(nor FLOKS a sin)
Uncomplicated and complicated urinary tract infections caused by susceptible gram-negative and gram-positive bacteria; sexually-transmitted disease (eg, uncomplicated urethral and cervical gonorrhea) caused by N. gonorrhoeae; prostatitis due to E. coli
Note: As of April 2007, the CDC no longer recommends the use of fluoroquinolones for the treatment of gonococcal disease.
Hypersensitivity to norfloxacin, quinolones, or any component of the formulation; history of tendonitis or tendon rupture associated with quinolone use
Fluoroquinolones are associated with disabling and potentially irreversible serious adverse reactions that have occurred together, including tendinitis and tendon rupture, peripheral neuropathy, and CNS effects. Discontinue norfloxacin immediately and avoid the use of fluoroquinolones in patients who experience any of these serious adverse reactions. Because fluoroquinolones are associated with serious adverse reactions, reserve norfloxacin for use in patients who have no alternative treatment options for uncomplicated urinary tract infections (including cystitis).
Exacerbation of myasthenia gravis:Fluoroquinolonesmay exacerbate muscle weakness in patients with myasthenia gravis. Avoid norfloxacin in patients with known history of myasthenia gravis.
Note: Noroxin is no longer available in the US.
Prostatitis: Oral: 400 mg every 12 hours for 4 to 6 weeks
Uncomplicated gonorrhea: Oral: 800 mg as a single dose. Note: As of April 2007, the CDC no longer recommends the use of fluoroquinolones for the treatment of uncomplicated gonococcal disease.
Urinary tract infections: Oral:
Uncomplicated due to E. coli, K. pneumoniae, P. mirabilis: 400 mg twice daily for 3 days
Uncomplicated due to other organisms: 400 mg twice daily for 7 to 10 days
Complicated: 400 mg twice daily for 10 to 21 days
Dysenteric enterocolitis(Shigella)(off-label use): 400 mg twice daily for 3 days (IDSA 2001)
Spontaneous bacterial peritonitis (SBP) (prevention) (off-label use):
Prior SBP or low protein ascites: Long-term prophylaxis: 400 mg once daily (AASLD [Runyon 2012]; EASL 2010)
Variceal hemorrhage: Short-term prophylaxis: 400 mg every 12 hours for 7 days (AASLD [Runyon 2012]; Fernandez 2006). May also administer norfloxacin 400 mg every 12 hours for 7 days after a course of IV ceftriaxone during active GI bleed (AASLD [Runyon 2012]).
Travelers diarrhea (off-label use): 400 mg twice daily for 3 days (Mattila 1993), single dose may also be effective.
Refer to adult dosing.
CrCl ≤30 mL/minute/1.73 m2: 400 mg once daily
No dosage adjustment provided in manufacturer 's labeling.
Hold antacids, sucralfate, or multivitamins/supplements containing iron, zinc, magnesium, or aluminum for 2 hours before or after giving norfloxacin; do not administer together. Best taken on an empty stomach with water (1 hour before or 2 hours after meals, milk, or other dairy products).
Oral formulations should be administered on an empty stomach with water (1 hour before or 2 hours after meals, milk, or other dairy products). Maintain fluid intake to ensure adequate hydration and urinary output.
Store at 25 ‚ °C (77 ‚ °F); excursions permitted to 15 ‚ °C to 30 ‚ °C (59 ‚ °F to 86 ‚ °F). Keep container tightly closed.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Tablet, Oral:
Noroxin: 400 mg [DSC]
A 20 mg/mL oral suspension may be made using tablets. Crush three 400 mg tablets and reduce to a fine powder. Add a small amount of a 1:1 mixture of Ora-Plus ‚ ® and Strawberry Syrup (made from a 1:5 mix of Strawberry Fountain Syrup and Simple Syrup, NF) and mix to a uniform paste; mix while adding the vehicle in geometric proportions to almost 60 mL; transfer to a calibrated bottle, rinse mortar with vehicle, and add quantity of vehicle sufficient to make 60 mL. Label shake well". Stable 56 days at room temperature or refrigerated. May administer chocolate syrup before medication administration or mix the suspension 1:1 with chocolate syrup to mask the bitter aftertaste and improve palatability.
