ZETRO Suspension

The treatment of patients with mild to moderate infections caused by susceptible strains of the designated micro-organisms in the specific conditions listed below:

- Lower respiratory tract infections (acute bacterial bronchitis and community acquired pneumonia in patients suitable for outpatient oral treatment and in patients who require initial intravenous therapy).

- Upper respiratory tract infections (acute sinusitis, acute streptococcal pharyngitis/tonsillitis and acute otitis media in children).

- Uncomplicated skin and skin structure infections.

- Sexually transmitted diseases (uncomplicated urethritis and cervicitis).

- Antimicrobial agents used in high doses for short periods of times to treat non-gonococcal urethritis may mask or delay the symptoms of incubating syphilis. All patients with sexually-transmitted urethritis or cervictitis should have a serologic test for syphilis and appropriate cultures for gonorrhea performed at the time of diagnosis. Appropriate antimicrobial therapy and follow-up tests for these diseases should be initiated if infection is confirmed.

- Pelvic inflammatory disease in patients who require initial intravenous therapy.

- Chlamydia trachomatis conjunctivitis and trachoma in adults and in children 12 months or older.

- Prevention of infection due to Mycobacterium avium-intracellulare Complex (MAC) disease in adults and children aged more than 12 years.

Dosage and administration

This tablets and suspension can be taken with or without food. The capsule formulation should be given at least an hour before or 2 hours after meals.

Adults

For all indications except for those given below, the usual dose is 500mg as a single dose daily for 3 days. Alternatively, an initial dose of 500mg maybe followed by 250mg daily for a further 4 days.

Sexually transmitted uncomplicated urethritis and cervicitis: 1g as a single dose.

Conjunctivitis and trachoma due to Chlamydia trachomatis: 1g either as a single dose or once weekly for up to 3 weeks.

Treatment of community acquired pneumonia following Ⅳtherapy: 500mg as a single daily dose to complete a 7-10day course of therapy.

Treatment of pelvic inflammatory disease following Ⅳtherapy: 250m as a single daily dose to complete a 7day course of therapy.

Prevention of disseminated Mycobacterium avium complex (MAC) disease in adults with HIV infection: 1200mg taken as a single dose once weekly, either alone, or in combination with rifabutin, at its recommended dosage.

Children

ZETRO should be used for children<25kg. The dose in children is 10mg/kg as a single dose on the first day followed by 5mg/kg/day on days 2-5.

Conjunctivitis and trachoma due to Chlamydia trachomatis in children 12 months or older: 20mg/kg either as a single dose or once weekly for up to 3 weeks.

Prevention of disseminated Mycobacterium avium complex (MAC) disease in children aged more than 12 years with HIV infection: 1200mg taken as a single dose once weekly, either alone, or in combination with rifabutin, at its recommended dosage.

Streptococcal pharyngitis and tonsillitis: 20mg/kg once daily for 3 consecutive days providing a total dose of 60mg/kg over a 3 day treatment period. Do not exceed a daily dose of 500mg (or 12.5mL of the reconstituted powder for oral suspension).

Acute Otitis Media: Total dose of 30mg/kg given as 30mg/kg as a single dose or 10m/kg as a single dose on the first day followed by 5mg/kg/day on days 2-5.

Directions for Preparing Oral Suspension

Add freshly boiled and cooled water up to the line mark on the bottle and shake well to dissolve the powder.

Discard any unused portion after 10days.

　- In patients with known hypersensitivity to azithromycin or any macrolide antibiotics.

- The theoretical possibility of ergotism contraindicated the concurrent use of azithromycin with ergot derivatives.

Gastrointestinal disturbances are the most frequent adverse effects but are usually mild. Transient elevations of liver enzyme values have been reported and rarely cholestatic jaundice. Rashes, headache, and dizziness may occur. Severe hypersensitivity reactions occur rarely but may be prolonged. Transient alterations in neutrophil counts have been seen in patients receiving azithromycin.

Antacids: In patients receiving both azithromycin and antacids, the drugs should not be taken simultaneously. Azithromycin should be taken at least 1 hour before or 2 hours after the antacid.

