LIVOX-500 Tablet

Sinusitis, Acute exacerbations of chronic bronchitis, Community Acquired Pneumonia, Complicated urinary tract infections and acute pyelonephritis, Uncomplicated skin and skin structure infections, Intra-abdominal infections.

Dosage

LIVOX is administered once or twice daily.

The dosage depends on the type and severity of infection and sensitivity of the presumed causative pathogen. The duration of therapy varies according to the course of the disease.

LIVOX should be continued for a minimum of 48-72 hours after the patient has become afebrile or evidence of bacterial eradication has been obtained.

The following daily dose recommendation can be given for LIVOX:

- Recommended daily dosage in patients with normal renal function:

Sinusitis: 500mg once daily for 10 days.

Acute exacerbation of chronic bronchitis: 500mg once daily for 5-10 days.

Community Acquired Pneumonia: 500mg once or twice daily for 10-14 days.

Pyelonephritis: 250mg once daily for 10 days.

Uncomplicated skin structure infections: 250-500mg once daily for 7-10 days.

Complicated skin and skin structure infections: 500mg twice daily for 10-14 days.

Intra-abdominal infections: 500mg once daily in combination with an antibiotic with anaerobic coverage for 10-14 days.

Above indications when bacteraemia or septicaemia is present 500mg twice daily for 10-14 days.

Hypersensitivity to levofloxacin, other quinolones, or any of the excipients,

Epilepsy,

History of tendon disorders related to fluoroquinolone administration,

Children or adolescents,

During pregnancy and lactation because animal studies have shown that levofloxacin may affect joint development in growing organisms.

- Gastro-intestinal symptoms may occur (gastric or abdominal symptoms, loss of appetite, nausea, vomiting, diarrhoea). The onset of diarrhoea, particularly if severe, persistent and/or bloody, during or after treatment with LIVOX, may less frequently indicate the appearance of pseudomembranous colitis. Suspicion of pseudomembranous colitis requires immediate cessation of administration and treatment with appropriate specific antibiotic therapy. Products inhibiting peristalsis are contra-indicated in this clinical satiation.

- Disturbances of the nervous system, e.g. headache, dizziness, sleep disturbances, unsteady gait and tremor (disturbances of muscular co-ordination), numbness and tingling in the limbs (paresthesiae; visual and auditory disturbances, disturbances of the senses of taste and smell, hallucinations, convulsions and psychotic reactions such as restlessness, agitation, anxiety, depression and confusion. In some cases, these reactions have occurred already after the first dose. In the event of such adverse reactions, LIVOX must be discontinued immediately and the doctor informed.

- Changes in the blood picture (leukopenia, eosinophilia, neutropenia, agranulocytosis, thrombocytopenia, pancytopenia, haemolytic anaemia), hepatitis and transient increases in liver enzymes and/or bilirubin and in serum creatinine have been observed. Interstitial nephritis and acute kidney failure may also occur.

- Allergic manifestation may occur, in particular hypersensitivity reactions of the skin such as pruritus, rash, urticaria and vasculitis. Isolated cases of severe bullous eruptions such as Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell’s syndrome) and erythema exsudativum multiforme have been reported. Photosensitivity reactions (skin reactions on exposure to strong sunlight and artificial UV rays) have been reported. There have been symptoms such as fever, allergic pneumonitis, angio-oedema, hypotension and anaphylactic-like shock. In the event of such reactions, LIVOX should be discontinued immediately. Medical treatment (therapy for shock) is imperative.

- Tendinitis (e.g. Achilles tendon) is less frequently observed with quinolones and if it is suspected, treatment with LIVOX must be halted immediately and appropriate treatment (e.g. immobilisation) must be initiated for the affected tendon. Other musculoskeletal side effects such as arthralgia and myalgia have been less frequently observed and less frequent occurrences include:

* tendon rupture (Achilles tendon) - this undesirable effect may occur within 48 hours of starting treatment and may be bilateral.

* muscular weakness, which may be of special importance in patients with myasthenia gravis. Isolated cases of rhabdomyolysis have been reported.

- Hypoglycaemia, especially in diabetics, may occur.

- Asthenia, fungal overgrowth and proliferation of other resistant micro-organisms may occur.

- Fluoroquinolones are known to possibly trigger attacks of porphyria in patients suffering from porphyria.

If mineral-containing antacids or iron preparations are taken at the same time, absorption of LIVOX tablets may be impaired. It is recommended that preparations containing divalent or trivalent cations such as iron salts, or magnesium- or aluminium-containing antacids should not be taken 2 hours before or after LIVOX tablet administration.

The bioavailability of LIVOX tablets is significantly reduced when administered together with sucralfate. If the patient is to receive both sucralfate and LIVOX tablets, it is best to administer sucralfate 2 hours after the LIVOX tablet administration.

No pharmacokinetic interactions of LIVOX were found with theophylline in a clinical study. However there are indications of a pronounced lowering of the cerebral seizure threshold when quinolones are given concurrently with other drugs that lower the seizure threshold (e.g. theophylline) or with fenbufen or similar NSAIDs.

Contraindicated.

LIVOX should be used with caution in patients predisposed to seizures, such as patients pre-existing central nervous system lesions, concomitant treatment with fenbufen and similar NSAIDs or with drugs which lower the cerebral seizure threshold such as theophylline.

LIVOX should not be given to patients under 18 years of age.

Even when used as instructed. LIVOX may alter reactivity to such as extent that the ability to drive or operate machinery may be impaired.

Although photosensitization is extremely rare with LIVOX, 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 photosensitization.

LIVOX may inhibit the growth of Mycobacterium tuberculosis, and therefore may give false-negative results in the bacteriological diagnosis of tuberculosis.

LIVOX is a synthetic broad spectrum antibacterial fluoroquinolone containing levofloxacin which is the S(-) enantiomer of the racemic drug substance ofloxacin for oral and intravenous administration. Levofloxacin acts on the DNA-DNA gyrase complex by inhibiting DNA gyrase (bacterial topoisomeraseⅡ), an enzyme required for DNA replication ,transcription, repair and recombination, and topoisomeraseⅣ.

LIVOX is bactericidal in vitro. Its antibacterial spectrum covers many Gram-positive and Gram-negative bacteria. Infections caused by the following organisms have been successfully treated with LIVOX in clinical trials:

Gram positive organisms: Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus faecalis.

Gram negative organisms: Acinetobacter calcoaceticus, Enterobacter cloacae, Escherichia coli, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella oxytoca, Klebsiella pneumoniae, Moraxella catarrhalis, Proteus mirabilis, Pseudomonas aeruginosa.

Other organisms: Chlamydia pneumoniae, Legionella pneumophila, Mycoplasma pneumoniae. In vitro there is cross-resistance between LIVOX and other fluoroquinolones.

Due to the mechanism of action, there is generally no cross-resistance between LIVOX and other classes of antibacterial agents.