Dosing

Dosing: Adult
Dysenteric enterocolitis (Shigella unlabeled use): Oral: 400 mg twice daily for 5 days
Prostatitis: Oral: 400 mg every 12 hours for 4-6 weeks
Traveler's diarrhea (unlabeled use): Oral: 400 mg twice daily for 3 days, single dose may also be effective
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 7-10 days
Complicated: 400 mg twice daily for 10-21 days

Dosing: Geriatric
Refer to adult dosing.

Dosing: Renal Impairment
Clcr ≤30 mL/minute/1.73 m2: Administer 400 mg every 24 hours.

Use

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.

Adverse Reactions

>1% to 10%:
Central nervous system: Headache (2% to 3%), dizziness (2% to 3%)
Gastrointestinal: Nausea (3% to 4%), abdominal cramping (2%)
Hematologic: Eosinophilia (1% to 2%)
Hepatic: Liver enzymes increased (1% to 2%)
≥0.3% to 1%:
Central nervous system: Fever, somnolence
Dermatologic: Hyperhidrosis, pruritus, rash
Gastrointestinal: Abdominal pain, anorectal pain, anorexia, constipation, diarrhea, dyspepsia, flatulence, loose stools, vomiting, xerostomia
Hematologic: Hematocrit/hemoglobin decreased (1%), leukopenia (1%), thrombocytopenia (1%)
Neuromuscular & skeletal: Back pain, paresthesia, weakness
Renal: Proteinuria (1%)
<0.3% (Limited to important or life-threatening): Abdominal swelling, acute renal failure, agranulocytosis, albuminuria, alkaline phosphatase increased, allergy, anaphylactoid reactions, anaphylaxis, angioedema, anxiety, arthralgia, arthritis, ataxia, bitter taste, blurred vision, BUN increased, bursitis, candiduria, chest pain, chills, cholestatic jaundice, cholesterol increased, confusion, CPK increased, crystalluria, cylinduria, depression, diplopia, dysgeusia, dysmenorrhea, dyspnea, edema, erythema, erythema multiforme, exacerbation of myasthenia gravis, exfoliative dermatitis, GI bleeding, glycosuria, Guillain-Barré syndrome, hearing loss, heartburn, hematuria, hemolytic anemia (sometimes associated with G6PD deficiency), hepatic failure, hepatic necrosis, hepatitis, hyper-/hypoglycemia, hyperkalemia, hypersensitivity, hypoesthesia, insomnia, interstitial nephritis, jaundice, LDH increased, MI, mouth ulcer, myalgia, myasthenia gravis exacerbation, myoclonus, neutropenia, nystagmus, palpitation, pancreatitis (rare), peripheral edema, peripheral neuropathy, photosensitivity/toxicity, postural hypotension, prothrombin time increased, pruritus ani, pseudomembraneous colitis, psychotic reactions, QTc prolongation, renal colic, seizure, serum creatinine increased, Stevens-Johnson syndrome, stomatitis, tendon rupture, tendonitis, tingling of fingers, tinnitus, torsade de pointes, toxic epidermal necrolysis, tremor, triglyceridemia, urticaria, vaginal candidiasis , vasculitis, ventricular arrhythmia

Contraindications

Hypersensitivity to norfloxacin, quinolones, or any component of the formulation; history of tendonitis or tendon rupture associated with quinolone use

Warnings / Precautions Drug

Boxed Warnings:
• Myasthenia gravis: See “Disease-related concerns” below.
• Tendon inflammation/rupture: See “Concerns related to adverse effects” below.
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).
• CNS stimulation: Tremor, restlessness, confusion, and very rarely hallucinations or seizures may occur; use with caution in patients with known or suspected CNS disorder. Discontinue in patients who experience significant CNS adverse effects (eg, dizziness, hallucinations, suicidal ideations or actions).
• 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.
• Peripheral neuropathy: The use of quinolones has been linked to peripheral neuropathy (rare); discontinue if symptoms of sensory or sensorimotor neuropathy occur.
• 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.
• Tendon inflammation/rupture: [U.S. Boxed Warning]: There have been reports of tendon inflammation and/or rupture with quinolone antibiotics; risk may be increased with concurrent corticosteroids, organ transplant recipients, and in patients >60 years of age. Rupture of the Achilles tendon sometimes requiring surgical repair has been reported most frequently; but other tendon sites (eg, rotator cuff, biceps) have also been reported. Strenuous physical activity may be an independent risk factor for tendonitis. Discontinue at first sign of tendon inflammation or pain. May occur even after discontinuation of therapy.
Disease-related concerns:
• Myasthenia gravis: [U.S. Boxed Warning]: May exacerbate muscle weakness related to myasthenia gravis. Cases of severe exacerbations, including the need for ventilatory support and deaths have been reported; avoid use in patients with myasthenia gravis.
• 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.
• Seizures: Use with caution in individuals at risk of seizures (CNS disorders or concurrent therapy with medications which may lower seizure threshold). Potential for seizures, although very rare, may be increased with concomitant NSAID therapy.
• 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.
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.
• Pediatrics: Safety and efficacy have not been established in children; other quinolones have caused transient arthropathy in children.
Metabolism/Transport Effects
Inhibits CYP1A2 (strong), 3A4 (moderate)

