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Antibiotic

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 7million prescriptions.

No harm has been found with use during pregnancy. The safety of the medication during breastfeeding is unclear. It was reported 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. 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.

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. Clostridium difficile infection has been reported with use of azithromycin. 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 threatning arrythmias such as torsades de pointes.

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. This 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. 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. Azithromycin's half life allows a large single dose to be administered and yet maintain bacteriostatic levels in the infected tissue for several days. Over the course of a week, about 6% of the administered dose appears as an unchanged drug in urine. The company Pliva patented it in 1981. Patent protection ended in 2005.

Azithromycin is available as a generic medication. Azithromycin is administered in film coated tablet, capsule, oral suspension, intravenous injection, granules for suspension in sachet, and ophthalmic solution. 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.

It is sold under many brand names worldwide including 3 Micina, A Sai Qi, Abacten, Abbott, Acex, Acithroc, Actazith, Agitro, Ai Mi Qi, Amixef, Amizin, Amovin, An Mei Qin, Ao Li Ping, Apotex, Lebanon, Aratro, Aruzilina, Arzomicin, Arzomidol, Asizith, Asomin, Astidal, Astro, Athofix, Athxin, Atizor, Atromizin, Avalon, AZ, AZA, Azacid, Azadose, Azalid, Azalide, AzaSite, Azath, Azatril, Azatril, Azax, Azee, Azeecor, Azeeta, Azelide, Azeltin, Azenil, Azeptin, Azerkym, Azi, Aziact, Azibact, Azibactron, Azibay, Azibect, Azibest, Azibiot, Azibiotic, Azicare, Azicin, Azicine, Aziclass, Azicom, Azicure, Azid, Azidose, Azidraw, Azifam, Azifarm, Azifast, Azifine, Azigen, Azigram, Azigreat, Azikare, Azilide, Azilife, Azilip, Azilup, Azimac, Azimax, Azimed, Azimepha, Azimex, Azimit, Azimix, Azimon, Azimore, Azimycin, Azimycine, Azin, Azindamon, Azinew, Azinex, Azinif, Azinil, Azintra, Aziom, Azipar, Aziped, Aziphar, Azipin, Azipro, Aziprome, Aziquilab, Azirace, Aziram, Aziresp, Aziride, Azirol, Azirom, Azirox, Azirute, Azirutec, Aziset, Azisis, Azison, Azissel, Aziswift, Azit, Azita, Azitam, Azitex, Azith, Azithral, Azithrin, Azithro, Azithrobeta, Azithrocin, Azithrocine, Azithromax, Azithromed, Azithromicina, Azithromycin, Azithromycine, Azithromycinum, Azithrovid, Azitic, Azitive, Azitome, Azitrac, Azitral, Azitrax, Azitredil, Azitrex, Azitrim, Azitrin, Azitrix, Azitro, Azitrobac, Azitrocin, Azitroerre, Azitrogal, Azitrolabsa, Azitrolid, Azitrolit, Azitrom, Azitromac, Azitromax, Azitromek, Azitromicin, Azitromicina, Azitromycin, Azitromycine, Azitrona, Azitropharma, Azitroteg, Azitrox, Azitsa, Azitus, Azivar, Azivirus, Aziwill, Aziwok, Azix, Azizox, Azmycin, Azo, Azobat, Azocin, Azoget, Azoheim, Azoksin, Azom, Azomac, Azomax, Azomex, Azomycin, Azomyne, Azores, Azorox, Azostar, Azot, Azoxin, Azras, Azro, Azrocin, Azrolid, Azromax, Azrosin, Aztin, Aztrin, Aztro, Aztrogecin, Azvig, Azycin, Azycyna, Azydrop, Azypin, Azytact, Azytan, Azyter, Azyter, Azyth, Azywell, Azza, Ba Qi, Bactizith, Bactrazol, Bai Ke De Rui, Batif, Bazyt, Bezanin, Bin Qi, Binozyt, BinQi, Biocine, Biozit, Bo Kang, Canbiox, Cetaxim, Charyn, Chen Yu, Cinalid, Cinetrin, Clamelle, Clearsing, Corzi, Cozith, Cronopen, Curazith, Delzosin, Dentazit, Disithrom, Doromax, Doyle, Elzithro, Eniz, Epica, Ethrimax, Ezith, Fabodrox, Fabramicina, Feng Da Qi, Figothrom, Floctil, Flumax, Fu Qi Hua Yuan, Fu Rui Xin, Fuqixing, Fuxin Hai Xin Pharm, Geozif, Geozit, Gitro, Goldamycin, Gramac, Gramokil, Hemomicin, Hemomycin, I Thro, Ilozin, Imexa, Inedol, Infectomycin, Iramicina, Itha, Jin Nuo, Jin Pai Qi, Jinbo, Jun Jie, Jun Wei Qing, Kai Qi, Kang Li Jian, Kang Qi, Katrozax, Ke Lin Da, Ke Yan Li, Koptin, Kuai Yu, L Thro, Laz, Legar, Lg Thral, Li Ke Si, Li Li Xing, Li Qi, Lin Bi, Lipuqi, Lipuxin, Lizhu Qile, Loromycin, Lu Jia Kang, Luo Bei Er, Luo Qi, Maazi, Macroazi, Macromax, Macrozit, Maczith, Makromicin, Maxmor, Mazit, Mazitrom, Medimacrol, Meithromax, Mezatrin, Ming Qi Xin, Misultina, Na Qi, Nadymax, Naxocina, Neblic, Nemezid, Neofarmiz, Nifostin, Nobaxin, Nokar, Novatrex, Novozithron, Novozitron, Nurox, Odaz, Odazyth, Onzet, Oranex, Oranex, Ordipha, Orobiotic, Pai