Source: European Medicines Agency (EU)
Hypersensitivity to any component of this product tablets or any chemically related quinolone antibacterials or to any of the other excipients listed in section 6.1.
Norfloxacin is contraindicated in patients with a history of tendinitis and/or tendon rupture related to fluoroquinolone administration (see sections 4.4 and 4.8).
Norfloxacina Sandoz is contra-indicated in prepubertal children and growing adolescents. As with other quinolones, Norfloxacina Sandoz has been shown to cause arthropathy in immature animals. The safety of Norfloxacina Sandoz in children has not been adequately explored and therefore the use of Norfloxacina Sandoz in prepubertal children or growing adolescents is contraindicated
Norfloxacin must not be used by children and growing adolescents or by pregnant and lactating women. This is because safety has not yet been sufficiently established for these groups of patients (see section 4.6 and 5.3).
Photosensitivity may occur in patients taking norfloxacin tablets or other quinolone-type drugs. Longer periods of exposure to the sun and stronger sunlight should be avoided during treatment. In the same way the use of solarium should be denied during this time. Treatment should be stopped if symptoms of photosensitivity occur.
As with other quinolones, tendinitis and/or tendon rupture (particularly affecting the Achilles tendon) have been observed rarely during and after norfloxacin use. Such reactions have particularly been noted in elderly patients and patients on glucocorticosteroids. At the first sign of pain or inflammation, norfloxacin therapy should be discontinued immediately and the patient should be given suitable pharmacological treatment.
In the case of epileptics and patients with existing CNS disorders (e.g. a low convulsive threshold, a history of convulsions, reduced cerebral blood flow, changes to brain structure or stroke), norfloxacin should only be given if the benefit clearly outweighs the risk, because of the possibility of CNS side effects in these patients. Convulsions have been reported in rare cases in patients receiving norfloxacin. Norfloxacin may lead to exacerbations and aggravation of the symptoms in patients with known or suspected psychiatric disorders, hallucinations and/or confusion. The usually appropriate emergency measures are indicated (e.g. keeping airways free, administer anticonvulsants).
In patients with severely impaired renal function, the advantages and disadvantages of use of norfloxacin tablets should be carefully weighed up in each individual case (see section 4.2). As the renal function is reduced by age particularly elderly belong to this group of patients. The urinary concentration of norfloxacin may be reduced if renal function is severely impaired since elimination of norfloxacin occurs predominantly by the renal route.
In case of prolonged treatment, the occurrence of crystalluria should be monitored. While crystalluria is not expected to occur under normal conditions with dosage regimen 400 mg twice daily, as a precaution, the daily recommended dosage should not be exceeded and the intake of sufficient fluids should be guaranteed to ensure proper state of hydration and adequate urinary output.
Norfloxacin can exacerbate the symptoms of myasthenia gravis which may result in life threatening weakness of respiratory muscles. Adequate counter measures should be taken at any sing of respiratory distress. In patients treated with norfloxacin, unmasking or exacerbation of myasthenia gravis has been reported. As this may include potentially life-threatening respiratory failure, patients with myasthenia gravis should be advised to immediately seek medical treatment if exacerbation of symptoms occurs (see section 4.8).
If vision becomes impaired or any effects on the eyes are experienced, an eye specialist should be consulted immediately (see sections 4.7 and 4.8)
Rarely, haemolytic reactions have been reported in patients with latent or actual defects in glucose-6-phosphate dehydrogenase activity who take quinolone antibacterial agents, including norfloxacin (see section 4.8).
Pseudomembranous colitis has been reported with nearly all antibacterial agents, including Norfloxacina Sandoz, and may range in severity from mild to life-threatening. Therefore it is important to consider this diagnosis in patients who present with diarrhea subsequent to the administration of antibacterial agents. Studies indicate that a toxin produced by Clostridium difficile is a primary cause of “antibiotic-associated colitis”.
If Clostridium difficile associated diarrhea (CDAD) is suspected or confirmed, ongoing antibiotic use not directed against C. difficile should be discontinued and appropriate therapy instituted immediately. Anti-peristaltic drugs are contraindicated in this situation.
Serious and occasionally fatal hypersensitivity (anaphylactic or anaphylactoid) reactions, some following the first dose, have been reported in patients receiving quinolone therapy. In such cases, therapy with Norfloxacina Sandoz must be discontinued immediately and appropriate emergency action must be started (e.g. antihistamines, glucocorticosteroids, sympathomimetics and ventilation if necessary).
