Nitrofurantoin Chemical formula
Synonyms: Furadoninum; Nitrofurantoiini; Nitrofurantoína; Nitrofurantoina; Nitrofurantoinas; Nitrofurantoïne; Nitrofurantoinum. 1-(5-Nitrofurfurylideneamino)hydantoin; 1-(5-Nitrofurfurylideneamino)imidazolidine-2,4-dione.
Cyrillic synonym: Нитрофурантоин.

💊 Chemical information

Chemical formula: C8H6N4O5 = 238.2.
CAS — 67-20-9 (anhydrous nitrofurantoin); 17140-81-7 ATC — J0 1 XE01.
ATC Vet — QJ0 1XE01.


In Chin. and Eur.. Int. and US specify anhydrous or monohydrate.

Ph. Eur. 6.2

(Nitrofurantoin). A yellow, odourless or almost odourless, crystalline powder or crystals. Very slightly soluble in water and in alcohol; soluble in dimethylformamide. Store at a temperature not exceeding 25°. Protect from light.

USP 31

(Nitrofurantoin). It is anhydrous or contains one molecule of water of hydration. Lemon-yellow, odourless crystals or fine powder. Nitrofurantoin and its solutions are discoloured by alkalis and by exposure to light, and are decomposed on contact with metals other than stainless steel or aluminium. Very slightly soluble in water and in alcohol; soluble in dimethylformamide. Store in airtight containers. Protect from light.

💊 Adverse Effects

The estimated incidence of adverse effects with nitrofurantoin has varied enormously, but may be around 10% overall; an incidence of serious reactions of about 0.001% for pulmonary, and 0.0007% for neurological reactions has been suggested. The most common adverse effects of nitrofurantoin involve the gastrointestinal tract. They are dose-related and generally include nausea, vomiting, and anorexia; abdominal pain and diarrhoea occur less frequently. It has been reported that adverse effects on the gastrointestinal tract are less common when nitrofurantoin is given in a macrocrystalline form or with food. Neurological adverse effects include headache, drowsiness, vertigo, dizziness, nystagmus, and benign intracranial hypertension. Severe and sometimes irreversible peripheral neuropathy has developed, particularly in patients with renal impairment and in those given prolonged therapy. Hypersensitivity reactions such as skin rashes, urticaria, pruritus, fever, sialadenitis, and angioedema may occur. Anaphylaxis, erythema multiforme, StevensJohnson syndrome, exfoliative dermatitis, pancreatitis, a lupus-like syndrome, myalgia, and arthralgia have also been reported. Patients with a history of asthma may experience acute asthmatic attacks. Acute pulmonary sensitivity reactions characterised by sudden onset of fever, chills, eosinophilia, cough, chest pain, dyspnoea, pulmonary infiltration or consolidation, and pleural effusion may occur within hours to a few days of beginning therapy, but they usually resolve on stopping treatment. Subacute or chronic pulmonary symptoms including interstitial pneumonitis and pulmonary fibrosis may develop more insidiously in patients on long-term therapy and the latter are not always reversible, particularly if therapy is continued after onset of symptoms. Hepatotoxicity including cholestatic jaundice, hepatitis, and hepatic necrosis may develop rarely, particularly in women, and may represent a hypersensitivity reaction. Other adverse effects include megaloblastic anaemia, leucopenia, granulocytopenia or agranulocytosis, thrombocytopenia, aplastic anaemia, and haemolytic anaemia in persons with a genetic G6PD deficiency. Transient alopecia has been reported. Nitrofurantoin may cause a brownish discoloration of the urine. There is limited evidence from animal studies that nitrofurantoin may be carcinogenic, although this has not been shown conclusively in humans.
1. Koch-Weser J, et al. Adverse reactions to sulfisoxazole, sulfamethoxazole, and nitrofurantoin: manifestations and specific reaction rates during 2118 courses of therapy. Arch Intern Med 1971; 128: 399–404
2. Holmberg L, et al. Adverse reactions to nitrofurantoin: analysis of 921 reports. Am J Med 1980; 69: 733–8
3. Penn RG, Griffin JP. Adverse reactions to nitrofurantoin in the United Kingdom, Sweden, and Holland. BMJ 1982; 284: 1440–2
4. D’Arcy PF. Nitrofurantoin. Drug Intell Clin Pharm 1985; 19: 540–7
5. Karpman E, Kurzrock EA. Adverse reactions of nitrofurantoin, trimethoprim and sulfamethoxazole in children. J Urol (Baltimore) 2004; 172: 448–53.

Effects on the lungs.

References1,2 to pulmonary toxicity associated with long-term nitrofurantoin treatment.
1. Adverse Drug Reactions Advisory Committee (ADRAC). Pulmonary toxicity with long-term nitrofurantoin. Aust Adverse Drug React Bull 2004; 23: 15. Also available at: http:// (accessed 11/01/08
2. Mendez JL, et al. Chronic nitrofurantoin-induced lung disease. Mayo Clin Proc 2005; 80: 1298–1302.

