Noroxin

Generic Name: Norfloxacin
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

• 
  

  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.)

  
  

REMS:

FDA approved a REMS for norfloxacin to ensure that the benefits of a drug outweigh the risks. The REMS may apply to one or more preparations of norfloxacin and consists of the following: medication guide. See the FDA REMS page () or the ASHP REMS Resource Center ().

Introduction

Antibacterial; fluoroquinolone.^{1 17 18 20}

Uses for Noroxin

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}

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 are drugs of choice when an anti-infective is indicated as an adjunct to fluid and electrolyte replacement;^{43 309 311 334} alternative agents for V. cholerae resistant to tetracyclines include co-trimoxazole, fluoroquinolones, or furazolidone.^{43 309 311 334 341}

Treatment of travelers’ diarrhea†.^{210 301 304 305 306 335 374} Replacement therapy with oral fluids and electrolytes may be sufficient for mild to moderate disease.^{210 304 305 335} Generally self-limited and may resolve within 3–4 days without anti-infective treatment;^{210 304 305 334} 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 may be indicated.^{210 304 305 334 374} Fluoroquinolones (ciprofloxacin, levofloxacin, norfloxacin, ofloxacin) usually drugs of choice when treatment, including self-treatment, is indicated.^{304 305 312 335 337 374} Azithromycin is a treatment alternative for those who should not receive fluoroquinolones (e.g., children, pregnant women) and may be a drug of choice for travelers in areas with a high prevalence of fluoroquinolone-resistant Campylobacter (e.g., Thailand, India) or those who have not responded after 48 hours of fluoroquinolone treatment.^{304 305 334 374} Rifaximin is another alternative for treatment of travelers' diarrhea caused by noninvasive E. coli.^{304 305 374}

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.^{109 131 193 301 304 307 308 335 337 374} CDC and others do not recommend anti-infective prophylaxis in most individuals traveling to areas of risk;^{210 304 305 308 312 334 374} the principal preventive measures are prudent dietary practices.^{210 304 329 330} 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,^{304 305 374} although the increasing incidence of quinolone resistance in pathogens that cause travelers' diarrhea (e.g., Campylobacter) should be considered.^{304 305}

Gonorrhea and Associated Infections

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

Although fluoroquinolones (ciprofloxacin, levofloxacin, ofloxacin) were previously considered drugs of choice for treatment of uncomplicated gonorrhea,^{319 358} CDC currently states that fluoroquinolones should not be used for treatment of gonorrhea or any associated infections involving N. gonorrhoeae (e.g., pelvic inflammatory disease [PID], epididymitis).^{328 358 359 360}

Quinolone-resistant N. gonorrhoeae (QRNG) has been reported with increasing frequency worldwide and is widespread in the US.^{319 320 328 338 358 359 360} (See Resistance in Neisseria gonorrhoeae under Cautions.)

For treatment of uncomplicated cervical, urethral, or rectal gonorrhea, CDC and others recommend IM ceftriaxone or oral cefixime; IM ceftriaxone is drug of choice for pharyngeal infections.^{319 328 358 359}

Noroxin 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.^{305 306 374}

Prevention of Travelers’ Diarrhea†

Oral

400 mg once daily.^{305 329 330 335 374}

Although anti-infective prophylaxis generally is discouraged,^{210 304 305 308 312 334 337 374} some clinicians state that it can be given during the period of risk (for ≤3 weeks) beginning the day of travel and continuing for 1 or 2 days after leaving the area of risk.^{329 330 335 374}

Gonorrhea

Uncomplicated Urethral, Endocervical, or Rectal† Gonorrhea

Oral

A single 800-mg dose.^{1 319}

Because of increased prevalence of quinolone-resistant Neisseria gonorrhoeae (QRNG), CDC no longer recommends fluoroquinolones for treatment of gonorrhea or any associated infections involving N. gonorrhoeae (e.g., PID, epididymitis).^{328 358 359 360} (See Gonorrhea and Associated Infections under Uses.)

Unless the presence of coexisting chlamydial infection has been excluded by appropriate testing, patients being treated for gonorrhea should also receive an anti-infective regimen effective for presumptive treatment of chlamydia (e.g., a single dose of oral azithromycin or a 7-day regimen of oral doxycycline).³¹⁹

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 Cl_cr ≤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 Noroxin

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.)

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 quinolones, including norfloxacin.¹

To prevent development of an irreversible condition, discontinue norfloxacin if symptoms of neuropathy (e.g., pain, burning, tingling, numbness, and/or weakness) occur or if there are deficits in light touch, pain, temperature, position sense, vibratory sensation, and/or motor strength.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.^{1 345 346 347 348 349 354} C. difficile-associated diarrhea and colitis (CDAD; also known as antibiotic-associated diarrhea and colitis or pseudomembranous colitis) has been reported with nearly all anti-infectives, including norfloxacin, and may range in severity from mild diarrhea to fatal colitis.^{1 242 267 345 346 347 348 349 351 355 356} 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} Hyper toxin-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

Consider CDAD if diarrhea develops during or after therapy and manage accordingly.^{1 345 346 347 348 349 354} Careful medical history is necessary since CDAD has been reported to occur as late as 2 months or longer after anti-infective therapy is discontinued.^{1 345 346 347 348 349}

If CDAD is suspected or confirmed, norfloxacin may need to be discontinued.^{1 345 346 347 348 349} Some mild cases may respond to discontinuance alone.^{345 346 347 348 349} Manage moderate to severe cases with fluid, electrolyte, and protein supplementation, appropriate anti-infective therapy active against C. difficile (e.g., oral metronidazole or vancomycin), and surgical evaluation when clinically indicated.^{1 345 346 347 348 349}

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.²⁹² 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.²⁹²

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

Myasthenia Gravis Patients

Possible exacerbation of signs of myasthenia gravis, which may lead to life-threatening weakness of respiratory muscles, reported with quinolones, including norfloxacin; use with caution in patients with myasthenia gravis.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 homeostatis) 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 several years.^{319 320 322 323 324 325 326 327 328 336 358}

Recent 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 states that fluoroquinolones should not be used to treat proven or suspected gonorrhea,^{328 358 359 360} including infections acquired within the US or acquired while traveling abroad.³¹⁹

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 the parents or caregivers.³³⁴

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 Noroxin

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

Noroxin 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