Interactions

Alfuzosin: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk C: Monitor therapy
Antacids: May decrease the absorption of Quinolone Antibiotics. Of concern only with oral administration of quinolones. Exceptions: Sodium Bicarbonate. Risk D: Consider therapy modification
Artemether: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk X: Avoid combination
BCG: Antibiotics may diminish the therapeutic effect of BCG. Risk X: Avoid combination
Bendamustine: CYP1A2 Inhibitors (Strong) may increase the serum concentration of Bendamustine. Concentrations of the active metabolites of bendamustine may be decreased. Risk C: Monitor therapy
Caffeine: Quinolone Antibiotics may decrease the metabolism of Caffeine. Risk C: Monitor therapy
Calcium Salts: May decrease the absorption of Quinolone Antibiotics. Of concern only with oral administration of both agents. Exceptions: Calcium Chloride. Risk D: Consider therapy modification
Chloroquine: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk C: Monitor therapy
Ciprofloxacin: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk C: Monitor therapy
Ciprofloxacin (Systemic): May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk C: Monitor therapy
Colchicine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Colchicine. Management: Reduce colchicine dose as directed when using with a moderate CYP3A4 inhibitor, and increase monitoring for colchicine-related toxicity. Use extra caution in patients with impaired renal and/or hepatic function. Risk D: Consider therapy modification
Corticosteroids (Systemic): Quinolone Antibiotics may enhance the adverse/toxic effect of Corticosteroids (Systemic). Risk of tendon-related side effects, including tendonitis and rupture, may be enhanced. Risk C: Monitor therapy
CycloSPORINE: Norfloxacin may decrease the metabolism of CycloSPORINE. Risk C: Monitor therapy
CycloSPORINE (Systemic): Norfloxacin may decrease the metabolism of CycloSPORINE (Systemic). Risk C: Monitor therapy
CYP1A2 Substrates: CYP1A2 Inhibitors (Strong) may decrease the metabolism of CYP1A2 Substrates. Risk D: Consider therapy modification
CYP3A4 Substrates: CYP3A4 Inhibitors (Moderate) may decrease the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
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. Risk D: Consider therapy modification
Dronedarone: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Dronedarone. Risk X: Avoid combination
Eplerenone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Eplerenone. Management: A lower starting dose of eplerenone (25 mg once daily for adults) is recommended in patients with hypertension who are also taking drugs that are moderate inhibitors of CYP3A4. Risk D: Consider therapy modification
Everolimus: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Everolimus. Management: Everolimus dose reductions are required for patients being treated for subependymal giant cell astrocytoma or renal cell carcinoma. See prescribing information for specific dose adjustment and monitoring recommendations. Risk D: Consider therapy modification
FentaNYL: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of FentaNYL. Management: Monitor patients extra closely for several days following initiation of the combination, and fentanyl dosage reductions should be made as appropriate. Risk D: Consider therapy modification
Gadobutrol: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk D: Consider therapy modification
Insulin: May enhance the hyperglycemic effect of Quinolone Antibiotics. Insulin may enhance the hypoglycemic effect of Quinolone Antibiotics. Risk C: Monitor therapy
Iron Salts: May decrease the absorption of Quinolone Antibiotics. Of concern only with oral administration of both agents. Exceptions: Ferric Gluconate; Ferumoxytol; Iron Dextran Complex; Iron Sucrose. Risk D: Consider therapy modification
Lanthanum: May decrease the serum concentration of Quinolone Antibiotics. Management: Administer oral quinolone antibiotics at least two hours before or after lanthanum. Risk D: Consider therapy modification
Lumefantrine: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk X: Avoid combination
Lurasidone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lurasidone. Risk D: Consider therapy modification
Magnesium Salts: May decrease the absorption of Quinolone Antibiotics. Of concern only with oral administration of both agents. Risk D: Consider therapy modification
Mycophenolate: Quinolone Antibiotics may decrease the serum concentration of Mycophenolate. Specifically, quinolones may decrease concentrations of the active metabolite of mycophenolate. Risk C: Monitor therapy
Nilotinib: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk X: Avoid combination
Nitrofurantoin: May diminish the therapeutic effect of Norfloxacin. Risk X: 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. Risk C: Monitor therapy
