AZIBOSTON 500

DOSAGE AND ADMINISTRATION

Dosage

Adults

The total dose of azithromycin is 1500 mg which should be given over 3 days (500 mg once daily) or 5 days (500 mg as a single dose on day 1, followed by 250 mg once daily on days 2 through 5).

In non-gonococcal urethritis and cervicitis and genital ulcer disease (chancroid), the dose is 1000 mg as a single oral dose.

In gonococcal urethritis and cervicitis, one single 2000 mg dose is recommended.

Pediatric patients

Aziboston 500 should only be administered to children weighing more than 45 kg when normal adult dose should be used. For children under 45 kg other pharmaceutical forms of azithromycine, e.g. suspensions, may be used..

Renal impairment

No dose adjustment is necessary in patients with mild to moderate renal impairment (GFR 10 - 80 ml/min). Caution should be exercised when azithromycin is administered to patients with severe renal impairment (GFR < 10 ml/min).

Hepatic impairment

Since azithromycin is metabolised in the liver and excreted in the bile, the drug should not be given to patients suffering from severe liver disease. No studies have been conducted regarding treatment of such patients with azithromycin.

ADMINISTRATION

AZIBOSTON 500 should be given as a single daily dose. The tablets may be taken with food. It is recommeded not to take aluminium- and magnesium-containing antacids and azithromycin simultaneously.

CONTRAINDICATIONS

Patients with known hypersensitivity to azithromycin, erythromycin, any macrolide or ketolide antibiotic.

Patients with a history of cholestatic jaundice/ hepatic dysfunction associated with prior use of azithromycin.

WARNINGS AND PRECAUTIONS

Hypersensitivity

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. Although rare, fatalities have been reported. 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.

Hepatotoxicity

Abnormal liver function, hepatitis, cholestatic jaundice, hepatic necrosis and hepatic failure have been reported, some of which have resulted in death. Discontinue azithromycin immediately if signs and symptoms of hepatitis occur.

Treatment of pneumonia

In the treatment of pneumonia, azithromycin has only been shown to be safe and effective in the treatment of community-acquired pneumonia (CAD) 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).

Clostridium difficile associated diarrhea

Clostridium difficile associated diarrhea (CDAD) has been reported with the use of nearly all antibacterial agents, including azithromycin, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile. 

C. difficile producing toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. Therefore, CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over 2 months after the administration of antibacterial agents. Discontinuation of therapy with azithromycin and the administration of specific treatment for C. difficile should be considered.

Prolongation of the QT interval

Prolonged cardiac repolarization and QT interval, imparting a risk of developing cardiac arrhythmia and torsades de pointes, have been seen in treatment with other macrolides, including azithromycin. Therefore caution is required when treating patients:

+ With congenital or documented QT prolongation

+ Currently receiving treatment with other active substance known to prolong QT interval such as antiarrhythmics of Classes Ia and III, cisapride and terfenadine

+ With electrolyte disturbance, particularly in case of hypokalemia and hypomagnesemia

+ With clinically relevant bradycardia, cardiac arrhythmia or severe cardiac insufficiency.

Elderly patients may be more susceptible to drug-associated effects on the QT interval.

Renal impairment

In patients with severe renal impairment (GFR <10 ml/min) a 33% increase in systemic exposure to azithromycin was observed.

Streptococcal infections

Penicillin is usually the first choice for treatment of pharyngitis/tonsillitis due to Streptococcus pyogenes and also for prophylaxis of acute rheumatic fever. Azithromycin is in general effective against streptococcus in the oropharynx, but no data are available that demonstrate the efficacy of azithromycin in preventing acute rheumatic fever.

Myasthenia gravis

Exacerbations of the symptoms of myasthenia gravis and new onset of myasthenia syndrome have been reported in patients receiving azithromycin therapy.

Superinfection

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

PREGNANCY AND LACTATION

Pregnancy 

Animal reproduction studies have been performed at doses up to moderately maternally toxic dose concentrations. In these studies, no evidence of harm to the foetus due to azithromycin was found. There are, however, 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.

Lactation

There are no data on secretion in breast milk. As many drugs are excreted in human milk, azithromycin should not be used in the treatment of a lactating woman unless the physician feels that the potential benefits justify the potential risks to the infant.

EFFECTS ON ABILITY TO DRIVE AND USE  MACHINES

There is no evidence to suggest that azithromycin may have an effect on a patient's ability to drive or operate machinery.

STORAGE CONDITION

In a dry place, below 30°C, protect from light.

SHELF-LIFE 

36 months from the manufacturing date.