Noroxin (Norfloxacin)

Norfloxacin is a fluoroquinolone anti-infective. In adults, it is used to treat complicated and uncomplicated urinary tract infections and prostatitis caused by susceptible organisms, as well as uncomplicated gonorrhoea.

Uses

Norfloxacin has also been used in adults to treat various gastrointestinal (GI) infections caused by susceptible organisms. Because only low blood levels of norfloxacin are reached after the usual oral doses, its use is generally limited to genitourinary or GI tract infections. Before starting norfloxacin, appropriate samples should be taken to identify the causative organism and in vitro susceptibility testing should be carried out.

Norfloxacin may be started before the test results are available. However, if the response to treatment is unsatisfactory, further samples should be taken and susceptibility testing repeated.

Urinary Tract Infections and Prostatitis

Uncomplicated Urinary Tract Infections

Oral norfloxacin is prescribed for adults with uncomplicated urinary tract infections (UTIs) caused by susceptible bacteria, including Escherichia coli (E. coli) and Klebsiella pneumoniae (K. pneumoniae). Some clinicians recommend reserving norfloxacin for complicated UTIs, particularly those involving multidrug-resistant bacteria, and advise against using it for uncomplicated cases unless first-line treatments are ineffective or not tolerated.

Studies suggest that a 7-10 day course of norfloxacin is as effective as co-trimoxazole, with fewer side effects. Norfloxacin has also shown similar effectiveness to amoxicillin for uncomplicated UTIs. Limited data suggest that a 3-day course may be enough, but more research is needed to assess relapse and recurrence rates.

While norfloxacin can be effective, it is generally not the first choice for uncomplicated UTIs because of concerns about antibiotic resistance and possible side effects. It is mainly considered when other treatments have failed or resistance has been confirmed.

Complicated Urinary Tract Infections

Oral norfloxacin is used in adults to treat complicated UTIs caused by susceptible E. coli, K. pneumoniae, Proteus mirabilis (P. mirabilis), Pseudomonas aeruginosa (Ps. aeruginosa), Serratia marcescens (S. marcescens), or Enterococcus faecalis (E. faecalis). Oral norfloxacin has generally been effective in adults with chronic bacteriuria or complicated UTIs caused by susceptible organisms, including Ps. aeruginosa. In a limited number of patients, oral norfloxacin appeared to be as effective as parenteral anti-infective therapy for non-bacteraemic hospital-acquired UTIs. However, further study is needed to compare the relative effectiveness of oral norfloxacin with the parenteral anti-infectives usually used for complicated UTIs. Some clinicians suggest that norfloxacin may be particularly useful for UTIs caused by organisms resistant to other anti-infectives (for example, beta-lactam antibiotics and aminoglycosides), and for chronic or complicated UTIs when parenteral anti-infective therapy is not needed.

Prostatitis

Oral norfloxacin is used to treat prostatitis caused by E. coli.

Gonorrhoea and Associated Infections

Oral norfloxacin is not generally used in the UK for uncomplicated gonorrhoea in adults, where treatment recommendations are guided by British sexual health guidance and usually centre on ceftriaxone-based management. Although a single 800-mg dose of norfloxacin has shown activity, its role is limited by concerns about treatment failure and the spread of fluoroquinolone-resistant Neisseria gonorrhoeae in the UK and internationally.

In the UK, uncomplicated gonorrhoea is generally managed with ceftriaxone-based treatment in line with national sexual health guidance. Reports of treatment failure with norfloxacin, together with widespread resistance, mean that fluoroquinolones are generally avoided, particularly when the infection may have been acquired in areas with known resistance.

While studies suggest that norfloxacin may be as effective as intramuscular (IM) spectinomycin for specific strains, its effectiveness for pharyngeal infections remains uncertain. Overall, UK practice places strong emphasis on monitoring resistance patterns, and gonorrhoea treatment follows current national recommendations rather than routine use of norfloxacin.

