Norfloxacin

Pronunciation

Class: Quinolones
VA Class: AM900
Chemical Name: 1-Ethyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid
CAS Number: 70458-96-7
Brands: Noroxin

Warning(s)

  • Systemic fluoroquinolones, including norfloxacin, are associated with an increased risk of tendinitis and tendon rupture in all age groups.1 372 373 This risk is further increased in older adults (usually those >60 years of age), individuals receiving concomitant corticosteroids, and kidney, heart, or lung transplant recipients.1 372 373 (See Tendinopathy and Tendon Rupture under Cautions.)

  • Fluoroquinolones, including norfloxacin, may exacerbate muscle weakness in patients with myasthenia gravis.1 Avoid norfloxacin in patients with known history of myasthenia gravis.1

Introduction

Antibacterial; fluoroquinolone.1 17 18 20

Uses for Norfloxacin

Urinary Tract Infections (UTIs) and Prostatitis

Treatment of uncomplicated UTIs (including cystitis) caused by susceptible Citrobacter freundii, Enterobacter aerogenes, E. cloacae, Escherichia coli, Klebsiella pneumoniae, Morganella morganii, Proteus mirabilis, P. vulgaris, Providencia rettgeri, Pseudomonas aeruginosa, or Serratia marcescens.1 107 114 115 116 117 118 123 124 127 128 129 134 135 201 230 231 280 283 309 Also used for treatment of uncomplicated UTIs caused by susceptible Staphylococcus aureus, S. epidermidis, S. saprophyticus, or Streptococcus agalactiae (group B streptococci), or Enterococcus faecalis.1 107 116 117 118 124 127 129 134 135 201 230 231

Treatment of complicated UTIs caused by susceptible E. coli, K. pneumoniae, P. mirabilis, Ps. aeruginosa, S. marcescens, or E. faecalis.1

Treatment of prostatitis caused by E. coli.1

Usually reserved for treatment of complicated UTIs, especially those caused by multidrug-resistant bacteria; generally not recommended for uncomplicated UTIs (e.g., acute cystitis) unless more commonly employed urinary anti-infectives are contraindicated or not tolerated.111 251 253

Slideshow: The Shocking Truth About Antibiotic Resistance

GI Infections

Treatment of gastroenteritis caused by susceptible enterotoxigenic E. coli,71 193 232 Aeromonas hydrophila,193 232 Plesiomonas shigelloides,71 Salmonella,71 193 232 or Shigella (including Sh. boydii,71 Sh. dysenteriae,36 71 131 193 Sh. flexneri,71 193 Sh. sonnei).71

Treatment of cholera, including infections caused by Vibrio cholerae serotypes 01 or 0139.310 311 341 344 Tetracyclines generally drugs of choice when an anti-infective indicated as an adjunct to fluid and electrolyte replacement;43 292 309 311 azithromycin also a recommended treatment.292 Alternatives for V. cholerae resistant to tetracyclines include co-trimoxazole, fluoroquinolones, or furazolidone.43 292 309 311 341

Treatment of travelers’ diarrhea.301 305 306 335 525 If caused by bacteria, may be self-limited and resolve within 3–5 days without anti-infective treatment;305 525 if diarrhea is moderate or severe, persists for >3 days, or is associated with fever or bloody stools, short-term (1–3 days) anti-infective treatment recommended.305 525 Fluoroquinolones (ciprofloxacin, levofloxacin, norfloxacin, ofloxacin) usually drugs of choice when treatment, including self-treatment, indicated.305 312 335 337 525 Azithromycin is a treatment alternative if fluoroquinolones should not be used (e.g., children, pregnant women) and a drug of choice for travelers in areas with high prevalence of fluoroquinolone-resistant Campylobacter (e.g., South and Southeast Asia) or when there is no response after 48 hours of fluoroquinolone treatment.305 525 Rifaximin is another alternative for treatment of travelers' diarrhea caused by noninvasive E. coli.305 525

