Azithromycin

1. Health Canada Product Monograph — Azithromycin

• Treats mild to moderate infections in adults, including streptococcal pharyngitis or tonsillitis as second-line therapy, acute bacterial exacerbations of chronic obstructive pulmonary disease, community-acquired pneumonia in appropriate outpatients, and uncomplicated skin and soft-tissue infections.
• Also used for certain genitourinary infections such as chlamydial or gonococcal urethritis and cervicitis and chancroid, and at a higher weekly dose to prevent disseminated Mycobacterium avium complex disease in patients with advanced HIV infection.

• Use only if clinically needed and the expected benefit outweighs any potential risk to the fetus.
• Large observational datasets have not consistently linked azithromycin to major birth defects, though some evidence suggests a possible increased miscarriage risk with exposure in early pregnancy.

• Avoid use during breastfeeding unless the expected benefit to the mother outweighs the potential risk to the infant, since azithromycin can accumulate in breast milk with continued therapy.
• Safety has not been studied in infants under 6 months of age.

• Pharmacokinetics are generally similar to younger adults and no dose adjustment is typically needed with normal renal and hepatic function, but elderly patients may be more susceptible to QT-interval prolongation and its associated arrhythmia risk.

• This monograph covers a tablet product whose respiratory and skin infection indications are specified for patients 16 years of age or older; it does not establish pediatric dosing, so verify age-appropriate use and dosing against a pediatric-specific product monograph.

• Adult dosing follows short-course regimens that vary by infection type, such as 500 mg daily for 3 days, or 500 mg on day one followed by 250 mg daily on days two through five; some genitourinary infections use a single higher-dose regimen, and MAC prevention uses 1200 mg once weekly.
• Tablets can be taken with or without food; complete the full prescribed regimen even though courses are often shorter than with other antibiotics.

If overdose is suspected, seek emergency medical attention immediately or contact your regional Poison Control Centre without delay.

• Overdose may cause ototoxicity (effects on hearing).
• Gastrointestinal side effects can occur with overdose.
• Activated charcoal may be given to help remove unabsorbed drug.
• General supportive care is recommended.
• Azithromycin has a fairly wide margin of safety; large cumulative doses given in clinical trials produced effects similar to those seen at normal doses.

• Azithromycin may cause diarrhea or loose stools.
• Nausea may occur.
• Abdominal pain may occur.
• Vomiting may occur.
• Indigestion (dyspepsia) may occur.
• Headache may occur.
• Dizziness may occur.
• Vaginal yeast infection (vaginitis) may occur.
• Skin rash or itching may occur.
• Decreased appetite may occur.

Serious side effects require immediate discussion with the prescriber or emergency care.

• QT-interval prolongation with a risk of serious arrhythmia, including torsade de pointes, can occur.
• Serious allergic reactions such as anaphylaxis and angioedema can occur, and symptoms have recurred in some patients after initial symptomatic treatment was stopped.
• Severe skin reactions such as Stevens-Johnson syndrome, toxic epidermal necrolysis, acute generalized exanthematous pustulosis, and drug reaction with eosinophilia and systemic symptoms can occur.
• Rare but serious liver injury, including hepatitis, cholestatic jaundice, hepatic necrosis, and liver failure, has been reported, some cases fatal.
• Clostridioides difficile-associated diarrhea and colitis can occur, sometimes appearing weeks after finishing treatment.
• Blood disorders such as hemolytic anemia, agranulocytosis, or thrombocytopenia have been reported.
• Exacerbation of myasthenia gravis or new-onset myasthenic syndrome has been reported.
• Serious kidney problems such as interstitial nephritis or acute renal failure have been reported.
• Central nervous system effects such as seizures, aggression, hallucinations, or severe agitation have been reported.
• Hearing loss or other hearing disturbances have been reported.
• Seek immediate medical attention for an irregular or racing heartbeat, fainting, facial or throat swelling, difficulty breathing, yellowing of the skin or eyes, or a severe rash with blistering or peeling skin.

• Use cautiously in patients with hepatic impairment, a history of QT prolongation or relevant cardiac arrhythmia, electrolyte disturbances, or concurrent use of other QT-prolonging medicines.
• Avoid in patients with a known history of myasthenia gravis, as azithromycin has been associated with exacerbations and new-onset myasthenic syndrome; use caution in significant renal impairment.

• Contraindicated in patients with a history of cholestatic jaundice or hepatic dysfunction linked to previous azithromycin use.
• Contraindicated in patients with hypersensitivity to azithromycin, erythromycin, or any macrolide or ketolide antibiotic.

• Ergot derivatives should not be combined with azithromycin because of the risk of acute ergot toxicity.
• Aluminum- or magnesium-containing antacids can reduce azithromycin absorption if taken at the same time and should be spaced apart from a dose.
• Coumarin-type oral anticoagulants such as warfarin may have their effect potentiated by azithromycin, so prothrombin time should be monitored closely.
• Cyclosporine levels can rise significantly when combined with azithromycin, so cyclosporine levels should be monitored and the dose adjusted if needed.
• Nelfinavir can raise azithromycin blood levels, requiring closer monitoring for azithromycin side effects.
• Rifabutin combined with azithromycin has been associated with neutropenia.
• Statins (HMG-CoA reductase inhibitors) combined with azithromycin have been linked to post-marketing reports of rhabdomyolysis.
• Theophylline levels may rise with concurrent azithromycin use, so plasma theophylline should be monitored carefully.
• Astemizole or terfenadine combined with azithromycin has been linked to QT prolongation, palpitations, or arrhythmias.
• Cisapride, hexobarbital, and phenytoin may reach higher blood levels when combined with azithromycin.
• Digoxin and colchicine levels may rise when combined with azithromycin, since it can increase levels of these P-glycoprotein substrate drugs; monitor for toxicity.
• Disopyramide's effect may be increased by azithromycin.
• Other QT-prolonging drugs, including certain antiarrhythmics, antipsychotics, antidepressants, and fluoroquinolones, increase the risk of dangerous heart rhythm effects when combined with azithromycin.

• Tablets can be taken with or without food.

• Take doses at consistent times for the prescribed regimen and complete the full course, even when it is a short multi-day or single-dose regimen.

• Store tablets at controlled room temperature (15 to 30 degrees C).

• Azithromycin is a macrolide antibiotic used for short-course treatment of infections such as bronchitis, pneumonia, skin infections, and certain sexually transmitted infections.
• Take it exactly as prescribed, usually as a short 1- to 5-day course or a single dose depending on the infection, and complete the entire regimen even though it is shorter than many other antibiotics.
• Common side effects include diarrhea, nausea, abdominal pain, headache, and vaginal yeast infection.
• Call your doctor's office right away if you notice an irregular or racing heartbeat, fainting, yellowing of the skin or eyes, facial or throat swelling, or a severe rash, since these can signal a serious reaction.
• Tablets can be taken with or without food, but separate dosing from antacids by at least two hours.
• Store tablets at controlled room temperature.