GI Infections

Norfloxacin has been effective when used in adults to treat gastroenteritis caused by susceptible strains of enterotoxigenic E. coli, Aeromonas hydrophila, Plesiomonas shigelloides, Salmonella, Shigella boydii, Shigella (Sh.) dysenteriae, Sh. flexneri, Sh. sonnei, Vibrio cholerae, or Vibrio (V.) parahaemolyticus. Although some strains of Helicobacter pylori (formerly Campylobacter pylori or C. pyloridis) are susceptible to norfloxacin in vitro, the medicine has been ineffective in eradicating the organism in vivo and has had little effect on gastritis symptoms in a limited number of patients with non-ulcer dyspepsia.

Cholera

Norfloxacin has been effective when used in the treatment of cholera. Although tetracyclines are generally the anti-infectives of choice for cholera alongside fluid and electrolyte replacement, when the infection is caused by strains of V. cholerae resistant to tetracyclines, alternatives include co-trimoxazole, fluoroquinolones, or furazolidone. In one study in adults with severe cholera and dehydration, norfloxacin was more effective than co-trimoxazole at reducing stool output and shortening the duration of diarrhoea, fluid requirements, and excretion of vibrio.

Shigella Infections

Oral norfloxacin is used to treat shigellosis caused by susceptible Shigella. Anti-infective therapy is generally indicated, alongside fluid and electrolyte replacement, for severe shigellosis because these medicines appear to shorten the duration of diarrhoea and the period of faecal excretion of Shigella. A fluoroquinolone (for example, ciprofloxacin, norfloxacin, ofloxacin) or ceftriaxone is considered a drug of choice for treating shigellosis when the susceptibility of the isolate is unknown; azithromycin has also been recommended, and co-trimoxazole or ampicillin may be effective if the strain is known to be susceptible to these medicines. In one controlled study in adults with acute shigellosis, an 800-mg oral dose of norfloxacin was as effective as 5 days of co-trimoxazole treatment.

Travellers' Diarrhoea

Norfloxacin is effective for short-term treatment and prevention of travellers' diarrhoea in adults travelling to high-risk areas. This is mainly caused by enterotoxigenic E. coli, but can also be caused by other pathogens such as Shigella and Salmonella. Treatment depends on how severe the illness is. Mild cases may only need oral rehydration, while moderate to severe cases may benefit from anti-infective treatment, which can shorten the illness considerably.

Fluoroquinolones such as norfloxacin, ciprofloxacin, levofloxacin, and ofloxacin are commonly used for treatment. Azithromycin is an alternative for children and pregnant women, especially in regions with high Campylobacter resistance. Co-trimoxazole can also be used, but resistance is a concern.

UK travel health advice generally discourages the routine prophylactic use of anti-infectives for most travellers because of resistance risks and the potential for side effects. Although prophylactic antibiotics have shown effectiveness in controlled studies, they are usually reserved for selected high-risk individuals. Instead, travellers should focus on preventive measures such as safe food and water practices to reduce the risk of diarrhoea.

Mechanism of Action

Norfloxacin is usually bactericidal. Like other fluoroquinolone anti-infectives, it inhibits deoxyribonucleic acid (DNA) synthesis in susceptible organisms by blocking type II DNA topoisomerases (DNA gyrase and topoisomerase IV). In vitro studies, particularly susceptibility tests, indicate that the antibacterial activity of norfloxacin is reduced in the presence of urine, especially acidic urine.

The clinical importance of this in vitro effect has not yet been determined. However, because norfloxacin concentrations reached in urine are usually much higher than the norfloxacin minimum inhibitory concentrations (MICs) for most urinary tract pathogens, the effect is probably not clinically important. Norfloxacin has a similar spectrum of activity to many other fluoroquinolones (for example, ciprofloxacin and ofloxacin). It is active in vitro against gram-negative aerobic bacteria, including Enterobacteriaceae and Pseudomonas aeruginosa.