Prevention of travelers’ diarrhea in individuals traveling for relatively short periods to areas where enterotoxigenic E. coli and other causative bacterial pathogens (e.g., Shigella) are known to be susceptible to the drug.109 131 193 301 307 308 335 337 525 CDC and others do not recommend anti-infective prophylaxis in most individuals traveling to areas of risk;305 308 312 525 the principal preventive measures are prudent dietary practices.329 330 525 If anti-infective prophylaxis is used (e.g., in immunocompromised individuals such as those with HIV infection), a fluoroquinolone (ciprofloxacin, levofloxacin, ofloxacin, norfloxacin) is recommended for nonpregnant adults;305 525 azithromycin and rifaximin are alternatives.305 Weigh use of anti-infective prophylaxis against use of prompt, early self-treatment with anti-infectives, a strategy that can limit duration of illness to 6–24 hours in most cases.525

Gonorrhea and Associated Infections

Has been used for treatment of uncomplicated urethral, endocervical, orrectal gonorrhea caused by susceptible Neisseria gonorrhoeae.1 17 18 21 71 111 119 132 193 195 196 229 297 298 301 319

Because quinolone-resistant N. gonorrhoeae (QRNG) is widely disseminated worldwide, including in the US319 320 328 338 358 360 (see Resistance in Neisseria gonorrhoeae under Cautions), CDC and others no longer recommend norfloxacin for treatment of gonorrhea or any associated infections that may involve N. gonorrhoeae (e.g., pelvic inflammatory disease [PID], epididymitis).319 328 358 360

Norfloxacin Dosage and Administration

Administration

Oral Administration

Administer orally.1

Give tablets with a glass of water at least 1 hour before or at least 2 hours after a meal or dairy products (e.g., milk, yogurt).1 2 (See Pharmacokinetics.)

Patients receiving norfloxacin should be well hydrated and should be instructed to drink fluids liberally.1 240 (See Renal Effects under Cautions.)

Dosage

Adults

Urinary Tract Infections (UTIs) and Prostatitis
Uncomplicated UTIs
Oral

400 mg every 12 hours.1 17 114 116 117 118 124 127 128 201 205 Usual duration is 3 days for treatment of uncomplicated UTIs caused by susceptible E. coli, K. pneumoniae, or P. mirabilis or 7–10 days for treatment of uncomplicated UTIs caused by other susceptible bacteria.1

Complicated UTIs
Oral

400 mg every 12 hours.1 17 114 116 128 135 201 205 Usual duration is ≥10–21 days.1 17 135

Acute or Chronic Prostatitis Caused by E. coli
Oral

400 mg every 12 hours for 28 days.1

GI Infections
Gastroenteritis Caused by Susceptible Bacteria
Oral

400 mg twice daily for 5 days.36 71 131 193 A duration of 3 days may be sufficient for some infections, including shigellosis or some E. coli infections.43

Cholera
Oral

400 mg twice daily for 3 days in conjunction with fluid and electrolyte replacement.341 344 A single 800-mg dose has been used in adults, but there is some evidence that a multiple-dose regimen is more effective than a single-dose regimen for treatment of severe cholera caused by V. cholerae 0139.341

Treatment of Travelers’ Diarrhea
Oral

400 mg twice daily for 1–3 days.305 306

Prevention of Travelers’ Diarrhea
Oral

400 mg once daily.305 329 330 335

Although anti-infective prophylaxis generally discouraged,305 308 312 337 525 some clinicians state it can be given during period of risk (for ≤3 weeks) beginning day of travel and continuing for 1 or 2 days after leaving area of risk.305 329 330 335

Gonorrhea
Uncomplicated Urethral, Endocervical, or Rectal Gonorrhea
Oral

Single 800-mg dose recommended by manufacturer.1

Not recommended by CDC or others for treatment of gonorrhea or any associated infections that may involve N. gonorrhoeae (e.g., PID, epididymitis).319 328 358 360 (See Gonorrhea and Associated Infections under Uses.)

