PRODUCT CHARACTERISTICS

Transcription

1 PRODUCT CHARACTERISTICS 1) PRODUCT TRADENAME NORFLOXACINA ABC 400 mg (hard capsules) 2) QUALITATIVE AND QUANTITATIVE COMPOSITION Each capsule contains: - Active ingredient: Norfloxacin 400 mg 3) PHARMACEUTICAL FORM/ PRODUCT TYPE - Capsules of 400 mg each. 4) CLINICAL INFORMATION Indications NORFLOXACINA ABC is indicated for the treatment of upper and lower urinary tract infections (cystitis, pyelitis, cystopyelitis, pyelonephritis) caused by bacteria susceptible to the product. Infections caused by multiply-resistant organisms have been successfully treated with the usual doses of NORFLOXACINA ABC Dosage and administration For the treatment of the urinary tract infection, the normal dosage for adults is 400 mg twice a day for 7-10 days. In women with uncomplicated acute cystitis, a therapy lasting 3 to 7 days has proved to be effective. Susceptibility of the causative agents to the drug should be tested, however therapy with NORFLOXACINA ABC may be initiated before obtaining the results of these tests. For subjects with renal impairment : see par. 4.4 Capsules should be taken with a glass of water one hour before or two hours after meal Contraindications NORFLOXACINA ABC is contraindicated in patients with a history of hypersensitivity to any component of this product or to any member of the quinolines antibacterials. Previous tendinitis after fluorequinolones treatment. Pregnancy and lactation: see specifically par. 4.6

2 Safety and efficacy in children have not been established; therefore norfloxacin should not be administered to prepubertal children or in those adolescents with incomplete bone development. Like all other organic acids, NORFLOXACINA ABC should not be used in patients with a history of convulsions or known factors predisposing to epileptic seizures (see par. 4.8.) 4.4. Warnings and precautions NORFLOXACINA ABC is used for the treatment of urinary tract infections in patients with renal function insufficiency. In patients with a creatinine clearance rate less than 30 ml/min/1,73 m2, the recommended dosage is one capsule of 400 mg a day. At this dosage the urinary concentration exceeds the MICs for most urinary pathogens susceptible to NORFLOXACINA ABC. During the therapy it is advisable to drink sufficient fluids in order to avoid crystalluria phenomena. NORFLOXACINA ABC is primarily eliminated through renal excretion, a severely decreased kidney function may significantly alter its urinary levels. Photosensitivity reactions have been observed in patients who are exposed to excessive sunlight while being treated with this group of medications. Excessive exposure to sunlight must be avoided, in case photosensitivity occurs, the administration of the drug should be discontinued. Tendinitis and tendon ruptures may rarely occur during fluorequinolones therapy. Predisposing factors to tendinitis and tendons ruptures are: age over 60 years, intense physical exercise, long-term treatment with corticosteroids, premature walking phase for patients in bed who have not fully recovered. KEEP OUT OF THE REACH OF CHILDREN Interaction with other drugs and other types of interaction Coadministration of probenecid does not alter serum concentrations of NORFLOXACINA ABC, but the urinary excretion of this medication diminishes. As with other antibactericidal organic acids, antagonism has been demonstrated "in vitro" between NORFLOXACINA ABC and nitrofurantoin. Elevated plasma levels of theophylline have been reported with concomitant use of quinolones. Rarely have been reported theophylline related side effects in patients on concomitant therapy with norfloxacin and theophylline. Therefore, monitoring of theophylline plasma levels should be considered and, if needed, the dosage of theophylline should be adjusted. Elevated serum levels of cyclosporin have been reported with concomitant use of norfloxacin. Therefore, when these two medicines are used concomitantly, cyclosporin serum levels should be monitored and cyclosporin dosage adjusted appropriately.

