Azithromycin, sold under the brand names Zithromax (in oral form) and Azasite (as an eye drop), is an antibiotic medication used to treat several bacterial infections. These include middle ear infections, strep throat, pneumonia, traveler's diarrhea, sexually transmitted infection, and certain other intestinal infections. Along with other medications, it may also be used for malaria. It is administered by mouth, into a vein, or as topical treatment for the eye.
Common side effects include nausea, vomiting, diarrhea and upset stomach. An allergic reaction, such as anaphylaxis, or a type of diarrhea caused by Clostridioides difficile is possible. Azithromycin causes QT prolongation that may cause life-threatening arrhythmias such as torsades de pointes. While some studies claim that no harm has been found with use during pregnancy, more recent studies with mice during late pregnancy has shown adverse effects on embryonic testicular and neural development of prenatal azithromycin exposure (PAzE). However, there need to be more well-controlled studies in pregnant women. Its safety during breastfeeding is not confirmed, but it is likely safe. Azithromycin is an azalide, a type of macrolide antibiotic. It works by decreasing the production of protein, thereby stopping bacterial growth.
Azithromycin was discovered in Croatia in 1980 by the pharmaceutical company Pliva and approved for medical use in 1988. It is on the World Health Organization's List of Essential Medicines. The World Health Organization lists it as an example under "Macrolides and ketolides" in its Critically Important Antimicrobials for Human Medicine (designed to help manage antimicrobial resistance). It is available as a generic medication and is sold under many brand names worldwide. In 2023, it was the 64th most commonly prescribed medication in the United States, with more than 10million prescriptions.
Medical uses Azithromycin is used to treat diverse infections, including: Acute bacterial sinusitis due to H. influenzae, M. catarrhalis, or S. pneumoniae. A 1999 study found Azithromycin to be faster in resolving symptoms as compared to amoxicillin / clavulanate. Acute otitis media caused by H. influenzae, M. catarrhalis or S. pneumoniae. A 2021 study concluded that Azithromycin was comparable to amoxicillin/clavulanate in its treatment and that it was safer and more tolerable in children. Community-acquired pneumonia due to C. pneumoniae, H. influenzae, M. pneumoniae, or S. pneumoniae. Genital ulcer disease (chancroid) in men due to H. ducreyi Pharyngitis or tonsillitis caused by S. pyogenes as an alternative to first-line therapy in individuals who cannot use first-line therapy Prevention and treatment of acute bacterial exacerbations of chronic obstructive pulmonary disease due to H. influenzae, M. catarrhalis, or S. pneumoniae. The benefits of long-term prophylaxis must be weighed on a patient-by-patient basis against the risk of cardiovascular and other adverse effects. Trachoma due to C. trachomatis Uncomplicated skin infections due to S. aureus, S. pyogenes, or S. agalactiae Whooping cough caused by B. pertussis. Scrub typhus caused by Orientia tsutsugamushi.
Bacterial susceptibility Azithromycin has relatively broad but shallow antibacterial activity. It inhibits some Gram-positive bacteria, some Gram-negative bacteria, and many atypical bacteria.
Aerobic and facultative Gram-positive microorganisms Staphylococcus aureus (Methicillin-sensitive only) Streptococcus agalactiae Streptococcus pneumoniae Streptococcus pyogenes
Aerobic and facultative anaerobic Gram-negative microorganisms Bordetella pertussis Haemophilus ducreyi Haemophilus influenzae Legionella pneumophila Moraxella catarrhalis Neisseria gonorrhoeae
Anaerobic microorganisms Peptostreptococcus species Prevotella bivia
Other microorganisms Chlamydia trachomatis Chlamydophila pneumoniae Mycoplasma genitalium Mycoplasma pneumoniae Ureaplasma urealyticum
Pregnancy and breastfeeding While some studies claim that no harm has been found with use during pregnancy, more recent studies with mice during late pregnancy has shown adverse effects on embryonic testicular and neural development of prenatal azithromycin exposure (PAzE). One recent study claims obvious fetus changes were observed under high-dose, mid-pregnancy and multi-course exposure. However, there need to be more well-controlled studies in pregnant women.
The safety of the medication during breastfeeding is unclear. Reports indicate that because only low levels are found in breast milk and the medication has also been used in young children, it is unlikely that breastfed infants would have adverse effects.
Airway diseases Azithromycin has beneficial effects in the treatment of asthma. It possesses antibacterial, antiviral, and anti-inflammatory properties which contribute to its effectiveness. Asthma exacerbations can be caused by chronic neutrophilic inflammation, and azithromycin is known to reduce this type of inflammation due to its immunomodulatory properties. The recommended dosage for controlling asthma exacerbations with azithromycin is either 500 mg or 250 mg taken orally as tablets three times a week. In adults with severe asthma, low-dose azithromycin may be prescribed as an add-on treatment when standard therapies such as inhaled corticosteroids or long-acting β2 agonists are not sufficient. Long-term use of azithromycin in patients with persistent symptomatic asthma aims to decrease the frequency of asthma exacerbations and improve their quality of life. While both its anti-inflammatory and antibacterial effects play important roles in treating asthma, studies suggest that responsiveness to azithromycin therapy depends on individual variations in lung bacterial burden and microbial composition, collectively referred to as the lung microbiome. The richness (diversity) of the lung microbiome has been identified as a key factor in determining the effectiveness of azithromycin treatment. Azithromycin has significant interactions with the patient's microbiome. Long-term use of azithromycin reduces the presence of H. influenzae bacteria in the airways but also increases resistance against macrolide antibiotics. The specific pharmacological mechanisms through which azithromycin interacts with the patient's microbiome remain unknown research continues to explore how changes in microbial composition influence drug efficacy and patient outcomes.