Prescribing Limits

Adults

Oral

Maximum 400 mg twice daily because of the risk of crystalluria.1

Special Populations

Renal Impairment

Dosage adjustments necessary in patients with severe renal impairment.1 2 7 8 17 143

Adults with Clcr ≤30 mL/minute per 1.73 m2 should receive 400 mg once daily.1

Geriatric Patients

No dosage adjustments except those related to renal impairment.1 (See Renal Impairment under Dosage and Administration.)

Select dosage with caution because of possible age-related decreases in renal impairment.1

Cautions for Norfloxacin

Contraindications

  • Hypersensitivity to norfloxacin or any quinolone.1 240

  • History of tendinitis or tendon rupture with norfloxacin or any quinolone.1

Warnings/Precautions

Warnings

Tendinopathy and Tendon Rupture

Fluoroquinolones, including norfloxacin, are associated with increased risk of tendinitis and tendon rupture in all age groups.1 372 373 This risk is further increased in older adults (usually those >60 years of age), individuals receiving concomitant corticosteroids, and kidney, heart, or lung transplant recipients.1 372 373

Other factors that may independently increase risk of tendon rupture include strenuous physical activity, renal failure, and previous tendon disorders such as rheumatoid arthritis.1 372 373 Tendinitis and tendon rupture have been reported in patients receiving fluoroquinolones who did not have any of these risk factors.1

Fluoroquinolone-associated tendinitis and tendon rupture most frequently involve the Achilles tendon and may require surgical repair.1 Tendinitis and tendon rupture in the rotator cuff (shoulder), hand, biceps, thumb, and other tendon sites also reported.1

Tendon rupture can occur during or following fluoroquinolone therapy and has been reported up to several months after completion of therapy.1

Discontinue if pain, swelling, inflammation, or rupture of a tendon occurs.1 372 373 Advise patients to rest and refrain from exercise and contact a clinician at the first sign of tendinitis or tendon rupture (e.g., pain, swelling, or inflammation of a tendon or weakness or inability to use a joint).1 372 373 (See Advice to Patients.)

Myasthenia Gravis Patients

May exacerbate muscle weakness in myasthenia gravis patients;1 need for ventilatory support and death reported.1

Avoid use in patients with known history of myasthenia gravis.1

Musculoskeletal Effects

Fluoroquinolones, including norfloxacin, cause arthropathy and osteochondrosis in immature animals of various species.1 2 233 240 362 363 364 365 366 369 370 Relevance of these adverse effects in immature animals to use in humans unknown.213 241 361 367 368 369 Safety and efficacy of norfloxacin not established in children and adolescents <18 years of age (see Pediatric Use under Cautions) or in pregnant or lactating women (see Pregnancy and see Lactation under Cautions).1

CNS Effects

Possibility of seizures, increased intracranial pressure, toxic psychoses, and CNS stimulation leading to tremors, restlessness, lightheadedness, confusion, and hallucinations.1 21 233 240 257 258

Use with caution in patients with known or suspected CNS disorders that may predispose to seizures or lower seizure threshold (e.g., severe cerebral arteriosclerosis, epilepsy).1

If a severe adverse CNS reaction (e.g., seizures, increased intracranial pressure, CNS stimulation, toxic psychosis) occurs, discontinue the drug and institute appropriate therapeutic measures.1

Peripheral Neuropathy

Sensory or sensorimotor axonal polyneuropathy affecting small and/or large axons resulting in paresthesias, hypoesthesias, dysesthesias, and weakness reported with fluoroquinolones, including norfloxacin.1 Symptoms may occur soon after initiation of the drug and may be irreversible.1

Immediately discontinue norfloxacin if symptoms of peripheral neuropathy (e.g., pain, burning, tingling, numbness, weakness) occur or if there are alterations in sensations (e.g., light touch, pain, temperature, position sense, vibratory sensation).1

Superinfection/Clostridium difficile-associated Diarrhea and Colitis (CDAD)

Possible emergence and overgrowth of nonsusceptible bacteria or fungi.1 Institute appropriate therapy if superinfection occurs.1