Fen, Pai Fu, Paiqi, Pediazith, Portex, Pu He, Pu Le Qi, Pu Yang, Qi Gu Mei, Qi Mai Xing, Qi Nuo, Qi Tai, Qi Xian, Qili, Qiyue, Rarpezit, Razimax, Razithro, Rezan, Ribotrex, Ribozith, Ricilina, Rizcin, Romycin, Rothin (Rakaposhi), Rozalid, Rozith, Ru Shuang Qi, Rui Qi, Rui Qi Lin, Rulide, Sai Jin Sha, Sai Le Xin, Sai Qi, Selimax, Sheng Nuo Ling, Shu Luo Kang, Simpli 3, Sisocin, Sitrox, Sohomac, Stromac, Su Shuang, Sumamed, Sumamox, Tailite, Talcilina, Tanezox, Te Li Xin, Tetris, Texis, Thoraxx, Throin, Thromaxin, Tong Tai Qi Li, Topt, Toraseptol, Tremac, Trex, Tri Azit, Triamid, Tridosil, Trimelin, Tritab, Tromiatlas, Tromix, Trozamil, Trozin, Trozocina, Trulimax, Tuoqi, Udox, Ultreon, Ultreon, Vectocilina, Vinzam, Visag, Vizicin, Wei Li Qinga, Wei Lu De, Wei Zong, Weihong, Xerexomair, Xi Le Xin, Xi Mei, Xin Da Kang, Xin Pu Rui, Xithrone, Ya Rui, Yan Sha, Yanic, Yi Nuo Da, Yi Song, Yi Xina, Yin Pei Kang, Yong Qi, You Ni Ke, Yu Qi, Z 3, Z PAK, Zady, Zaiqi, Zaret, Zarom, Zathrin, Zedbac, Zeemide, Zenith, Zentavion, Zetamac, Zetamax, Zeto, Zetron, Zevlen, Zibramax, Zicho, Zigilex, Zikti, Zimacrol, Zimax, Zimicina, Zindel, Zinfect, Zirom, Zisrocin, Zistic, Zit Od, Zitab, Zitax, Zithrax, Zithrin, Zithro Due, Zithrobest, Zithrodose, Zithrogen, Zithrokan, Zithrolide, Zithromax, Zithrome, Zithromed, Zithroplus, Zithrotel, Zithrox, Zithroxyn, Zithtec, Zitinn, Zitmac, Zitraval, Zitrax, Zitrex, Zitric, Zitrim, Zitrobid, Zitrobiotic, Zithrolect, Zitrocin, Zitrocin, Zitrogram, Zitrolab, Zitromax, Zitroneo, Zitrotek, Ziyoazi, Zmax, Zocin, Zomax, Zotax, Zycin, and Zythrocin. Despite the efficiency of treating rosacea with azithromycin, the exact mechanism of why azithromycin is effective in treating rosacea are not completely understood. It is unclear whether its antibacterial or immunomodulatory properties or a combination of both mechanisms contribute to its efficacy. Azithromycin may prevent mast cell degranulation and thus can suppress inflammation of dorsal root ganglia through various signaling pathways such as decreased numbers of CD4+ T cells which are particularly relevant since they mediate the response of hair follicle antigens. Inflammation in rosacea is thought to be associated with increased production of reactive oxygen species (ROS) by inflammatory cells. The ability of azithromycin to decrease ROS production can help reduce oxidative stress and inflammation, but this remains speculation. Despite early evidence showing azithromycin slowed down coronavirus multiplication in laboratory settings, further research indicates it to be ineffective as a treatment for COVID 19 in humans. Azithromycin in conjunction with of chloroquine or hydroxychloroquine has been associated with deleterious outcomes in COVID 19 patients, including drug induced QT prolongation. After a large scale trial showed no benefit of using azithromycin in treating COVID 19, the UK's National Institute for Health and Care Excellence (NICE) updated its guidance and no longer recommends the medication for COVID 19. Azithromycin therapy in cystic fibrosis patients yields a modest respiratory function improvement, reduces exacerbation risk, and extends time to exacerbation up to six months; still, long term efficacy data is a subject of ongoing research. Potential benefits of azithromycin therapy is azithromycin's good safety profile, minimal treatment burden, and cost effectiveness, but the drawbacks are gastrointestinal side effects with weekly dosing, which are ameliorated by a split dose regimen. The potential role of azithromycin in inhibiting the autophagic destruction of non tuberculous mycobacteria (NTM) within macrophages has garnered significant attention. This mechanism may contribute to the observed correlation between long term macrolide monotherapy and an increased risk of NTM infection and the emergence of macrolide resistant strains. Azithromycin's interference with autophagy could potentially predispose patients with cystic fibrosis to mycobacterial infections. Despite repeated refutations of a direct association between azithromycin use and NTM infection, there remains a high level of concern regarding the potential for the development of NTM strains resistant to macrolides. Azithromycin has been shown to be an effective preventive measure against many postpartum infections in mothers following planned vaginal births; still, its impact on neonatal outcomes remains inconclusive and is the subject of ongoing research.