Norfloxacin

Norfloxacin is a fluoroquinolone antibacterial agent, structurally related to nalidixic acid. Due to it's relatively poor oral bioavailability, its clinical use is limited to the treatment of urinary tract infections and uncomplicated gonorrhea. Norfloxacin is also approved for use as an ophthalmic solution for bacterial conjunctivitis. It has the shortest half-life of all currently available fluoroquinolones. It was initially approved for systemic use by the FDA in October 1986. Norfloxacin is bactericidal via its effects on DNA gyrase, an enzyme responsible for counteracting the excessive supercoiling of DNA during replication or transcription. Although human cells do not contain DNA gyrase, they do contain a topoisomerase enzyme that functions in the same manner. This mammalian enzyme is not affected by bactericidal concentrations of quinolones. Norfloxacin is unclear how inhibition of DNA gyrase leads to bacterial cell death. Both rapid and slow growing organisms are inhibited by fluoroquinolones.

Norfloxacin is primarily indicated in conditions like Bacterial enteric infections, Cervicitis, Chronic prostatitis, Chronic relapsing UTIS, Gonorrhea, Urethritis, Urinary tract infection, UTI, and can also be given in adjunctive therapy as an alternative drug of choice in Eye infections.

Norfloxacin is contraindicated in conditions like Epilepsy, Hypersensitivity.

The severe or irreversible adverse effects of Norfloxacin, which give rise to further complications include Hepatitis, Hemolytic anemia, Seizures, Exfoliative dermatitis, Interstitial nephritis. The signs and symptoms that are produced after the acute overdosage of Norfloxacin include Crystalluria, Drowsiness, Acute renal failure, GI disturbances. The symptomatic adverse reactions produced by Norfloxacin are more or less tolerable and if they become severe, they can be treated symptomatically, these include Headache, Nausea, Vomiting, Diarrhea, Fever, Constipation, Insomnia, Dry mouth, Rashes, GI symptoms, Depression, Arthralgia, Heart burn, Crystalluria, Tendinitis.

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). • Aortic aneurysm and dissection: Fluoroquinolones have been associated with aortic aneurysm ruptures or dissection within 2 months following use, particularly in elderly patients. Fluoroquinolones should not be used in patients with a known history of aortic aneurysm or those at increased risk, including patients with peripheral atherosclerotic vascular diseases, hypertension, genetic disorders involving blood vessel changes (eg, Marfan syndrome, Ehlers-Danlos syndrome), and elderly patients, unless no other treatment options are available. Longer treatment duration (eg, >14 days) may increase risk (Lee 2018). • 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. • 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. • 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. Special populations: • Elderly: Adverse effects (eg, tendon rupture, QT changes) may be increased in the elderly. • G6PD deficiency: Hemolytic reactions may (rarely) occur with fluoroquinolone use in patients with G6PD deficiency (Luzzatto 2020). • 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).

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). • Aortic aneurysm and dissection: Fluoroquinolones have been associated with aortic aneurysm ruptures or dissection within 2 months following use, particularly in elderly patients. Fluoroquinolones should not be used in patients with a known history of aortic aneurysm or those at increased risk, including patients with peripheral atherosclerotic vascular diseases, hypertension, genetic disorders involving blood vessel changes (eg, Marfan syndrome, Ehlers-Danlos syndrome), and elderly patients, unless no other treatment options are available. Longer treatment duration (eg, >14 days) may increase risk (Lee 2018). • 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. • 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. • 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. Special populations: • Elderly: Adverse effects (eg, tendon rupture, QT changes) may be increased in the elderly. • G6PD deficiency: Hemolytic reactions may (rarely) occur with fluoroquinolone use in patients with G6PD deficiency (Luzzatto 2020). • 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).

0.3 % (0.3 (0.3)) 6 hourly Ophthalmic — 400 mg (400 (400)) 12 hourly PO — For 7 to 10 days