Treatment with anti-infectives alters normal colon flora and may permit overgrowth of Clostridium difficile.1 345 347 348 354 C. difficile infection (CDI) and C. difficile-associated diarrhea and colitis (CDAD; also known as antibiotic-associated diarrhea and colitis or pseudomembranous colitis) reported with nearly all anti-infectives, including norfloxacin, and may range in severity from mild diarrhea to fatal colitis.1 242 267 345 347 348 351 355 356 C. difficile produces toxins A and B, which contribute to the development of CDAD;1 345 hypertoxin-producing strains of C. difficile are associated with increased morbidity and mortality since they may be refractory to anti-infectives and colectomy may be required.1

Outbreaks of severe CDAD caused by fluoroquinolone-resistant C. difficile have been reported with increasing frequency over the last several years.350 351 352 353 355

Consider CDAD if diarrhea develops during or after therapy and manage accordingly.1 345 347 348 354 Obtain careful medical history since CDAD may occur as late as 2 months or longer after anti-infective therapy is discontinued.1 345 347 348

If CDAD is suspected or confirmed, discontinue anti-infective therapy not directed against C. difficile whenever possible.1 345 347 348 Initiate appropriate supportive therapy (e.g., fluid and electrolyte management, protein supplementation), anti-infective therapy directed against C. difficile (e.g., metronidazole, vancomycin), and surgical evaluation as clinically indicated.1 345 347 348

Sensitivity Reactions

Hypersensitivity Reactions

Serious and occasionally fatal (anaphylactic) hypersensitivity reactions, which may occur following first dose, reported with some quinolones, including norfloxacin.1 193 293 294 295

Some reactions have been accompanied by cardiovascular collapse, loss of consciousness, tingling, pharyngeal or facial edema, dyspnea, urticaria, and itching.1 293 294 295

In addition, other possible severe and potentially fatal reactions (may be hypersensitivity reactions or of unknown etiology) have been reported, most frequently after multiple doses.1 These include fever, rash or other severe dermatologic reactions (e.g., toxic epidermal necrolysis, Stevens-Johnson syndrome), vasculitis, arthralgia, myalgia, serum sickness, allergic pneumonitis, interstitial nephritis, acute renal insufficiency or failure, hepatitis, jaundice, acute hepatic necrosis or failure, anemia (including hemolytic and aplastic), thrombocytopenia (including thrombotic thrombocytopenic purpura), leukopenia, agranulocytosis, pancytopenia, and/or other hematologic effects.1

Discontinue norfloxacin at first appearance of rash, jaundice, or any other sign of hypersensitivity and institute appropriate therapy as indicated (e.g., epinephrine, corticosteroids, and maintenance of an adequate airway and oxygen).1

Photosensitivity Reactions

Moderate to severe photosensitivity/phototoxicity reactions have been reported with fluoroquinolones, including norfloxacin.1

Phototoxicity may manifest as exaggerated sunburn reactions (e.g., burning, erythema, exudation, vesicles, blistering, edema) on areas exposed to sun or artificial ultraviolet (UV) light (usually the face, neck, extensor surfaces of forearms, dorsa of hands).1

Relative potential of the various fluoroquinolones to cause photosensitivity/phototoxicity unclear.291 Factors that contribute to susceptibility to this adverse effect during fluoroquinolone therapy include patient's skin pigmentation, frequency and duration of exposure to sun and UV light, use of protective clothing and sunscreen, concomitant use of other drugs, and dosage and duration of fluoroquinolone therapy.291

Avoid unnecessary or excessive exposure to sunlight or artificial UV light (tanning beds, UVA/UVB treatment) while receiving norfloxacin.1 If patient needs to be outdoors, they should wear loose-fitting clothing that protects skin from sun exposure and use other sun protection measures (sunscreen).1

Discontinue norfloxacin if photosensitivity or phototoxicity (sunburn-like reaction, skin eruption) occurs.1

General Precautions

Renal Effects

Possible crystalluria;1 2 21 71 138 193 generally associated with alkaline urine and high dosage.21 138 193 221

Adequate fluid intake necessary to ensure proper hydration and adequate urinary output;1 2 240 avoid alkaline urine and do not exceed usual dosage.1 2 240