3 Quinolones (including norfloxacin) may enhance the effect of the oral anticoagulant warfarin and of its derivates. When these products are coadministered with quinolones, prothrombin time or other suitable coagulation tests should be carefully monitored. Multivitamins, products containing iron and zinc, antacids and sucralfate should not be taken concomitantly with, or within 2 hours of, the administration of norfloxacin because they may interfere with absorption, reducing the serum and urine levels of norfloxacin. Some quinolones, including norfloxacin, have also indicated to interfere with the metabolism of caffeine. This may lead to a reduced clearance of caffeine and an extension of its plasma half-life. Studies on animals reported that quinolones combined with fenbufen can cause convulsions. Therefore, concomitant administration of quinolones and fenbufen should be avoided Pregnancy and lactation Norfloxacin has been detected in blood, cord, amniotic fluid and milk, therefore NORFLOXACINA ABC should not be used during pregnancy and lactation Occupational hazards This medicine may cause dizziness and confusion. Patients who require alertness in their occupational activities (driving, operating machinery) should be warned Adverse effects The incidence of medicine related side effects reported during clinical trials was about 3%. The most common side effects have been gastrointestinal, neuropsychiatric and skin reactions. In order of frequency of occurrence, these include: nausea, headache, dizziness, tiredness, rash, abdominal pain, dyspepsia, depression, insomnia, constipation, flatulence, gastralgia. Less frequently: anorexia, dry mouth, diarrhoea, fever, vomiting, erythema, anxiety, agitation, irritability, euphoria, disorientation, hallucinations, tinnitus, epiphora. As with other medicines of this group, also sight, hearing and taste disorders have been observed (diplopia, tinnitus and hyperacusis, impaired taste). There have been rare reports of convulsions in patients without a previous history of convulsions, however a definite causal relationship has not been established yet. Furthermore adverse effects have been observed in laboratory values such as: eosinophilia, elevations of serum transaminases and alkaline phosphatase, leucopenia, neutropenia, thrombocytopenia and, more rarely, increased uremia and serum creatinine, decreased hematocrit. The following additional adverse effects have been reported since the medication was marketed: hypersensitivity reactions including anaphylaxis, interstitial nephritis, angioedema, vasculitis, urticaria, arthritis, myalgia and arthralgia,

4 photosensitivity, Stevens-Johnson Syndrome, toxic epidermal necrolysis, exfoliative dermatitis, erythema multiforme, pruritus, pseudomembraneous colitis, pancreatitis (rare), mental confusion. While using this product, serious anaphylactic reactions may occur (tongue or glottis oedema, dyspnea, hypertonia to dangerous shock). Any side effect other than those listed above should be immediately reported to the physician or pharmacist Overdosage No specific information is available on the treatment of overdosage with NORFLOXACIN ABC. Adequate hydration must be maintained 5) PHARMACOLOGY 5.1. Pharmacodymamics Norfloxacin is a new bactericidal organic acid. Norfloxacin has a broad spectrum antimicrobial activity against Gram-positive and Gram-negative aerobic pathogens. The fluorine atom at the 6 position provides increased potency against Gramnegative organisms and the piperazine moiety at the 7 position is responsible for the activity against Pseudomonas. Norfloxacin is generally active against organisms that are resistant to the nalidix, oxolinic and pipemidic acids, cinoxacin and flumequine. Norfloxacin does not have cross-resistance with structurally unrelated antibacterial agents such as penicillins, cephalosporins, tetracyclines, macrolides, aminoglycosides, sulfonamides, 2-4 diaminopyrimidines and their combinations (e.g. cotrimoxazole). Analysis of the overall clinical experience with NORFLOXACINA ABC revealed a high correlation between the results of susceptibility tests conducted "in vitro" and the bacteriological and clinical efficacy of the medication in humans. NORFLOXACINA ABC is active "in vitro" against the following bacteria found in urinary tract infections: E. coli, Proteus mirabilis, Proteus spp.(indole positive), Providencia spp., Serratia spp., Citrobacter spp., Edwardsiella tarda, Hafnia spp., Pseudomonas aeruginosa, Alcaligenes spp., Flavobacterium spp., Staphylococcus saprophyticus, Staphylococcus spp. (included penicillase-producing and most methicillin-resistant strains), Enterococci. Moreover it is active against: Shigella spp., Salmonella typhi, Salmonella spp., Campylobacter spp., Yersinia enterocolitica, Vibrio cholerae, Vibrio parahemolyticus, Bacillus cereus, Neisseria gonorrohoeae, Ureaplasma urealyticum and Hemophylus influentiae. It is not active against anaerobes such as: Actynomyces spp., Fusobacterium spp., Bacteroides spp., Clostridium spp. other than C. perfrigens. 5.2 Pharmacokinetics

