TRADE NAME: NORACIN 400MG FILM COATED TABLETS GENERIC NAME: COMPOSITION: Each film coated tablet contains: Active ingredient: Norfloxacin 400 mg : Excipients Microcrystalline cellulose (Avicel PH102), Colloidal silicon dioxide (Aerosil 200), Polysorbate 80 (Tween 80), Cross carmellose sodium (Ac-Di-Sol), Magnesium stearate. Composition of film coat: Eudragit L100 (eq. to l12.5% 40mg), Castor oil, Ethyl alcohol. PHARMACEUTICAL FORM: Film Coated Tablets. White to pale yellow rounded biconvex scored Film coated tablets. PHARMACOLOGICAL ACTION: PHARMACODYNAMICS: Mechanism of action Microbiology Norfloxacin has in vitro activity against a broad spectrum of gram-negative and some gram-positive aerobic bacteria. Norfloxacin inhibits bacterial deoxyribonucleic acid synthesis and is bactericidal. At the molecular level, three specific events are attributed to norfloxacin in Escherichia coli cells: inhibition of the ATP dependent DNA supercoiling reaction catalysed by DNA gyrase; inhibition of the relaxation of supercoiled DNA; promotion of double stranded DNA breakage. Resistance to norfloxacin due to spontaneous mutation in vitro is a rare occurrence (range 10-9 to 10-12 cells). Resistance of the organism has developed during therapy with norfloxacin in less than 1% of patients treated. Organisms in which development of resistance is greatest are the following: Pseudomonas aeruginosa, Klebsiella pneumoniae, Acinetobacter sp., Enterococci. For this reason, when there is a lack of satisfactory clinical response, culture and susceptibility testing should be repeated. Norfloxacin is active in vitro against the following organisms. Bacteria Found in Urinary Tract Infections Aerobic bacteria. gram-positive bacteria including Streptococcus faecalis (Enterococcus), Staphylococcus aureus, Staph. epidermidis, Staph. saprophyticus. Gram-negative bacteria including Citrobacter diversus, C. freundii, Enterobacter cloacae, Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa. Bacteria Found in Gastrointestinal Infections Shigella, E. coli, Salmonella typhi. In addition, norfloxacin is active against Neisseria gonorrhoeae. Norfloxacin is not generally active against obligate anaerobes. Nalidixic acid resistant organisms are generally susceptible to norfloxacin in vitro; however, these organisms may have higher minimum inhibitory concentrations (MIC) to norfloxacin than nalidixic acid susceptible strains. There is generally no cross resistance between norfloxacin and other classes of antibacterial agents. Therefore, norfloxacin often demonstrates activity against indicated organisms resistant to the aminoglycosides (including gentamicin) penicillins, cephalosporins, tetracyclines, macrolides and sulfonamides, including combinations of sulfamethoxazole and trimethoprim. Antagonism has been demonstrated in vitro between norfloxacin and nitrofurantoin. PHARMACOKINETICS: Absorption In fasting healthy volunteers, approximately 30 to 40 % of an oral dose of norfloxacin is absorbed. Absorption is rapid following single doses of 200 mg and 400 mg. At the respective doses, mean peak serum and plasma concentrations of 0.8 and 1.5 μg/mL are attained approximately 1 hour after dosing. The presence of food may decrease absorption. The effective half-life of norfloxacin in serum and plasma is 3 to 4 hours. Steady-state concentrations of norfloxacin will be attained within 2 days of dosing. Distribution The serum protein binding of norfloxacin is between 10 and 15%. Metabolism Within 24 hours of drug administration, 26 to 32% of the administered dose is recovered in the urine as norfloxacin with an additional 5 to 8% being recovered in the urine as six metabolites of considerably less antimicrobial potency. Excretion The absorbed norfloxacin is eliminated mainly through renal excretion. Renal excretion occurs by both glomerular filtration and tubular secretion as evidenced by the high rate of renal clearance (approximately 275 mL/min). Within 24 hours of drug administration, 26 to 32% of the administered dose is recovered in the urine as norfloxacin with an additional 5 to 8% being recovered in the urine as six metabolites of considerably less antimicrobial potency. However, urinary recovery may occasionally be very low. Only a small percentage (less than 1%) of the dose is recovered thereafter. Two to three hours after a single 400 mg dose, urinary concentrations of 200 μg/mL or more are attained in the urine. In healthy volunteers, mean urinary concentrations of