The medicine is also active in vitro against many gram-positive aerobic bacteria, including penicillinase-producing, non-penicillinase-producing, and oxacillin-resistant staphylococci (previously known as methicillin-resistant staphylococci). However, many strains of streptococci are relatively resistant to the medicine. Obligately anaerobic bacteria are generally resistant to norfloxacin.

The medicine has some in vitro activity against Chlamydia, Mycoplasma, and some Mycobacterium, but it is inactive against fungi and viruses.

Pharmacokinetics

• Absorption: Norfloxacin is rapidly absorbed from the GI tract, although food can delay absorption. Peak plasma concentrations occur within 1-2 hours of a dose, with 30-50% of the dose absorbed. Antacids containing magnesium or aluminium reduce its bioavailability.
• Distribution: Norfloxacin is widely distributed in various tissues, including the kidneys, liver, and prostatic tissue. Biliary concentrations can be much higher than serum levels, and it crosses the placenta. However, it is not detected in breast milk after a 200-mg dose.
• Elimination: The half-life in adults with normal renal function is 2.3-4 hours; this increases with renal impairment. Approximately 30% of a dose is excreted unchanged in the urine within 24-48 hours. Norfloxacin undergoes minimal metabolism, producing less active metabolites.

Norfloxacin is mainly eliminated by the kidneys, and dose adjustment may be needed in patients with impaired renal function.

Administration

Norfloxacin is taken by mouth. It should be taken with a glass of water at least 1 hour before or at least 2 hours after a meal or after consuming milk or other dairy products. Patients taking norfloxacin should stay well hydrated and drink plenty of fluids. To reduce the risk of interference with GI absorption, patients should be told not to take antacids containing magnesium or aluminium, sucralfate, metal cations such as iron or zinc (including multivitamin preparations containing zinc), or buffered didanosine preparations at the same time as norfloxacin or within 2 hours of a dose.

Dosage

Dosage forms of norfloxacin:

• Co Norfloxacin 400 mg Tablet;
• Novo-Norfloxacin 400 mg Tablet;
• Pms-Norfloxacin 400 mg Tablet;
• Apo-Norflox 400 mg Tablet;
• Noroxin 400 mg tablet.

Because of the risk of crystalluria, the manufacturer recommends that the usual dose of 400 mg twice daily should not be exceeded in adults with normal renal function.

Drug-Drug Interactions

This medicine may interact with some drugs.

