Tarivid 200 Mg Film-Coated Tablets
Out of date information, search anotherSUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Tarivid 200 mg Film-coated Tablets
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Tarivid 200mg Film-coated Tablets contain 200mg of ofloxacin.
For a full list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Film coated tablets.
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 the 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. Tarivid Film-coated tablets should be swallowed with liquid; they should not be taken within two hours of magnesium/aluminium containing antacids, sucralfate, zinc or iron preparations since reduction of absorption of ofloxacin can occur.
Lower urinary tract infection: 200-400 mg daily.
Upper urinary tract infection: 200-400 mg daily increasing, if necessary, to 400 mg twice a day.
Lower respiratory tract infection: 400 mg daily increasing, if necessary, to 400 mg twice daily.
Uncomplicated urethral and cervical gonorrhoea: A single dose of 400 mg. Non-gonococcal urethritis and cervicitis: 400 mg daily in single or divided doses. Skin and soft tissue infections: 400 mg 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 20-50 ml/minute (serum creatinine 1.5-5.0 mg/dl) the dosage should be reduced by half (100-200 mg daily). If creatinine clearance is less than 20 ml/minute (serum creatinine greater than 5 mg/dl) 100 mg should be given every 24 hours. In patients undergoing haemodialysis or peritoneal dialysis, 100 mg should be given every 24 hours.
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 the infection and the 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 contra-indicated in patients with a history of epilepsy or with a lowered seizure threshold.
Ofloxacin is contra-indicated 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 precautions for use
Ofloxacin is not the drug of first choice for pneumonia caused by Pneumococci or Mycoplama, or angina tonsillaris caused by P-haemolytic Streptococci.
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.
Clostridium difficile-associated disease
Diarrhoea, particularly if severe, persistent and/or bloody, during or after treatment with ofloxacin, may be symptomatic of pseudo-membranous colitis. If pseudomembranous 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
In case of convulsive seizures, treatment with ofloxacin should be discontinued (see section 4.5 lowering of the cerebral seizure threshold).
Cardiac Disorders
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:
• congenital long QT syndrome
• concomitant use of drugs that are known to prolong the QT interval (e.g.
Class IA and III anti-arrhythmics, 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 Ofloxacin, in these populations.
(See section 4.2 Elderly, section 4.5, section 4.8 section 4.9).
Patients being treated with ofloxacin should not expose themselves unnecessarily to strong sunlight and should avoid UV rays (sun lamps, solaria).
Patients with 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 behaviour 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
Ofloxacin should be used with caution in patients with a history of myasthenia gravis.
Administration of antibiotics, especially of prolonged, may lead to proliferation of resistant micro-organisms. The patient’s condition must therefore be checked at regular intervals. If a secondary infection occurs, appropriate measures must be taken.
Peripheral neuropathy
Sensory or sensorimotor peripheral neuropathy has been reported in patients receiving fluoroquinolones, including ofloxacin. Ofloxacin should be discontinued if the patient experiences symptoms of neuropathy in order to prevent the development of an irreversible condition.
Hypoglycaemia
As with all quinolones, hypoglycaemia has been reported, usually in diabetic patients receiving concomitant treatment with an oral hypoglycaemic agent (e.g. glibenclamide) or with insulin. In these diabetic patients, careful monitoring of blood glucose is recommended.
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. Ofloxacin should therefore be administered with caution in such patients.
Patients with rare hereditary disorders
Patients with rare hereditary disorders of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
4.5 Interaction with other medicinal products and other forms of interaction Drugs known to prolong QT interval
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).
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 Tarivid and anticoagulants.
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. However ofloxacin is not thought to cause a pharmacokinetic interaction with theophylline, unlike some other fluoroquinolones.
Further lowering of the cerebral seizure threshold may also occur with certain nonsteroidal anti-inflammatory drugs.
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.
With high doses of quinolones, impairment of excretion and an increase in serum levels may occur when co-administered with other drugs that undergo renal tubular secretion (e.g. probenecid, cimetidine, frusemide and methotrexate).
Interaction 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
Coagulation tests should be monitored in patients treated with vitamin K antagonists because of a possible increase in the effect of coumarin derivatives.
4.6 Pregnancy and lactation
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)
4.7 Effects on ability to drive and use machines
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.
