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Norfloxacin

Pronunciation

Pronunciation

(nor FLOKS a sin)

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Slideshow: The Shocking Truth About Antibiotic Resistance

Tablet, Oral:

Noroxin: 400 mg [DSC]

Brand Names: U.S.

  • Noroxin [DSC]

Pharmacologic Category

  • Antibiotic, Fluoroquinolone

Pharmacology

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

Absorption

Oral: Rapid, up to 40%

Metabolism

Hepatic

Excretion

Urine (26% to 32% as unchanged drug; 5% to 8% as metabolites); feces (30%)

Time to Peak

Serum: 1-2 hours

Half-Life Elimination

3-4 hours; Renal impairment (CrCl ≤30 mL/minute): 6.5 hours; Elderly: 4 hours

Protein Binding

10% to 15%

Special Populations: Renal Function Impairment

Renal insufficiency increases half-life.

Use: Labeled Indications

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.

Use: Unlabeled

Shigella dysentery type 1; traveler's diarrhea

Contraindications

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

Dosage

Note: Noroxin is no longer available in the US.

Usual dosage range:

Adults: Oral: 400 mg every 12 hours (maximum: 800 mg/day)

Indication-specific dosing:

Adults: Oral:

Prostatitis: 400 mg every 12 hours for 4 to 6 weeks

Uncomplicated gonorrhea: 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:

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]).

Traveler's diarrhea (off-label use): 400 mg twice daily for 3 days (Mattila 1993), single dose may also be effective.

Dosage adjustment in renal impairment: CrCl ≤30 mL/minute/1.73 m2: 400 mg once daily

Dosage adjustment in hepatic impairment: No dosage adjustment provided in manufacturer’s labeling.

Extemporaneously Prepared

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):577-9.11296605

Administration

Hold antacids, sucralfate, or multivitamins/supplements containing iron, zinc, magnesium, or aluminum for 2 hours 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).

Dietary Considerations

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.

Storage

Store at 25°C (77°F). Keep container tightly closed.

Drug Interactions

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

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 Pyrophosphate Citrate; Ferumoxytol; Iron Dextran Complex; Iron Sucrose. 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. 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

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 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

Adverse Reactions

>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-Barré 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

ALERT: U.S. Boxed Warning

Tendinitis and tendon rupture:

Fluoroquinolones, including norfloxacin, are associated with an increased risk of tendinitis and tendon rupture in all ages. This risk is further increased in older patients, usually older than 60 years, in patients taking corticosteroid drugs, and in patients with kidney, heart, or lung transplants.

Myasthenia gravis:

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

Warnings/Precautions

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 effects: Tremor, restlessness, confusion, and very rarely hallucinations, increased intracranial pressure (including pseudotumor cerebri) 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: Peripheral neuropathy has been reported (rare); may occur soon after initiation of therapy and may be irreversible; 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:[US Boxed Warning]: There have been reports of tendon inflammation and/or rupture with quinolone antibiotics in all ages; risk may be increased with concurrent corticosteroids, solid 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. Inflammation and rupture may occur bilaterally. Cases have been reported within the first 48 hours, during, and up to several months after discontinuation of therapy. Strenuous physical activity may be an independent risk factor for tendonitis. Discontinue at first sign of tendon inflammation or pain. Use with caution in patients with a history of tendon disorders.

Disease-related concerns:

• Myasthenia gravis: [US 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.

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.

Monitoring Parameters

Monitor CBC, renal and hepatic function periodically if therapy is prolonged.

Pregnancy Risk Factor

C

Pregnancy Considerations

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).

Patient Education

• 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.

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