1. Antacids. Antacids containing magnesium hydroxide or aluminium hydroxide may reduce the absorption of oral norfloxacin, and the drugs should not be taken at the same time. Patients should be told not to take antacids at the same time as norfloxacin or within 2 hours of a dose. The mechanism of this interaction has not been fully explained. However, studies using ciprofloxacin suggest that antacids containing magnesium and aluminium ions may bind to quinolones and form insoluble complexes in the GI tract.
2. Antifungal Agents. Norfloxacin has no antifungal activity when used alone. However, some in vitro studies involving Candida have suggested that norfloxacin may enhance the activity of certain antifungal agents, including amphotericin B, flucytosine, ketoconazole, miconazole, and nystatin. The evidence is conflicting, and at least one in vitro study found that norfloxacin did not affect the activity of amphotericin B. Further studies are needed to clarify whether norfloxacin has any clinically relevant antifungal-enhancing effect when used with an antifungal medicine. In the UK, miconazole is used locally, including as an oral gel, and sufficient systemic absorption may occur for interactions to be relevant.
3. Aminoglycosides. The antibacterial activities of norfloxacin and aminoglycosides may be additive or partly synergistic in vitro against gram-negative bacteria (for example, Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, Morganella morganii, Proteus). However, synergism between the drugs appears unpredictable, and indifference or antagonism has also been reported when norfloxacin was used with an aminoglycoside against Enterobacteriaceae or Ps. aeruginosa.
4. Coumarin Anticoagulants. Starting oral norfloxacin in patients stabilised on warfarin has resulted in prolonged prothrombin time in several patients and, in at least one patient, using the drugs together resulted in increased prothrombin time and fatal pontine haemorrhage. The mechanism of this interaction has not been determined. However, norfloxacin may displace the anticoagulants from serum albumin-binding sites. Norfloxacin should be used cautiously in patients receiving a coumarin anticoagulant, and prothrombin time or another suitable coagulation test should be monitored closely.
5. Cyclosporine. Taking cyclosporine and norfloxacin together has increased serum concentrations of cyclosporine. Therefore, the manufacturer recommends monitoring cyclosporine serum concentrations and making appropriate dose adjustments in patients receiving it with norfloxacin.
6. Didanosine. Didanosine chewable/dispersible buffered tablets, buffered powder for oral solution, or paediatric powder for oral solution prepared as an admixture with antacid may interfere with oral absorption of norfloxacin. To reduce the risk of interaction, patients should be told not to take didanosine preparations at the same time as norfloxacin or within 2 hours of a dose.
7. Iron, Multivitamins, and Mineral Supplements. Oral multivitamins and mineral supplements containing divalent or trivalent cations such as iron or zinc may interfere with oral absorption of norfloxacin, resulting in decreased serum and urine concentrations of the quinolone. Therefore, these multivitamins and/or mineral supplements should not be taken at the same time as norfloxacin or within 2 hours of a dose.
8. Nitrofurantoin. In vitro, nitrofurantoin antagonises the antibacterial activity of norfloxacin. Since antagonism could occur in vivo, norfloxacin and nitrofurantoin should not be used at the same time.
9. Other Anti-infectives. In vitro, chloramphenicol, rifampicin, or tetracycline can inhibit the bactericidal activity of norfloxacin. In one in vitro study, the combination of norfloxacin with chloramphenicol or tetracycline was antagonistic against all Salmonella isolates tested. In an in vitro study using strains of Ps. aeruginosa resistant to aminoglycosides and carbenicillin, the antibacterial activities of imipenem and norfloxacin were synergistic or partly synergistic against about one-third of the strains tested and indifferent against about two-thirds; antagonism did not occur. In vitro studies using gram-positive and gram-negative bacteria indicate that neither synergism nor antagonism occurs when norfloxacin is used with a beta-lactam antibiotic (for example, ampicillin, cefotaxime, cefoxitin).
10. Probenecid. Taking probenecid with norfloxacin substantially decreases urinary excretion of norfloxacin, possibly by blocking the renal tubular secretion of the anti-infective. However, serum concentrations and half-life of norfloxacin are generally not affected.
11. Sucralfate. Taking sucralfate with norfloxacin may interfere with oral absorption of norfloxacin, resulting in decreased serum and urine concentrations of the quinolone, and some clinicians state that using ofloxacin with sucralfate at the same time is not recommended. If concomitant use of ofloxacin and sucralfate is necessary, the manufacturer and some clinicians recommend that sucralfate doses should not be taken at the same time as norfloxacin or within 2 hours of a dose.
12. Xanthine Derivatives. Using some quinolones (for example, ciprofloxacin and norfloxacin) at the same time as theophylline has increased plasma theophylline concentrations and decreased drug clearance. This may increase the risk of theophylline-related side effects. Taking norfloxacin with an extended-release theophylline preparation in a limited number of individuals produced slight increases in serum theophylline concentrations compared with some other quinolone derivatives. In other studies, taking norfloxacin in patients stabilised on theophylline resulted in, at most, an 18% increase in plasma theophylline concentrations and a decrease in theophylline clearance of 5-28%. Some clinicians suggest that the interaction between norfloxacin and theophylline may not be clinically important in most patients. However, there have been reports of theophylline-related side effects in patients taking norfloxacin at the same time. Therefore, some clinicians suggest that norfloxacin should be used cautiously in patients receiving theophylline. The manufacturer of norfloxacin states that monitoring plasma theophylline concentrations should be considered, and theophylline dosage should be adjusted as required. Some quinolones (for example, ciprofloxacin) have also been reported to alter the pharmacokinetics of caffeine, and the possibility of exaggerated or prolonged effects of caffeine during concomitant use with a quinolone should be considered.
13. Oral contraceptives. Plasma concentrations of oral contraceptive steroids were unchanged by norfloxacin.

