Ofloxacin 400mg Tablets
Out of date information, search anotherSUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Ofloxacin 400mg Tablets
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Tablets containing 400 mg of ofloxacin.
For the full list of excipients, see section 6.1
3. PHARMACEUTICAL FORM
Film coated tablets.
The tablets are white capsule shaped and scored on both sides with ‘BL’ and ‘400’ embossed on one face of the tablet.
4. CLINICAL PARTICULARS
4.1. Therapeutic indications
Ofloxacin is a synthetic 4-fluoroquinolone antibacterial agent with bactericidal activity against a wide range of Gram-negative and Gram-positive organisms. It is indicated for the treatment of the following infections when caused by sensitive organisms: Upper and lower urinary tract infections; lower respiratory tract infections; uncomplicated urethral and cervical gonorrhoea; non-gonococcal urethritis and cervicitis, skin and soft tissue infections.
4.2. Posology and method of administration
General dosage recommendations: The dose of ofloxacin is determined by the type and severity of infection. The dosage range for adults is 200mg to 800mg daily. Up to 400mg may be given as a single dose, preferably in the morning. Larger doses should be given as two divided doses. Generally, individual doses are to be given at approximately equal intervals. Ofloxacin tablets should be swallowed with liquid; they should not be taken within 2 hours of magnesium/aluminium containing antacids, sucralfate, zinc or iron preparations since reduction of absorption of ofloxacin can occur.
Lower urinary tract infection: 200-400mg daily.
Upper urinary tract infection: 200-400mg daily increasing, if necessary, to 400mg twice a day.
Lower respiratory tract infection: 400 mg daily increasing, if necessary, to 400mg twice daily.
Uncomplicated urethral and cervical gonorrhoea: A single dose of 400mg
Non-gonococcal urethritis and cervicitis: 400mg daily in single or divided doses.
Skin and soft tissue infections: 400mg twice daily.
Impaired renal function: following a normal initial dose, dosage should be reduced in patients with impairment of renal function. When creatinine clearance is 20-50ml/minute (serum creatinine 1.5-5.0mg/dl) the dosage should be reduced by half (100-200mg daily). If creatinine clearance is less than 20ml/minute (serum creatinine greater than 5mg/dl) 100mg should be given every 24hours. In patients undergoing haemodialysis or peritoneal dialysis, 100mg should be given every 24 hours.
When creatinine clearance cannot be measured, it can be estimated with reference to the serum creatinine level using the following Cockcroft's formula for adults:
weight(kg) x (140 -age in years)
Men: ClCr (ml/min) = ---------------------------------------
72 x serum creatinine (mg/dl)
or
weight(kg) x (140 -age in years)
ClCr (ml/min) = --------------------------------------
0.814 x serum creatinine (pmol/l)
Women: ClCr (ml/min) = 0.85 x (above value)
Posology in hepatic insufficiency (e g. cirrhosis with ascites)
It is recommended that a maximum daily dose of 400 mg of ofloxacin be not exceeded, because of possible reduction of excretion.
Impaired liver function: The excretion of ofloxacin may be reduced in patients with severe hepatic dysfunction.
Elderly: No adjustment of dosage is required in the elderly, other than that imposed by consideration of renal or hepatic function (see section 4.4 QT interval prolongation).
Children: Ofloxacin is not indicated for use in children or growing adolescents.
Duration of treatment: Duration of treatment is dependent on the severity of infection and response to treatment. The usual treatment period is 5-10 days except in uncomplicated gonorrhoea, where a single dose is recommended.
Treatment should not exceed 2 months duration.
4.3. Contraindications
Ofloxacin should not be used in patients with known hypersensitivity to 4-quinolone antibacterials, or any of the tablet excipients.
Ofloxacin should not be used in patients with a past history of tendinitis.
Ofloxacin, like other 4-quinolones, is contraindicated in patients with a history of epilepsy or with a lowered seizure threshold. Ofloxacin is contraindicated in children or growing adolescents, and in pregnant or breast-feeding women, since animal experiments do not entirely exclude the risk of damage to the cartilage of joints in the growing subject.
Patients with latent or actual defects in glucose-6-phosphate dehydrogenase activity may be prone to haemolytic reactions when treated with quinolone antibacterial agents.
