Azithromycin - Warnings and Precautions

5 WARNINGS AND PRECAUTIONS • Serious (including fatal) allergic and skin reactions: Discontinue azithromycin if reaction occurs. • Hepatotoxicity: Severe, and sometimes fatal, hepatotoxicity has been reported.

Discontinue azithromycin immediately if signs and symptoms of hepatitis occur. • Infantile Hypertrophic Pyloric Stenosis (IHPS): Following the use of azithromycin in neonates (treatment up to 42 days of life), IHPS has been reported.

Direct parents and caregivers to contact their physician if vomiting or irritability with feeding occurs. • Prolongation of QT interval and cases of torsades de pointes have been reported.

This risk which can be fatal should be considered in patients with certain cardiovascular disorders including known QT prolongation or history torsades de pointes , those with proarrhythmic conditions, and with other drugs that prolong the QT interval. • Cardiovascular Death: Some observational studies have shown an approximately two-fold increased short-term potential risk of acute cardiovascular death in adults exposed to azithromycin relative to other antibacterial drugs, including amoxicillin.

Consider balancing this potential risk with treatment benefits when prescribing azithromycin. ( Error! Hyperlink reference not valid. ) • Clostridioides difficile -Associated Diarrhea: Evaluate patients if diarrhea occurs. ( Error! Hyperlink reference not valid. ) • Azithromycin may exacerbate muscle weakness in persons with myasthenia gravis. ( Error! Hyperlink reference not valid. ) 5.1 Hypersensitivity Serious allergic reactions, including angioedema, anaphylaxis, and dermatologic reactions including Acute Generalized Exanthematous Pustulosis (AGEP), Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported in patients on azithromycin therapy [see Contraindications ].

Fatalities have been reported.

Cases of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) have also 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.

The relationship of these episodes to the long tissue half-life of azithromycin and subsequent prolonged exposure to antigen is presently unknown.

If an allergic reaction occurs, the drug should be discontinued and appropriate therapy should be instituted.

Physicians should be aware that allergic symptoms may reappear when symptomatic therapy has been discontinued.

5.2 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.

5.3 Infantile Hypertrophic Pyloric Stenosis (IHPS) Following the use of azithromycin in neonates (treatment up to 42 days of life), IHPS has been reported.

Direct parents and caregivers to contact their physician if vomiting or irritability with feeding occurs.

5.4 QT Prolongation Prolonged cardiac repolarization and QT interval, imparting a risk of developing cardiac arrhythmia and torsades de pointes , have been seen with treatment with macrolides, including azithromycin.

Cases of torsades de pointes have been spontaneously reported during postmarketing surveillance in patients receiving azithromycin.

Providers should consider the risk of QT prolongation which can be fatal when weighing the risks and benefits of azithromycin for at-risk groups including: • patients with known prolongation of the QT interval, a history of torsades de pointes , congenital long QT syndrome, bradyarrhythmias or uncompensated heart failure • patients on drugs known to prolong the QT interval • patients with ongoing proarrhythmic conditions such as uncorrected hypokalemia or hypomagnesemia, clinically significant bradycardia, and in patients receiving Class IA (quinidine, procainamide) or Class III (dofetilide, amiodarone, sotalol) antiarrhythmic agents.

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

5.5 Cardiovascular Death Some observational studies have shown an approximately two-fold increased short-term potential risk of acute cardiovascular death in adults exposed to azithromycin relative to other antibacterial drugs, including amoxicillin.

The five-day cardiovascular mortality observed in these studies ranged from 20 to 400 per million azithromycin treatment courses.

This potential risk was noted to be greater during the first five days of azithromycin use and does not appear to be limited to those patients with preexisting cardiovascular diseases.

The data in these observational studies are insufficient to establish or exclude a causal relationship between acute cardiovascular death and azithromycin use.

Consider balancing this potential risk with treatment benefits when prescribing azithromycin.