5 Norfloxacin is readily absorbed after oral administration. Mean serum half-life is about 3-4 hours and it is not dose-depending. In healthy volunteers, the absorption of norfloxacin after a 400 mg dose corresponds to 30-40%, plasma concentrations to 1,5 µg/ml, while urinary concentrations reach mean values of 200 µg/ml or more and remain at bactericidal levels (30 µg/ml) for at least 12 hours. In healthy elderly volunteers (aged 65-75, with a normal renal function for their age), norfloxacin is eliminated more slowly because of their slightly decreased kidney function. The absorption of the drug dose not appear to be altered. However, in these elderly patients, the effective half-life of norfloxacin is 4 hours. The disposition of norfloxacin in patients with creatinine clearance greater than 30ml/min/1,73 m 2 is similar to that in healthy volunteers. In patients with creatinine clearance less than 30 ml/min/1,73 m 2 the renal elimination of norfloxacin decreases significantly and the effective serum half-life is about 6 hours. Drug absorption does not appear to be altered by the decreased renal function. Norfloxacin is eliminated through renal and biliary excretion. Within 24 hours, 33-48% of the drug is recovered free or metabolized in the urine. The parent compound is more than 70% of the total excretion. The bactericidal activity of norfloxacin is not affected by the ph of urine. Protein binding is less than 15%. 5.3 Preclinical safety data When norfloxacin was administered to old dogs for 3-5 months in dosages 4 times the recommended human doses, it caused the formation of a small bladder and erosions of the cartilage in weightbearing joints. Similar changes also occurred when using chemically related medicines. 6 months old or older dogs were not affected by these alterations. Teratology studies in mice and rats and fertility studies in mice at oral doses 30 to 50 times the usual dose for humans did not indicate teratogenic or fetal toxic effects. Embryotoxicity was observed in rabbits at doses of 100 mg/kg/day. This was secondary to maternal toxicity and it is a non-specific antimicrobial effect in the rabbits due to an unusual sensitivity to antibiotic induced changes in the gut microflora. Although the product was not teratogenic, in "cynomolgus" monkeys, at several times the therapeutic human dosage an increased number of miscarriages was observed. 6) PHARMACEUTICAL INFORMATION 6.1 List of Excipients: Hydration water, sodium laurylsulphate, starch, titanium dioxide (E171), synthetic yellow iron oxide (E172), gelatine.

6 6.2 Incompatibility No incompatibilities to other substances have been reported 6.3 Shelf life Capsules (400 mg per capsule): 36 months 6.4 Special precaution for storage Product should be stored at the standard "room conditions" recommended by F.U. Ed Nature and contents of container Hard gelatine capsules are contained in blister PVC/foil package inside a lithographed cardboard box. Blisters containing mg capsules Directions for use The product can be handled without any particular precaution See "Dosage and administration". 7. NAME AND BUSINESS ADDRESS OF THE MARKETING AUTHORIZATION HOLDER ABC FARMACEUTICI SPA Corso Vittorio Emanuele II, 72 - TORINO - 8. NUMBER OF MARKETING AUTHORIZATION Code no FIRST AUTHORIZATION/ RENEWAL DATE: May 2005 (renewal A.I.C.) 10. PARTIAL TEXT REVIEW: June 2011