4.4 Special warnings and special precautions for use
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).
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.
Severe bullous reactions 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.
Hypersensitivity and allergic reactions have been reported for fluoroquinolones after first administration. Anaphylactic and anphylactoid 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. Ofloxacin is not the drug of first choice for pneumonia caused by Pneumococci or Mycoplama, or angina tonsillaris caused by B-haemolytic Streptococci.
Administration of antibiotics, especially if prolonged, may lead to proliferation of resistant microorganisms. The patient’s condition must therefore be checked at regular intervals. If a secondary infection occurs, appropriate measures must be taken.
Clostridium difficile-associated disease
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 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-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
Patients predisposed to seizures
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 other quinolones, 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 (see section 4.5 lowering of the cerebral seizure threshold).
Tendonitis
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. 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).
Patients with renal impairment
Since ofloxacin is mainly excreted by the kidneys, the dose of ofloxacin should be adjusted in patients with renal impairment (see section 4.2: Dosage and Administration).
Patients with a history of psychotic disorder
Psychotic reactions have been reported in patients receiving fluoroquinolones. In some cases these have progressed to suicidal thoughts or self-endangering behavior including suicide attempt, sometimes after a single dose. 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.
Patients with impaired liver function
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, pruritis or tender abdomen. (See section 4.8: Undesirable effects)
Patients treated with vitamin K antagonists
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)
Myasthenia gravis
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
Prevention of photosensitisation
Photosensitisation has been reported with ofloxacin (see section 4.8). It is recommended that Patients being treated with ofloxacin should not expose themselves unnecessarily to strong sunlight and should avoid UV rays (sunlamps, solaria) during treatment and for 48 hours following treatment discontinuation in order to prevent photosensitisation.
Superinfection
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.
QT interval prolongation
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:
• Elderly patients and women may be more sensitive to QTc-prolonging medications. Therefore, caution should be taken when using fluoroquinolones, including ofloxacin, in these populations.
• uncorrected electrolyte imbalance (e.g. hypokalaemia, hypomagnesaemia)
• Congenital long QT interval
• Cardiac disease (e.g. heart failure, myocardial infarction, bradycardia)
• Concomitant use of drugs that are known to prolong the QT interval (e.g. Class IA and III antiarrythmics, tricyclic antidepressants, macrolides, antipsychotics).
See also section 4.2 Elderly and Section 4.5, section 4.8, section 4.9).
Dysglycemia: As with all quinolones, disturbances in blood glucose, including both hypoglycaemia and hyperglycemia 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.
Peripheral neuropathy
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 in order to prevent the development of an irreversible condition (see section 4.8).
Patients with glucose-6-phosphate-dehydrogenase deficiency
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.
Vision disorders
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).
Interference with laboratory tests
In patients treated with ofloxacin, determination of opiates in urine may give falsepositive results. It may be necessary to confirm positive opiate screens by more specific method.
4.5 Interactions with other medicinal products and other forms of interaction
Drugs known to prolong QT interval
Ofloxacin, like other flouroquinolones, should be used with caution in patients receiving drugs known to prolong the QT interval (e.g. Class I A and III antiarrythmics, tricyclic antidepressants, macrolides, antipsychotics). (See section 4.4 Cardiac Disorders).
Antacids, Sucralfate, Metal Cations
Co-administered magnesium/aluminium antacids, sucralfate, zinc or iron preparations can reduce absorption. Therefore, ofloxacin should be taken 2 hours before such preparations.
Prolongation of bleeding time has been reported during concomitant administration of Ofloxacin tablets and anticoagulants.
Theophylline, fenbufen or similar non-steroidal antiinflammatory drugs
There may be a further lowering of the cerebral seizure threshold when quinolones are given concurrently with other drugs which lower the seizure threshold e.g. theophylline, nonsteroidal anti-inflammatory drugs, or other agents. However, ofloxacin is not thought to cause a pharmacokinetic interaction with theophylline, unlike some other fluoroquinolones.
In case of convulsive seizures, treatment with ofloxacin should be discontinued.
Probenecid, cimetidine, furosemide and methotrexate
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.
Glibenclamide
Ofloxacin may cause a slight increase in serum concentrations of glibenclamide administered concurrently; patients treated with this combination should be closely monitored.