Johnson CE, Price J, and Hession JM, "Stability of Norfloxacin in an Extemporaneously Prepared Oral Liquid," Am J Health Syst Pharm, 2001, 58(7):577-9.[PMID: 11296605]Aminolevulinic Acid: Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid. Monitor therapy
Antacids: May decrease the absorption of Quinolone Antibiotics. Of concern only with oral administration of quinolones. Exceptions: Sodium Bicarbonate. Consider therapy modification
BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Avoid combination
BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Monitor therapy
Blood Glucose Lowering Agents: Quinolone Antibiotics may enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Quinolone Antibiotics may diminish the therapeutic effect of Blood Glucose Lowering Agents. Specifically, if an agent is being used to treat diabetes, loss of blood sugar control may occur with quinolone use. Monitor therapy
Caffeine and Caffeine Containing Products: Norfloxacin may increase the serum concentration of Caffeine and Caffeine Containing Products. Monitor therapy
Calcium Salts: May decrease the absorption of Quinolone Antibiotics. Of concern only with oral administration of both agents. Exceptions: Calcium Chloride. Consider therapy modification
Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Avoid combination
Corticosteroids (Systemic): May enhance the adverse/toxic effect of Quinolone Antibiotics. Specifically, the risk of tendonitis and tendon rupture may be increased. Monitor therapy
CycloSPORINE (Systemic): Norfloxacin may decrease the metabolism of CycloSPORINE (Systemic). Monitor therapy
Didanosine: Quinolone Antibiotics may decrease the serum concentration of Didanosine. Didanosine may decrease the serum concentration of Quinolone Antibiotics. Management: Administer oral quinolones at least 2 hours before or 6 hours after didanosine. Monitor for decreased therapeutic effects of quinolones, particularly if doses cannot be separated as recommended. This does not apply to unbuffered enteric coated didanosine. Consider therapy modification
Highest Risk QTc-Prolonging Agents: QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying) may enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Management: Avoid such combinations when possible. Use should be accompanied by close monitoring for evidence of QT prolongation or other alterations of cardiac rhythm. Consider therapy modification
Iron Salts: May decrease the serum concentration of Quinolone Antibiotics. Management: Administer oral quinolones at least several hours before (4 h for moxi- and sparfloxacin, 2 h for others) or after (8 h for moxi-, 6 h for cipro-, 4 h for lome-, 3 h for gemi-, and 2 h for levo-, nor-, or ofloxacin or nalidixic acid) oral iron salts. Exceptions: Ferric Carboxymaltose; Ferric Gluconate; Ferric Hydroxide Polymaltose Complex; Ferric Pyrophosphate Citrate; Ferumoxytol; Iron Dextran Complex; Iron Sucrose. Consider therapy modification
Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Monitor therapy
Lanthanum: May decrease the serum concentration of Quinolone Antibiotics. Management: Administer oral quinolone antibiotics at least two hours before or after lanthanum. Consider therapy modification
Magnesium Salts: May decrease the serum concentration of Quinolone Antibiotics. Management: Administer oral quinolones at least several hours before (4 h for moxi- and sparfloxacin, 2 h for others) or after (8 h for moxi-, 6 h for cipro-, 4 h for lome-, 3 h for gemi-, and 2 h for levo-, nor-, or ofloxacin or nalidixic acid) oral magnesium salts. Consider therapy modification
MiFEPRIStone: May enhance the QTc-prolonging effect of QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying). Management: Though the drugs listed here have uncertain QT-prolonging effects, they all have some possible association with QT prolongation and should generally be avoided when possible. Consider therapy modification
Moderate Risk QTc-Prolonging Agents: QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying) may enhance the QTc-prolonging effect of Moderate Risk QTc-Prolonging Agents. Monitor therapy
Multivitamins/Minerals (with ADEK, Folate, Iron): May decrease the serum concentration of Quinolone Antibiotics. Specifically, polyvalent cations in multivitamin products may decrease the absorption of orally administered quinolone antibiotics. Management: Interactions can be minimized by administering the oral quinolone at least 2 hours before, or 6 hours after, the dose of a multivitamin that contains polyvalent cations (i.e., calcium, iron, magnesium, selenium, zinc). Consider therapy modification