Food-Drug Interactions

Norfloxacin has several food-drug interactions that can affect its absorption and effectiveness. In particular, dairy products such as milk and yoghurt should be avoided, as they can reduce the absorption of norfloxacin by around 50% when taken together. In addition, antacids or supplements containing minerals such as calcium, iron, or magnesium should not be taken within two hours of norfloxacin, as they may also affect its bioavailability.

Side Effects

Oral norfloxacin is generally well tolerated at the doses used to treat urinary tract infections, and its side effects are similar to those reported with other quinolone anti-infectives (for example, ciprofloxacin and ofloxacin).

Norfloxacin is a fluoroquinolone antibacterial medicine with properties similar to ciprofloxacin, although it is less potent in vitro.

Norfloxacin inhibits cytochrome P450 1A2 (CYP1A2) and can therefore increase the effects of other drugs by reducing their clearance.

Organs and Systems

• Sensory systems: A corneal ulcer associated with deposits of norfloxacin in the right eye has been reported in a 40-year-old man with right trigeminal and facial nerve palsies and reduced tear secretion. He stopped using norfloxacin ophthalmic solution and recovered.
• Psychological, psychiatric. There have been reports of hallucinations with norfloxacin.
• Haematological. Eosinophilia occurred in a 35-year-old man with alcoholic cirrhosis taking norfloxacin 400 mg twice daily (bid) for prophylaxis of spontaneous bacterial peritonitis.
• Gastrointestinal. In a prospective study of women with urinary tract infections treated with pivmecillinam 400 mg twice daily for 3 days or norfloxacin 400 mg twice daily for 3 days, 36% of the pivmecillinam-treated patients and 39% of the norfloxacin-treated patients reported side effects. Gastrointestinal symptoms were the most frequent. Of the patients who took norfloxacin, 4.3% had vaginal candidiasis.
• Liver. Acute hepatitis has been reported with norfloxacin.
• Pancreas. Norfloxacin can cause pancreatitis.
• Urinary tract. Acute interstitial nephritis, probably related to norfloxacin, has been reported.
• Musculoskeletal. Myalgia has been attributed to norfloxacin.

Side effects have been reported in about 3.5-10% of patients taking norfloxacin, and in 1% or fewer they were severe enough to stop treatment.

In clinical trials, the side effects reported most often affected the gastrointestinal (GI) tract or central nervous system (CNS). However, in post-marketing use, rash has been the most commonly reported side effect.

Side effects have occurred in about 7% of patients taking a single 800-mg oral dose of norfloxacin to treat uncomplicated gonorrhoea. Dizziness, nausea and abdominal cramping were reported most often with this single-dose regimen, occurring in 2-3.5% of patients. Diarrhoea, vomiting, anorexia, constipation, dyspepsia, headache, tingling in the fingers, hyperhidrosis, reduced haemoglobin and haematocrit, and a reduced platelet count have also been reported. Increased aspartate aminotransferase (AST) (SGOT) concentrations were reported in 1% or fewer of patients receiving the single-dose regimen.

GI Effects

Nausea is one of the most common side effects of norfloxacin. It has been reported in about 1-4% of patients taking the medicine. Other GI side effects reported in 1% or fewer of patients include abdominal pain, cramping, loose stools, diarrhoea, vomiting, anorexia, dyspepsia, dysphagia, dysgeusia, stomatitis, dry mouth, a bitter taste, heartburn, digestive upset, constipation, flatulence and pruritus ani.