Interactions with laboratory tests:
Determination of opiates or porphyrins in urine may give false-positive results during treatment with ofloxacin. It may be necessary to confirm positive opiate or porphyrin screens by more specific methods.
Vitamin K antagonists
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, therefore, should be monitored in patients treated with vitamin K antagonists (see section 4.4)
4.6. Fertility, pregnancy and lactation
Pregnancy
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)
Breast-feeding
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)
4.7. Effects on ability to drive and use machines
Since there have been occasional reports of somnolence, impairment of skills, dizziness/vertigo and visual disturbances, patients should know how they react to Ofloxacin Tablets before they drive or operate machinery. These effects may be enhanced by alcohol.
4.8 Undesirable effects
The information given below is based on data from clinical studies and on extensive post marketing experience.
|
class |
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 available data)* |
|
Infections and infestations |
Fungal infection, Pathogen resistance | ||||
|
Blood and the lymphatic system disorders |
Anaemia Haemolytic anaemia, Leukopenia, Eosinophilia, Thrombocytop |
Agranulocytos is Bone marrow failure |
|
enia | |||||
|
Immune system disorders |
Anaphylactic reaction*, Anaphylactoid reaction*, Angioedema* |
Anaphylactic shock*, Anaphylactoid shock* | |||
|
Metabolism and Nutrition disorders |
Anorexia |
Hypoglycaemi a in diabetics treated with hypoglycaemi c agents (see Section 4.4) Hyperglycae mia Hypoglycae mic coma | |||
|
Psychiatric disorders |
Agitation, Sleep disorder, Insomnia |
Psychotic disorder (for eg. hallucination), Anxiety, Confusional state, Nightmares, Depression |
Psychotic disorder and depression with self-endangering behaviour including suicidal ideation or suicide attempt (see Section 4.4) Nervousness | ||
|
Nervous system disorders |
Dizziness, Headache |
Somnolence, Paraesthesia, Dysgeusia, Parosmia |
Peripheral sensory neuropathy* Peripheral sensory motor neuropathy* Convulsion*, Extrapyramidal symptoms or other disorders of muscular |
Tremor Dyskinesia Ageusia Syncope |
|
coordination | |||||
|
Eye disorders |
Eye irritation |
Visual disturbance | |||
|
Ear and labyrinth disorders |
Vertigo |
Tinnitus, Hearing loss |
Hearing impaired | ||
|
Cardiac disorders |
Tachycardia |
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) | |||
|
Vascular disorders |
applies only to the solution for infusion: Phlebitis |
Hypotension |
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. | ||
|
Respiratory, thoracic and mediastinal disorders |
Cough, Nasopharyngi tis |
Dyspnoea, Bronchospasm |
Allergic pneumonitis, Severe dyspnoea | ||
|
Gastrointestin al disorders |
Abdominal pain, Diarrhoea, |
Enterocolitis, sometimes haemorrhagic |
Pseudomembra nous colitis* |
Dyspepsia Flatulence Constipation Pancreatitis |
|
Nausea, Vomiting |
Jaundice cholestatic | ||||
|
Hepatobilary disorders |
Hepatic enzymes increased (ALAT, ASAT, LDH, gamma-GT and/or alkaline phosphatase) Blood bilirubin increased |
Hepatitis, which may be severe | |||
|
Skin and subcutaneous tissue disorders |
Pruritus, Rash |
Urticaria, Hot flushes, Hyperhidrosis Pustular rash |
Erythema multiforme, Toxic epidermal necrolysis, Photosensitivit y reaction *, Drug eruption Vascular purpura, Vasculitis, which can lead in exceptional cases to skin necrosis |
Stevens- Johnson syndrome; Acute generalized exanthemous pustulosis; drug rash Stomatitis | |
|
Musculoskele tal and Connective tissue disorders |
Tendonitis |
Arthralgia, Myalgia, Tendon rupture (e.g. Achilles tendon) which may occur within 48 hours of treatment start and may be bilateral. |
Rhabdomyoly sis and/or Myopathy, Muscular weakness Muscle tear, muscle rupture Ligament rupture Arthritis |
|
Renal and Urinary disorders |
Serum creatinine increased |
Acute renal failure |
Acute interstitial nephritis | ||
|
Congenital and familial/genet ic disorders |
Attacks of porphyria in patients with porphyria | ||||
|
General disorders and administration site conditions |
applies only to the solution for infusion: Infusion site reaction (pain, reddening ) |
Asthenia Pyrexia Pain (including pain in back, chest, and extremities) |
* postmarketing experience
Reporting of Suspected Adverse Reactions
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 suspected adverse reactions via the Yellow Card Scheme at:www.mhra.gov.uk/yellowcard
4.9. Overdose
In the event of overdose, symptomatic treatment should be implemented. ECG monitoring should be undertaken, because of the possibility of QT interval prolongation.
