ZITHROMAX

What it is

ZITHROMAX is azithromycin dihydrate, available as a powder for injection for infusion containing 500 mg of azithromycin, providing 100 mg/mL solution following reconstitution. The product is a white to off white lyophilised powder. Azithromycin is the first of a class of antibiotics designated chemically as azalides, a subclass of macrolides, 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

For treatment of adult patients with community acquired pneumonia, the dose is 500 mg as a single daily intravenous dose for at least two days, 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.

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. If an allergic reaction occurs, the drug should be discontinued and appropriate therapy should be instituted. Physicians should be aware that reappearance of the allergic symptoms may occur when symptomatic therapy is discontinued. Antibiotic-associated pseudomembranous colitis has been reported with the use of azithromycin. A toxin produced by Clostridioides difficile appears to be the primary cause. The severity of the colitis may range from mild to life-threatening. Ventricular arrhythmias associated with prolonged QT interval, including ventricular tachycardia and torsades de pointes have been reported with azithromycin. Prescribers should consider the risk of QT prolongation (which can be fatal) when weighing the 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, cardiac arrhythmia or cardiac insufficiency, 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. The data in these observational studies are insufficient to establish or exclude a causal relationship. This potential risk was 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.

Contraindications

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

PBS listing

The powder for oral suspension 200 mg per 5 mL is listed on the PBS with one item, restriction type restricted, ex-manufacturer price A$11.57. The tablet 500 mg is listed with three PBS items, restriction type restricted, ex-manufacturer price A$20.29. The tablet 600 mg is listed with two PBS items, restriction type streamlined, ex-manufacturer price A$55.38.

Regulatory history

ZITHROMAX 500 mg tablet was first registered on the ARTG on 25 February 1997, along with the 250 mg tablet formulation. The 600 mg tablet and 200 mg/5 mL powder for oral suspension were first listed on 5 September 1997. The intravenous formulation, ZITHROMAX IV 500 mg powder for injection, was first listed on the ARTG on 19 November 2002.