Multivitamins/Minerals (with AE, No Iron): May decrease the serum concentration of Quinolone Antibiotics. Specifically, minerals in the multivitamin/mineral product may impair absorption of quinolone antibiotics. Management: Interactions can be minimized by administering the oral quinolone at least 2 hours before, or 6 hours after, the dose of a multivitamin that contains polyvalent cations (i.e., calcium, iron, magnesium, selenium, zinc). Consider therapy modification
Mycophenolate: Quinolone Antibiotics may decrease the serum concentration of Mycophenolate. Specifically, quinolones may decrease concentrations of the active metabolite of mycophenolate. Monitor therapy
Nadifloxacin: May enhance the adverse/toxic effect of Quinolone Antibiotics. Avoid combination
Nitrofurantoin: May diminish the therapeutic effect of Norfloxacin. Avoid combination
Nonsteroidal Anti-Inflammatory Agents: May enhance the neuroexcitatory and/or seizure-potentiating effect of Quinolone Antibiotics. Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Quinolone Antibiotics. Monitor therapy
Porfimer: Photosensitizing Agents may enhance the photosensitizing effect of Porfimer. Monitor therapy
Probenecid: May decrease the excretion of Quinolone Antibiotics. Specifically, probenecid may decreased the renal excretion of quinolone antibiotics. Probenecid may increase the serum concentration of Quinolone Antibiotics. Monitor therapy
Quinapril: May decrease the serum concentration of Quinolone Antibiotics. Management: Separate doses of quinapril and oral quinolones by at least 2 hours in order to reduce the risk of interaction. Monitor for reduced efficacy of the quinolone if these products are used concomitantly. Consider therapy modification
Sevelamer: May decrease the absorption of Quinolone Antibiotics. Management: Administer oral quinolones at least 2 hours before or 6 hours after sevelamer. Consider therapy modification
Sodium Picosulfate: Antibiotics may diminish the therapeutic effect of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. Consider therapy modification
Strontium Ranelate: May decrease the serum concentration of Quinolone Antibiotics. Management: In order to minimize any potential impact of strontium ranelate on quinolone antibiotic concentrations, it is recommended that strontium ranelate treatment be interrupted during quinolone therapy. Avoid combination
Sucralfate: May decrease the serum concentration of Quinolone Antibiotics. Management: Administer oral quinolones at least 2 hours before or 6 hours after the sucralfate dose. Greater separation of doses may further lessen the risk for a significant interaction. Consider therapy modification
Theophylline Derivatives: Quinolone Antibiotics may decrease the metabolism of Theophylline Derivatives. Ciprofloxacin and enoxacin are of greatest concern. Theophylline/quinolone therapy might augment the seizure-producing potential of each of the individual agents. Exceptions: Dyphylline. Consider therapy modification
TiZANidine: CYP1A2 Inhibitors (Weak) may increase the serum concentration of TiZANidine. Management: Avoid these combinations when possible. If combined use cannot be avoided, initiate tizanidine at an adult dose of 2 mg and increase in 2-4 mg increments based on patient response. Monitor for increased effects of tizanidine, including adverse reactions. Consider therapy modification
Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Vaccination with live attenuated typhoid vaccine (Ty21a) should be avoided in patients being treated with systemic antibacterial agents. Use of this vaccine should be postponed until at least 3 days after cessation of antibacterial agents. Consider therapy modification
Varenicline: Quinolone Antibiotics may increase the serum concentration of Varenicline. Management: Monitor for increased varenicline adverse effects with concurrent use of levofloxacin or other quinolone antibiotics, particularly in patients with severe renal impairment. International product labeling recommendations vary. Consult appropriate labeling. Monitor therapy
Verteporfin: Photosensitizing Agents may enhance the photosensitizing effect of Verteporfin. Monitor therapy
Vitamin K Antagonists (eg, warfarin): Quinolone Antibiotics may enhance the anticoagulant effect of Vitamin K Antagonists. Monitor therapy
Zinc Salts: May decrease the serum concentration of Quinolone Antibiotics. Management: Administer oral quinolones at least several hours before (4 h for moxi- and sparfloxacin, 2 h for others) or after (8 h for moxi-, 6 h for cipro-, 4 h for lome-, 3 h for gemi-, and 2 h for levo-, nor-, or ofloxacin or nalidixic acid) oral zinc salts. Exceptions: Zinc Chloride. Consider therapy modification
Monitor CBC, renal and hepatic function periodically if therapy is prolonged.
