization's List of Essential Medicines. [12] It is available as a generic medication. [10] In 2021, it was the 135th most commonly prescribed medication in the United States, with more than 4 million prescriptions. [13] [14]
Uses include the treatment of uncomplicated urinary tract infections (UTIs) and prophylaxis against urinary tract infections in people prone to recurrent urinary tract infections. [8]
Increasing bacterial antibiotic resistance to other commonly used agents, such as trimethoprim/sulfamethoxazole and fluoroquinolones, has led to increased interest in using nitrofurantoin. [15] [16] The efficacy of nitrofurantoin in treating urinary tract infections combined with a low rate of bacterial resistance to this agent makes it one of the first-line agents for treating uncomplicated urinary tract infections as recommended by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases. [17]
Nitrofurantoin is not recommended for the treatment of pyelonephritis, [17] and intra-abdominal abscess, [18] because of extremely poor tissue penetration and low blood levels. [10]
Nitrofurantoin has been shown to have good activity against:[ citation needed ]
It is used in the treatment of infections caused by these organisms. [19]
Many or all strains of the following genera are resistant to nitrofurantoin: [19]
Nitrofurantoin is pregnancy category A in Australia. [3] It is one of the few drugs commonly used in pregnancy to treat urinary tract infections. [20] There is a potential risk of hemolytic anemia in the newborn when used near time of delivery. [3] Newborns of women given this drug late in pregnancy had a higher risk of developing neonatal jaundice. [21]
Evidence of safety in early pregnancy is mixed as of 2017. [22] The American College of Obstetricians and Gynecologists states that while they can be used in the first trimester other options may be preferred. [22] They remain a first line treatment in the second trimester. [22] A 2015 meta analysis found no increased risk from first trimester use in cohort studies that was a slight increase of malformations in case control studies. [23]
Nitrofurantoin is contraindicated in patients with decreased renal function (CrCl < 60 ml/min) due to systemic accumulation and subtherapeutic levels reached in the urinary tract. [8] However, a retrospective chart review suggests the data for this cutoff are slim and a cutoff of CrCl < 40 ml/min would be more appropriate. [24] Many of the severe side effects of this drug are more common in the elderly and those with renal impairment, as this causes the drug to be retained in the body and reach higher systemic levels. Thus, the drug is not recommended for the elderly population according to 2012 AGS Beers Criteria. [25]
Nitrofurantoin is also contraindicated in babies up to the age of one month, as they have immature enzyme systems in their red blood cells (glutathione instability), so nitrofurantoin must not be used because it can cause haemolytic anaemia. Nitrofurantoin is contraindicated in patients with glucose-6-phosphate dehydrogenase deficiency (G6PD) because of risk of intravascular hemolysis resulting in anemia. [8]
The most common side effects of nitrofurantoin are nausea, headache, and flatulence. Less common adverse events (occurring in less than 1% of those taking the drug) include: [8]
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. [26] [27] These reactions usually develop 3–8 days after the first dose of nitrofurantoin, but may occur from a few hours to a few weeks after starting the drug. Symptoms include fever, dyspnea, chills, cough, pleuritic chest pain, headache, back pain, and epigastric pain. Chest radiograph will often show unilateral or bilateral infiltrates similar to pulmonary edema. [28]
Chronic pulmonary reactions caused by nitrofurantoin include diffuse interstitial pneumonitis, pulmonary fibrosis, or both. [8] This uncommon reaction may occur 1 month to 6 years after starting the drug and is usually related to its total lifetime dose.[ citation needed ] This reaction manifests with progressive shortness of breath. [29] It is important to recognize nitrofurantoin as possible cause of symptoms and discontinue the drug when the suspicion of pulmonary side effects arises as it can be reversible if the drug is stopped early. [27]
Liver reactions, including hepatitis, cholestatic jaundice, chronic active hepatitis, and hepatic necrosis, occur rarely. [30]
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. [31]
Organisms are said to be susceptible to nitrofurantoin if their minimum inhibitory concentration is 32 μg/mL or less. The peak blood concentration of nitrofurantoin following an oral dose of nitrofurantoin 100 mg is less than 1 μg/mL and may be undetectable. Its bioavailability is about 90% and the urinary excretion is 40% [32] tissue penetration is negligible; the drug is well concentrated in the urine: 75% of the dose is rapidly metabolised by the liver, but 25% of the dose is excreted in the urine unchanged, reliably achieving levels of 200 μg/mL or more. In studies of dogs, the majority of urinary excretion is through glomerular filtration with some tubular secretion. [33] There is also tubular absorption which is increased with urine acidification. [33] However the activity of nitrofurantoin is also pH dependent and mean inhibitory concentration rises sharply with increased pH above 6. [33] Nitrofurantoin cannot be used to treat infections other than simple cystitis.