Hematologic Effects

Hemolytic reactions reported rarely in patients with latent or actual defects in glucose-6-phosphate dehydrogenase (G-6-PD).1

Prolongation of QT Interval

Prolonged QT interval and ventricular arrhythmias (including torsades de pointes) reported with some fluoroquinolones, including norfloxacin.1

Avoid or use with caution in patients receiving class IA (e.g., quinidine, procainamide) or class III (e.g., amiodarone, sotalol) antiarrhythmic agents or other drugs that may affect QT interval (e.g., cisapride [available in the US only under a limited-access protocol], erythromycin, antipsychotic agents, tricyclic antidepressants) and in patients with risk factors for torsades de pointes (e.g., known QT prolongation, uncorrected hypokalemia).1

Laboratory Monitoring

Periodically assess organ system functions, including renal, hepatic, and hematopoietic, during prolonged therapy.1

Selection and Use of Anti-infectives

When prescribing a fluoroquinolone, consider potential benefits and risks for the individual patient.372 373 Most patients tolerate the drugs, but serious adverse reactions (e.g., CNS effects, QT prolongation, C. difficile-associated diarrhea and colitis, damage to liver, kidneys, or bone marrow, alterations in glucose homeostasis) may occur rarely.372 373

To reduce development of drug-resistant bacteria and maintain effectiveness of norfloxacin and other antibacterials, use only for treatment or prevention of infections proven or strongly suspected to be caused by susceptible bacteria.1

When selecting or modifying anti-infective therapy, use results of culture and in vitro susceptibility testing.1 In the absence of such data, consider local epidemiology and susceptibility patterns when selecting anti-infectives for empiric therapy.1

Resistance in Neisseria gonorrhoeae

N. gonorrhoeae with decreased susceptibility to norfloxacin and other fluoroquinolones (quinolone-resistant N. gonorrhoeae; QRNG) has been reported with increasing frequency over the past decade.319 320 322 323 324 325 326 327 328 336 358

US data indicate that QRNG has continued to increase among men who have sex with men and among heterosexual males and is now present in all regions of the country.358

CDC and others state that fluoroquinolones, including norfloxacin, should not be used to treat gonorrhea or any associated infections that may involve N. gonorrhoeae (e.g., PID, epididymitis).319 328 358 360

Specific Populations

Pregnancy

Category C.1

Lactation

Not known whether distributed into milk;1 other quinolones are distributed into milk.1 Discontinue nursing or the drug.1

Pediatric Use

Safety and efficacy not established in children and adolescents <18 years of age.1 Norfloxacin causes arthropathy in juvenile animals.1 233 (See Musculoskeletal Effects under Cautions.)

AAP states use of fluoroquinolones may be justified in children <18 years of age in special circumstances after careful assessment of the risks and benefits for the individual patient and after these benefits and risks have been explained to parents and/or caregivers.110 292

Geriatric Use

No substantial differences in safety and efficacy relative to younger adults, but increased risk of some adverse effects cannot be ruled out.1

Risk of severe tendon disorders, including tendon rupture, is increased in geriatric adults >60 years of age.1 372 373 This risk is further increased in those receiving concomitant corticosteroids.1 372 373 (See Tendinopathy and Tendon Rupture under Cautions.) Use caution in geriatric adults, especially those receiving concomitant corticosteroids.1

Risk of QT interval prolongation leading to ventricular arrhythmias may be increased in geriatric patients, especially those receiving concurrent therapy with other drugs that can prolong QT interval (e.g., class IA or III antiarrhythmic agents) or with risk factors for torsades de pointes (e.g., known QT prolongation, uncorrected hypokalemia).1 (See Prolongation of QT Interval under Cautions.)