The most important signs to be expected following acute overdosage are CNS symptoms such as confusion, dizziness, impairment of consciousness and convulsive seizures, increases in QT interval as well as gastrointestinal reactions such as nausea and mucosal erosions.
CNS effects including confusional state, convulsion, hallucination, and tremor have been observed in post marketing experience
In the case of overdose symptomatic treatment should be implemented, ECG monitoring should be undertaken, because of the possibility of QT interval prolongation.
In the case of overdose steps to remove any unabsorbed ofloxacin e.g. gastric lavage, administration of adsorbents and sodium sulphate, if possible during the first 30 minutes, are recommended; antacids are recommended for protection of the gastric mucosa. A fraction of ofloxacin may be removed from the body with haemodialysis. Peritoneal dialysis and CAPD are not effective in removing ofloxacin from the body. No specific antidote exists.
Elimination of ofloxacin may be increased by forced diuresis.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic Group: Quinolone antibacterials, Fluoroquinolones. ATC code J01M A01.
Ofloxacin is a quinolone-carboxylic acid derivative with a wide range of antibacterial activity against both Gram-positive and Gram-negative organisms. It is active after oral administration. It inhibits bacterial DNA replication by blocking DNA topoisomerases, in particular DNA gyrase.
Therapeutic doses of ofloxacin are devoid of pharmacological effects on the voluntary or autonomic nervous systems.
Microbiological results indicate that the following pathogens may be regarded as sensitive: Staphylococcus aureus (including methicillin resistant staphylococci), Staphylococcus epidermidis, Neisseria species, Escherichia coli, Citrobacter, Klebsiella, Enterobacter, Hafnia, Proteus (indole-negative and indole-positive strains), Haemophilus influenzae, Chlamydiae, Legionella, Gardnerella.
Variable sensitivity is shown by Streptococci, Serratia marcescens, Pseudomonas aeruginosa and Mycoplasmas
Anaerobic bacteria (e.g. Fusobacterium species, Bacteroides species, Eubacterium species, Peptococci, Peptostreptococci) are normally resistant.
5.2. Pharmacokinetic properties
Ofloxacin is almost completely absorbed after oral administration. Maximal blood levels occur 1-3 hours after dosing and the elimination half-life is 4-6 hours. Ofloxacin is primarily excreted unchanged in the urine.
In renal insufficiency the dose should be reduced.
No clinically relevant interactions were seen with food and no interaction was found between ofloxacin and theophylline.
5.3. Preclinical safety data
Not applicable.
6. PHARMACEUTICAL PARTICULARS
6.1. List of excipients
Microcrystalline cellulose, Sodium starch glycolate, Hydroxypropyl cellulose, Magnesium stearate, Hypromellose 2910, Macrogol 400, Titanium dioxide (E171).
6.2. Incompatibilities
None applicable.
6.3. Shelf life
3 years.
6.4. Special precautions for storage
Do not store above 25°C.
Store in the original package.
6.5 Nature and contents of container
Ofloxacin 400mg Tablets are available in blister packs of 5, 10 and 50 tablets in Alu/PVC blisters.
6.6. Instructions for use and handling
Not applicable.
Bristol Laboratories Ltd Unit 3, Canalside, Northbridge Road, Berkhamsted, Hertfordshire HP4 1EG United Kingdom
8. MARKETING AUTHORISATION NUMBER(S)
Ofloxacin 400mg Tablets - PL 17907/0025
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
22/03/2004
10 DATE OF REVISION OF THE TEXT
20/02/2015