Noroxin (Norfloxacin) - Antibacterial drugs

Norfloxacin is a fluoroquinolone anti-infective agent. Norfloxacin is used in adults to treat complicated and uncomplicated urinary tract infections and prostatitis caused by susceptible organisms and to treat uncomplicated gonorrhea.

Uses

Norfloxacin has also been used in adults to treat various GI infections caused by susceptible organisms. Because only low serum concentrations of Norfloxacin are attained after oral administration of usual dosages, use of the drug is generally limited to genitourinary or GI tract infections. Before initiation of norfloxacin therapy, appropriate specimens should be obtained to identify the causative organism and in vitro susceptibility tests.

Norfloxacin may be initiated, however, before obtaining the results of these tests. If the clinical response to norfloxacin therapy is unsatisfactory, additional specimens should be obtained and susceptibility tests repeated.

Urinary Tract Infections and Prostatitis

Uncomplicated Urinary Tract Infections

Oral Norfloxacin is prescribed for adults with uncomplicated urinary tract infections (UTIs) caused by various susceptible bacteria, including Escherichia coli and Klebsiella pneumoniae. Some clinicians recommend reserving Norfloxacin for complicated UTIs, particularly those involving multidrug-resistant bacteria and advise against its use for uncomplicated cases unless first-line treatments are ineffective or intolerable.

Studies indicate that a 7-10 day course of Norfloxacin is as effective as co-trimoxazole, with fewer side effects. Additionally, Norfloxacin has shown efficacy comparable to amoxicillin for treating uncomplicated UTIs. Limited data suggest that a 3-day treatment may be sufficient, but further research is needed to assess relapse and recurrence rates.

While Norfloxacin can be effective, it is generally not the first choice for uncomplicated UTIs due to concerns about antibiotic resistance and potential side effects. It should be considered primarily when other treatments fail, or resistance is confirmed.

Complicated Urinary Tract Infections

Oral Norfloxacin is used in adults to treat complicated UTIs caused by susceptible E. coli, K. pneumoniae, P. mirabilis, Ps. aeruginosa, S. marcescens, or 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 therapy appeared to be as effective as parenteral anti-infective therapy for treating nonbacteremic, nosocomial UTIs. However, further study is needed to compare the relative efficacy of oral Norfloxacin and parenteral anti-infectives usually used to treat complicated UTIs. Some clinicians suggest that Norfloxacin may be particularly useful for the treatment of UTIs caused by organisms resistant to other anti-infectives (e.g., b-lactam antibiotics, aminoglycosides) and for the treatment of chronic or complicated UTIs if parenteral anti-infective therapy is not warranted.

Prostatitis

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

Gonorrhea and Associated Infections

Oral Norfloxacin is an alternative treatment for uncomplicated gonorrhea in adults, recommended by the CDC alongside other options like ceftriaxone and cefixime. Although a single 800-mg dose of Norfloxacin appears effective, its use is limited due to concerns about treatment failures and the emergence of fluoroquinolone-resistant Neisseria gonorrhoeae strains in various regions, including the U.S. and Asia.

The CDC primarily recommends a single intramuscular dose of ceftriaxone for uncomplicated gonorrhea, with alternatives including certain fluoroquinolones when necessary. Treatment failures with Norfloxacin have been reported, and fluoroquinolones are discouraged for infections acquired in areas with known resistance.

While studies suggest that Norfloxacin may be as effective as IM spectinomycin for specific strains, its efficacy for pharyngeal infections remains uncertain. Overall, the CDC emphasizes the importance of monitoring resistance patterns and suggests dual therapy with ceftriaxone and azithromycin when treating gonorrhea to enhance efficacy and reduce resistance risks.

GI Infections

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

Cholera

Norfloxacin has been effective when used in the treatment of cholera. Although tetracyclines generally are the anti-infectives of choice for the treatment of cholera in conjunction with fluid and electrolyte replacement therapy, when the infection is caused by strains of V. cholerae resistant to tetracyclines, alternative agents include co-trimoxazole, fluoroquinolones, or furazolidone. In one study in adults with severe cholera and dehydration, Norfloxacin was more effective than co-trimoxazole in reducing stool output and decreasing the duration of diarrhea, 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 in addition to fluid and electrolyte replacement for treating severe cases of shigellosis since anti-infectives appear to shorten the duration of diarrhea and period of fecal excretion of Shigella. A Fluoroquinolone (e.g., ciprofloxacin, Norfloxacin, ofloxacin) or ceftriaxone are considered drugs of choice for the treatment of shigellosis when the susceptibility of the isolate is unknown; azithromycin also has been recommended, and co-trimoxazole or ampicillin may be effective if the strain is known to be susceptible to these drugs. 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 therapy.

