Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2016 Publisher: Generics [UK] Limited t/a Mylan, Station Close, Potters Bar, Hertfordshire, EN6 1TL
The use of ofloxacin is contraindicated as follows:
Ofloxacin tablets are not the drug of first choice in pneumonia caused by Streptococcus pneumoniae or Chlamydia pneumoniae.
Are very likely to possess co-resistance to fluoroquinolones, including ofloxacin. Therefore ofloxacin is not recommended for the treatment of known or suspected MRSA infections unless laboratory results have confirmed susceptibility of the organism to ofloxacin (and commonly recommended antibacterial agents for the treatment of MRSA-infections are considered inappropriate).
The most common pathogen involved in urinary tract infections – varies across the European Union. Prescribers are advised to take into account the local prevalence of resistance in E. coli to fluoroquinolones.
Cases of severe bullous skin reactions such as Stevens-Johnson syndrome or toxic epidermal necrolysis have been reported with ofloxacin (see section 4.8). Patients should be advised to contact their doctor immediately prior to continuing treatment if skin and/or mucosal reactions occur.
Tendonitis, rarely observed with quinolones, may occasionally lead to rupture involving Achilles tendon in particular. Tendinitis and tendon rupture, sometimes bilateral, may occur within 48 hours of starting treatment with ofloxacin and have been reported up to several months after discontinuation of ofloxacin. The risk of tendinitis and tendon rupture is increased in patients aged over 60 years and in patients using corticosteroids. The daily dose should be adjusted in elderly patients based on creatinine clearance (see section 4.2). Close monitoring of these patients is therefore necessary if they are prescribed ofloxacin. All patients should consult their physician if they experience symptoms of tendinitis. If tendinitis is suspected, treatment with ofloxacin must be halted immediately, and appropriate treatment (e.g. immobilisation) must be initiated for the affected tendon (see sections 4.3 and 4.8).
Hypersensitivity and allergic reactions have been reported for fluoroquinolones after first administration. Anaphylactic and anaphylactoid reactions can progress to life-threatening shock, even after the first administration. In these cases ofloxacin should be discontinued and suitable treatment (e.g. treatment for shock) should be initiated.
Diarrhoea, especially if severe, persistent and/or bloody, occurring during or after treatment with ofloxacin (including several weeks after treatment), may indicate a condition caused by Clostridium difficile, the most severe form of which is pseudomembranous colitis (CDAD) CDAD may range in severity from mild to life threatening, the most severe form of which is pseudomembranous colitis (see section 4.8). It is therefore important to consider this diagnosis in patients who develop serious diarrhoea during or after treatment with ofloxacin. If pseudo-membraneous colitis is suspected, treatment should be discontinued immediately.
Appropriate specific antibiotic therapy must be started without delay (e.g. oral vancomycin, oral teicoplanin or metronidazole). Medicinal products that inhibit peristalsis are contraindicated in such cases.
Quinolones may lower the seizure threshold and may trigger seizures. Ofloxacin is contraindicated in patients with a history epilepsy or with a known predisposition to seizures (see section 4.3).
Patients with a known predisposition to seizures may include those with pre-existing central nervous system lesions, concomitant treatment with fenbufen and similar non-steroidal anti-inflammatory drugs (NSAIDs), or with drugs which lower the cerebral seizure threshold, such as theophylline (see section 4.5 interactions).
In case of convulsive seizures, treatment with ofloxacin should be discontinued (see section 4.5).
Since ofloxacin is eliminated primarily via the kidneys, the dose should be adjusted in patients with impaired renal function (see section 4.2).
Psychotic reactions have been reported in patients receiving fluoroquinolones including ofloxacin. In some cases these have progressed to suicidal thoughts or self-endangering behavior including suicide attempt, sometimes after a single dose of ofloxacin (see section 4.8). In the event that a patient develops these reactions, ofloxacin should be discontinued and appropriate measures instituted.
Ofloxacin should be used with caution in patients with a history of psychotic disorder or in patients with psychiatric disease.
Ofloxacin should be used with caution in patients with impaired liver function, as liver damage may occur. Cases of fulminant hepatitis potentially leading to liver failure (including fatal cases) have been reported with fluoroquinolones. Patients should be advised to stop treatment and contact their doctor if signs and symptoms of hepatic disease develop such as anorexia, jaundice, dark urine, pruritus or tender abdomen (see section 4.8).