4.8 Undesirable effects
|
System organ class |
Common ( 1/100 to <1/10 ) |
Uncommo n £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, Thrombo cytopenia |
Agranulocytosis Bone marrow failure | |||
|
Immune system disorders |
Anaphylactic reaction*, Anaphylactoi d reaction*, Angioedema* |
Anaphylactic shock*, Anaphylactoid shock* | |||
|
Metabolism and Nutrition disorders |
Anorexia |
Hypoglycaemia in diabetics treated with hypoglycaemic agents (see Section 4.4) | |||
|
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) |
|
System organ class |
Common ( 1/100 to <1/10 ) |
Uncommo n £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)* |
|
Nervous system disorders |
Dizziness, Headache |
Somnolence, Paraesthesia, Dysgeusia, Parosmia |
Peripheral sensory neuropathy* Peripheral sensory motor neuropathy* Convulsion*, Extra-pyramidal symptoms or other disorders of muscular coordination | ||
|
Eye disorders |
Eye irritation |
Visual disturbance | |||
|
Ear and labyrinth disorders |
Vertigo |
Tinnitus, Hearing loss | |||
|
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, Naso pharyngitis |
Dyspnoea, Bronchospas m |
Allergic pneumonitis, Severe dyspnoea |
|
System organ class |
Common ( 1/100 to <1/10 ) |
Uncommo n £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)* |
|
Gastro intestinal disorders |
Abdominal pain, Diarrhoea, Nausea, Vomiting |
Enterocolitis, sometimes haemorrhagic |
Pseudo membranous colitis* | ||
|
Hepato-bilary disorders |
Hepatic enzymes increased (ALAT, ASAT, LDH, gamma-GT and/or alkaline phosphatase) Blood bilirubin increased |
Jaundice cholestatic |
Hepatitis, which may be severe* | ||
|
Skin and subcutaneous tissue disorders |
Pruritus, Rash |
Urticaria, Hot flushes, Hyperhidrosis Pustular rash |
Erythema multiforme, Toxic epidermal necrolysis, Photosensitivity reaction*, Drug eruption Vascular purpura, Vasculitis, which can lead in exceptional cases to skin necrosis |
Stevens-Johnson syndrome; Acute generalized exanthemous pustulosis; drug rash | |
|
Musculoskelet al 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. |
Rhabdomyolysis and/or Myopathy, Muscular weakness Muscle tear, muscle rupture | ||
|
Renal and Urinary disorders |
Serum creatinine increased |
Acute renal failure |
Acute interstitial nephritis | ||
|
Congenital and familial/geneti c disorders |
Attacks of porphyria in patients with porphyria |
|
System organ class |
Common ( 1/100 to <1/10 ) |
Uncommo n £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)* |
|
General disorders and administration site conditions |
applies only to the solution for infusion: Infusion site reaction (pain, reddening) |
* 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 any suspected adverse reactions via Yellow Card Scheme at: www.mhra.gov.uk/yellowcard
4.9 Overdose
The most important signs to be expected following acute overdosage are CNS symptoms such as confusion, dizziness, impairment of consciousness and convulsive seizures as well as gastrointestinal reactions such as nausea and mucosal erosions.
In the case of overdose steps to remove any unabsorbed ofloxacin eg gastric lavage, administration of adsorbants and sodium sulphate, if possible during the first 30 minutes, are recommended; antacids are recommended for protection of the gastric mucosa.
Elimination of ofloxacin may be increased by forced diuresis.
In the event of overdose, symptomatic treatment should be implemented. ECG monitoring should be undertaken, because of the possibility of QT interval prolongation.
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 negative and gram positive organisms.
It is active after oral administration. It inhibits bacterial DNA replication by blocking DNA topo-isomerases, 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 meticillin 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.
Tarivid is not active against Treponema pallidum
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
Maize starch, lactose, hyprolose, carmellose NS300, magnesium stearate, hypromellose (2910), titanium dioxide (E17 1) talc, macrogol 8000.
6.2 Incompatibilities
Not applicable.
Shelf life
6.3
3 years
6.4 Special precautions for storage
This medicinal product does not require any special storage conditions.
6.5 Nature and contents of container
Blister packs of 10, 20 and 100 tablets. Not all pack sizes may be marketed.
6.6 Special precautions for disposal
No special requirements.
7
MARKETING AUTHORISATION HOLDER
Aventis Pharma Limited
One Onslow Street
Guildford
Surrey
GU1 4YS
UK
or trading as:-
Sanofi-aventis or Sanofi
One Onslow Street
Guildford
Surrey
GU1 4YS
UK
8 MARKETING AUTHORISATION NUMBER(S)
PL 04425/0216
DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
12th April 2002.
10
DATE OF REVISION OF THE TEXT
12/12/2013