Travelers’ Diarrhea

Norfloxacin is effective for short-term treatment and prevention of travelers’ diarrhea in adults traveling to high-risk areas, primarily caused by enterotoxigenic E. coli but also by other pathogens like Shigella and Salmonella. Treatment varies with illness severity; mild cases may only require oral rehydration, while moderate to severe cases may benefit from anti-infective agents, reducing the illness duration significantly.

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 faces resistance issues.

The CDC advises against prophylactic use of anti-infectives for most travelers due to resistance risks and adverse reactions. Although prophylactic antibiotics have shown effectiveness in controlled studies, their use is generally not recommended unless for high-risk individuals. Instead, travelers should focus on preventive measures like safe food and water practices to minimize the risk of developing diarrhea.

Mechanism of Action

Norfloxacin is usually bactericidal in action. Like other fluoroquinolone anti-infectives, Norfloxacin inhibits DNA synthesis in susceptible organisms by inhibiting type II DNA topoisomerases (DNA gyrase, topoisomerase IV). In vitro studies, particularly those involving in vitro susceptibility tests, indicate that the antibacterial activity of Norfloxacin is decreased in the presence of urine, especially acidic urine.

The clinical importance of this in vitro effect has yet to be determined to date; however, because norfloxacin concentrations attained in urine are usually substantially higher than norfloxacin MICs for most urinary tract pathogens, the effect probably is not clinically important. Spectrum Norfloxacin has a spectrum of activity similar to many other fluoroquinolones (e.g., ciprofloxacin, ofloxacin). Norfloxacin is active in vitro against gram-negative aerobic bacteria, including Enterobacteriaceae and Pseudomonas aeruginosa.

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

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

Pharmacokinetics

Absorption: Norfloxacin is rapidly absorbed from the GI tract, but food can delay absorption. Peak plasma concentrations occur within 1-2 hours after a dose, with 30-50% of the dose absorbed. Antacids containing magnesium or aluminum reduce its bioavailability.
Distribution: Norfloxacin is distributed widely in various tissues, including the kidneys, liver, and prostatic tissue. Biliary concentrations can be significantly higher than serum levels, and they cross the placenta. Still, they are 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 urine within 24-48 hours. Norfloxacin undergoes minimal metabolism, producing less active metabolites.

Norfloxacin is primarily eliminated through renal mechanisms, and dosage adjustments may be necessary for patients with impaired renal function.

Administration

Norfloxacin is administered orally. The drug should be given with a glass of water at least 1 hour before or at least 2 hours after a meal or ingestion of milk or other dairy products. Patients receiving Norfloxacin should be well-hydrated and instructed to drink fluids liberally. To minimize the possibility of interference with the GI absorption of Norfloxacin, patients should be instructed not to ingest antacids containing magnesium or aluminum, sucralfate, metal cations such as iron or zinc (including multivitamin preparations containing zinc), or buffered didanosine preparations concomitantly with or within 2 hours of a norfloxacin 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 dosage of 400 mg twice daily not be exceeded in adults with normal renal function.

Indication	Dosage	Duration
Complicated Urinary Tract Infections	400 mg twice daily	10-21 days
Uncomplicated Urinary Tract Infections (E. coli, K. pneumoniae, P. mirabilis)	400 mg twice daily	3 days
Uncomplicated Urinary Tract Infections (other organisms)	400 mg twice daily	7-10 days
Acute or Chronic Prostatitis (E. coli)	400 mg every 12 hours	28 days
Uncomplicated Gonorrhea	800 mg as a single dose	Single dose
Gastroenteritis	400 mg twice daily	5 days
Shigellosis or GI infections (E. coli)	400 mg twice daily	3 days
Severe Travelers’ Diarrhea	400 mg twice daily	Up to 3 days until symptoms resolve
Prophylaxis for Travelers’ Diarrhea	400 mg once daily	Up to 3 weeks

Drug-Drug Interactions

This medication may interact with some drugs.