norfloxacin remain above 30 μg/mL for approximately 12 hours following a 400 mg dose. The urinary pH may affect the solubility of norfloxacin. Norfloxacin is least soluble at urinary pH of 7.5 with solubility increasing at pHs above and below this value. The disposition of norfloxacin in patients with creatinine clearance rates greater than 30 mL/min/1.73 m2 is similar to that in healthy volunteers. In patients with creatinine clearance rates equal to or less than 30 mL/min/1.73 m2, the renal elimination of norfloxacin decreases so that the effective serum half-life is 8.6 to 11.5 hours. In these patients, alteration of dosage is necessary. Drug absorption appears unaffected by decreasing renal function. In healthy elderly volunteers (65 to 75 years of age with normal renal function for their age), norfloxacin is eliminated more slowly because of their slightly decreased renal function. Drug absorption appears unaffected. The effective half-life of norfloxacin in these elderly subjects is 4 hours. Faecal recovery accounts for another 30% of the administered dose. This represents the unabsorbed drug along with a small contribution through biliary excretion. After a single 400 mg dose of norfloxacin, mean antimicrobial activities equivalent to norfloxacin 278, 773 and 82 μg/g of faeces were obtained at 12, 24 and 48 hours, respectively. INDICATIONS: -Treatment of adults with complicated urinary tract infections that are caused by susceptible strains of microorganisms. - Norfloxacin should be reserved for use in patients who have no other treatment options for acute bacterial sinusitis (ABS), acute bacterial exacerbation of chronic sinusitis (ABECB) especially if these are caused by Gram negative bacteria & Uncomplicated urinary tract infections. -Treatment of adults with gastrointestinal infections, in particular shigellosis and traveller’s diarrhoea. Note: Specimens for culture and susceptibility testing should be obtained prior to and during treatment if clinical response warrants. Consideration should be given to available official guidance on the appropriate use of antibacterial agents. - Norfloxacin should not be used in the following indications: • To treat infections that might get better without treatment or are not severe (such as throat infections); • To treat non-bacterial infections, e.g. non-bacterial (chronic) prostatitis; • For preventing traveller’s diarrhoea or recurring lower urinary tract infections (urine infections that do not extend beyond the bladder); • To treat mild or moderate bacterial infections unless other antibacterial medicines commonly recommended for these infections cannot be used. DOSAGE AND ADMINISTRATION: NORACIN tablets are intended for oral administration. NORACIN tablets should be taken 1 hour before or 2 hours after a meal with a glass of water. Patients receiving norfloxacin should be well hydrated. Multivitamins, other products containing iron or zinc, antacids containing magnesium and aluminium, sucralfate or Videx (didanosine) chewable/buffered tablets or the paediatric powder for oral solution, should not be taken within two hours of administration of norfloxacin. Urinary Tract Infection Normal Renal Function The recommended dosage of norfloxacin for the treatment of urinary tract infection is 400 mg twice daily for 7 to 10 days. For uncomplicated lower urinary tract infections, the recommended dosage is 400 mg twice daily for 3 days. In one study of uncomplicated lower urinary tract infections, treatment for 7 days resulted in somewhat better eradication rates than treatment for 3 days. Maximum total daily dosage should not exceed 800 mg per day. Impaired Renal Function Norfloxacin may be used for the treatment of urinary tract infections in patients with renal insufficiency. In patients with a creatinine clearance rate of 30 mL/min/1.73 m2 or less, the recommended dosage is one 400 mg tablet once daily for the duration given above. At this dosage, the urinary concentration exceeds the MICs for most urinary pathogens susceptible to norfloxacin, even when the creatinine clearance is less than 10 mL/min/1.73 m2. However, such patients should be observed carefully for adverse effects due to possible drug retention. When only the serum creatinine level is available, the following formula (based on sex, weight and age of the patient) may be used to convert this value into creatinine clearance. The serum creatinine should represent a steady state of renal function. Please refer to Equation 1.