Caution should be taken when using fluoroquinolones, including Norfloxacina Sandoz, in patients with known risk factors for prolongation of the QT interval such as, for example:
Epidemiologic studies report an increased risk of aortic aneurysm and dissection after intake of fluoroquinolones, particularly in the older population.
Therefore, fluoroquinolones should only be used after careful benefit-risk assessment and after consideration of other therapeutic options in patients with positive family history of aneurysm disease, or in patients diagnosed with pre-existing aortic aneurysm and/or aortic dissection, or in presence of other risk factors or conditions predisposing for aortic aneurysm and dissection (e.g. Marfan syndrome, vascular Ehlers-Danlos syndrome, Takayasu arteritis, giant cell arteritis, Behcet’s disease, hypertension, known atherosclerosis).
In case of sudden abdominal, chest or back pain, patients should be advised to immediately consult a physician in an emergency department.
Peripheral sensory neuropathy and peripheral sensory motor neuropathy have been reported in patients receiving fluoroquinolones which can be rapid in its onset. Norfloxacin should be discontinued if the patient experiences symptoms of neuropathy in order to prevent the development of an irreversible condition.
Quinolones, including norfloxacin, have been shown in vitro to inhibit CYP1A2. Concomitant use with drugs metabolized by CYP1A2 (e.g. caffeine, clozapine, ropinirole, theophylline, tizanidine) may result in increased levels of these drugs, with the potential risk of increased toxicity. Patients taking any concomitant drugs metabolized by CYP1A2 should be carefully monitored
Elevated plasma concentrations of theophylline have been reported during concomitant use of theophylline and quinolones. Adverse reactions caused by theophylline have also been reported sporadically during concomitant use of norfloxacine and theophylline. The theopylline concentration in plasma should thus be monitored and the dosage of theopylline adjusted if necessary.
Elevated serum concentrations of ciclosporine have been reported with concomitant use of norfloxacin. Cicloporine serum levels should be monitored and appropriate ciclosporin dosage adjustments made when these drugs are used concomitantly.
Quinolones, including norfloxacin, may enhance the effects of oral anticoagulants, including warfarin or its derivatives or similar agents. When concomitant administration of these products cannot be avoided, measurements of prothrombin time or other suitable coagulation tests should be carried out.
The concomitant administration of quinolones including norfloxacin with glibenclamide (a sulphonylurea agent) has, on rare occasions, resulted in severe hypoglycaemia. Therefore monitoring of blood glucose is recommended when these agents are co-administered.
Co-administration of probenecid does not affect serum concentrations of norfloxacin, but urinary excretion of the drug diminishes.
As with other organic acid antibacterials, antagonism has been demonstrated in vitro between norfloxacin and nitrofurantoin. Concomitant use of norfloxacin and nitrofurantoin should therefore be avoided.
Multivitamins, products containing iron or zinc, antacids or sucralfate should not be administered concomitantly with, or within 2 hours of, the administration of norfloxacin, because they may interfere with absorption, resulting in lower serum and urine levels of norfloxacin.
Products containing didanosine should not be administered concomitantly with, or within 2 hours of, the administration of norfloxacin, because the products may interfere with absorption resulting in lower serum and urine levels of norfloxacin.
Some quinolones, including norfloxacin, have also been shown to inhibit the metabolism of caffeine. This may lead to reduced clearance of caffeine and a prolongation of its half-life that may lead to accumulation of caffeine in plasma when products containing caffeine are consumed while taking norfloxacin.
The concomitant administration of a non-steroidal anti-inflammatory drug (NSAID) with a quinolone, including norfloxacin, may increase the risk of CNS stimulation and convulsive seizures. Therefore Norfloxacina Sandoz should be used with caution in individuals receiving NSAIDs concomitantly.
Animal data have shown that quinolones in combination with fenbufen can lead to convulsions. Therefore, concomitant administration of quinolones and fenbufen should be avoided.
Lowered bioavailability of mycophenolic acid was observed in healthy volunteers receiving combined treatment with norfloxacin and metronidazole.
Calcium preparations, multivitamin preparations, preparations containing iron or zinc, antacids, and sucralfate should not be ingested simultaneously with Norfloxacina Sandoz 400 mg film-coated tablets, as this could reduce norfloxacin absorption leading to decreased concentrations in the serum and urine. Norfloxacina Sandoz 400 mg film-coated tablets should be taken either 2 hours before or at least 4 hours after ingesting such products. This restriction does not apply to H2-receptor antagonisttype antacids.