Substantially eliminated by the kidney and age-related decline in renal function may increase risk of adverse reactions.1

Consider age-related decreases in renal function when selecting dosage; renal function monitoring may be useful.1

Renal Impairment

Increased norfloxacin serum concentrations and prolonged half-life.1 17 18

Dosage adjustments necessary in patients with severe renal impairment.1 2 7 8 17 143 (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

GI effects (nausea, abdominal cramping);1 17 18 21 71 116 124 193 205 233 CNS effects (headache, dizziness, asthenia);1 17 18 21 71 116 124 193 205 233 rash.1

Interactions for Norfloxacin

Drugs Metabolized by Hepatic Microsomal Enzymes

Inhibits cytochrome P-450 (CYP) isoenzyme 1A2.1 Potential pharmacokinetic interaction with CYP1A2 substrates (e.g., caffeine, clozapine, ropinirole, tacrine, theophylline, tizanidine) resulting in increased drug concentrations if given in usual dosages.1 Carefully monitor patients receiving norfloxacin concomitantly with drugs metabolized by CYP1A2.1

Drugs that Prolong QT Interval

Potential pharmacologic interaction (additive effect on QT interval prolongation).1 Avoid or use with caution in patients receiving class IA (e.g., quinidine, procainamide) or class III (e.g., amiodarone, sotalol) antiarrhythmic agents or other drugs that may affect QT interval (e.g., cisapride, erythromycin, antipsychotic agents, tricyclic antidepressants).1 (See Prolongation of QT Interval under Cautions.)

Specific Drugs

Drug

Interaction

Comments

Aminoglycosides

In vitro evidence of additive or synergistic antibacterial effects against some Enterobacteriaceae and Ps. aeruginosa;150 155 177 synergism unpredictable and indifference or antagonism also has been reported48 155

Antacids (aluminum- or magnesium-containing)

Decreased absorption of norfloxacin1 2 18 71 240 266

Administer norfloxacin tablets at least 2 hours before or after such antacids1 219

Anticoagulants, oral (warfarin)

Potential for enhanced warfarin effects1 276 289

Use with caution;276 289 monitor PT or other appropriate coagulation tests1

β-lactam antibiotics

No in vitro evidence of synergism or antagonism against gram-positive or -negative bacteria when used with ampicillin, cefotaxime, or cefoxitin48

Caffeine

Possible prolonged half-life of caffeine with some quinolones (e.g., ciprofloxacin)241 244 269 270 271 272 273

The possibility of exaggerated or prolonged effects of caffeine during concomitant use with a quinolone should be considered244 270

Corticosteroids

Increased risk of tendinitis or tendon rupture, especially in patients >60 years of age1 372 373

Cyclosporine

Possible increased concentrations of cyclosporine1

Monitor cyclosporine concentrations and adjust cyclosporine dosage if needed1

Didanosine

Decreased absorption of norfloxacin with buffered didanosine preparations1

Administer norfloxacin tablets at least 2 hours before or after buffered didanosine preparations (pediatric oral solution admixed with antacid)1

Glyburide

Severe hypoglycemia reported1

Monitor blood glucose1

Iron preparations

Decreased absorption of norfloxacin1

Administer norfloxacin tablets at least 2 hours before or after ferrous sulfate and dietary supplements containing iron1

Multivitamins and mineral supplements

Decreased absorption of norfloxacin1

Administer norfloxacin tablets at least 2 hours before or after supplements containing zinc or iron1

Nitrofurantoin

Some in vitro evidence of antagonism between norfloxacin and nitrofurantoin1

Clinical importance unknown; should not be used concomitantly1

NSAIAs

Increased risk of CNS stimulation and convulsive seizures1

Animal studies suggest norfloxacin may have greater convulsant activity than some other fluoroquinolones (e.g., levofloxacin) and the potential risk associated with concomitant therapy may vary depending on the specific NSAIA357

Use with caution1

Probenecid

Decreased clearance of norfloxacin;1 2 3 139 serum concentrations139 and half-life of norfloxacin generally not affected2 3

Sucralfate

Possible decreased GI absorption of norfloxacin1 333

Some clinicians suggest that concomitant use should be avoided; if used concomitantly, give norfloxacin tablets at least 2 hours before or after sucralfate1 333