>1% to 10%:
Central nervous system: Dizziness (2% to 3%), headache (2% to 3%)
Gastrointestinal: Nausea (3% to 4%), abdominal cramping (2%)
Hematologic and oncologic: Eosinophilia (1% to 2%)
Hepatic: Liver enzymes increased (1% to 2%)
≥0.3% to 1%:
Central nervous system: Drowsiness
Dermatologic: Hyperhidrosis, pruritus, rash
Endocrine & metabolic: Decreased WBC count (1%), increased serum alkaline phosphatase (1%)
Gastrointestinal: Abdominal pain, anorectal pain, anorexia, constipation, diarrhea, dyspepsia, flatulence, loose stools, vomiting, xerostomia
Genitourinary: Proteinuria (1%)
Hematologic and oncologic: Decreased platelet count (1%), leukopenia (1%), thrombocytopenia (1%), decreased hematocrit, decreased hemoglobin
Neuromuscular & skeletal: Weakness (1%), back pain
Miscellaneous: Fever
<0.3% (Limited to important or life-threatening): Acute renal failure, agranulocytosis, albuminuria, anaphylactoid reaction, anaphylaxis, angioedema, anxiety, arthralgia, arthritis, ataxia, bursitis, chest pain, cholestatic jaundice, Clostridium difficile-associated diarrhea, depression, diplopia, DRESS syndrome, dysgeusia, dysmenorrhea, erythema multiforme, exacerbation of myasthenia gravis, exfoliative dermatitis, gastrointestinal hemorrhage, Guillain-Barre syndrome, hearing loss, hematuria, hemolytic anemia (sometimes associated with G6PD deficiency), hepatic failure, hepatic necrosis, hepatitis, hepatotoxicity (idiosyncratic) (Chalasani, 2014), hyperglycemia, hyperkalemia, hypersensitivity reactions, hypertriglyceridemia, hypoglycemia, insomnia, interstitial nephritis, myocardial infarction, myoclonus, neutropenia, nystagmus, orthostatic hypotension, pancreatitis (rare), paresthesia, peripheral neuropathy (may be irreversible), phototoxicity, prolonged Q-T interval on ECG, pseudotumor cerebri, seizure, skin photosensitivity, Stevens-Johnson syndrome, stomatitis, tendonitis, tinnitus, torsades de pointes, toxic epidermal necrolysis, uveitis, vasculitis, ventricular arrhythmia, vulvovaginal candidiasis
Serious adverse reactions:
- [US Boxed Warning]: Fluoroquinolones are associated with disabling and potentially irreversible serious adverse reactions that may occur together, including tendinitis and tendon rupture, peripheral neuropathy, and CNS effects. Discontinue norfloxacin immediately and avoid use of fluoroquinolones in patients who experience any of these serious adverse reactions. Patients of any age or without pre-existing risk factors have experienced these reactions; may occur within hours to weeks after initiation.
- CNS effects: Fluoroquinolones have been associated with an increased risk of CNS effects including seizures, increased intracranial pressure (including pseudotumor cerebri), and toxic psychosis; may also cause nervousness, agitation, insomnia, anxiety, nightmares, paranoia, dizziness, confusion, tremors, hallucinations, depression, and suicidal thoughts or actions. May occur following the first dose; discontinue immediately and avoid further use of fluoroquinolones in patients who experience these reactions. Use with caution in patients with known or suspected CNS disorder, or risk factors that may predispose to seizures or lower the seizure threshold.
- Peripheral neuropathy: Fluoroquinolones have been associated with an increased risk of peripheral neuropathy; may occur soon after initiation of therapy and may be irreversible; discontinue if symptoms of sensory or sensorimotor neuropathy occur. Avoid use in patients who have previously experienced peripheral neuropathy.
- Tendinitis/tendon rupture: Fluoroquinolones have been associated with an increased risk of tendonitis and tendon rupture in all ages; risk may be increased with concurrent corticosteroids, solid organ transplant recipients, and in patients >60 years of age, but has also occurred in patients without these risk factors. Rupture of the Achilles tendon has been reported most frequently; but other tendon sites (eg, rotator cuff, biceps, hand) have also been reported. Inflammation and rupture may occur bilaterally. Cases have been reported within hours or days of initiation, and up to several months after discontinuation of therapy. Strenuous physical activity, renal failure, and previous tendon disorders may be independent risk factor for tendon rupture. Discontinue at first sign of tendon pain, swelling, inflammation or rupture. Avoid use in patients with a history of tendon disorders or who have experienced tendinitis or tendon rupture.
Concerns related to adverse effects:
- Altered cardiac conduction: Fluoroquinolones may prolong QTc interval; avoid use in patients with a history of QTc prolongation, uncorrected hypokalemia, hypomagnesemia, or concurrent administration of other medications known to prolong the QT interval (including Class Ia and Class III antiarrhythmics, cisapride, erythromycin, antipsychotics, and tricyclic antidepressants).