Antacids. Antacids containing magnesium hydroxide or aluminum hydroxide may decrease the absorption of oral Norfloxacin, and the drugs should not be administered concomitantly. Patients should be instructed not to ingest antacids concomitantly with or within 2 hours of a norfloxacin dose. The mechanism of this interaction has not been fully elucidated to date. Still, studies using ciprofloxacin indicate that antacids containing magnesium and aluminum ions may bind to and form insoluble complexes with quinolones in the GI tract.
Antifungal Agents. Norfloxacin is inactive against fungi when used alone. Still, results of some in vitro studies using Candida suggest that the drug may enhance the antifungal activity of antifungal agents (e.g., amphotericin B, flucytosine, ketoconazole, miconazole [systemic form no longer commercially available in the U.S.], nystatin). However, there are conflicting reports on this interaction. In at least one in vitro study, Norfloxacin did not affect the antifungal activity of amphotericin B. Further study is needed to evaluate the antifungal effect when Norfloxacin is used with an antifungal agent.
Aminoglycosides. The antibacterial activities of Norfloxacin and aminoglycosides may be additive or partially synergistic in vitro against gram-negative bacteria (e.g., Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, Morganella morganii, Proteus). However, synergism between the drugs appears unpredictable, and indifference or antagonism was also reported when Norfloxacin was used with an aminoglycoside against Enterobacteriaceae or Ps. aeruginosa.
Coumarin Anticoagulants. Initiation of oral norfloxacin therapy in patients stabilized on warfarin has resulted in prolongation of the prothrombin time in several patients and, in at least one patient, concomitant use of the drugs resulted in an increased prothrombin time and fatal pontine hemorrhage. The mechanism of this interaction has not been determined to date. Still, Norfloxacin may displace the anticoagulants from serum albumin-binding sites. Norfloxacin should be cautiously administered in patients receiving a coumarin anticoagulant, and prothrombin time or another appropriate coagulation test should be closely monitored.
Cyclosporine. Concomitant use of cyclosporine and Norfloxacin has increased serum concentrations of cyclosporine. Therefore, the manufacturer recommends monitoring cyclosporine serum concentrations and making appropriate dosage adjustments in patients receiving the drug concomitantly with Norfloxacin.
Didanosine. Didanosine chewable/dispersible buffered tablets, buffered powder for oral solution, or pediatric powder for oral solution prepared as an admixture with antacid may interfere with oral absorption of Norfloxacin. To minimize the possibility of interaction, patients should be instructed not to ingest didanosine preparations concomitantly with or within 2 hours of a norfloxacin dose.
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 ingested concomitantly with or within 2 hours of a norfloxacin dose.
Nitrofurantoin. In vitro, nitrofurantoin antagonizes the antibacterial activity of Norfloxacin. Since antagonism could occur in vivo, Norfloxacin and nitrofurantoin should not be used concomitantly.
Other Anti-infectives. In vitro, chloramphenicol, rifampin, or tetracycline can inhibit the bactericidal activity of Norfloxacin. In an in vitro study, the combination of Norfloxacin, 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 partially synergistic against about one-third and indifferent against about two-thirds of strains tested; 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 b-lactam antibiotic (e.g., ampicillin, cefotaxime, cefoxitin).
Probenecid. Concomitant administration of probenecid substantially decreases urinary excretion of Norfloxacin, possibly by blocking the renal tubular secretion of the anti-infective. Still, serum concentrations and half-life of Norfloxacin generally are not affected.
Sucralfate. Concomitant administration of sucralfate may interfere with oral absorption of Norfloxacin, resulting in decreased serum and urine concentrations of the quinolone, and some clinicians state that concomitant use of ofloxacin with sucralfate is not recommended. If concomitant use of ofloxacin and sucralfate is necessary, the manufacturer and some clinicians recommend that doses of sucralfate not be ingested concomitantly with or within 2 hours of a norfloxacin dose.
Xanthine Derivatives. Concomitant use of some quinolones (e.g., ciprofloxacin, Norfloxacin) in patients receiving theophylline has increased plasma theophylline concentrations and decreased drug clearance. It may increase the risk of theophylline-related adverse effects. Concomitant administration of Norfloxacin and an extended-release theophylline preparation to a limited number of individuals produced slight increases in serum theophylline concentrations compared with some other quinolone derivatives. In other studies, concomitant administration of Norfloxacin in patients stabilized 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 adverse effects in patients receiving Norfloxacin concomitantly. Therefore, some clinicians suggest that Norfloxacin be used cautiously in patients receiving theophylline. The manufacturer of Norfloxacin states that consideration should be given to monitoring plasma theophylline concentrations, and theophylline dosage should be adjusted as required. Some quinolones (e.g., 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.
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. Notably, dairy products such as milk and yogurt should be avoided, as they can reduce the absorption of Norfloxacin by approximately 50% when taken together. Additionally, antacids or supplements containing minerals like calcium, iron, or magnesium should not be consumed within two hours of taking Norfloxacin, as they may also interfere with its bioavailability.

