Azithromycin

Azithromycin is an antibiotic used for the treatment of a number of bacterial infections.[2] This includes middle ear infections, strep throat, pneumonia, traveler's diarrhea, and certain other intestinal infections.[2] It can also be used for a number of sexually transmitted infections, including chlamydia and gonorrhea infections.[2] Along with other medications, it may also be used for malaria.[2] It can be taken by mouth or intravenously with doses once per day.[2]

Azithromycin
Clinical data
Trade namesZithromax, Azithrocin, others[1]
Other names9-deoxy-9α-aza-9α-methyl-9α-homoerythromycin A
AHFS/Drugs.comMonograph
MedlinePlusa697037
License data
Pregnancy
category
  • AU: B1
  • US: B (No risk in non-human studies)
    Routes of
    administration    		By mouth (capsule, tablet or suspension), intravenous, eye drop
    Drug classMacrolide antibiotic
    ATC code
    Legal status
    Legal status
    Pharmacokinetic data
    Bioavailability38% for 250 mg capsules
    MetabolismLiver
    Elimination half-life11–14 h (single dose) 68 h (multiple dosing)
    ExcretionBiliary, kidney (4.5%)
    Identifiers
    CAS Number
    PubChem CID
    IUPHAR/BPS
    DrugBank
    ChemSpider
    UNII
    KEGG
    ChEBI
    ChEMBL
    NIAID ChemDB
    CompTox Dashboard (EPA)
    ECHA InfoCard100.126.551
    Chemical and physical data
    FormulaC38H72N2O12
    Molar mass748.984 g·mol−1 g·mol−1
    3D model (JSmol)
      (verify)

    Common side effects include nausea, vomiting, diarrhea and upset stomach.[2] An allergic reaction, such as anaphylaxis, QT prolongation, or a type of diarrhea caused by Clostridium difficile is possible.[2] No harm has been found with its use during pregnancy.[2] Its safety during breastfeeding is not confirmed, but it is likely safe.[3] Azithromycin is an azalide, a type of macrolide antibiotic.[2] It works by decreasing the production of protein, thereby stopping bacterial growth.[2]

    Azithromycin was discovered in 1980 and approved for medical use in 1988.[4][5] It is on the World Health Organization's List of Essential Medicines, which lists the most effective and safe medicines needed in a health system.[6] It is available as a generic medication[7] and is sold under many trade names worldwide.[1] The wholesale cost in the developing world is about US$0.18 to US$2.98 per dose.[8] In the United States, it is about US$4 for a course of treatment as of 2018.[9] In 2016, it was the 49th most prescribed medication in the United States with more than 15 million prescriptions.[10]

    Medical uses

    Azithromycin is used to treat many different infections, including:

    • 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.[11]
    • Community-acquired pneumonia due to C. pneumoniae, H. influenzae, M. pneumoniae, or S. pneumoniae[12]
    • Uncomplicated skin infections due to S. aureus, S. pyogenes, or S. agalactiae
    • Urethritis and cervicitis due to C. trachomatis or N. gonorrhoeae. In combination with ceftriaxone, azithromycin is part of the United States Centers for Disease Control-recommended regimen for the treatment of gonorrhea. Azithromycin is active as monotherapy in most cases, but the combination with ceftriaxone is recommended based on the relatively low barrier to resistance development in gonococci and due to frequent co-infection with C. trachomatis and N. gonorrhoeae.[13]
    • Trachoma due to C. trachomatis[14]
    • Genital ulcer disease (chancroid) in men due to H. ducrey
    • Acute bacterial sinusitis due to H. influenzae, M. catarrhalis, or S. pneumoniae. Other agents, such as amoxicillin/clavulanate are generally preferred, however.[15][16]
    • Acute otitis media caused by H. influenzae, M. catarrhalis or S. pneumoniae. Azithromycin is not, however, a first-line agent for this condition. Amoxicillin or another beta lactam antibiotic is generally preferred.[17]
    • Pharyngitis or tonsillitis caused by S. pyogenes as an alternative to first-line therapy in individuals who cannot use first-line therapy[18]