Theophylline

Possible increased theophylline concentrations and increased risk of theophylline-related adverse effects1 18 21 205 216 224 225 234 244 245 246 255

Although risk of norfloxacin inducing substantial alterations in theophylline pharmacokinetics appears to be less than with some other quinolones (e.g., ciprofloxacin),244 245 246 255 256 theophylline-related adverse effects have been reported in patients receiving norfloxacin concomitantly1

Some clinicians suggest that the interaction between norfloxacin and theophylline may not be clinically important in most patients;234 255 256 275 287 others suggest that norfloxacin should be used with caution in patients receiving theophylline205 219 244 246 255

Manufacturer of norfloxacin states that consideration should be given to monitoring plasma theophylline concentrations and theophylline dosage should be adjusted as required1

Norfloxacin Pharmacokinetics

Absorption

Bioavailability

Rapidly, but incompletely, absorbed from GI tract following oral administration.1 2 3 4 17 18 21 22 136 142 205

At least 30–50% of an oral dose is absorbed from GI tract;1 2 4 peak serum concentrations generally attained within 1–2 hours.1 2 3 4 7 17 18 22 138 142 144 Steady-state serum concentrations attained by the second day of therapy.1

Food

Food and/or dairy products (milk, yogurt) in the GI tract may decrease absorption.1 2 3 17 339 340

Distribution

Extent

Distributed into renal parenchyma,1 6 17 205 gallbladder,17 136 205 liver,17 prostatic tissue,1 6 17 141 205 testicles,1 seminal fluid,1 140 uterus,1 fallopian tubes,1 cervical and vaginal tissue,1 blister fluid,3 18 22 142 144 tonsils,17 maxillary sinus mucosa,17 sputum,17 and bile.1 2 3 17 136

Crosses the placenta and is distributed into cord blood and amniotic fluid.2 3 17 Not known whether norfloxacin is distributed into milk;1 2 17 some other quinolones (e.g., ciprofloxacin, ofloxacin) are distributed into milk.1 2 281

Plasma Protein Binding

10–15% bound to serum proteins.1 2 3 17

Elimination

Metabolism

Partially metabolized by modification of the piperazinyl group to 6 metabolites,1 2 3 17 19 22 151 designated —1, —2, —3, —4[1], —4[2], and —5.2 Although some of the metabolites are microbiologically active, they are less active than the parent drug.1 2 3 17 19 22 151

Elimination Route

Eliminated by renal and nonrenal mechanisms.1 2 3 5 17 18 21

Norfloxacin and its metabolites excreted in urine,1 2 17 18 19 21 138 139 with unchanged norfloxacin being excreted by both glomerular filtration and tubular secretion.3 139 Norfloxacin also excreted in feces,1 2 5 14 194 236 principally as unabsorbed drug17 221 and, to a small extent, via biliary elimination.1 17

Approximately 25–40% of a dose excreted in urine as unchanged drug and 5–10% as metabolites within 24–48 hours;1 2 3 17 ≥30% (range: 10–50%) is excreted in feces within 48 hours.1 5

Does not appear to be removed by hemodialysis;143 not known whether the drug is removed by peritoneal dialysis.221

Half-life

Adults with normal renal function: 2.3–4 hours.1 2 7 8 18 21 22 71 142 143 144

Special Populations

Geriatric individuals 65–75 years of age with renal function normal for their age: half-life averages 4 hours.1 2

Limited data suggest that half-life is not substantially affected by hepatic impairment.4

In adults with renal impairment, half-life of norfloxacin averages 4.4, 6.6, or 7.6 hours in those with Clcr 30–80, 10–29, or <10 mL/minute per 1.73 m2, respectively.143

Stability

Storage

Oral

Tablets

Tight container at 25°C (may be exposed to 15–30°C).1

Actions and Spectrum

Advice to Patients

  • Advise patients that antibacterials (including norfloxacin) should only be used to treat bacterial infections and not used to treat viral infections (e.g., the common cold).1

  • Importance of completing full course of therapy, even if feeling better after a few days.1