- Glucose regulation: Fluoroquinolones have been associated with the development of serious, and sometimes fatal, hypoglycemia. These events have occurred most often in elderly patients with diabetes, but have also been reported in patients without a prior history of diabetes. Prompt identification and treatment of hypoglycemia is essential. Individual quinolones may differ in their potential to cause this effect. It was most evident with gatifloxacin (no longer marketed as s systemic formulation). Hyperglycemia has also been associated with the use of fluoroquinolones. Patients should be monitored closely for signs/symptoms of disordered glucose regulation.
- Hypersensitivity reactions: Severe hypersensitivity reactions, including anaphylaxis, have occurred with quinolone therapy. The spectrum of these reactions can vary widely; reactions may present as typical allergic symptoms (eg, itching, urticaria, rash, edema) after a single dose, or may manifest as severe idiosyncratic dermatologic (eg, Stevens-Johnson, toxic epidermal necrolysis), vascular (eg, vasculitis), pulmonary (eg, pneumonitis), renal (eg, nephritis), hepatic (eg, hepatic failure or necrosis), and/or hematologic (eg, anemia, cytopenias) events, usually after multiple doses. Prompt discontinuation of drug should occur if skin rash or other symptoms arise.
- Phototoxicity: Avoid excessive sunlight and take precautions to limit exposure (eg, loose fitting clothing, sunscreen); may cause moderate-to-severe phototoxicity reactions. Discontinue use if photosensitivity occurs.
- Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.
Disease-related concerns:
- Myasthenia gravis: [US Boxed Warning]: May exacerbate muscle weakness related to myasthenia gravis; avoid use in patients with known history of myasthenia gravis. Cases of severe exacerbations, including the need for ventilatory support and deaths have been reported.
- Renal impairment: Use caution with renal impairment; dose adjustment required. May increase risk of tendon rupture.
- Rheumatoid arthritis: Use with caution in patients with rheumatoid arthritis; may increase risk of tendon rupture.
- Syphilis: Since norfloxacin is ineffective in the treatment of syphilis and may mask symptoms, all patients should be tested for syphilis at the time of gonorrheal diagnosis and 3 months later.
Concurrent drug therapy issues:
- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
Special populations:
- Elderly: Adverse effects (eg, tendon rupture, QT changes) may be increased in the elderly.
- G6PD deficiency: Hemolytic reactions may (rarely) occur with quinolone use in patients with latent or actual G6PD deficiency.
- Pediatric: Safety and efficacy have not been established in children; other quinolones have caused transient arthropathy in children.
Other warnings/precautions:
- Appropriate use: [US Boxed Warning]: Reserve use of norfloxacin for treatment of uncomplicated urinary tract infections, including cystitis, for patients who have no alternative treatment options because of the risk of disabling and potentially serious adverse reactions (eg, tendinitis and tendon rupture, peripheral neuropathy, CNS effects).
C
Adverse events have been observed in some animal reproduction studies. Norfloxacin crosses the placenta, distributing to cord blood and amniotic fluid (Wise 1984). Based on available data, an increased risk of teratogenic effects has not been observed following norfloxacin use during pregnancy (Bar-Oz 2009; Padberg 2014).
Norfloxacin is a DNA gyrase inhibitor. DNA gyrase is an essential bacterial enzyme that maintains the superhelical structure of DNA. DNA gyrase is required for DNA replication and transcription, DNA repair, recombination, and transposition; bactericidal
Oral: Rapid, up to 40%
Hepatic
Urine (26% to 32% as unchanged drug; 5% to 8% as metabolites); feces (30%)
Serum: 1 to 2 hours
3 to 4 hours; Renal impairment (CrCl ≤30 mL/minute): 6.5 hours; Elderly: 4 hours
10% to 15%
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience headache, abdominal cramps, nausea, or diarrhea. Have patient report immediately to prescriber signs of tendon inflammation or rupture (eg, pain, bruising, or swelling in the back of the ankle, shoulder, hand, or other joints), signs of depression (ie, suicidal ideation, anxiety, emotional instability, illogical thinking), signs of hepatic impairment, angina, arrhythmia, severe dizziness, syncope, considerable asthenia, vision changes, illogical thinking, hallucinations, dyspnea, ecchymosis, hemorrhaging, tremors, abnormal gait, urinary retention, oliguria, vaginitis, stomatitis, signs of neuropathy of extremities, or signs of pseudomembranous colitis (rare) (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.