FORMULA:
Each Azax Film Tablet, which has notched sides at double bisect, contains 524 mg azithromycin dihydrate and also titanium dioxide as coloring agent.

PHARMACOLOGICAL PROPERTIES:

Pharmacodynamic properties:
Azithromycin is a derivative of erythromycin and belongs to azalide group, a subclass of macrolide antibiotics.
Azithromycin acts by binding to the 50S ribosomal subunit of susceptible microorganisms and, thus, interfering with microbial protein synthesis. Nucleic acid synthesis is not affected. Azithromycin concentrates in phagocytes and fibroblasts as demonstrated by in vitro incubation techniques. Using such methodology, the ratio of intracellular to extracellular concentration was >30 after one hour incubation. In vivo studies suggest that concentration in phagocytes may contribute to drug distribution to inflamed tissues.

INDICATIONS:
Azax Film Tablet is indicated for the treatment of patients with mild to moderate infections caused by susceptible strains of the designated microorganisms in the specific conditions listed below.

• Acute bacterial exacerbations of chronic obstructive pulmonary disease due to Haemophilus influenzae, Moraxella catarrhalis or Streptococcus pneumoniae .
• Acute bacterial sinusitis due to Haemophilus influenzae, Moraxella catarrhalis or Streptococcus pneumoniae.
• Community -acquired pneumonia due to Chlamydia pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae or Streptococcus pneumoniae in patients appropriate for oral therapy.
• Pharyngitis/tonsillitis caused by Streptococcus pyogenes as an alternative to first-line therapy in individuals who cannot use first-line therapy.
• Uncomplicated skin and skin structure infections due to Staphylococcus aureus, Streptococcus pyogenes , or Streptococcus agalactiae.
• Urethritis and cervicitis due to Chlamydia trachomatis or Neisseria gonorrhoeae.
• Genital ulcer disease due to Haemophilus ducreyi (chancroid).

CONTRAINDICATIONS:
Azax Film Tablet is contraindicated in patients with known hypersensitivity to azithromycin, erythromycin or any macrolide antibiotic.

DRUG INTERACTIONS and OTHER INTERACTIONS:
Antacids: The AUC of azithromycin was unaffected by co-administration of an antacid containing aluminum and magnesium hydroxide with azithromycin capsules; however, the Cmax was reduced by 24%. Patients should also be cautioned not to take aluminum- and magnesium-containing antacids and Azax Film Tablet simultaneously.

Theophylline: When used in therapeutic doses, azithromycin had a modest effect on the pharmacokinetics of theophylline (intravenous and oral).

Warfarin: Azithromycin did not affect the prothrombin time response to a single dose of warfarin. However, prudent medical practice dictates careful monitoring of prothrombin time in all patients treated with azithromycin and warfarin concomitantly.

Digoxin: Azithromycin causes elevated digoxin concentrations when used concomitantly.

Ergotamine or dihydroergotamine: Acute ergot toxicity characterized by severe peripheral vasospasm and dysesthesia may occur due to concomitant therapy. Patients should also be cautioned not to take ergotamine or dihydroergotamine and Azax Film Tablet simultaneously.

SIDE EFFECTS / ADVERSE EVENTS:
In clinical trials, most of the reported side effects were mild to moderate in severity and were reversible upon discontinuation of the drug. Approximately 0.7% of the patients (adults and pediatric patients) from the 5-day multiple-dose clinical trials discontinued azithromycin therapy because of treatment-related side effects. Most of the side effects leading to discontinuation were related to the gastrointestinal tract, e.g., nausea, vomiting, diarrhea, or abdominal pain. Potentially serious side effects of angioedema and cholestatic jaundice were reported rarely.

Overall, the most common treatment-related side effects in adult patients receiving multiple-dose regimens of azithromycin were related to the gastrointestinal system with diarrhea/loose stools (5%), nausea (3%) and abdominal pain (3%) being the most frequently reported.

No other treatment-related side effects occurred in patients on the multiple-dose regimens of azithromycin with a frequency greater than 1%. Side effects that occurred with a frequency of 1% or less included the following: palpitations, chest pain, dyspepsia, flatulence, vomiting, melena, cholestatic jaundice, monilia, vaginitis, nephritis, dizziness, headache, vertigo, somnolence, fatigue, rash, pruritus, photosensitivity and angioedema.