    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 gonorrhea reported to be highly resistant to azithromycin was found in the population in 2015. Neisseria gonorrhoeae is normally susceptible to azithromycin,[19] but the drug is not widely used as monotherapy due to a low barrier to resistance development.[13] Extensive use of azithromycin has resulted in growing Streptococcus pneumoniae resistance.[20]

    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.[2] However, there are no adequate well-controlled studies in pregnant women.[21]

    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.[3] Nevertheless, it is recommended that the drug be used with caution during breastfeeding.[2]

    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.[22] Clostridium difficile infection has been reported with use of azithromycin.[2] Azithromycin does not affect the efficacy of birth control unlike some other antibiotics such as rifampin. Hearing loss has been reported.[23]

    Occasionally, patients have developed cholestatic hepatitis or delirium. Accidental intravenous overdose in an infant caused severe heart block, resulting in residual encephalopathy.[24][25]

    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.[26][27][28]

    Pharmacology

    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.[21]

    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 (Tmax) 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.[29]

    Following a single dose of 500 mg, the apparent terminal elimination half-life of azithromycin is 68 hours.[29] 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 in Croatia, Yugoslavia — 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.[30] Patent protection ended in 2005.[31]

    Society and culture
    Zithromax (azithromycin) 250 mg tablets (CA)

    Cost

    It is available as a generic medication.[7] The wholesale cost is about US$0.18 to US$2.98 per dose.[8] In the United States it is about US$4 for a course of treatment as of 2018.[9] In India it is about US$1.7 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.[1]

    Usage

    In 2010, azithromycin was the most prescribed antibiotic for outpatients in the US,[32] whereas in Sweden where outpatient antibiotic use is a third as prevalent, macrolides are only on 3% of prescriptions.[33]

    Brand name listings

    It is sold under many trade 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.[1]

    It is sold as a combination drug with cefixime as Anex-AZ, Azifine-C, Aziter-C, Brutacef-AZ, Cezee, Fixicom-AZ, Emtax-AZ, Olcefone-AZ, Starfix-AZ, Zeph-AZ, Zicin-CX, and Zifi-AZ.[1]

    It is also sold as a combination drug with nimesulide as Zitroflam; in a combination with tinidazole and fluconazole as Trivafluc, and in a combination with ambroxol as Zathrin-AX, Laz-AX and Azro-AM.[1]

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    13. "Gonococcal Infections - 2015 STD Treatment Guidelines". Archived from the original on 2016-03-01.
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    15. Rosenfeld RM, Piccirillo JF, Chandrasekhar SS, Brook I, Ashok Kumar K, Kramper M, Orlandi RR, Palmer JN, Patel ZM, Peters A, Walsh SA, Corrigan MD (2015). "Clinical practice guideline (update): adult sinusitis". Otolaryngol Head Neck Surg. 152 (2 Suppl): S1–S39. doi:10.1177/0194599815572097. PMID 25832968.
    16. Hauk L (2014). "AAP releases guideline on diagnosis and management of acute bacterial sinusitis in children one to 18 years of age". Am Fam Physician. 89 (8): 676–81. PMID 24784128.
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    18. Randel A (2013). "IDSA Updates Guideline for Managing Group A Streptococcal Pharyngitis". Am Fam Physician. 88 (5): 338–40. PMID 24010402.
    19. The Guardian newspaper: 'Super-gonorrhoea' outbreak in Leeds, 18 September 2015 Archived 18 September 2015 at the Wayback Machine
    20. Lippincott Illustrated Reviews : Pharmacology Sixth Edition. p. 506.
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    24. Tilelli, John A.; Smith, Kathleen M.; Pettignano, Robert (2006). "Life-Threatening Bradyarrhythmia After Massive Azithromycin Overdose". Pharmacotherapy. 26 (1): 147–50. doi:10.1592/phco.2006.26.1.147. PMID 16506357.
    25. Baselt, R. (2008). Disposition of Toxic Drugs and Chemicals in Man (8th ed.). Foster City, CA: Biomedical Publications. pp. 132–133.
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