Nitrofurantoin detailed information
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| Clinical data | |
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| Routes of administration | oral |
| ATC code | |
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| Pharmacokinetic data | |
| Bioavailability | 40% |
| Metabolism | liver (75%) |
| Elimination half-life | 20 minutes |
| Excretion | urine and bile |
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| E number | {{#property:P628}} |
| ECHA InfoCard | {{#property:P2566}}Lua error in Module:EditAtWikidata at line 36: attempt to index field 'wikibase' (a nil value). |
| Chemical and physical data | |
| Formula | C8H6N4O5 |
| Molar mass | 238.16 |
Nitrofurantoin is an antibiotic. It is usually used in treating urinary tract infection. Like many other drugs, it is often used for killing E Coli.
Pharmacology
Organisms are said to be susceptible to nitrofurantoin if their Minimum inhibitory concentration (MIC) is 32μg/ml or less. The peak blood concentration of nitrofurantoin following an oral dose of nitrofurantoin 100mg, is less than 1 μg/ml and may be undetectable; 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. For this reason, nitrofurantoin cannot be used to treat anything other than simple cystitis.
At the concentrations achieved in urine, nitrofurantoin is bacteriocidal. The mechanism of action of nitrofurantoin is unique and complex. The drug works by damaging bacterial DNA, since its reduced form is highly reactive. 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,[1] respiration, pyruvate metabolism and other macromolecules within the cell. It is not known which of the actions of nitrofurantoin is primarily responsible for its bacteriocidal acitivity.
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.[2] 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.
Uses
The normal adult dose of nitrofurantoin is 50 to 100 mg four times daily for seven days. If a long-acting preparation (e.g., Macrobid) is used then the dose is 100mg twice daily. The pediatric dose is 3mg/kg/day in four divided doses. Nitrofurantoin should be taken with food, as this improves the absorption of the drug by 45%.
Nitrofurantoin is only clinically proven for use against E. coli or Staph. saprophyticus. It may also have in vitro activity against:
- Coagulase-negative staphylococci
- Enterococcus faecalis,
- Staphylococcus aureus,
- Streptococcus agalactiae,
- Citrobacter species,
- Klebsiella species,
and is used in the treatment of infections caused by these organisms. Only a minority of Enterobacter species and Klebsiella species are sensitive to nitrofurantoin; nitrofurantoin has no activity against
- Acinetobacter species,
- Morganella species,
- Proteus species,
- Providentia species,
- Serratia species, or
- Pseudomonas species.
Nitrofurantoin must never be used to treat pyelonephritis,[3] renal abscess, and pyeloempyema because of extremely poor tissue penetration and low blood levels. Urinary catheter infections may be treated with nitrofurantoin if there are no systemic features; the catheter must be changed after 48 hours of antibiotics and treatment is ineffective if the catheter is not replaced or removed.
Adverse effects
Nitrofurantoin can cause nausea and vomiting, fever, rash, hypersensitivity pneumonitis. When given for long periods of time, nitrofurantoin can cause progressive pulmonary interstitial fibrosis. All these side effects are much more common in the elderly.
Patients should be informed that nitrofurantoin colours urine a dark orange-brown; this is completely harmless.
Neonates (babies up to the age of one month) have immature enzyme systems in their red blood cells (glutathione instability) and nitrofurantoin must therefore not be used because it can cause haemolytic anaemia. For the same reason, nitrofurantoin should not be given to pregnant women after 38 weeks of pregnancy, or who are about to give birth.
Nitrofurantoin is contraindicated in patients with decreased renal function (CrCl < 60ml/min) due to systemic accumulation and subtherapeutic levels reached in the urinary tract.
Precautions
Nitrofurantoin must be taken with food and can cause bleeding in the stomach, vomiting and other gastrointestinal disruptions if these warnings are not adhered to. Nitrofurantoin is contraindicated in patients with glucose-6-phosphate dehydrogenase deficiency because of risk of extravascular hemolysis resulting in anemia.
Trade names
- Furadantin (U.S., UK)
- Macrobid (long acting preparation for twice daily dosing available in U.S., Canada, and UK)
- Macrodantin (U.S., UK)
- furatin( inda medica INDIA)
References
- ↑ Tu Y, McCalla DR (1975). "Effect of activated nitrofurans on DNA,". Biochem Biophys Acta. 402: 142&ndash, 49.
- ↑ McCalla DR, Kaiser C, Green MHL (1978). "Genetics of nitrofurazone resistance in Escherichia coli". J Bacteriol. 133: 10&ndash, 16.
- ↑ Richards WA; et al. (1955). "Nitrofurantoin: Clinical and laboratory studies in urinary tract infections". Arch Intern Med. 96: 437&ndash, 50.
- drugs.com for Macrodantin
- Meds-Help.com for Nitrofurantoin side effects, interactions and information
- RxList for Macrobid (Nitrofurantoin)
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- Antibiotics
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