WARNINGS / PRECAUTIONS:
Serious allergic reactions, including angioedema, anaphylaxis, and dermatologic reactions including Stevens Johnson Syndrome and toxic epidermal necrolysis have been reported rarely in patients on azithromycin therapy. Despite initially successful symptomatic treatment of the allergic symptoms, when symptomatic therapy was discontinued, the allergic symptoms recurred soon thereafter in some patients without further azithromycin exposure. These patients required prolonged periods of observation and symptomatic treatment.

In the treatment of pneumonia, azithromycin has only been shown to be safe and effective in the treatment of community-acquired pneumonia due to Chlamydia pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae or Streptococcus pneumoniae in patients appropriate for oral therapy. Azithromycin should not be used in patients with pneumonia who are judged to be inappropriate for oral therapy because of moderate to severe illness or risk factors such as any of the following: patients with cystic fibrosis, patients with nosocomially acquired infections, patients with known or suspected bacteremia, patients requiring hospitalization, elderly or debilitated patients, or patients with significant underlying health problems that may compromise their ability to respond to their illness (including immunodeficiency or functional asplenia).

Pseudomembranous colitis has been reported with nearly all antibacterial agents and may range in severity from mild to life-threatening. Therefore, it is important to consider this diagnosis in patients who present with diarrhea subsequent to the administration of antibacterial agents.

Because azithromycin is principally eliminated via the liver, caution should be exercised when azithromycin is administered to patients with impaired hepatic function. Due to the limited data in subjects with GFR <10 mL/min, caution should be exercised when prescribing azithromycin in these patients. Long-term studies in animals have not been performed to evaluate carcinogenic potential. Azithromycin has shown no mutagenic potential in standard laboratory tests.

As usual for any kind of antibacterial therapy, it is advisable to examine the patients in order to determine secondary infections due ton non-bacterial origin, including fungi.

Teratogenic Effects:
Pregnancy Category B. There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, azithromycin should be used during pregnancy only if clearly needed.

Nursing Mothers:
It is not known whether azithromycin is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when azithromycin is administered to a nursing woman.

Geriatric Use:
Pharmacokinetic parameters in older volunteers (65-85 years old) were similar to those in younger volunteers (18-40 years old) for the 5-day therapeutic regimen. Dosage adjustment does not appear to be necessary for older patients with normal renal and hepatic function receiving treatment with this dosage regimen.

Pediatric Use:
Pediatric use of azithromycin were studied in children between 6 months and 12 years of age.

Azithromycin, at the recommended dose, should not be relied upon to treat syphilis. Antimicrobial agents used in high doses for short periods of time to treat non-gonococcal urethritis may mask or delay the symptoms of incubating syphilis. All patients with sexually-transmitted urethritis or cervicitis 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. Appropriate culture and susceptibility tests should be performed before treatment to determine the causative organism and its susceptibility to azithromycin.

DOSAGE and ADMINISTRATION:
Adults and teenagers above 16 years of age:

Infection	Recommended Dose/Duration of Therapy
Community-acquired pneumonia (mild severity) Pharyngitis/tonsillitis (second line therapy) Skin/skin structure (uncomplicated)	500 mg as a single dose on Day 1, followed by 250 mg once daily on Days 2 through 5.
Acute bacterial exacerbations of chronic obstructive pulmonary disease (mild to moderate)	500 mg QD × 3 days OR 500 mg as a single dose on Day 1, followed by 250 mg once daily on Days 2 through 5.
Acute bacterial sinusitis	500 mg QD × 3 days
Genital ulcer disease (chancroid)	One single 1 gram dose
Non-gonococcal urethritis and cervicitis	One single 1 gram dose
Gonococcal urethritis and cervicitis	One single 2 gram dose

Azax Film Tablet can be taken with or without food.

OVERDOSE:
Information regarding overdose is insufficient. In order to remove the ingested material gastric lavage may be helpful and then general supportive treatment is advisable.

HOW SUPPLIED:
Azax Film Tablet is presented in blister packages of 3 tablets.