Tavanic I.V. 750 5 mg / 1ml Infusion

In adults, treatment of mild bacterial infections due to levofloxacin-susceptible micro-organisms:

• Acute bacterial sinusitis due to H. influenzae, S. pneumoniae, S. aureus, M. catarrhalis and H. parainfluenzae.
• Acute exacerbations of chronic bronchitis due to H. influenzae, methillin-sensitive S. aureus, M. catarrhalis, H. parainfluenzae and S. pneumoniae.
• Community acquired pneumonia due to H. influenzae, S. pneumoniae, H. parainfluenzae, Mycoplasma pneumoniae, Chlamydia pneumoniae and Legionella pneumophila.
• Hospital acquired pneumonia due to H. influenzae, S. pneumoniae, and methicillin-sensitive S. aureus.

TAVANIC I.V. 750 solution for infusion is only intended for slow intravenous infusion. TAVANIC I.V. 750 solution for infusion should be infused slowly over a period of not less than 90 minutes for a dosage of 750 mg. TAVANIC I.V. 750 solution for infusion should be used immediately after perforation of the rubber stopper in order to prevent any bacterial contamination. No protection from light is necessary during infusion. TAVANIC I.V. 750 solution for infusion should not be mixed with heparin or alkaline solutions (e.g. sodium hydrogen carbonate). If its compatibility with other infusion solutions has not been proven, TAVANIC I.V. 750 should as a rule be applied separately. TAVANIC I.V. 750 is compatible with the following infusion solutions:

• 0,9 % sodium chloride solution USP (Isotonic saline solution)
• 5, 0 % dextrose injection, USP
• 2,5 % dextrose in Ringer solution
• combination solutions for parenteral nutrition (amino acids, carbohydrates, electrolytes).

It is usually possible to switch from initial intravenous treatment to the oral route after a few days, according to the condition of the patient. Given the bioequivalence of the parenteral and oral forms, the same dosage can be used.

Dosage: TAVANIC I.V. 750 is administered intravenously once daily. The following daily dose recommendations can be given for TAVANIC I.V. 750:

• Acute bacterial sinusitis due to H. influenzae, S. pneumoniae S. aureus, M. catarrhalis and H. parainfluenzae: 750 mg once daily for 5 days.
• Acute exacerbations of chronic bronchitis due to H. influenzae, methicillin-sensitive S. aureus, M. catarrhalis, H. parainfluenzae and S. pneumoniae: 750 mg once daily for 3 - 5 days.
• Community acquired pneumonia due to H. influenzae, S. pneumoniae, H. parainfluenzae, Mycoplasma pneumoniae, Chlamydia pneumoniae and Legionella pneumophila: 750 mg once daily for 5 days.
• Hospital acquired pneumonia due to H. influenzae, S. pneumoniae, and methicillin-sensitive S. aureus: 750 mg once daily for 10 to 14 days.

Recommended daily dosage in patients with impaired renal function: Dosage must be adjusted in patients with impaired renal function (creatinine clearance (u2264 50 ml/min) according to the degree of impairment:

• With a creatinine clearance between 20 and 50 ml/min: In patients meant to be taking 750 mg once daily, a normal single dose should be given initially; and then 750 mg should be administered every 48 hours.
• With a creatinine clearance between 10 and 19 ml/min: In patients meant to be taking 750 mg once daily, a normal single dose should be given initially and then reduced to TAVANIC 500 mg every 48 hours.
• With a creatinine clearance of less than 10 ml/min or in patients on haemodialysis or CAPD (Continuous Ambulatory Peritoneal Dialysis): If the prescribed dosage is 750 mg once daily, a normal single dose should be given initially and then this dose should be reduced to TAVANIC 500 mg every 48 hours.

No adjustment of dosage is required in the elderly or in patients with impaired liver function.

• Hypersensitivity to levofloxacin, other quinolones or any of the excipients.
• Epilepsy.
• History of tendon disorders related to fluoroquinolone administration.
• Children or adolescents.
• Pregnancy and lactation (see PREGNANCY AND LACTATION).

TAVANIC I.V. 750 SHOULD NOT BE GIVEN TO PATIENTS UNDER 18 YEARS OF AGE. TAVANIC I.V. 750 should be used with extreme caution in patients predisposed to seizures, such as 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.

Pseudomembranous colitis: Diarrhoea, particularly if severe, persistent and/or bloody, during or after treatment with TAVANIC I.V. 750, may be symptomatic of pseudomembranous colitis due to Clostridium difficile. If pseudomembranous colitis is suspected, TAVANIC I.V. 750 must be stopped immediately.

Tendinitis: Tendinitis, rarely observed with quinolones, may occasionally lead to rupture involving the Achilles tendon in particular. This undesirable effect may occur within 48 hours of starting treatment and may be bilateral. Elderly patients are more prone to tendinitis. The risk of tendon rupture may be increased by co-administration of corticosteroids. If tendinitis is suspected, treatment with TAVANIC I.V. 750 must be halted immediately.

Even when used as instructed, TAVANIC I.V. 750 may alter reactivity to such an extent that the ability to drive or operate machinery may be impaired. Although photosensitisation is extremely rare with TAVANIC I.V. 750, it is recommended that patients should not expose themselves unnecessarily to strong sunlight or to artificial UV rays (e.g. sunray lamp, solarium), in order to prevent photosensitisation.

TAVANIC I.V. 750 may inhibit the growth of Mycobacterium tuberculosis, and therefore may give false-negative results in the bacteriological diagnosis of tuberculosis. Patients with renal impairment: Since TAVANIC I.V. 750 is excreted mainly by the kidneys, the dose of TAVANIC I.V. 750 should be adjusted in patients with renal impairment.

