AZITHROMYCIN

What it is

AZITHROMYCIN MEDSURGE is a powder for injection for infusion containing 500 mg of azithromycin dihydrate, providing 100 mg/mL solution following reconstitution. It is presented as a white to off-white lyophilised powder. Azithromycin works by inhibiting protein synthesis in bacteria by binding to the 50S ribosomal subunit and preventing translocation of peptides. Azithromycin is the first of a class of antibiotics designated chemically as azalides, a subclass of macrolides, and is chemically derived by insertion of a nitrogen atom into the lactone ring of erythromycin A.

Approved indications

— Community acquired pneumonia caused by susceptible organisms in patients who require initial intravenous therapy.

Dosing overview

The dose of AZITHROMYCIN MEDSURGE for the treatment of adult patients with community acquired pneumonia is 500 mg as a single daily intravenous dose for at least two days. Intravenous therapy should be followed by oral therapy of 500 mg azithromycin administered as a single daily dose to complete a 7 to 10 day course of therapy. The infusate concentration and rate of infusion should be either 1 mg/mL over 3 hours or 2 mg/mL over 1 hour. No dose adjustment is necessary in elderly patients requiring azithromycin therapy. No dose adjustment is needed in patients with glomerular filtration rate 10–80 mL/min. Caution should be exercised when azithromycin is administered to patients with glomerular filtration rate less than 10 mL/min. The same dosage as in patients with normal hepatic function may be used in patients with mild to moderate hepatic impairment.

Key safety warnings

Rare, serious allergic reactions, including angioedema and anaphylaxis (rarely fatal); dermatologic reactions including acute generalised exanthematous pustulosis, Stevens-Johnson syndrome, toxic epidermal necrolysis (rarely fatal); and drug reaction with eosinophilia and systemic symptoms have been reported in patients on azithromycin therapy. Despite initially successful symptomatic treatment of allergic symptoms, allergic symptoms have recurred in some patients when symptomatic therapy was discontinued without further azithromycin exposure, requiring prolonged periods of observation and symptomatic treatment, with the relationship to the long tissue half-life of azithromycin and subsequent prolonged exposure to antigen unknown. Antibiotic-associated pseudomembranous colitis has been reported with azithromycin use, with a toxin produced by Clostridioides difficile appearing to be the primary cause, with severity ranging from mild to life-threatening and occurring up to several weeks after cessation of antibiotic therapy. There has been limited assessment of azithromycin's potential to prolong the QT interval, with no significant electrocardiogram abnormalities reported in clinical studies, although ventricular arrhythmias associated with prolonged QT interval, including ventricular tachycardia and torsades de pointes, have been reported with macrolide products including azithromycin. Prescribers should consider the risk of QT prolongation when weighing risks and benefits for at-risk groups including patients predisposed to QT interval prolongation, patients taking other medications known to prolong the QT interval, patients with electrolyte disturbance, patients with clinically relevant bradycardia or cardiac arrhythmia, and elderly patients. Some observational studies have shown an approximately two-fold increased short-term potential rare risk of acute cardiovascular death in adults exposed to azithromycin relative to other antibacterial drugs, although data are insufficient to establish or exclude a causal relationship, with this potential risk noted to be greater during the first five days of azithromycin use. Exacerbations of the symptoms of myasthenia gravis have been reported in patients receiving azithromycin therapy. Abnormal liver function, hepatitis, cholestatic jaundice, hepatic necrosis, and hepatic failure have been reported, some of which have resulted in death.

Contraindications

Azithromycin is contraindicated in patients with known hypersensitivity to azithromycin, erythromycin, any other macrolide or ketolide antibiotic, or to any of the excipients.

Regulatory history

AZITHROMYCIN MEDSURGE was first listed on the Australian Register of Therapeutic Goods on 31 January 2024 as ARTG 403712, under licence category RE.