Effects on Fecal Flora

Norfloxacin selectively affects the normal bowel flora, reducing gram-negative aerobic bacteria while leaving anaerobic and gram-positive flora largely intact. Normal bacterial counts usually return to baseline within 1-2 weeks after stopping the medicine. Although norfloxacin has limited activity against Clostridium difficile, pseudomembranous colitis has rarely been reported, suggesting that high faecal concentrations of the medicine may protect against this condition. More research is needed to clarify the relationship between fluoroquinolone use and C. difficile-associated colitis.

Nervous System Effects

Headache has been reported in up to 3% of patients, and dizziness in up to 2% of patients taking norfloxacin. Other nervous system side effects occurring in up to 1% of patients include light-headedness, asthenia, drowsiness, tiredness, depression, insomnia, anxiety, irritability, nervousness, euphoria, confusion or disorientation, abnormal dreams, hallucinations, personality changes, psychotic reactions, ataxia, paraesthesia and polyneuropathy, including Guillain-Barre syndrome. Seizures, myoclonus and tremor have rarely been reported in patients taking norfloxacin. Other severe CNS side effects, including increased intracranial pressure and toxic psychoses, have been reported with some other fluoroquinolones (for example, ciprofloxacin).

Dermatologic and Sensitivity Reactions

Eosinophilia has been seen in up to 1.8% of patients taking norfloxacin, while rash, fever and pruritus have been reported in up to 1% of cases. Severe hypersensitivity reactions, including anaphylaxis, angioedema and toxic epidermal necrolysis, have occurred, sometimes after the first dose. The manufacturer advises stopping norfloxacin at the first sign of a rash or hypersensitivity and giving appropriate treatment for severe reactions. Norfloxacin can also cause photosensitivity, so care is needed with sun exposure during treatment.

Genitourinary Effects

Increased serum creatinine and blood urea nitrogen (BUN) concentrations have rarely been reported in patients taking norfloxacin, along with cases of interstitial nephritis and renal failure. Although a direct causal link has not been firmly established, acute renal failure was reported in one older patient. Crystalluria can occur with higher doses (800-1600 mg) and urine pH levels between 6.5-7.8. However, it has not been associated with renal toxicity in humans. Patients are advised to avoid excessive doses and maintain adequate fluid intake to reduce the risk of crystalluria.

Musculoskeletal Effects

Achilles, shoulder and hand tendon ruptures requiring surgical repair or causing prolonged disability have been reported in patients taking fluoroquinolones, including norfloxacin. Patients who develop tendon pain, inflammation or rupture should stop the medicine immediately. Fluoroquinolones may also worsen myasthenia gravis, leading to severe respiratory muscle weakness. Although tendinitis and tendon rupture are rare, they can occur within days to months of starting treatment, particularly in older adults or those taking corticosteroids. Animal studies indicate that fluoroquinolones can cause cartilage erosion and joint problems, which raises concerns about their use in humans and in immature animals.

Hepatobiliary Effects

Hepatitis, jaundice (including cholestatic jaundice), and increased serum concentrations of AST (SGOT), alanine aminotransferase (ALT) (SGPT), and alkaline phosphatase have been reported in less than 2% of patients taking norfloxacin. Increased serum lactate dehydrogenase (LDH) concentrations have rarely been reported.

Hematologic Effects

Reduced leukocyte or neutrophil counts have been reported in about 2% of patients taking norfloxacin; thrombocytopenia has also been reported. In one patient, there was some evidence that leukopenia resulted from an immunologic rather than a toxic mechanism. Reduced haemoglobin concentration, reduced haematocrit and haemolytic anaemia have occurred rarely. Prolongation of prothrombin time occurred in at least one patient taking norfloxacin.

Other Adverse Effects

Back pain, hyperhidrosis and symptomatic hypoglycaemia have been reported in patients taking norfloxacin. Tinnitus and transient hearing loss have also rarely been reported. Diplopia and weakness have been reported as well. Although other visual disturbances have been reported with some fluoroquinolones (for example, ciprofloxacin), these side effects have not been reported with norfloxacin, and there has been no evidence of ocular toxicity in animal studies using the medicine.