• Theophylline, fenbufen or similar non-steroidal anti-inflammatory medicines: No pharmacokinetic interactions of TAVANIC I.V. 750 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, non-steroidal anti-inflammatory medicines or other agents which lower the seizure threshold.
• Probenecid and cimetidine: Caution should be exercised when TAVANIC I.V. 750 is co-administered with medicines that affect the tubular renal secretion such as probenecid and cimetidine, especially in renal impaired patients.
• Vitamin K antagonist: Increased coagulation tests (PT/INR) and/or bleeding which may be severe, has been reported in patients treated with TAVANIC I.V. 750 in combination with a vitamin K antagonist (e.g. warfarin). Coagulation tests should be monitored in patients treated with vitamin K antagonists.
• Medicines known to prolong QT-interval: TAVANIC I.V. 750 should be used with caution in patients receiving medicines known to prolong the QT interval (e.g. Class IA and III antidysrhythmics, tricyclic antidepressants, macrolides) (see SPECIAL PRECAUTIONS).

TAVANIC I.V. 750 is contraindicated for use during pregnancy and lactation (see CONTRAINDICATIONS).

Even when used as instructed, TAVANIC I.V. 750 may alter reactivity to such an extent that the ability to drive or operate machinery may be impaired.

Adverse reactions have been ranked according to CIOMS recommendation and frequency rating as follows: Very common: u2265 10 %; Common: u2265 1 % and < 10 %; Uncommon: u2265 0,1 % and < 1 %; Rare: u2265 0,01 % and < 0,1 %; Very rare: < 0,01 %; Not known.

Cardiac disorders: Rare: tachycardia. Not known: electrocardiogram QT prolonged.

Blood and lymphatic system disorders: Uncommon: leukopenia, eosinophilia. Rare: neutropenia, thrombocytopenia. Not known: pancytopenia, agranulocytosis, haemolytic anaemia.

Nervous system disorders: Common: headache, dizziness, vertigo. Uncommon: somnolence, tremor, dysgeusia. Rare: paraesthesia, convulsion. Not known: peripheral sensory neuropathy, peripheral sensory motor neuropathy, parosmia.

Eye disorders: Rare: visual disturbance.

Ear and labyrinth disorders: Uncommon: vertigo. Not known: hearing impaired.

Respiratory, thoracic and mediastinal disorders: Uncommon: dyspnoea. Very rare: allergic pneumonitis. Not known: bronchospasm.

Gastrointestinal disorders: Common: diarrhoea, vomiting, nausea. Uncommon: abdominal pain, dyspepsia. Not known: diarrhoea haemorrhagic, which may be indicative of enterocolitis, including pseudomembranous colitis.

Renal and urinary disorders: Uncommon: blood creatinine increased. Rare: renal failure acute (e.g. due to nephritis interstitial).

Skin and subcutaneous tissue disorders: Uncommon: rash, pruritus, urticaria. Not known: toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, photosensitivity reaction.

Musculoskeletal and connective tissue disorders: Uncommon: arthralgia, myalgia. Rare: tendon disorders including tendinitis (e.g. Achilles tendon), muscular weakness, which may be of special importance in patients with myasthenia gravis. Not known: rhabdomyolysis, tendon rupture (e.g. Achilles tendon).

Metabolism and nutrition disorders: Uncommon: anorexia. Rare: hypoglycaemia, particularly in diabetic patients.

Infections and infestations: Uncommon: fungal infection, pathogen resistance. Very rare: fungal overgrowth and proliferation of other resistant micro-organisms.

Vascular disorders: Common: phlebitis. Rare: hypotension.

General disorders and administration site conditions: Common: infusion site reaction (pain, reddening). Uncommon: asthenia. Rare: pyrexia. Very rare: disturbances of taste and smell, fever.

Immune system disorders: Rare: angioedema. Not known: anaphylactic shock, anaphylactoid shock. Anaphylactic and anaphylactoid reactions may sometimes occur even after the first dose.

Hepato-biliary disorders: Common: hepatic enzyme increased (e.g. ALT/AST). Uncommon: blood bilirubin increased. Not known: severe liver injury, including cases with acute liver failure, have been reported with TAVANIC I.V. 750, primarily in patients with severe underlying diseases (e.g. sepsis), hepatitis.

Psychiatric disorders: Common: insomnia. Uncommon: anxiety, confusional state. Rare: psychotic disorder (with e.g. hallucination), depression, agitation. Not known: psychotic disorder with self-endangering behaviour including suicidal ideation or suicide attempt.

Other possible undesirable effects related to the class of fluoroquinolones: Very rare: extrapyramidal symptoms and other disorders of muscular coordination, hypersensitivity vasculitis, attacks of porphyria in patients with porphyria.

Signs and symptoms: According to studies in animals, the most important signs to be expected following acute overdosage of TAVANIC I.V. 750 are central nervous system symptoms such as confusion, dizziness, impairment of consciousness, and convulsive seizures. CNS effects including confusional state, convulsions, hallucinations and tremor have been observed in post-marketing experience. Gastrointestinal reactions such as nausea and mucosal erosions. In clinical pharmacology studies performed with a supra-therapeutic dose increase in QT-interval has been seen.

Management: In the event of overdose the patient should be carefully observed (including ECG monitoring) and symptomatic treatment should be implemented. Haemodialysis, including peritoneal dialysis and CAPD, are not effective in removing TAVANIC I.V. 750 from the body. No specific antidote exists.