A team of researchers at the pharmaceutical company Pliva in Zagreb, Croatia discovered azithromycin in 1980. The company Pliva patented it in 1981. In 1986, Pliva and Pfizer signed a licensing agreement, which gave Pfizer exclusive rights for the sale of azithromycin in Western Europe and the United States. Pliva put its azithromycin on the market in Central and Eastern Europe. Pfizer launched azithromycin under Pliva's license in other markets under the brand name Zithromax in 1991. Patent protection ended in 2005.
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 2021, it was the 97th most commonly prescribed medication in the United States, with more than 7 million prescriptions.
In 2010, azithromycin was the most prescribed antibiotic for outpatients in the US, whereas in Sweden, where outpatient antibiotic use is a third as prevalent, macrolides are only on 3% of prescriptions. In 2017, and 2022, azithromycin was the second most prescribed antibiotic for outpatients in the United States.
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-threatning arrythmias such as torsades de pointes.