Source: Υπουργείο Υγείας (CY) Revision Year: 2020 Publisher: MEDOCHEMIE LTD, 1-10 Constantinoupoleos street, 3011 Limassol, Cyprus
The use of norfloxacin should be avoided in patients who have experienced serious adverse reactions in the past when using quinolone or fluoroquinolone containing products (see section 4.8). Treatment of these patients with norfloxacin should only be initiated in the absence of alternative treatment options and after careful benefit/risk assessment (see also section 4.3).
Epidemiologic studies report an increased risk of aortic aneurysm and dissection, particularly in elderly patients, and of aortic and mitral valve regurgitation after intake of fluoroquinolones. Cases of aortic aneurysm and dissection, sometimes complicated by rupture (including fatal ones), and of regurgitation/incompetence of any of the heart valves have been reported in patients receiving fluoroquinolones (see section 4.8).
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 congenital heart valve disease, or in patients diagnosed with pre-existing aortic aneurysm and/or aortic dissection or heart valve disease, or in presence of other risk factors or conditions predisposing
The risk of aortic aneurysm and dissection, and their rupture may also be increased in patients treated concurrently with systemic corticosteroids.
In case of sudden abdominal, chest or back pain, patients should be advised to immediately consult a physician in an emergency department.
Patients should be advised to seek immediate medical attention in case of acute dyspnoea, new onset of heart palpitations, or development of oedema of the abdomen or lower extremities.
In common with other quinolones, norfloxacin has been demonstrated to cause arthropathy in immature animals. Safety of norfloxacin has not been adequately investigated in children and use in pre-pubertal children or growing adolescents is contraindicated.
Causality has not been established, but there are rare reports of convulsions in association with norfloxacin. Unless the clinical need is imperative, norfloxacin should not be used in patients with either a history of convulsions or with known factors that predispose to seizures.
There have been reports of photosensitivity reactions in patients exposed to excessive sunlight while on therapy with quinolones. Patients should avoid excessive sunlight, should photosensitivity reactions occur norfloxacin should be discontinued.
Patients with latent or actual glucose-6-phosphate dehydrogenase activity defects taking quinolones, including norfloxacin, have experienced rare haemolytic reactions.
Use quinolones with caution in patients with myasthenia gravis. They may exacerbate the signs of myasthenia gravis and lead to life threatening weakness of the respiratory muscles.
Very rare cases of prolonged (continuing months or years), disabling and potentially irreversible serious adverse drug reactions affecting different, sometimes multiple, body systems (musculoskeletal, nervous, psychiatric and senses) have been reported in patients receiving quinolones and fluoroquinolones irrespective of their age and pre-existing risk factors. Norfloxacin should be discontinued immediately at the first signs or symptoms of any serious adverse reaction and patients should be advised to contact their prescriber for advice.
Tendinitis and tendon rupture (especially but not limited to Achilles tendon), sometimes bilateral, may occur as early as within 48 hours of starting treatment with quinolones and fluoroquinolones and have been reported to occur even up to several months after discontinuation of treatment. The risk of tendinitis and tendon rupture is increased in older patients, patients with renal impairment, patients with solid organ transplants, and those treated concurrently with corticosteroids. Therefore, concomitant use of corticosteroids should be avoided.
At the first sign of tendinitis (e.g. painful swelling, inflammation) the treatment with norfloxacin should be discontinued and alternative treatment should be considered. The affected limb(s) should be appropriately treated (e.g. immobilisation). Corticosteroids should not be used if signs of tendinopathy occur.
Cases of sensory or sensorimotor polyneuropathy resulting in paraesthesia, hypaesthesia, dysesthesia, or weakness have been reported in patients receiving quinolones and fluoroquinolones. Patients under treatment with norfloxacin should be advised to inform their doctor prior to continuing treatment if symptoms of neuropathy such as pain, burning, tingling, numbness, or weakness develop in order to prevent the development of potentially irreversible condition (see section 4.8).
Caution should be taken when using fluoroquinolones, including Gyrablock, in patients with known risk factors for prolongation of the QT interval such as, for example: congenital long QT syndrome, concomitant use of drugs that are known to prolong the QT interval (e.g. Class IA and III antiarrhythmics, tricyclic antidepressants, macrolides, antipsychotics), uncorrected electrolyte imbalance (e.g. hypokalaemia, hypomagnesaemia), cardiac disease (e.g. heart failure, myocardial infarction, bradycardia).
Elderly patients and women may be more sensitive to QTc-prolonging medications. Therefore, caution should be taken when using fluoroquinolones, including Gyrablock, in these populations. (See section 4.2 Elderly, section 4.5, section 4.8, section 4.9).
If vision becomes impaired or any effects on the eyes are experienced, an eye specialist should be consulted immediately.
As with all quinolones, disturbances in blood glucose, including both hypoglycaemia and hyperglycaemia have been reported (see section 4.8), usually in diabetic patients receiving concomitant treatment with an oral hypoglycaemic agent (e.g., glibenclamide) or with insulin. Cases of hypoglycaemic coma have been reported. In diabetic patients, careful monitoring of blood glucose is recommended.
Antacids: Should not be administered concomitantly or within two hours before or two hours after norfloxacin as they interfere with absorption resulting in lower serum/urine levels of norfloxacin.
Caffeine: Norfloxacin interferes with caffeine metabolism resulting in reduced caffeine clearance and prolongation of caffeine half life.