Due to possible increase in coagulation tests (PT/INR) and/or bleeding in patients treated with fluoroquinolones, including ofloxacin, in combination with a vitamin K antagonist (e.g. warfarin), coagulation tests should be monitored when these drugs are given concomitantly (see section 4.5).
Fluoroquinolones, including ofloxacin, have neuromuscular blocking activity and may exacerbate muscle weakness in patients with myasthenia gravis. Postmarketing serious adverse reactions, including deaths and the requirement for respiratory support, have been associated with fluoroquinolone use in patients with myasthenia gravis. Ofloxacin is not recommended in patients with a known history of myasthenia gravis.
As with other antibiotics, the use of ofloxacin, especially if prolonged, may result in overgrowth of non-susceptible organisms, especially Enteracci, resistant strains of some organisms or Candida. Repeated evaluation of the patient’s condition is essential and periodic in vitro susceptibility tests may be useful. If secondary infection occurs during therapy, appropriate measures should be taken.
Photosensitisation has been reported with ofloxacin (see section 4.8). It is recommended that patients should not expose themselves unnecessarily to strong sunlight or to artificial UV rays (e.g. sunray lamp, solarium), during treatment and for 48 hours following treatment discontinuation in order to prevent photosensitisation.
Very rare cases of QT interval proplongation have been reported in patients taking fluoroquinolones.
Caution should be taken when using fluoroquinolones, including ofloxacin, in patients with known risk factors for prolongation of the QT interval such as, for example:
(See section 4.2 Elderly, section 4.5, section 4.8 and section 4.9).
As with all quinolones, disturbances in blood glucose, including both hypoglycaemia and hyperglycaemia have been reported, 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 these diabetic patients, careful monitoring of blood glucose is recommended (see section 4.8).
Sensory or sensorimotor peripheral neuropathy has been reported in patients receiving fluoroquinolones, including ofloxacin, which can be rapid in its onset. Ofloxacin should be discontinued if the patient experiences symptoms of neuropathy. This would minimise the possible risk of developing an irreversible condition (see section 4.8).
Patients with latent or diagnosed glucose-6-phosphate-dehydrogenase deficiency may be predisposed to haemolytic reactions if they are treated with quinolones. Therefore if ofloxacin has to be used in these patients, potential occurrence of haemolysis should be monitored.
In patients treated with ofloxacin, determination of opiates or porphyrin levels in urine may give false-positive results. It may be necessary to confirm positive opiate or porphyrin screens by more specific methods.
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).
Ofloxacin contains lactose anhydrous. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, or glucose-galactose malabsorption should not take this medicine.
For treatment of severe and/or life-threatening infections parenteral therapy is indicated.
Co-administered magnesium/aluminum antacids, sucralfate, zinc or iron preparations and didanosine chewable/buffered tablets can reduce absorption of ofloxacin tablets. Therefore, ofloxacin should be taken 2 hours before such preparations.
No pharmacokinetic interactions of ofloxacin were found with theophylline in a clinical study. However, a pronounced lowering of the cerebral seizure threshold may occur when quinolones are given concurrently with theophylline, nonsteroidal antiinflammatory drugs, or other agents, which lower the seizure threshold.
Probenecid decreased the total clearance of ofloxacin by 24%, and increased AUC by 16%. The proposed mechanism is a competition or inhibition for active transport at the renal tubular excretion. Caution should be exercised when ofloxacin is coadministered with drugs that affect the tubular renal secretion such as probenecid, cimetidine, furosemide and methotrexate.
Ofloxacin, 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, and antipsychotics) (see section 4.4 QT interval prolongation).
Increased coagulation tests (PT/INR) and/or bleeding, which may be severe, have been reported in patients treated with ofloxacin in combination with a vitamin K antagonist (e.g. warfarin). Coagulation tests should, therefore, be monitored in patients treated with vitamin K antagonists because of a possible increase in the effect of coumarin derivatives (see section 4.4).
Ofloxacin may cause a slight increase in plasma glibenclamide levels when administered concurrently, it is therefore recommended that patients treated concomitantly with ofloxacin and glibenclamide be monitored particularly closely. Since hypoglycaemia is then more likely to occur, close monitoring of blood sugar levels is recommended in such cases.
Based on a limited amount of human data, the use of fluoroquinolones in the first trimester of pregnancy has not been associated with an increased risk of major malformations or other adverse effects on pregnancy outcome. Animal studies have shown damage to the joint cartilage in immature animals but no teratogenic effects (see section 5.3). Therefore ofloxacin must not be used during pregnancy (see section 4.3).