At the concentrations achieved in urine (>100 μg/mL), nitrofurantoin is a bactericide. It is bacteriostatic against most susceptible organisms at concentrations less than 32 μg/mL. [8]
Nitrofurantoin and the quinolone antibiotics are mutually antagonistic in vitro. It is not known whether this is of clinical significance. [8]
Resistance to nitrofurantoin may be chromosomal or plasmid-mediated and involves inhibition of nitrofuran reductase. [34] 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. [35]
Nitrofurantoin is concentrated in the urine, leading to higher and more effective levels in the urinary tract than in other tissues or compartments. [27] With a 100 mg oral dose, plasma levels are typically less than 1 μg/mL while in the urine it reaches 200 μg/mL. [36]
The drug works by damaging bacterial DNA, since its reduced form is highly reactive. [8] This is made possible by the rapid reduction of nitrofurantoin inside the bacterial cell by flavoproteins (nitrofuran reductase) to multiple reactive intermediates that attack ribosomal proteins, DNA, [37] respiration, pyruvate metabolism and other macromolecules within the cell. Nitrofurantoin exerts greater effects on bacterial cells than mammalian cells because bacterial cells activate the drug more rapidly. It is not known which of the actions of nitrofurantoin is primarily responsible for its bactericidal activity. The broad mechanism of action for nitrofurantoin is likely responsible for the low development of resistance to its effects, as it affects many different processes important to the bacterial cell. [8]
Nitrofurantoin has been available for the treatment of lower urinary tract infections (UTIs) since 1953. [11]
Nitrofurantoin is marketed under many names in countries worldwide. [38]
Residues from the breakdown of nitrofuran veterinary antibiotics, including nitrofurantoin, have been found in chicken in Vietnam, China, Brazil, and Thailand. [39] The European Union prohibited the use of nitrofurans in food producing animals by classifying it in ANNEX IV (list of pharmacologically active substances for which no maximum residue limits can be fixed) of the Council Regulation 2377/90. The Food and Drug Administration (FDA) of the United States has prohibited furaltadone since February 1985 and withdrew the approval for the other nitrofuran drugs (except some topical uses) in January 1992. The topical use of furazolidone and nitrofurazone was prohibited in 2002. Australia prohibited the use of nitrofurans in food production in 1992. Japan did not allocate MRLs for nitrofurans leading to the implementation of a "zero tolerance or no residue standard". In Thailand, the Ministry of Health issued in 2001 Proclamation No. 231 MRL of veterinary drug in food which did not allocate MRL for nitrofurans. The Ministry of Agriculture and Cooperatives had already prohibited importation and use of furazolidone and nitrofurazone in animal feed in 1999 which was extended to all nitrofurans in 2002. Several metabolites of nitrofurans, such as furazolidone, furaltadone and nitrofurazone cause cancer or genetic damage in rats. [39]
Ciprofloxacin is a fluoroquinolone antibiotic used to treat a number of bacterial infections. This includes bone and joint infections, intra-abdominal infections, certain types of infectious diarrhea, respiratory tract infections, skin infections, typhoid fever, and urinary tract infections, among others. For some infections it is used in addition to other antibiotics. It can be taken by mouth, as eye drops, as ear drops, or intravenously.
A urinary tract infection (UTI) is an infection that affects a part of the urinary tract. Lower urinary tract infections may involve the bladder (cystitis) or urethra (urethritis) while upper urinary tract infections affect the kidney (pyelonephritis). Symptoms from a lower urinary tract infection include suprapubic pain, painful urination (dysuria), frequency and urgency of urination despite having an empty bladder. Symptoms of a kidney infection, on the other hand, are more systemic and include fever or flank pain usually in addition to the symptoms of a lower UTI. Rarely, the urine may appear bloody. Symptoms may be vague or non-specific at the extremities of age.
Trimethoprim (TMP) is an antibiotic used mainly in the treatment of bladder infections. Other uses include for middle ear infections and travelers' diarrhea. With sulfamethoxazole or dapsone it may be used for Pneumocystis pneumonia in people with HIV/AIDS. It is taken orally.
Levofloxacin, sold under the brand name Levaquin among others, is a broad-spectrum antibiotic of the fluoroquinolone drug class. It is the left-handed isomer of the medication ofloxacin. It is used to treat a number of bacterial infections including acute bacterial sinusitis, pneumonia, H. pylori, urinary tract infections, Legionnaires' disease, chronic bacterial prostatitis, and some types of gastroenteritis. Along with other antibiotics it may be used to treat tuberculosis, meningitis, or pelvic inflammatory disease. It is available by mouth, intravenously, and in eye drop form.