💊 Precautions

Nitrofurantoin should not be given to patients with renal impairment since antibacterial concentrations in the urine may not be attained and toxic concentrations in the plasma can occur. Nitrofurantoin is also contraindicated in patients known to be hypersensitive to nitrofurans, in those with G6PD deficiency, and in infants (in the UK it is contra-indicated below 3 months of age, though the USA permits use from 1 month old). Nitrofurantoin should be used with care in the elderly, who may be at increased risk of toxicity, particularly acute pulmonary reactions. All patients undergoing prolonged therapy should be monitored for changes in pulmonary function, and the drug withdrawn at the first signs of pulmonary damage. Care is required in patients with pre-existing pulmonary, hepatic, neurological, or allergic disorders, and in those with conditions (such as anaemia, diabetes mellitus, electrolyte imbalance, debility, or vitamin B deficiency) which may predispose to peripheral neuropathy. Nitrofurantoin should be withdrawn if signs of peripheral neuropathy develop. Although hepatic reactions such as hepatitis, cholestatic jaundice, and hepatic necrosis rarely occur, fatalities have been reported. Patients should be monitored, and the drug stopped immediately if hepatitis occurs. Nitrofurantoin may cause false positive reactions in urine tests for glucose using copper reduction methods.

Breast feeding.

The American Academy of Pediatrics considers that, although nitrofurantoin is excreted into breast milk, it is usually compatible with breast feeding, but caution is necessary in breast-fed infants with G6PD deficiency.1 The BNFC suggests that the amount ingested may be enough to produce haemolysis in G6PD-deficient infants; it recommends that nitrofurantoin should be avoided in mothers who are breast feeding.
1. American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 2001; 108: 776–89. Correction. ibid.; 1029. Also available at: pediatrics%3b108/3/776 (accessed 11/01/08)


Nitrofurantoin has been associated with acute attacks of porphyria and is considered to be unsafe in porphyric patients.


Licensed product information contraindicates the use of nitrofurantoin in pregnant patients at term (38 to 42 weeks’ of gestation), or during labour and delivery, because of the possibility of producing haemolytic anaemia in the neonate.

💊 Interactions

Nitrofurantoin and the quinolone antibacterials are antagonistic in vitro but the clinical significance is unknown. The antibacterial activity of nitrofurantoin may be decreased in the presence of carbonic anhydrase inhibitors and other drugs that alkalinise the urine. Probenecid or sulfinpyrazone should not be given with nitrofurantoin as they may reduce its excretion. Magnesium trisilicate may reduce the absorption of nitrofurantoin but it is not clear whether this applies to other antacids.


For reference to the effect of nitrofurantoin on phenytoin.


An elderly patient who had been taking nitrofurantoin daily for 5 years developed combined hepatic and pulmonary toxicity 2 months after also starting fluconazole therapy.1Although either drug may have caused the hepatic toxicity, possible pharmacokinetic changes induced by an interaction with fluconazole may have precipitated the nitrofurantoin-induced pulmonary toxicity.
1. Linnebur SA, Parnes BL. Pulmonary and hepatic toxicity due to nitrofurantoin and fluconazole treatment. Ann Pharmacother 2004; 38: 612–16.

Hormonal contraceptives.

For mention of a possible decrease in contraceptive efficacy when nitrofurantoin was used with oral contraceptives, see under Hormonal Contraceptives.

💊 Antimicrobial Action

Nitrofurantoin is bactericidal in vitro to most Gram
positive and Gram-negative urinary-tract pathogens. The mode of action is uncertain but appears to depend on the formation of reactive intermediates by reduction; this process occurs more efficiently in bacterial than in mammalian cells. It is effective against the enterococci in vitro, as well as various other Gram-positive species including staphylococci, streptococci, and corynebacteria, although this is of little clinical significance. Most strains of Escherichia coli are particularly sensitive to nitrofurantoin but Enterobacter and Klebsiella spp. are less susceptible and some may be resistant. Pseudomonas aeruginosa is resistant as are most strains of Proteus spp. Nitrofurantoin is most active in acid urine, and if the pH exceeds 8 most of the antibacterial activity is lost. Resistance rarely develops during nitrofurantoin treatment but may occur during prolonged treatment. Plasmid-encoded resistance has been reported in E. coli. Resistance may be due to the loss of nitrofuran reductases which generate the active intermediates.