Side Effects

Oral Norfloxacin is generally well tolerated at dosages used in the treatment of urinary tract infections, and adverse effects of the drug are similar to those reported with other quinolone anti-infectives (e.g., ciprofloxacin, ofloxacin).

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

Norfloxacin inhibits CYP1A2 and can, therefore, enhance 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.
Hematologic. Eosinophilia occurred in a 35-year-old man with alcoholic cirrhosis taking Norfloxacin 400 mg bd for prophylaxis of spontaneous bacterial peritonitis.
Gastrointestinal. In a prospective study of women with urinary tract infections treated with pivmecillinam 400 mg bd for 3 days or norfloxacin 400 mg bd for 3 days, 36% of the pivmecillinam-treated patients and 39% of the norfloxacin-treated patients reported adverse events. Gastrointestinal symptoms were 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.

Adverse effects have been reported in about 3.5-10% of patients receiving Norfloxacin and have been severe enough to require discontinuance in 1% or less of patients.

The most frequent adverse effects of the drug reported during clinical trials involved the GI tract or CNS; however, the adverse effect most frequently reported in postmarketing experience is rash.

Adverse effects have occurred in about 7% of patients receiving a single 800-mg oral dose of Norfloxacin for the treatment of uncomplicated gonorrhea. Dizziness, nausea, and abdominal cramping are the adverse effects reported most frequently in patients receiving this single-dose regimen, and these effects have been reported in 2-3.5% of patients. In addition, diarrhea, vomiting, anorexia, constipation, dyspepsia, headache, tingling of the fingers, hyperhidrosis, decreased hemoglobin and hematocrit and decreased platelet count. Increased AST (SGOT) concentrations were reported in 1% or less of patients receiving the single-dose regimen.

GI Effects

Nausea is one of the most frequent adverse effects of Norfloxacin. It has been reported in about 1-4% of patients receiving the drug. Other adverse GI effects include abdominal pain, cramping, loose stools, diarrhea, vomiting, anorexia, dyspepsia, dysphagia, dysgeusia, stomatitis, dry mouth, bitter taste, heartburn, digestive disorders, constipation, flatulence, pruritus ani, have been reported in 1% or less of patients.

Effects on Fecal Flora

Norfloxacin selectively affects normal bowel flora, reducing gram-negative aerobic bacteria while leaving anaerobic and gram-positive flora largely intact. Normal bacterial counts typically return to baseline within 1-2 weeks after discontinuing the drug. Although Norfloxacin has limited activity against Clostridium difficile, pseudomembranous colitis is rarely reported, suggesting that high fecal concentrations of the drug may protect against this condition. Further 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 has been reported in up to 2% of patients receiving Norfloxacin. Other adverse nervous system effects occurring in up to 1% of patients include lightheadedness, asthenia, drowsiness, tiredness, depression, insomnia, anxiety, irritability, nervousness, euphoria, confusion or disorientation, dream abnormalities, hallucinations, personality changes, psychotic reactions, ataxia, paresthesia, and polyneuropathy including Guillain-Barre syndrome. Seizures, myoclonus, and tremors have been reported rarely in patients receiving Norfloxacin. Other severe adverse CNS effects, including increased intracranial pressure and toxic psychoses, have been reported with some other fluoroquinolones (e.g., ciprofloxacin).

Dermatologic and Sensitivity Reactions

Eosinophilia has been observed in up to 1.8% of patients taking Norfloxacin, with rash, fever, and pruritus 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 discontinuing Norfloxacin at the first sign of rash or hypersensitivity and providing appropriate treatment for severe reactions. Additionally, Norfloxacin can cause photosensitivity, necessitating caution with sun exposure during therapy.

Genitourinary Effects

Increased serum creatinine and BUN concentrations have been rarely reported in patients receiving Norfloxacin, along with cases of interstitial nephritis and renal failure. Although a direct causal link is not firmly established, acute renal failure was noted in a geriatric patient. Crystalluria can occur with higher doses (800-1600 mg) and urine pH levels between 6.5-7.8. Still, it has not been associated with renal toxicity in humans. Patients are advised to avoid excessive dosing 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 experiencing tendon pain, inflammation, or rupture should discontinue the drug immediately. Additionally, fluoroquinolones may exacerbate myasthenia gravis, leading to severe respiratory muscle weakness. While tendonitis and ruptures are rare, they can occur within days to months of starting therapy, particularly in older adults or those on corticosteroids. Animal studies indicate that fluoroquinolones can cause cartilage erosion and joint issues, raising concerns about their use in humans and immature animals.