Ofloxacin is excreted into human breast milk in small amounts. Because of the potential for arthropathy and other serious toxicity in the nursing infant, breast-feeding should be discontinued during treatment with ofloxacin (see section 4.3).
Since there have been occasional reports of drowsiness/somnolence, impairment of skills, dizziness/vertigo and visual disturbances, which may impair the patient’s ability to concentrate and react, and therefore may constitute a risk in situations where these abilities are of special importance (e.g. driving a car or operating machinery), patients should know how they react to ofloxacin before they drive or operate machinery. These effects may be enhanced by alcohol.
The information given below is based on data from clinical studies and on extensive post marketing experience.
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 available data)*
Uncommon: Fungal infection, Pathogen resistance
Very rare: Anaemia, Haemolytic anaemia, Leucopenia, Eosinophilia, Thrombocytopenia
Not known: Agranulocytosis, Bone marrow failure, Pancytopenia
Rare: Anaphylactic reaction*, Anaphylactoid reaction*, Angioedema*
Very rare: Anaphylactic shock*, Anaphylactoid shock*
Rare: Anorexia
Not known: Hypoglycaemia in diabetics treated with hypoglycaemic agents (see section 4.4), Hyperglycaemia, Hypoglycaemic coma
Uncommon: Agitation, Sleep disorder, Insomnia
Rare: Psychotic disorder (for e.g. hallucination), Anxiety, Confusional state, Nightmares, Depression
Not known: Psychotic disorder and depression with self-endangering behaviour including suicidal ideation or suicide attempt (see Section 4.4), Nervousness
Uncommon: Dizziness, Headache
Rare: Somnolence, Paraesthesia, Dysgeusia, Parosmia
Very rare: Peripheral sensory neuropathy*, Peripheral sensory motor neuropathy* , Convulsion*, Extra-pyramidal symptoms or other disorders of muscular coordination
Not known: Tremor, Dykinesia, Ageusia, Syncope
Uncommon: Eye irritation
Rare: Visual disturbance
Not known: Uveitis
Uncommon: Vertigo
Very rare: Tinnitus, Hearing loss
Not known: Hearing impaired
Rare: Tachycardia
Not known: Ventricular arrhythmias and torsades de pointes (reported predominantly in patients with risk factors for QT prolongation), ECG QT prolonged (see section 4.4 and 4.9)
Rare: Hypotension
Uncommon: Cough, Nasopharyngitis
Rare: Dyspnoea, Bronchospasm
Not known: Allergic pneumonitis, Severe dyspnoea
Uncommon: Abdominal pain, Diarrhoea, Nausea, Vomiting
Rare: Enterocolitis, sometimes haemorrhagic
Very rare: Pseudomembranous colitis*
Not known: Dyspepsia, Flatulence, Constipation, Pancreatitis
Rare: Hepatic enzymes increased (ALAT, ASAT, LDH, gamma-GT and/or alkaline phosphatase), Blood bilirubin increased
Very rare: Jaundice cholestatic
Not known: Hepatitis, which may be severe*, Severe liver injury, including cases with acute liver failure, sometimes fatal, have been reported with ofloxacin, primarily in patients with underlying liver disorders (see section 4.4).
Uncommon: Pruritus, Rash
Rare: Urticaria, Hot flushes, Hyperhidrosis, Pustular rash
Very rare: Erythema multiforme, Toxic epidermal necrolysis, Photo-sensitivity reaction*, Drug eruption, Vascular purpura, Vasculitis, which can lead in exceptional cases to skin necrosis
Not known: Stevens-Johnson syndrome, Acute generalised exanthemous pustulosis, Drug rash, Stomatitis, Exfoliative dermatitis
Rare: Tendonitis
Very rare: Arthralgia, Myalgia, Tendon rupture (e.g. Achilles tendon) which may occur within 48 hours of treatment start and may be bilateral
Not known: Rhabdomyolysis and/or Myopathy, Muscular weakness, Muscle tear, Muscle rupture, Ligament rupture, Arthritis
Rare: Serum creatinine increased
Very rare: Acute renal failure
Not known: Acute interstitial nephritis
Not known: Attacks of porphyria in patients with porphyria
Not known: Asthenia, Pyrexia, Pain (including pain in back, chest and extremities)
* postmarketing experience
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 Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.
Not applicable
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