💊 Pharmacokinetics

Nitrofurantoin is readily absorbed from the gastrointestinal tract. The absorption rate is dependent on crystal size. The macrocrystalline form has slower dissolution and absorption rates, produces lower serum concentrations than the microcrystalline form, and takes longer to achieve peak concentrations in the urine. The presence of food in the gastrointestinal tract may increase the bioavailability of nitrofurantoin and prolong the duration of therapeutic urinary concentrations. Preparations of nitrofurantoin from different sources may not be bioequivalent, and care may be necessary if changing from one brand to another. On absorption, concentrations in blood and body tissues are low because of rapid elimination, and antibacterial concentrations are not achieved. Nitrofurantoin crosses the placenta and the blood-brain barrier and traces have been detected in breast milk. There is some disagreement about the degree of protein binding, and although figures of up to about 60% are quoted by some sources, others suggest that the figure should be as much as 90%. The plasma half-life is reported to range from 0.3 to 1 hour. Nitrofurantoin is metabolised in the liver and most body tissues while about 30 to 40% of a dose is excreted rapidly in the urine as unchanged nitrofurantoin. Some tubular reabsorption may occur in acid urine. Average doses give a concentration of 50 to 200 micrograms/mL in the urine in patients with normal renal function.

💊 Uses and Administration

Nitrofurantoin is a nitrofuran antibacterial that is used in the treatment of uncomplicated lower urinary-tract infections, including prophylaxis or long-term suppressive therapy in recurrent infection. It is given orally, in a usual dose of 50 to 100 mg four times daily, with food or milk. Treatment is usually continued for 7 days. A dual-release formulation, consisting of macrocrystalline nitrofurantoin and nitro furantoin monohydrate, is available in some countries and is given in a dose of 100 mg twice daily. A usual long-term prophylactic dose is 50 to 100 mg at bedtime. For details of doses in children, see below.
1. Guay DR. An update on the role of nitrofurans in the management of urinary tract infections. Drugs 2001; 61: 353–64.

Administration in children.

In the UK, nitrofurantoin may be given to children aged 3 months to 12 years for the treatment of urinary-tract infection in a usual oral dose of 3 mg/kg daily given in 4 divided doses; 1 mg/kg may be given at night for long-term prophylactic therapy. However, a systematic review1 concluded, on the basis of the rather low-grade evidence available, that the adverse effects of nitrofurantoin may outweigh its benefits and render it unacceptable for long-term therapy. Higher oral doses of 5 to 7 mg/kg daily in 4 divided doses are recommended for the treatment of urinary-tract infection in the USA in children aged 1 month and above; for long-term prophylactic therapy 1 mg/kg daily given in one or two divided doses is considered adequate. Older children may be given usual adult doses (see above).
1. Williams GJ, et al. Long-term antibiotics for preventing recurrent urinary tract infection in children. Available in The Cochrane Database of Systematic Reviews; Issu
3. Chichester: John Wiley; 2006 (accessed 11/01/08).

💊 Preparations

BP 2008: Nitrofurantoin Oral Suspension; Nitrofurantoin Tablets; USP 31: Nitrofurantoin Capsules; Nitrofurantoin Oral Suspension; Nitrofurantoin Tablets.

Proprietary Preparations

Arg.: Furadantina; Austral.: Furadantin; Macrodantin; Ralodantin†; Austria: Furadantin; Belg.: Furadantine; Braz.: Hantina; Macrodantina; Nitrofen; Urogem; Canad.: Macrobid; Macrodantin†; Novo-Furantoin; Chile: Macrodantina; Macrosan; Matidan; Cz.: Furantoin†; Nifurantin†; Fin.: NitrofurC; Fr.: Furadantine; Furadoine; Microdoine; Ger.: Furadantin; Nifurantin; Nifuretten; Uro-Tablinen; Gr.: Furolin; India: Furadantin; Irl.: Furadantin; Macrobid; Macrodantin; Israel: Macrodantin†; Uvamin; Ital.: Furadantin; Furedan; Furil; Macrodantin; Neo-Furadantin; Mex.: Biofurin; Furadantina; Furitex; Futroken; Macrodantina; Macrofurin; Promac; Suronit; Neth.: Furabid; Furadantine MC; Norw.: Furadantin; NZ: Furadantin; Nifuran; Philipp.: Macrodantin; Pol.: Siraliden; Port.: Furadantina; S.Afr.: Furadantin; Macrodantin; Spain: Furantoina; Furobactina; Swed.: Furadantin; Switz.: Furadantine; Urodin; Uvamine retard; Turk.: Piyeloseptyl; UK: Furadantin; Macrobid; Macrodantin; USA: Furadantin; Macrobid; Macrodantin; Venez.: Furadina†; Macrodantina. Multi-ingredient: Arg.: Bagociletas con Anestesia; Bagociletas sin Anestesia†; Braz.: Urofen†; Uropac; Ger.: Nifurantin B 6; Urospasmon sine†; Urospasmon†; India: Nephrogesic; Mex.: Furanton†; Turk.: Uriseptin.
Published May 08, 2019.