Hepatobiliary Effects

Hepatitis, jaundice (including cholestatic jaundice), and increased serum concentrations of AST (SGOT), ALT (SGPT), and alkaline phosphatase have been reported in less than 2% of patients receiving Norfloxacin. Increased serum LDH concentrations have been reported rarely.

Hematologic Effects

Decreased leukocyte or neutrophil counts have been reported in about 2% of patients receiving Norfloxacin; thrombocytopenia also has been reported. In one patient, there was some evidence that leukopenia resulted from an immunologic rather than a toxic mechanism. Decreased hemoglobin concentration, decreased hematocrit, and hemolytic anemia have occurred rarely. Prolongation of prothrombin time occurred in at least one patient receiving Norfloxacin.

Other Adverse Effects

Back pain, hyperhidrosis, and symptomatic hypoglycemia have been reported in patients receiving Norfloxacin. Tinnitus and transient hearing loss also have been reported rarely in patients receiving the drug. Diplopia and weakness have been reported. Although other visual disturbances have been reported with some fluoroquinolones (e.g., ciprofloxacin), these adverse effects have not been reported with Norfloxacin, and there has been no evidence of ocular toxicity in animal studies using the drug.

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 informed to discontinue the drug and contact their physician at the first sign of a rash or any hypersensitivity symptoms.

Crystalluria may occur, particularly with high doses, so patients should maintain adequate hydration and avoid exceeding recommended dosages. Caution is advised for individuals with CNS disorders, as Norfloxacin may exacerbate conditions like seizures and myasthenia gravis. Additionally, patients should be aware of the potential for dizziness or lightheadedness. They should avoid excessive sun exposure due to the risk of phototoxicity.

Pediatric Precautions

Because Norfloxacin causes arthropathy in immature animals, the manufacturer states that the drug should not be used in children or adolescents younger than 18. Some clinicians state that the drug may be used cautiously in adolescents if skeletal growth is complete. The American Academy of Pediatrics (AAP) states that use of fluoroquinolones (e.g., ciprofloxacin, levofloxacin, lomefloxacin, Norfloxacin, ofloxacin, sparfloxacin) in children younger than 18 years of age may be justified in particular circumstances; however, the drugs should be used only after careful assessment of the risks and benefits for the individual patient and after these benefits and risks have been explained to the parents or caregivers.

The AAP states that fluoroquinolones may be helpful when no other oral agent is available (to avoid the use of a parenteral agent) or when the pediatric patient has an infection caused by multidrug-resistant gram-negative bacteria, such as certain strains of Pseudomonas or Mycobacterium. Therefore, possible uses of fluoroquinolones in pediatric patients include the treatment of urinary tract infections caused by P. aeruginosa or other multidrug-resistant gram-negative bacteria, chronic suppurative otitis media, or malignant otitis externa, chronic osteomyelitis, exacerbation of cystic fibrosis, mycobacterial infection, or other gram-negative bacterial infections in immunocompromised patients when prolonged oral therapy is desired.

A single oral dose of Norfloxacin 6 times the usual human dose caused lameness in immature dogs; histologic evaluation of these dogs’ weight-bearing joints revealed permanent cartilage lesions. Most other quinolones (e.g., ciprofloxacin, 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 (i.e., Ames test) or mammalian (i.e., 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 mutagenic 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 dosages 8-9 times the usual human dosage for up to 96 weeks.

Pregnancy, Fertility and Lactation

Norfloxacin is contraindicated in pregnant and nursing women due to potential risks, including embryotoxicity observed in animal studies. It has caused an embryonic loss in cynomolgus monkeys at high doses and has been associated with slight maternal toxicity. Although no teratogenic effects were noted in various animal species at lower doses, the drug can cross the placenta. It may 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 LD50 of the drug is greater than 4 g/kg in mice and rats. If acute overdosage of Norfloxacin occurs, the stomach should be emptied by inducing emesis or gastric lavage.

Supportive and symptomatic treatment should be initiated, and the patient should be observed; adequate hydration must be maintained to minimize the risk of crystalluria.

Preparations

Norfloxacin Oral Tablets, film- 400 mg Noroxin®, coated Merck, Noroxin, Norflox, Norbactin, Apo-Norflox, Chibroxin (ophthalmic use), Actiflox-T, Alflox, Norfloxacin – 1 A Pharma, Norfloxacin STADA.