Azithromycin

Medical uses

Azithromycin is used to treat many different infections, including:

Bacterial susceptibility

Azithromycin has relatively broad but shallow antibacterial activity. It inhibits some Gram-positive bacteria, some Gram-negative bacteria, and many atypical bacteria.

A strain of gonnorhea reported to be highly resistant to azithromycin was found in the population in 2015. Neisseria gonorrhoeae is normally susceptible to azithromycin, but the drug is not widely used as monotherapy due to a low barrier to resistance development.

Aerobic and facultative Gram-positive microorganisms

Aerobic and facultative Gram-negative microorganisms

Anaerobic microorganisms

Other microorganisms

Pregnancy and breastfeeding

No harm has been found with use during pregnancy. However, there are no adequate well-controlled studies in pregnant women.

Safety of the medication during breastfeeding is unclear. It has been reported that because only low levels are found in breastmilk and the medication has also been used in young children, it is unlikely that breastfed infants would suffer adverse effects. Nevertheless, it is recommended that the drug be used with caution during breastfeeding.

Adverse effects

Most common side 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, dermatologic reactions, and anaphylaxis have been reported. As with all antimicrobial agents, pseudomembranous colitis can occur during and up to several weeks after azithromycin therapy. In the past, physicians cautioned women that antibiotics can reduce the effectiveness of oral contraceptives. However, antibiotics, with the exception of rifampin and rifabutin, do not affect the effectiveness of hormonal contraceptives. This change in advice comes because to date, no evidence conclusively demonstrates antibiotics (other than rifampicin or rifabutin) affect these contraceptives.

Occasionally, patients have developed cholestatic hepatitis or delirium. Accidental intravenous overdose in an infant caused severe heart block, resulting in residual encephalopathy. Clostridium difficile has been reported with use of azithromycin.

In 2013 the 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 QT interval prolongation, low blood levels of potassium or magnesium, a slower than normal heart rate, or those who use certain drugs to treat abnormal heart rhythms.

Mechanism of action

Azithromycin prevents bacteria from growing by interfering with their protein synthesis. It binds to the 50S subunit of the bacterial ribosome, thus inhibiting translation of mRNA. Nucleic acid synthesis is not affected.

Pharmacokinetics

Azithromycin is an acid-stable antibiotic, so it can be taken orally with no need of protection from gastric acids. It is readily absorbed, but absorption is greater on an empty stomach. Time to peak concentration (T_max) in adults is 2.1 to 3.2 hours for oral dosage forms. Due to its high concentration in phagocytes, azithromycin is actively transported to the site of infection. During active phagocytosis, large concentrations are released. The concentration of azithromycin in the tissues can be over 50 times higher than in plasma due to ion trapping and its high lipid solubility. Azithromycin's half-life allows a large single dose to be administered and yet maintain bacteriostatic levels in the infected tissue for several days.

Following a single dose of 500 mg, the apparent terminal elimination half-life of azithromycin is 68 hours. Biliary excretion of azithromycin, predominantly unchanged, is a major route of elimination. Over the course of a week, about 6% of the administered dose appears as unchanged drug in urine.

History

A team of researchers at the pharmaceutical company Pliva—Gabrijela Kobrehel, Gorjana Radobolja-Lazarevski, and Zrinka Tamburašev, led by Dr. Slobodan Đokić—discovered azithromycin in 1980. It was patented 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 under the brand name Sumamed in 1988. Pfizer launched azithromycin under Pliva's license in other markets under the brand name Zithromax in 1991.

Cost

It is available as a generic medication. The wholesale cost is about 0.18 to 2.98 USD per dose. In the United States it is about 33 USD for a course of treatment.

Available forms

Azithromycin is commonly administered in film-coated tablet, capsule, oral suspension, intravenous injection, granules for suspension in sachet, and ophthalmic solution.

Usage

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.

Brands

It is sold under many trade names worldwide and in combinations with cefixime, nimesulide, ambroxol, and with both tinidazole and fluconazole.