Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2019 Publisher: Aventis Pharma Limited, 410 Thames Valley Park Drive, Reading, Berkshire, RG6 1PT, UK Trading as: Sanofi, 410 Thames Valley Park Drive, Reading, Berkshire, RG6 1PT, UK
The use of ofloxacin 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 ofloxacin should only be initiated in the absence of alternative treatment options and after careful benefit/risk assessment (see also section 4.3).
Methicillin-resistant S. aureus 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).
Ofloxacin is not the drug of first choice for pneumonia caused by Pneumococci or Mycoplasma or infection caused by β-haemolytic Streptococci.
Resistance to fluoroquinolones of E. coli – 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.
Due to increase in resistance to N. gonorhoeae, ofloxacin should not be used as empirical treatment option in suspected gonococcal infection (urethral gonococcal infection, pelvic inflammatory disease and epididymo-orchitis), unless the pathogen has been identified and confirmed as susceptible to ofloxacin. If clinical improvement is not achieved in 3 days of treatment, the therapy should be reconsidered.
For pelvic inflammatory disease, ofloxacin should only be considered in combination with anaerobe coverage.
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.
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.
Diarrhoea, particularly if severe, persistent and/or bloody, during or after treatment with ofloxacin (including several weeks after treatment), may be symptomatic of pseudo- membranous colitis (CDAD). CDAD may range in severity from mild to life threatening, the most severe form 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-membranous colitis is suspected, ofloxacin must be stopped immediately.
Appropriate specific antibiotic therapy must be started without delay (e.g. oral vancomycin, oral teicoplanin or metronidazole). Products inhibiting the peristalsis are contraindicated in this clinical situation.
Quinolones may lower the seizure threshold and may trigger seizures. Ofloxacin is contraindicated in patients with a history of epilepsy (see section 4.3) and, as with otherquinolones, ofloxacin should be used with extreme caution in patients predisposed to seizures.
Such patients may be patients with pre-existing central nervous system lesions, concomitant treatment with fenbufen and similar non-steroidal anti-inflammatory drugs 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.
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. Ofloxacin 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 ofloxacin 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.
Since ofloxacin is mainly excreted by the kidneys, the dose of ofloxacin should be adjusted in patients with renal impairment (see section 4.2).
Very rare cases of QT interval prolongation 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, section 4.5, section 4.8 and section 4.9).
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.
Psychotic reactions have been reported in patients receiving fluoroquinolones. In some cases these have progressed to suicidal thoughts or self-endangering behaviour including suicide attempt, sometimes after a single dose (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: Undesirable effects).
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
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
As with other antibiotics, the use of ofloxacin, especially if prolonged, may result in overgrowth of non-susceptible organisms. Repeated evaluation of the patient’s condition is essential. If secondary infection occurs during therapy, appropriate measures should be taken.
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 ofloxacin 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)
As with all quinolones, disturbances in blood glucose, including both hyperglycaemia and hypoglycaemia 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).
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.
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).
In patients treated with ofloxacin, determination of opiates in urine may give false- positive results. It may be necessary to confirm positive opiate screens by more specific method.
Patients with rare hereditary disorders of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
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 anti- arrhythmics, tricyclic antidepressants, macrolides, antipsychotics) (See section 4.4).
Prolongation of bleeding time has been reported during concomitant administration of Tarivid and anticoagulants.
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 anti- inflammatory drugs, or other agents, which lower the seizure threshold.
In case of convulsive seizures, treatment with ofloxacin should be discontinued.
Ofloxacin may cause a slight increase in serum concentrations of glibenclamide administered concurrently; patients treated with this combination should be closely monitored.
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 co-administered with drugs that affect the tubular renal secretion such as probenecid, cimetidine, furosemide and methotrexate.
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 be monitored in patients treated with vitamin K antagonists (see section 4.4) because of a possible increase in the effect of coumarin derivatives.
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. Therefore ofloxacin should not be used during pregnancy (See section 4.3: Contraindications).
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: Contraindications).
Since there have been occasional reports of somnolence, impairment of skills, dizziness and visual disturbances, patients should know how they react to Tarivid before they drive or operate machinery. These effects may be enhanced by alcohol.
Common (≥1/100 to <1/10,000), 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, Leukopenia, Eosinophilia, Thrombocytopenia
Not known: Agranulocytosis, Bone marrow failure
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, Dyskinesia, Ageusia, Syncope, Benign intracranial hypertension (Pseudotumor cerebri)
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, torsades de pointes (reported predominantly in patients with risk factors for QT prolongation), ECG QT prolonged (see section 4.4 and 4.9)
Common: applies only to the solution for infusion: Phlebitis
Rare: Hypotension
Not known: applies only to the solution for infusion: During infusion of ofloxacin, tachycardia and hypotension may occur. Such a decrease in blood pressure may, in very rare cases, be severe.
Uncommon: Cough, Nasopharyngitis
Rare: Dyspnoea, Bronchospasm
Not known: Allergic pneumonitis, Severe dyspnoea
Uncommon: Abdominal pain, Diarrhoea, Nausea, Vomiting
Rare: Enterocolitis, sometimes haemorrhagic
Very rare: Pseudo-membranous colitis*, Jaundice cholestatic
Not known: Dyspepsia, Flatulence, Constipation, Pancreatitis
Rare: Hepatic enzymes increased (ALAT, ASAT, LDH, gamma-GT and/or alkaline phosphatase), Blood bilirubin increased
Not known: Hepatitis, which may be severe**; Severe liver injury, including cases of 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 generalized 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
Common: applies onlytothe solution for infusion: Infusion site reaction (pain, reddening)
Not known: Asthenia, Pyrexia, Pain (including pain in the back, chest and extremities)
* 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).
** 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 Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.
Tarivid IV should be administered alone unless compatibility with other infusion fluids has been demonstrated. Compatible infusion solutions include isotonic sodium chloride, Ringer’s solution and 5 % glucose solution. Heparin and ofloxacin are incompatible.
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