Not indicated in peads ( ) —

Not used in children ( ) —

Agents with Blood Glucose Lowering Effects: Quinolones may enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Quinolones may diminish the therapeutic effect of Agents with Blood Glucose Lowering Effects. Specifically, if an agent is being used to treat diabetes, loss of blood sugar control may occur with quinolone use. Monitor therapy Aminolevulinic Acid (Systemic): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Systemic). Avoid combination Aminolevulinic Acid (Topical): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Topical). Monitor therapy Amphetamines: May enhance the cardiotoxic effect of Quinolones. Monitor therapy Antacids: May decrease the absorption of Quinolones. Of concern only with oral administration of quinolones. Management: Avoid concurrent administration of quinolones and antacids to minimize the impact of this interaction. Recommendations for optimal dose separation vary by specific quinolone. 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 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 Quinolones. Of concern only with oral administration of both agents. Management: Consider administering an oral quinolone at least 2 hours before or 6 hours after the dose of an oral calcium supplement to minimize this interaction. Monitor for decrease therapeutic effects of quinolones during coadministration. Consider therapy modification Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Management: Avoid cholera vaccine in patients receiving systemic antibiotics, and within 14 days following the use of oral or parenteral antibiotics. Avoid combination Corticosteroids (Systemic): May enhance the adverse/toxic effect of Quinolones. 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 Delamanid: Quinolones may enhance the QTc-prolonging effect of Delamanid. Management: Avoid concomitant use if possible. If coadministration is unavoidable, frequent monitoring of electrocardiograms (ECGs) throughout the full delamanid treatment period should occur. Consider therapy modification Didanosine: Quinolones may decrease the serum concentration of Didanosine. Didanosine may decrease the serum concentration of Quinolones. 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 Haloperidol: QT-prolonging Agents (Indeterminate Risk - Avoid) may enhance the QTc-prolonging effect of Haloperidol. Monitor therapy Heroin: Quinolones may enhance the adverse/toxic effect of Heroin. Monitor therapy Iron Preparations: May decrease the serum concentration of Quinolones. Management: Give 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/dela-, 4 h for lome-, 3 h for gemi-, and 2 h for enox-, levo-, nor-, oflox-, peflox, or nalidixic acid) oral iron. 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 Quinolones. Management: Administer oral quinolone antibiotics at least one hour before or four hours after lanthanum. Consider therapy modification Magnesium Salts: May decrease the serum concentration of Quinolones. Management: Administer oral quinolones several hours before (4 h for moxi/pe/spar/enox-, 2 h for others) or after (8 h for moxi-, 6 h for cipro/dela-, 4 h for lome/pe/enox-, 3 h for gemi-, and 2 h for levo-, nor-, or ofloxacin or nalidixic acid) oral magnesium salts. Consider therapy modification Methylphenidate: May enhance the cardiotoxic effect of Quinolones. Monitor therapy Multivitamins/Minerals (with ADEK, Folate, Iron): May decrease the serum concentration of Quinolones. Specifically, polyvalent cations in multivitamin products may decrease the absorption of orally administered quinolone antibiotics. Management: Administer oral quinolones at least 2 hours before, or 6 hours after, the dose of a multivitamin that contains polyvalent cations (ie, calcium, iron, magnesium, selenium, zinc). Monitor for decreased quinolone efficacy. Consider therapy modification Multivitamins/Minerals (with AE, No Iron): May decrease the serum concentration of Quinolones. Specifically, minerals in the multivitamin/mineral product may impair absorption of quinolone antibiotics. Management: Administer oral quinolones at least 2 hours before, or 6 hours after, the dose of a multivitamin that contains polyvalent cations (ie, calcium, iron, magnesium, selenium, zinc). Monitor for decreased therapeutic effects of quinolones. Consider therapy modification Mycophenolate: Quinolones 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 Quinolones. 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 Quinolones. Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Quinolones. Monitor therapy Porfimer: Photosensitizing Agents may enhance the photosensitizing effect of Porfimer. Monitor therapy Probenecid: May decrease the excretion of Quinolones. Specifically, probenecid may decreased the renal excretion of quinolone antibiotics. Probenecid may increase the serum concentration of Quinolones. Monitor therapy QT-prolonging Agents (Highest Risk): QT-prolonging Agents (Indeterminate Risk - Avoid) may enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Monitor therapy Sevelamer: May decrease the absorption of Quinolones. 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 Quinolones. 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 Quinolones. Management: Avoid concurrent administration of quinolones and sucralfate to minimize the impact of this interaction. Recommendations for optimal dose separation vary by specific quinolone. Consider therapy modification Theophylline Derivatives: Quinolones may increase the serum concentration of Theophylline Derivatives. Monitor therapy Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Avoid use of live attenuated typhoid vaccine (Ty21a) in patients being treated with systemic antibacterial agents. Postpone vaccination until 3 days after cessation of antibiotics and avoid starting antibiotics within 3 days of last vaccine dose. Consider therapy modification Varenicline: Quinolones 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): Quinolones may enhance the anticoagulant effect of Vitamin K Antagonists. Monitor therapy Zinc Salts: May decrease the serum concentration of Quinolones. Management: Give oral quinolones at several hours before (4 h for moxi- and sparfloxacin, 2 h for others) or after (8 h for moxi-, 6 h for cipro/dela-, 4 h for lome-, 3 h for gemi-, and 2 h for enox-, levo-, nor-, pe- or ofloxacin or nalidixic acid) oral zinc salts. Consider therapy modification

Tab, Eye Soln Store Below 40°C. Protect from Sunlight, Moisture and Heat.