Cyclosporin: Norfloxacin concomitantly administered results in elevation of cyclosporin plasma levels. Cyclosporin plasma levels should be monitored and the dosage adjusted as required.
Didanosine: Should not be administered concomitantly or within two hours before or two hours after norfloxacin as they interfere with absorption resulting in lower serum/urine levels of norfloxacin.
Fenbufen: Use in combination with quinolones can lead to convulsions in animals. Use in combination should be avoided.
Glibenclamide: Concomitant use of norfloxacin and glibenclamide has, on occasions, resulted in severe hypoglycaemia. In this case monitoring of blood glucose is recommended.
Iron: Products containing iron should not be administered concomitantly or within two hours before or two hours after norfloxacin as they interfere with absorption resulting in lower serum/urine levels of norfloxacin.
Multivitamins: Should not be administered concomitantly or within two hours before or two hours after norfloxacin as they interfere with absorption resulting in lower serum/urine levels of norfloxacin.
Nitrofurantoin: in vitro antagonism has been shown.
Probenecid: Norfloxacin serum concentrations are not affected by co-administration of probenecid but urinary excretion of norfloxacin is decreased.
Sucralfate: Should not be administered concomitantly or within two hours before or two hours after norfloxacin as it interferes with absorption resulting in lower serum/urine levels of norfloxacin.
Theophylline: Concomitant therapy may lead to elevation of theophylline plasma levels and side effects, theophylline plasma levels should be monitored and the dose adjusted if required.
Warfarin: Norfloxacin may enhance significantly the anticoagulant effects of warfarin or its derivatives due to displacement from serum binding sites. If concomitant therapy is needed, prothrombin time should be monitored and dosage adjusted if required.
Zinc: Products containing zinc should not be administered concomitantly or within two hours before or two hours after norfloxacin as it interferes with absorption resulting in lower serum/urine levels of norfloxacin.
Drugs known to prolong QT interval: Gyrablock, 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).
There is inadequate evidence for safety in pregnancy, use is not recommended (see also section5.3). No data is available on the excretion of norfloxacin in breast milk, use in breast- feeding is not recommended.
There are no reports of a specific effect. Some patients may experience dizziness or similar side effect. Patients should be cautioned not to drive or operate machinery until they are sure they are not affected.
The adverse reactions are presented taking into consideration MedDRA frequency and system organ class database convention: Very common (≥1/10), Common (≥1/100 to <1/10), Uncommon (≥1/1,000 to <1/100), Rare (≥1/10,000 to <1/1,000), Very rare (<1/10,000), Not known (cannot be estimated from the available data).
The overall incidence of drug–related side effects reported during clinical trials was approximately 3%.
The most common side effects have been gastro-intestinal, neuropsychiatric and skin reactions and include nausea, headache, dizziness, rash, heartburn, abdominal pain/cramps and diarrhea.
Less commonly, other side effects such as anorexia, sleep disturbances, depression, anxiety/nervousness, irritability, euphoria, disorientation, hallucination, tinnitus and epiphora have been reported.
Abnormal laboratory side effects observed during clinical trials included:
Leucopenia, elevation of ALAT (SGPT), ASAT (SGOT), eosinophilia, neutropenia, thrombocytopenia.
With more widespread use the following additional side effects have been reported:
Not known: haemolytic anaemia, sometimes associated with glucose-6-phosphate dehydrogenase deficiency.
Not known: hypersensitivity reactions including anaphylaxis, angioedema, dyspnoea, vasculitis, urticaria, arthritis, myalgia, arthralgia and interstitial nephritis.
Very common: headache, dizziness
Uncommon: anorexia, sleep disturbances, depression, anxiety/nervousness, irritability, euphoria, disorientation, hallucination, tinnitus and epiphora
Not known: polyneuropathy including Guillaine-Barre syndrome, confusion, paraesthesia, psychic disturbances including psychotic reactions, convulsions, tremors, myoclonus.
Not known: visual disturbances (see section 4.4).
Very common: heartburn
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).
Very common: nausea, abdominal pain/cramps and diarrhea.
Pseudomembranous colitis, hepatitis, jaundice including cholestatic jaundice and elevated liver function test results. Dysgeusia.
Rare: pancreatitis.
Very common: rash
Photosensitivity, Stevens-Johnson syndrome, toxic epidermal necrolysis, exfoliative dermatitis, erythema multiforme, pruritus.
Not known: tendinitis, tendon rupture, exacerbation of myasthenia gravis, elevated levels of creatinine kinase (CK).
Not known: vaginal candidiasis, renal failure.
* Very rare cases of prolonged (up to months or years), disabling and potentially irreversible serious drug reactions affecting several, sometimes multiple, system organ classes and senses (including reactions such as tendonitis, tendon rupture, arthralgia, pain in extremities, gait disturbance, neuropathies associated with paraesthesia, depression, fatigue, memory impairment, sleep disorders, and impairment of hearing, vision, taste and smell) have been reported in association with the use of quinolones and fluoroquinolones in some cases irrespective of pre-existing risk factors (see Section 4.4).
** Cases of aortic aneurysm and dissection, sometimes complicated by rupture (including fatal ones), and of regurgitation/incompetence of any of the heart valves have been reported in patients receiving fluoroquinolones (see section 4.4).
Reporting suspected adverse reactions is an important way to gather more information to continuously monitor the benefit/risk balance of the medicinal product. Any suspected adverse reactions should be reported to Pharmaceutical Services, Ministry of Health, CY-1475, www.moh.gov.cy/phs, Fax: +357 22608649.
None known.
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