Oral nutritional solutions and dairy products (mild or liquid milk products such as yoghurt) reduce the absorption of norfloxacin. Norfloxacin should therefore be taken at least 1 hour before or 2 hours after such products.
Norfloxacina Sandoz400 mg film-coated tablets, like other fluoroquinolones, should be used with caution in patients receiving drugs known to prolong the QT interval (e.g. Class IA and III antiarrhythmics, tricyclic antidepressants, macrolides, antipsychotics) (see section 4.4).
Norfloxacina Sandoz should not be used during pregnancy. Norfloxacin and related substances have been shown to cause damage to the articular cartilage in growing animals. The occurrence of such adverse effects in humans cannot be excluded. Norfloxacin passes in the umbilical cord blood and amniotic fluid.
When a 200-mg dose of Norfloxacina Sandoz was administered to nursing mothers, norfloxacin was not detected in human milk. However, because the dose studied was low, because other drugs in this class are secreted in human milk, and because damage of articular cartilage in a growing organism was demonstrated, norfloxacin should only be administered during lactation when strictly indicated.
Even when used correctly, Norfloxacina Sandoz 400 mg film-coated tablets may alter patients' reactivity to the point that their ability to drive or operate machinery is impaired, especially at the start of treatment, on increasing the dose or switching medication, and in conjunction with alcohol. Fluoroquinolones including norfloxacin may result in an impairment of the patient’s ability to drive or operate machinery due to transient loss of vision (see section 4.8). Patients should be advised to see how they react to norfloxacin before driving or operating machinery.
The following adverse reactions have been observed in clinical studies or obtained from postmarketing reports: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1000), very rare (<1/10,000), not known (cannot be estimated from the available data)
Uncommon: vaginal candidiasis
Common: eosinophilia, leucopenia, neutropenia
Uncommon: thrombocytopenia, reduced hematocrit and prolonged prothrombin time, hemolytic anemia sometimes associated with Glucose-6-phosphateDehydrogenase deficiency.
Very rare: agranulocytosis
Rare: angioedema, hypersensitivity reaction, vasculitis, anaphylactic reaction, dyspnea, urticaria, petechiae, hemorrhagic bullae, papules with vasculitis.
Uncommon: anorexia
Uncommon: depression, sleep disturbances, nervousness, anxiety
Rare: disorientation, irritability, euphoria, hallucination, psychic disturbances, confusion, psychotic reactions
Common: headache, dizziness, lightheadedness and drowsiness
Uncommon: paraesthesia, sensory disturbances, dysgeusia, bitter taste, convulsions tremor, polyneuropathy including Guillain-Barré syndrome, myoclonus including exacerbation of myasthenia gravis, tiredness, mood swings, paresthesia, insomnia, depression, anxiety, nervousness, irritability, hallucinations, polyneuropathy including Guillain-Barré syndrome, (epilepsylike) convulsions, possible exacerbation of myasthenia gravis (see section 4.4).
Uncommon: visual disturbances, increased lacrimation
Not known: transient loss of vision
Uncommon: tinnitus
Very rare: hearing loss
Uncommon: palpitation
Very rare: QT-prolongation has been reported.
Not known: ventricular arrhythmia and torsades de pointes (reported predominantly in patients with risk factors for QT prolongation), ECG QT prolonged (see section 4.4 and 4.9).
Common: nausea, abdominal pain/cramps, nausea
Uncommon: diarrhea, heartburn, vomiting, anorexia, pancreatitis, dry mouth, flatulence, dyspepsia, dysphagia, constipation
Rare: pseudomembranous colitis
Common: elevation of ALAT (SGPT), ASAT (SGOT)
Rare: jaundice, hepatitis, cholestatic hepatitis
Common: rash
Uncommon: pruritus, urticarial, severe skin reactions, exfoliative dermatitis, Lyell' syndrome and erythema multiforme (Stevens-Johnson syndrome), photosensitivity, pruritus.
Rare: photosensitivity
Very rare: rhabdomyolysis
Not known: leucocytoclastic vasculitis, drug rash with eosinophilia and systemic symptoms (DRESS syndrome).
Rare: arthralgia, myalgia, arthritis, tendinitis, tendon rupture
Common: elevated serum creatinine
Uncommon: elevation of serum urea, crystalluria.
Rare: interstitial nephritis, renal failure
Common: elevated alkaline phosphatase and LDH
Very rare: elevated creatinine kinase (CK)
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V*.
Not applicable.
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