Azithromycin appears to be effective in the treatment of chronic obstructive pulmonary disease through its suppression of inflammatory processes. Azithromycin is potentially useful in sinusitis via this mechanism. Azithromycin is believed to produce its effects through suppressing certain immune responses that may contribute to inflammation of the airways.
Adverse effects Most common adverse effects are diarrhea (5%), nausea (3%), abdominal pain (3%), and vomiting. Fewer than 1% of people stop taking the drug due to side effects. Nervousness, skin reactions, and anaphylaxis have been reported. Clostridioides difficile infection has been reported with use of azithromycin. Azithromycin does not affect the efficacy of birth control unlike some other antibiotics such as rifampin. Hearing loss has been reported.
Occasionally, people have developed cholestatic hepatitis or delirium. Accidental intravenous overdose in an infant caused severe heart block, resulting in residual encephalopathy.
In 2013, the US Food and Drug Administration (FDA) issued a warning that azithromycin "can cause abnormal changes in the electrical activity of the heart that may lead to a potentially fatal irregular heart rhythm". The FDA noted in the warning a 2012 study that found the drug may increase the risk of death, especially in those with heart problems, compared with those on other antibiotics such as amoxicillin or no antibiotic. The warning indicated people with preexisting conditions are at particular risk, such as those with abnormalities in the QT interval, low blood levels of potassium or magnesium, a slower than normal heart rate, or those who use certain drugs to treat abnormal heart rhythms. The warning mentioned that azithromycin causes QT prolongation that may cause life-threatening arrhythmias such as torsades de pointes.
Interactions Colchicine Azithromycin, should not be taken with colchicine as it may lead to colchicine toxicity. Symptoms of colchicine toxicity include gastrointestinal upset, fever, myalgia, pancytopenia, and organ failure.
Drugs metabolized by CYP3A4 CYP3A4 is an enzyme that metabolizes many drugs in the liver. Some drugs can inhibit CYP3A4, which means they reduce its activity and increase the blood levels of the drugs that depend on it for elimination. Such inhibition can lead to adverse effects or drug-drug interactions.
Azithromycin is a member of macrolides that are a class of antibiotics with a cyclic structure with a lactone ring and sugar moieties. Macrolides can inhibit CYP3A4 by a mechanism called mechanism-based inhibition (MBI), which involves the formation of reactive metabolites that bind covalently and irreversibly to the enzyme, rendering it inactive. Mechanism-based inhibition is more serious and long-lasting than reversible inhibition, as it requires the synthesis of new enzyme molecules to restore the activity.
The degree of mechanism-based inhibition by macrolides depends on the size and structure of their lactone ring. Clarithromycin and erythromycin have a 14-membered lactone ring, which is more prone to demethylation by CYP3A4 and subsequent formation of nitrosoalkenes, the reactive metabolites that cause mechanism-based inhibition. Azithromycin, on the other hand, has a 15-membered lactone ring, which is less susceptible to demethylation and nitrosoalkene formation. Therefore, azithromycin is a weak inhibitor of CYP3A4, while clarithromycin and erythromycin are strong inhibitors which increase the area under the curve (AUC) value of co-administered drugs more than five-fold. AUC it is a measure of the drug exposure in the body over time. By inhibiting CYP3A4, macrolide antibitiotics, such as erythromycin and clarithromycin, but not azithromycin, can significantly increase the AUC of the drugs that depend on it for clearance, which can lead to higher risk of adverse effects or drug-drug interactions. Azithromycin stands apart from other macrolide antibiotics because it is a weak inhibitor of CYP3A4, and does not significantly increase AUC value of co-administered drugs.
The difference in CYP3A4 inhibition by macrolides has clinical implications, for example for people who take statins, which are cholesterol-lowering drugs that are mainly metabolized by CYP3A4. Co-administration of clarithromycin or erythromycin with statins can increase the risk of statin-induced myopathy, a condition that causes muscle pain and damage. Azithromycin, however, does not significantly affect the pharmacokinetics of statins and is considered a safer alternative than other macrolide antibiotics.
Pharmacology Mechanism of action Azithromycin prevents bacteria from growing by interfering with their protein synthesis. The antibiotic binds to the large 50S subunit of the bacterial ribosome, thus inhibiting translation of mRNA. Nucleic acid synthesis is not affected.
Pharmacokinetics