Precautions and Contraindications

Norfloxacin is contraindicated in patients with a history of hypersensitivity to the drug or other quinolones, as it can cause severe hypersensitivity reactions, sometimes after the first dose. Patients should be told to stop taking the medicine and contact their doctor at the first sign of a rash or any symptoms of hypersensitivity.

Crystalluria may occur, particularly with high doses, so patients should keep well hydrated and avoid exceeding the recommended dose. Caution is advised in people with CNS disorders, as norfloxacin may worsen conditions such as seizures and myasthenia gravis. Patients should also be aware that it can cause dizziness or light-headedness. They should avoid too much sun exposure because of the risk of phototoxicity.

Pediatric Precautions

Because norfloxacin causes arthropathy in immature animals, the manufacturer states that it should not be used in children or adolescents younger than 18. Some clinicians state that it may be used cautiously in adolescents if skeletal growth is complete. In UK practice, fluoroquinolones are generally reserved for particular circumstances in patients younger than 18 years, and only after careful assessment of the risks and benefits for the individual patient and discussion with parents or carers.

In UK clinical practice, fluoroquinolones may be considered in children when no suitable oral alternative is available, to avoid the use of a parenteral agent, or when the patient has an infection caused by multidrug-resistant gram-negative bacteria, such as certain strains of Pseudomonas or Mycobacterium. Potential uses in paediatric patients therefore include urinary tract infections caused by P. aeruginosa or other multidrug-resistant gram-negative bacteria, chronic suppurative otitis media or malignant otitis externa, chronic osteomyelitis, exacerbations of cystic fibrosis, mycobacterial infection, or other gram-negative bacterial infections in immunocompromised patients when prolonged oral therapy is required.

A single oral dose of norfloxacin 6 times the usual human dose caused lameness in immature dogs; histologic evaluation of the weight-bearing joints of these dogs revealed permanent cartilage lesions. Most other quinolones (for example, ciprofloxacin and ofloxacin) also cause cartilage erosions in weight-bearing joints and other signs of arthropathy in immature animals of various species.

Mutagenicity and Carcinogenicity

Norfloxacin was not mutagenic in the dominant lethal test in mice. It did not cause chromosomal aberrations in hamsters or rats receiving doses 30-60 times the usual human dose. In vitro studies using microbial (that is, Ames test) or mammalian (that is, Chinese hamster fibroblasts, V-79 mammalian cell assay) cell systems have not shown norfloxacin to be mutagenic. Although norfloxacin was weakly positive in the Rec-assay for DNA repair, other mutagenicity assays, including more sensitive tests such as the V-79 mammalian cell assay, did not show evidence of mutagenicity. Results from the hepatocyte DNA repair assay have been equivocal. There was no evidence of carcinogenicity in rats receiving norfloxacin for 19 months, and there was no increase in neoplastic changes in rats receiving norfloxacin doses 8-9 times the usual human dose for up to 96 weeks.

Pregnancy, Fertility and Lactation

Norfloxacin is contraindicated in pregnant and breastfeeding women because of potential risks, including embryotoxicity seen in animal studies. It has caused embryonic loss in cynomolgus monkeys at high doses and has been associated with slight maternal toxicity. Although no teratogenic effects were seen in various animal species at lower doses, the medicine can cross the placenta. It may also be excreted in breast milk, raising concerns for nursing infants. Given these risks and the availability of safer alternatives, norfloxacin should generally be avoided during pregnancy and breastfeeding.

Acute Toxicity

Limited information is available on the acute toxicity of norfloxacin. The oral median lethal dose (LD50) of the medicine is greater than 4 g/kg in mice and rats. If acute overdose of norfloxacin occurs, the stomach should be emptied by inducing emesis or gastric lavage.

Supportive and symptomatic treatment should be started, and the patient should be observed. Adequate hydration must be maintained to minimise the risk of crystalluria.