Norfloxacin

Antibiotic Class:

Quinolone

Antimicrobial Spectrum:

Gram positive bacteria:  methicillin-susceptible Staphylococcus epidermidis, Staphylococcus saprophyticus

Gram negative bacteria:  Enterobacteriaceae, H. influenzae, other Haemophilus spp., N. gonorrhoeae, N. meningitides, M. catarrhalis, P. aeruginosa,

Mechanism of Action:

Inhibition of topoisomerase (DNA gyrase) enzymes, which inhibits relaxation of supercoiled DNA and promotes breakage of double stranded DNA.

Pharmacodynamics:

Fluoroquinolones produce both concentration-dependent  (peak:MIC), and a combination of concentration and time-dependent killing (AUC:MIC).

Pharmacokinetics:

400mg dose; Cmax: 1.5mg/ml; Volume of distribution: 1.7 L/kg; Table 2  

Adverse Effects:

CNS:  headache, insomnia, dizziness; hallucinations, depression, psychotic reactions (rare)

Connective tissue:  tendon injury

Renal:  interstitial nephritis

Cardiovascular:  QTC prolongation, torsades de pointes, arrhythmias

Dosage:

Oral: 400mg tablet

Adults:

Gonorrhea: 800 mg PO as a single dose

Prostatitis: 400 mg PO every 12 hr x 28 days

Complicated UTI: 400 mg PO every 12 hr x 10-21 days

Uncomplicated UTI: (E. coli, K pneumoniae, P. mirabilis)400 mg PO every 12 hr x 3 days

Uncomplicated UTI: (other organisms) 400 mg ORALLY every 12 hr x 7-10 days

Pediatric:

Efficacy and safety not established in patients less than 18 years of age

Table 4

Disease state based dosing:

Renal failure of CrCl < 30ml/min: 400mg PO q24h

Hepatic failure:  No dosing changes recommended at this time.

Contraindications/Warnings/Precautions:

Precautions: 

• Prolongation of QT interval; avoid concurrent use with other drugs that prolong QT interval and in patients with risk factors for torsades de pointes (hypokalemia, significant bradycardia, cardiomyopathy)
• Patients with glucose 6-phosphate dehydrogenase deficiency
• Diabetes mellitus; disturbances of blood glucose have been reported, usually in diabetic patients receiving concomitant treatment with an oral hypoglycemic agent or with insulin

Drug Interactions:

Divalent cations:  aluminum, magnesium zinc, iron, calcium, antacids, sucralfate – reduced bioavailability of quinolones (can cause therapeutic failure)

Theophylline, caffeine, xanthines: clearance of these is inhibited with fluoroquinolones

Pregnancy:

Category C: Risk unknown. Human studies inadequate.

Monitoring Requirements:

Therapeutic:  Culture and sensitivities, signs and symptoms of infection

Toxic:  Urinalysis, BUN, Creatinine, AST and ALT, Physicial examination: encephalopathic changes

Brand names/Manufacturer:

CHIBROXIN (Merck Sharp & Dohme – BRAZIL, SINGAPORE, CHILE, MALAYSIA, USA – Opthalmic solution)

FLOXEN (Pharmaniaga – MALAYSIA, HONG KONG)

JANACIN (Biolab – THAILAND, HONG KONG, MALAYSIA)

LEXINOR (AstraZeneca – SWEDEN, HONG KONG, THAILAND, FINLAND, MALAYSIA)

NOROXIN (Merck Sharp & Dohme - SOUTH AFRICA, SWITZERLAND, PORTUGAL, MEXICO, NEW ZEALAND, AUSTRALIA, CHILE, CANADA)

ZOROXIN (Merck Sharp & Dohme – BELGIUM, AUSTRIA, DENMARK)