  • Advise patients that skipping doses or not completing the full course of therapy may decrease effectiveness and increase the likelihood that bacteria will develop resistance and will not be treatable with norfloxacin or other antibacterials in the future.1

  • Importance of taking norfloxacin tablets at least 1 hour before or at least 2 hours after a meal or dairy products (e.g., milk, yogurt) since absorption of the drug may be decreased.1

  • Importance of taking norfloxacin tablets at least 2 hours before or after multivitamins containing iron or zinc; aluminum- or magnesium-containing antacids; or didanosine chewable/dispersible buffered tablets, buffered powder for oral solution, or pediatric powder for oral solution prepared as an admixture with antacid.1

  • Importance of taking norfloxacin tablets with a glass of water and drinking sufficient quantities of fluids during therapy.1

  • Increased risk of tendinitis and tendon rupture in all age groups and further increased risk in adults >60 years of age, individuals receiving corticosteroids, and kidney, heart, or lung transplant recipients.1 372 373 Importance of resting and refraining from exercise at the first sign of tendinitis or tendon rupture (e.g., pain, swelling, or inflammation of a tendon, weakness or inability to use a joint) and discontinuing the drug and contacting a clinician regarding changing to an anti-infective that is not a fluoroquinolone.1 372 373 (See Tendinopathy and Tendon Rupture under Cautions.)

  • Advise patients that norfloxacin may worsen myasthenia gravis symptoms; importance of immediately contacting clinician if any worsening muscle weakness or breathing problems occur.1

  • Potential for norfloxacin to cause dizziness and lightheadedness; need for caution when operating machinery or driving a motor vehicle until effects of drug on individual are known.1

  • May be associated with hypersensitivity reactions (including anaphylactic reactions), even following the first dose.1 Importance of immediately discontinuing the drug and informing clinician at the first sign of rash, jaundice, or any other sign of hypersensitivity.1

  • Risk of photosensitivity/phototoxicity reactions following exposure to sun or UV light while receiving fluoroquinolones.1 Importance of avoiding or minimizing exposure to sunlight or artificial UV light (e.g., tanning beds, UVA/UVB treatment) and using protective measures (e.g., wearing loose-fitting clothes, sunscreen) if outdoors during norfloxacin therapy.1 Discontinue norfloxacin and inform a clinician if a sunburn-like reaction or skin eruption occurs.1

  • Advise patients that seizures have been reported and to contact clinicians before taking norfloxacin if they have a history of seizures.1

  • Advise patients that peripheral neuropathies have been reported with norfloxacin and that symptoms may occur soon after initiation of the drug and may be irreversible.1 Importance of immediately discontinuing the drug and contacting clinician if symptoms of peripheral neuropathy (e.g., pain, burning, tingling, numbness, weakness) occur.1

  • Advise patients that diarrhea is a common problem caused by anti-infectives and usually ends when the drug is discontinued.1 Importance of contacting a clinician if watery and bloody stools (with or without stomach cramps and fever) occur during or as late as 2 months or longer after the last dose.1

  • Advise patients that norfloxacin may cause ECG changes (QT prolongation) and the importance of informing clinician of personal or family history of QT interval prolongation or proarrhythmic conditions (e.g., hypokalemia, bradycardia, recent myocardial ischemia).1

  • Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs, especially drugs that may affect QT interval (e.g., cisapride, erythromycin, antipsychotic agents, tricyclic antidepressants) or antiarrhythmic agents (e.g., amiodarone, quinidine, procainamide, sotalol).1

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

  • Importance of advising patients of other important precautionary information.1 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Norfloxacin

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, film-coated

400 mg

Noroxin

Merck

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Noroxin 400MG Tablets (MERCK SHARP &amp; DOHME): 20/$85.51 or 60/$235.14

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions October 15, 2013. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

1. Merck Sharp & Dohme Corp. Noroxin (norfloxacin) film-coated tablets prescribing information. Whitehouse Station, NJ; 2013 Jul.

2. Merck Sharp & Dohme. Noroxin (norfloxacin) formulary information monograph. West Point, PA; 1986.

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