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Drug Details

Tarivid IV Infusion Solution

• Generic Name
  ofloxacin
• Presentation
  Solution for Infusion.
• Description
  Ofloxacin, 2 mg/ml.
• 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: Lower Respiratory Tract: Acute and chronic infections.

  Upper and Lower Urinary Tract: Acute and chronic lower urinary tract infections; acute and chronic upper urinary tract infections (pyelonephritis). Septicaemia. Skin and soft tissue infections. 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), Salmonella, Shigella, Acinetobacter, Yersinia enterocolitica, Campylobacter jejuni, Aeromonas, Plesiomonas, Vibrio cholerae, Vibrio parahaemolyticus, Haemophilus influenzae, Chlamydiae, Legionella, Gardenerella.

  Variable sensitivity is shown by Streptococci, Serratia marcescens, Pseudomonas aeruginosa, Clostridium species and Mycoplasmas. Anaerobic bacteria (e.g. Fusobacterium species, Bacteroides species, Eubacterium species, Peptococci, Peptostreptococci) are normally resistant. Tarivid is not active against Treponema pallidum.

• Adult Dosage
  

  General dosage recommendations: The dose of ofloxacin is determined by the type and severity of the infection.

  Adults: The usual intravenous dosages in adults are:

  Complicated urinary tract infection: 200 mg daily.

  Lower respiratory tract infection: 200 mg twice daily.

  Septicaemia: 200 mg twice daily.

  Skin and soft tissue infections: 400 mg twice daily.

  The infusion time for Tarivid IV should not be less than 30 minutes for 200 mg. Generally, individual doses are to be given at approximately equal intervals.

  The dose may be increased to 400 mg twice daily in severe or complicated infections.

  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.

  Duration of treatment: The duration of treatment is determined according to the response of the causative organisms and the clinical picture. As with all antibacterial agents, treatment with Tarivid should be continued for at least 3 days after the body temperature has returned to normal and the symptoms have subsided.

  In most cases of acute infection, a course of treatment lasting 7 to 10 days is sufficient. Once the patient's condition has improved, the mode of administration should be changed from parenteral to oral, normally at the same total daily dose.

  Treatment should not exceed 2 months duration.

• Child Dosage
  

  Ofloxacin is not indicated for use in children or growing adolescents.

• Elderly Dosage
  

  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).

• Contra Indications
  

  Hypersensitivity to the active substance or to any of the 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.

• Special Precautions
  

  Ofloxacin is not the drug of first choice for pneumonia caused by Pneumococci or Mycoplama, or angina tonsillaris caused by β-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 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

  In case of convulsive seizures, treatment with ofloxacin should be discontinued.

   

  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, hypromagnesaemia)

  • elderly

  • cardiac disease (e.g. heart failure, myocardial infarction, bradycardia)

  Patients being treated with ofloxacin should not expose themselves unnecessarily to strong sunlight and should avoid UV rays (sunlamps, 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 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.

   

  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.

  Myasthenia gravis

  Ofloxacin should be used with caution in patients with a history of myasthenia gravis.

  Sudden reductions in blood pressure may occur when Tarivid IV is administered with hypotensive agents. In such cases, or if the drug is given concomitantly with barbiturate anaesthetics, cardiovascular function should be monitored.

  Administration of antibiotics, especially if 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.

• Interactions
  

  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). 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.

• Adverse Drug Reactions
  

  In rare cases after i.v. infusion, a reduction in blood pressure may occur. If this effect is marked, the infusion should be stopped. Pain, reddening of the infusion site and thrombophlebitis have been reported in rare cases.

  The overall frequency of adverse reactions from the clinical trial data base is about 7%. The commonest events involved the gastrointestinal system (about 5.0%) and the nervous system (about 2.0%).

  The following provides a tabulation based on post marketing experience where occasional represents a frequency of 0.1-1.0%, rare <0.1%, very rare <0.01% and isolated cases <0.01%.

  Digestive and liver side effects:

  Occasional: Nausea and vomiting, diarrhoea, abdominal pain, gastric symptoms. (Diarrhoea may sometimes be a symptom of enterocolitis which may, in some cases, be haemorrhagic).

  Rare: Loss of appetite, increase in liver enzymes and/or bilirubin.

  Very rare: cholestatic jaundice, hepatitis or severe liver damage may develop. A particular form of enterocolitis that can occur with antibiotics is pseudomembranous colitis (in most cases due to Clostridium difficile). Even if Clostridium difficile is only suspected, administration of ofloxacin should be discontinued immediately, and appropriate treatment given. Drugs that inhibit peristalsis should not be administered in such cases.

  Central nervous system:

  Occasional: Headache, dizziness, sleep disorders, restlessness.

  Rare: Confusion, nightmares, anxiety, depression, hallucinations and psychotic reactions, drowsiness, unsteady gait and tremor (due to disorders of muscular co-ordination), neuropathy, numbness and paraesthesia, sensory or sensorimotor peripheral neuropathy (see Section 4.4 Special Warnings and Precautions for Use), visual disturbances, disturbances of taste and smell (including, in exceptional cases, loss of function), extrapyramidal symptoms.

  Very rare: Convulsions, hearing disorders (including, in exceptional cases, loss of hearing).

  Isolated cases: Psychotic reactions and depression with self-endangering behaviour including suicidal ideation or acts.

  These reactions have occurred in some patients after the first dose of ofloxacin. In such cases, discontinue treatment immediately.

  Cardiovascular system:

  Tachycardia and a temporary decrease in blood pressure have been reported.

  Rare: circulatory collapse (due to pronounced drop in blood pressure).

  Haematological side effects:

  Very rare: anaemia, leucopenia (including agranulocytosis), thrombocytopenia, pancytopenia. Only in some cases are these due to bone marrow depression. In very rare cases, haemolytic anaemia may develop.

  Renal side effects:

  Rare: Disturbances of kidney function.

  Isolated cases: Acute interstitial nephritis, or an increase in serum creatinine, which may progress to acute renal failure.

  Allergic and skin side effects:

  Occasional: Skin rash, itching.

  Very rare: Rash on exposure to strong sunlight, other severe skin reactions. Hypersensitivity reactions, immediate or delayed, usually involving the skin (e.g. erythema multiforme, Stevens-Johnson syndrome, Lyell's syndrome and vasculitis) may occur. In exceptional circumstances, vasculitis can lead to skin lesions including necrosis and may also involve internal organs. There are rarely other signs of anaphylaxis such as tachycardia, fever, dyspnoea, shock, angioneurotic oedema, vasculitic reactions, eosinophilia. In these cases treatment should be discontinued immediately and where appropriate, supportive treatment given.

  Isolated cases: Pneumonitis.

  Other side effects:

  Rare: Malaise.

  Very rare: Excessive rise or fall in blood-sugar levels. Weakness, joint and muscle pains (in isolated cases these may be symptoms of rhabdomyolysis).

  Isolated cases: Tendon discomfort, including inflammation and rupture of tendons (e.g. the Achilles tendon) particularly in patients treated concurrently with corticosteroids. In the event of signs of inflammation of a tendon, treatment with Tarivid must be halted immediately and appropriate treatment must be initiated for the affected tendon.

  The possibility cannot be ruled out that ofloxacin may trigger an attack of porphyria in predisposed patients.

  Except in very rare instances (e.g. isolated cases of smell, taste and hearing disorders) the adverse effects observed subsided after discontinuation of ofloxacin.