Ofloxacin is a quinolone antibiotic useful for the treatment of a number of bacterial infections. When taken by mouth or injection into a vein, these include pneumonia, cellulitis, urinary tract infections, prostatitis, plague, and certain types of infectious diarrhea. Other uses, along with other medications, include treating multidrug resistant tuberculosis. An eye drop may be used for a superficial bacterial infection of the eye and an ear drop may be used for otitis media when a hole in the ear drum is present.
Cefixime, sold under the brand name Suprax among others, is an antibiotic medication used to treat a number of bacterial infections. These infections include otitis media, strep throat, pneumonia, urinary tract infections, gonorrhea, and Lyme disease. For gonorrhea typically only one dose is required. In the United States it is a second-line treatment to ceftriaxone for gonorrhea. It is taken by mouth.
Pyelonephritis is inflammation of the kidney, typically due to a bacterial infection. Symptoms most often include fever and flank tenderness. Other symptoms may include nausea, burning with urination, and frequent urination. Complications may include pus around the kidney, sepsis, or kidney failure.
Furazolidone is a nitrofuran antibacterial agent and monoamine oxidase inhibitor (MAOI). It is marketed by Roberts Laboratories under the brand name Furoxone and by GlaxoSmithKline as Dependal-M.
Cefaclor, sold under the trade name Ceclor among others, is a second-generation cephalosporin antibiotic used to treat certain bacterial infections such as pneumonia and infections of the ear, lung, skin, throat, and urinary tract. It is also available from other manufacturers as a generic.
Tobramycin is an aminoglycoside antibiotic derived from Streptomyces tenebrarius that is used to treat various types of bacterial infections, particularly Gram-negative infections. It is especially effective against species of Pseudomonas.
Cefotaxime is an antibiotic used to treat a number of bacterial infections in human, other animals and plant tissue culture. Specifically in humans it is used to treat joint infections, pelvic inflammatory disease, meningitis, pneumonia, urinary tract infections, sepsis, gonorrhea, and cellulitis. It is given either by injection into a vein or muscle.
Norfloxacin, sold under the brand name Noroxin among others, is an antibiotic that belongs to the class of fluoroquinolone antibiotics. It is used to treat urinary tract infections, gynecological infections, inflammation of the prostate gland, gonorrhea and bladder infection. Eye drops were approved for use in children older than one year of age.
Cefoxitin is a second-generation cephamycin antibiotic developed by Merck & Co., Inc. from Cephamycin C in the year following its discovery, 1972. It was synthesized in order to create an antibiotic with a broader spectrum. It is often grouped with the second-generation cephalosporins. Cefoxitin requires a prescription and as of 2010 is sold under the brand name Mefoxin by Bioniche Pharma, LLC. The generic version of cefoxitin is known as cefoxitin sodium.
Nitrofurans are a class of drugs typically used as antibiotics or antimicrobials. The defining structural component is a furan ring with a nitro group.
Cefditoren, also known as cefditoren pivoxil is an antibiotic used to treat infections caused by Gram-positive and Gram-negative bacteria that are resistant to other antibiotics. It is mainly used for treatment of community acquired pneumonia. It is taken by mouth and is in the cephalosporin family of antibiotics, which is part of the broader beta-lactam group of antibiotics.
Fosfomycin, sold under the brand name Monurol among others, is an antibiotic primarily used to treat lower urinary tract infections. It is not indicated for kidney infections. Occasionally it is used for prostate infections. It is generally taken by mouth.
Bacteriuria is the presence of bacteria in urine. Bacteriuria accompanied by symptoms is a urinary tract infection while that without is known as asymptomatic bacteriuria. Diagnosis is by urinalysis or urine culture. Escherichia coli is the most common bacterium found. People without symptoms should generally not be tested for the condition. Differential diagnosis include contamination.
Ceftolozane/tazobactam, sold under the brand name Zerbaxa, is a fixed-dose combination antibiotic medication used for the treatment of complicated urinary tract infections and complicated intra-abdominal infections in adults. Ceftolozane is a cephalosporin antibiotic, developed for the treatment of infections with gram-negative bacteria that are resistant to conventional antibiotics. It was studied for urinary tract infections, intra-abdominal infections and ventilator-associated bacterial pneumonia.
Gepotidacin (INN) is an experimental antibiotic that acts as a topoisomerase type II inhibitor. It is being studied for the treatment of uncomplicated urinary tract infection and infection with Neisseria gonorrhoeae (gonorrhea), including multidrug resistant strains.
Urinary anti-infective agent, also known as urinary antiseptic, is medication that can eliminate microorganisms causing urinary tract infection (UTI). UTI can be categorized into two primary types: cystitis, which refers to lower urinary tract or bladder infection, and pyelonephritis, which indicates upper urinary tract or kidney infection. Escherichia coli is the predominant microbial trigger of UTIs, accounting for 75% to 95% of reported cases. Other pathogens such as Proteus mirabilis, Klebsiella pneumoniae, and Staphylococcus saprophyticus can also cause UTIs.
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