Cyclosporine: Caution should be exercised before considering concurrent administration of these drugs. If co- administration of these drugs is necessary, cyclosporine levels should be monitored and the dose adjusted accordingly.

Theophylline: Theophylline levels may be increased in patients taking azithromycin.

Coumarin-type oral anticoagulants: Consideration should be given to the frequency of monitoring prothrombin time, when azithromycin is used in patients receiving coumarin-type oral anticoagulants.

Digoxin: In patients receiving concomitant azithromycin, a related azalide antibiotic, and digoxin, the possibility of raised digoxin levels should be borne in mind.

Pregnancy

There are no adequate and well-controlled studies in pregnant women. Therefore, azithromycin should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers

It is not known whether azithromycin is excreted into human milk. Azithromycin should only be used in lactating women where adequate alternatives are not available.

　- Azithromycin should not be used in patients with pneumonia who are judged to be inappropriate for oral therapy because of risk factors such as:

 Patients with cystic fibrosis.

 Patients with nosocomially acquired infections.

 Patients with known or suspected bacteremia.

 Patients requiring hospitalization.

 Elderly or debilitated patients.

 Patients with significant underlying health problems that may compromise their ability to respond to their illness (including immunodeficiency or functional asplenia).

- It is important to consider the diagnosis of pseudomembranous colitis in patients who develop diarrhea or colitis in association with antibiotic use (this may occur up to several weeks after cessation of antibiotic therapy). Mild cases may respond to drug discontinuation alone. In moderate to severe cases appropriate therapy with a suitable oral antibacterial agent may be required.

- No dose adjustment is needed in patients with mild or moderate renal impairment.

- Caution should be exercised when azithromycin is administered to patients with severe renal impairment (GFR<10mL/min).

- Since azithromycin is metabolized in the liver and excreted in the bile, the drug should not be given to patients suffering from severe liver disease.

- As with any antibiotic preparation, observation for signs of superinfection with non-susceptive organisms including fungi, is recommended.

- Venticular arrhythmias associated with prolonged QT interval, including ventricular tachycardia and torsades de pointes have been reported with macrolide products. Azithromycin should be used with caution in patients taking other medications known to prolong the QT interval.

Azithromycin exerts it antibacterial action by binding to the 50S ribosomal subunit of susceptible organisms and thus interfering with microbial protein synthesis and inhibition of peptide translocation. Nucleic acid synthesis is not effected.

Microbiology:

Azithromycin has shown to be active against most isolates of the following micro-organisms, both in vitro ad in clinical infections.

Aerobic and facultative gram-positive organisms.

Streptococcus pneumoniae, penicillin-resistant, penicillin-intermediate, Streptococcus pyogenes, Staphylococcus aureus, Streptococcus agalactiae, Streptococci (Groups C,F,G) Viridans group streptococci, Corynebacterium diptheriae, Azithromycin demonstrates cross-resistance with erythromycin-resistant Gram-positive strains, including Streptococcus faecalis (enterococcus) and most strains of methicillin-resistant staphylococci.

Aerobic and facultative gram-negative organisms.

Haemophilus ducreyi, Haemophilus influenzae, Moraxella catarrhalis, Neisseria gonorrhoeae, Bordetella pertussis, Legionella pneumophila, Haemophilus parainfluenzae, Acinetobacter species, Yersinia species,

Shigella species, Pasteurella species, Vibrio cholerae and parahaemolyticus, Plesiomonas shigelloides.

Anaerobic micro-organisms

Peptostreptococcus species, Prevotella bivia, Bacteroides fragilis and Bacteroides species, Clostridium perfringens, Peptococcus species, Fusobacterium necrophorum and Propionibacterium acnes.

Others

Chlamydia pneumoniae, Chlamydia trachomatis, Mycoplasma pneumoniae, Ureaplasma urealyticum, Escherichia coli, Salmonella, Shigella spp., Mycobacterium avium, Toxoplasma gondii, Plasmodium falciparum.