Pimecrolimus: CYP3A4 Inhibitors (Moderate) may decrease the metabolism of Pimecrolimus. Risk C: Monitor therapy
Pimozide: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Pimozide. Risk X: Avoid combination
Porfimer: Photosensitizing Agents may enhance the photosensitizing effect of Porfimer. Risk C: Monitor therapy
Probenecid: May increase the serum concentration of Quinolone Antibiotics. Risk C: Monitor therapy
QTc-Prolonging Agents: May enhance the adverse/toxic effect of other QTc-Prolonging Agents. Their effects can be additive, causing life-threatening ventricular arrhythmias. Risk D: Consider therapy modification
QUEtiapine: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk X: Avoid combination
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. Risk D: Consider therapy modification
QuiNINE: QTc-Prolonging Agents may enhance the QTc-prolonging effect of QuiNINE. QuiNINE may enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk X: Avoid combination
Salmeterol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Salmeterol. Risk C: Monitor therapy
Saxagliptin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Saxagliptin. Risk C: Monitor therapy
Sevelamer: May decrease the absorption of Quinolone Antibiotics. Risk D: Consider therapy modification
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. Risk D: Consider therapy modification
Sulfonylureas: Quinolone Antibiotics may enhance the hypoglycemic effect of Sulfonylureas. This appears to be particularly concerning early in the course of combination therapy. Quinolone Antibiotics may diminish the hypoglycemic effect of Sulfonylureas. With longer-term combination, there is a greater risk of hyperglycemia. Risk C: Monitor therapy
Tetrabenazine: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Tetrabenazine. Risk X: Avoid combination
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. Risk D: Consider therapy modification
Thioridazine: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Thioridazine. Risk X: Avoid combination
Tolvaptan: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tolvaptan. Risk X: Avoid combination
Toremifene: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Toremifene. The risk for potentially dangerous arrhythmias may be increased. Risk X: Avoid combination
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 24 hours after cessation of antibacterial agents. Risk D: Consider therapy modification
Vandetanib: QTc-Prolonging Agents may enhance the arrhythmogenic effect of Vandetanib. Risk X: Avoid combination
Varenicline: Quinolone Antibiotics may increase the serum concentration of Varenicline. Management: Monitor for increased varenicline adverse effects with concomitant use of levofloxacin or other quinolone antibiotics, particulary in patients with severe renal impairment. International product labeling recommendations vary. Consult appropriate labeling. Risk C: Monitor therapy
Vemurafenib: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Vemurafenib. Risk X: Avoid combination
Vilazodone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Vilazodone. Risk C: Monitor therapy
Vitamin K Antagonists (eg, warfarin): Quinolone Antibiotics may enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy
Zinc Salts: May decrease the absorption of Quinolone Antibiotics. Of concern only with oral administration of both agents. Risk D: Consider therapy modification
Ziprasidone: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Ziprasidone. The risk of a severe arrhythmia may be increased. Risk X: Avoid combination

Pregnancy

C
Pregnancy Implications
Adverse events have been observed in some animal studies; therefore, the manufacturer classifies norfloxacin as pregnancy category C. Norfloxacin crosses the placenta, distributing to cord blood and amniotic fluid. An increased risk of teratogenic effects has not been observed in animals or humans following norfloxacin use during pregnancy; however, because of concerns of cartilage damage in immature animals, norfloxacin should only be used during pregnancy if a safer option is not available.

Lactation

Excretion in breast milk unknown/not recommended
Breast-Feeding Considerations
Norfloxacin was not detected in the milk of nursing mothers administered an oral 200 mg dose. It is not known if concentrations would be detectable after a higher dose or multiple doses. Breast-feeding is not recommended by the manufacturer.

Mechanism of Action

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

Pharmacodynamics / Kinetics

Absorption: Oral: Rapid, up to 40%
Protein binding: 10% to 15%
Metabolism: Hepatic
Half-life elimination: 3-4 hours; Renal impairment (Clcr ≤30 mL/minute): 6.5 hours; Elderly: 4 hours
Time to peak, serum: 1-2 hours
Excretion: Urine (26% to 32% as unchanged drug; 5% to 8% as metabolites); feces (39%)