Norfloxacin

Norfloxacin is a antibacterial agent belonging to fluoroquinolone.

Norfloxacin is used in the treatment of Uncomplicated and complicated urinary tract infections. It is also used to treat Spontaneous bacterial peritonitis, prophylaxis.

Norfloxacin get rapidly but incompletely absorbed from the gastrointestinal tract (approx 30-40%). Food and dairy products decrease the absorption and get penetrates well into tissues of the genitourinary tract; detected in bile, prostatic fluid and amniotic fluid. Crosses the placenta. Plasma protein binding: 10-15% and get metabolised in the liver into several metabolites and get excreted Mainly via urine (26-32% as unchanged drug, 5-8% as metabolites); faeces (30%).

The Tmax of Norfloxacin was achieved at 1-2 hours after administration

Norfloxacin shows common side effects like insomnia, confusion, hallucination, nervousness, disorientation, depression, anxiety, mood changes. Renal and urinary disorders: Crystalluria (high doses).

Norfloxacin is available as tablets.

Norfloxacin is available in India, Germany, Canada, France.

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.

Norfloxacin is available in the form of tablets.

• Tablets:- Norfloxacin tablets should be taken with or without water.

Norfloxacin is used in the treatment of Uncomplicated and complicated urinary tract infections.It is also used to treat Spontaneous bacterial peritonitis, prophylaxis.

Norfloxacin is a fluoroquinolone derivative with a broad spectrum of bactericidal activity. It exerts its antibacterial activity by inhibiting deoxyribonucleic acid (DNA) gyrase, a bacterial enzyme necessary for DNA replication, transcription, repair, recombination and transposition.

Norfloxacin is approved for use in the following clinical indications

Urinary tract infection:- Uncomplicated and complicated urinary tract infections (UTIs) caused by susceptible gram-negative and gram-positive bacteria; sexually transmitted disease (eg, uncomplicated urethral and cervical gonorrhea) caused by N. gonorrhoeae.

Although not approved there have been certain off label use documented for Norfloxacin:-

Spontaneous bacterial peritonitis, prophylaxis

Spontaneous bacterial peritonitis, prophylaxis (off-label use):

Note: For secondary prophylaxis in patients with prior spontaneous bacterial peritonitis (SBP) and primary prophylaxis in patients at high risk for SBP (eg, low ascites protein [<1.5 g/dL] with advanced liver failure or impaired kidney function). Some experts also use for prophylaxis during hospitalization in patients with cirrhosis and either acute GI bleeding or ascites protein <1 g/dL.

Oral: 400 mg once daily. For patients with cirrhosis and acute GI bleeding, some experts use 400 mg twice daily following, or as an alternative to parenteral prophylaxis, for a total antibiotic duration of 7 days

Urinary tract infection:

Cystitis, acute uncomplicated or acute simple cystitis (infection limited to the bladder without signs/symptoms of upper tract, prostate, or systemic infection) (alternative agent):

Note: Use is discouraged due to safety concerns and increasing resistance; reserve for those who have no alternative treatment options (Ref). However, for men who have severe symptoms or there is concern for early prostate involvement, some experts prefer fluoroquinolones.

Oral: 400 mg twice daily for 3 days (females) or 5 days (males).

Urinary tract infection, complicated (including pyelonephritis):

Note: If the prevalence of fluoroquinolone resistance is >10%, an initial dose of a long-acting parenteral antimicrobial (eg, ceftriaxone) followed by oral therapy is recommended for outpatients.

Oral: 400 mg twice daily for 5 to 7 days

Uncomplicated gonorrhea:

Oral: 800 mg as a single dose.

Note: Norfloxacin is not a preferred therapy for gonorrhea due to resistance

Dosage Adjustment in Kidney Patient

• eGFR ≥30 mL/minute/1.73 m2: No dosage adjustment necessary.

• eGFR ≤30 mL/minute/1.73 m2: 400 mg once daily.

Dosage Adjustment in Hepatic impairment Patient

● No Dosage Adjustment is necessary .

Dosage Adjustment for Pediatric Patients:-

No Dose Adjustment is necessary

Dosing: Kidney Impairment:

Pediatric

• Adolescents ≥17 years: Same as adult dosage.

Adult

eGFR≥30ml/minute/1.73m2: No dosage adjustment necessary

eGFR≥30ml/minute/1.73m2: 400mg once daily.

Norfloxacin is available in 400 mg strength.

Norfloxacin is available in the form of Tablets.

Take after eating and with a full glass of water to decrease gastric upset.

● Hypersensitivity to norfloxacin or other quinolones. History of tendon disorders, tendinitis or tendon rupture. Pre-pubertal children

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.

• 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.

Norfloxacin may cause liver problems, and using it with substantial quantities of ethanol may increase that risk.

Norfloxacin is present in breast milk.

Concentrations of Norfloxacin in breast milk increase with supplementation. When used as a dietary supplement, the recommended dietary allowance of Norfloxacin is increased in breastfeeding patients compared to nonbreastfeeding patients. Doses of Norfloxacin for the treatment of dyslipidemias are greater than those used as a dietary supplement. Due to the potential for serious adverse reactions in the breastfed infant (including hepatoxicity), the manufacturer recommends that breastfeeding be discontinued when Norfloxacin is used for treatment of dyslipidemias

Oral formulations should be administered on an empty stomach with water (at least 1 hour before or 2 hours after meals, milk, or other dairy products). Maintain fluid intake to ensure adequate hydration and urinary output.

• Increased risk of QT prolongation with agents known to prolong the QT interval (e.g. class IA and III antiarrhythmic drugs, macrolides, antipsychotics, TCAs).

May increase the plasma levels of theophylline and ciclosporin.

Rarely, may cause severe hypoglycaemia when given with glibenclamide.

Antacids, sucralfate, multivitamins or drugs containing Fe or Zn may decrease the absorption of norfloxacin.

May increase the risk of CNS stimulation and convulsive seizures with NSAIDs. May enhance the effects of anticoagulants (e.g. warfarin).

May inhibit the metabolism of caffeine.

Diminished urinary excretion with probenecid.

Increased risk of tendinitis and tendon rupture with corticosteroids.

The common side effects of Norfloxacin include the following

Common

● Diarrhea, dizziness, epistaxis, erythema multiforme, HTN, MI, neuropsychiatric symptoms, polyuria

Geriatric Use

No Dosage Adjustment is necessary

1. https://pubmed.ncbi.nlm.nih.gov/1091001/

2. https://clinicaltrials.gov/ct2/show/NCT01422915

3. https://clinicaltrials.gov/ct2/show/NCT02263547

4. https://www.medicines.org.uk/emc/product/128/smpc.

1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1364710/

2. https://reference.medscape.com/drug/colestid-Norfloxacin -342452

3. https://go.drugbank.com/drugs/DB00375

4. https://www.sciencedirect.com/topics/medicine-and-dentistry/Norfloxacin

5. https://europepmc.org/article/med/6988203