Azithromycin
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| Systematic (IUPAC) name | |
| (2R,3S,4R,5R,8R,10R,11R,12S,13S,14R)-2-ethyl-3,4,10-trihydroxy-3,5,6,8,10,12,14-heptamethyl-15-oxo- 11-{[3,4,6-trideoxy-3-(dimethylamino)-β-D-xylo-]oxy}-1-oxa-6-azacyclopentadec-13-yl 2,6-dideoxy-3-C-methyl-3-O-methyl-α-L-ribo-hexopyranoside | |
| Clinical data | |
| Trade names | Zithromax, Azithrocin, Azin |
| AHFS/Drugs.com | monograph |
| MedlinePlus | a697037 |
| Licence data | US FDA:link |
| Pregnancy cat. | B1 (AU) B (US) |
| Legal status | ℞-only (US) |
| Routes | Oral (capsule or suspension), intravenous, ophthalmic |
| Pharmacokinetic data | |
| Bioavailability | 38% for 250 mg capsules |
| Metabolism | Hepatic |
| Half-life | 11–14 h (single dose)
68 h (multiple dosing) |
| Excretion | Biliary, renal (4.5%) |
| Identifiers | |
| CAS number | 83905-01-5  |
| ATC code | J01FA10 S01AA26 |
| PubChem | CID 55185 |
| DrugBank | DB00207 |
| ChemSpider | 10482163 |
| UNII | J2KLZ20U1M |
| KEGG | D07486 |
| ChEBI | CHEBI:2955 |
| ChEMBL | CHEMBL529 |
| NIAID ChemDB | 007311 |
| Synonyms | 9-deoxy-9a-aza-9a-methyl-9a-homoerythromycin A |
| Chemical data | |
| Formula | C38H72N2O12 |
| Mol. mass | 748.984 g·mol−1 |
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Azithromycin (Zithromax, Azithrocin, Zmax, Azin)[1] is an azalide, a subclass of macrolide antibiotics. Azithromycin is one of the world's best-selling antibiotics.[2][not in citation given (See discussion.)] It is derived from erythromycin, with a methyl-substituted nitrogen atom incorporated into the lactone ring, thus making the lactone ring 15-membered.
Azithromycin is used to treat or prevent certain bacterial infections, most often those causing middle ear infections, strep throat, pneumonia, typhoid, bronchitis and sinusitis. In recent years, it has been used primarily to prevent bacterial infections in infants and those with weaker immune systems. It is also effective against certain sexually transmitted infections, such as nongonococcal urethritis, chlamydia, and cervicitis. Recent studies have indicated it also to be effective against late-onset asthma, but these findings are controversial and not widely accepted.[3][4]
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Medical uses[edit]
Azithromycin is used to treat many different infections, including acute otitis media, nonstreptococcal bacterial pharyngitis, gastrointestinal infections such as traveler's diarrhea, respiratory tract infections such as pneumonia, cellulitis, babesiosis, Bartonella infection, chancroid cholera, donovanosis, leptospirosis, Lyme disease, malaria, Mycobacterium avium complex disease, Neisseria meningitis, pelvic inflammatory disease, pertussis, scrub typhus, toxoplasmosis, and salmonellosis.[5] It is used to prevent bacterial endocarditis and some sexually transmitted infections including those from unprotected sex or sexual assault.[5] It is also effective against localized dental infections, uncomplicated skin and skin structure infections, urethritis and cervicitis and also genital ulcer disease.
It has a similar antimicrobial spectrum as erythromycin, but is more effective against certain Gram-negative bacteria, in particular, Haemophilus influenzae (although it would not be the first choice of treatment in this infection).[6] Azithromycin resistance has been described[7] and is endemic in many areas. Long-term use in treating Staphylococcus aureus infections with azithromycin may increase bacterial resistance to this and other macrolide antibiotics.[8]
Azithromycin has been shown to be effective against malaria when used in combination with artesunate or quinine; the optimal dose for this is not yet known.[9]
Adverse effects[edit]
Most common side effects are gastrointestinal: diarrhea (5%), nausea (3%), abdominal pain (3%), and vomiting. Fewer than 1% of patients 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, new research shows that antibiotics, with the exception of rifampin and rifabutin, do not affect the effectiveness of hormonal contraceptives, such as the pill, patch or vaginal ring.[10] This change in advice comes because to date there is no evidence which conclusively demonstrates that antibiotics (other than rifampicin or rifabutin) affect these contraceptives.
Azithromycin suspension has an objectionable taste, so can be difficult to administer to young children, i.e., 2–5 years, who may spit it out.[11]
Occasionally, patients have developed cholestatic hepatitis or delirium. Accidental intravenous overdosage in an infant caused severe heart block, resulting in residual encephalopathy.[12][13]
In 2013, the FDA issued a warning saying 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 released by the New England Journal of Medicine 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 that people with preexistent 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 of certain drugs used to treat abnormal heart rhythms, or arrhythmias.[14][15][16][17][18]
Mechanism of action[edit]
Azithromycin prevents bacteria from growing by interfering with their protein synthesis. It binds to the 50S subunit of the bacterial ribosome, and thus inhibits translation of mRNA. Nucleic acid synthesis is not affected.[19]
Spectrum of bacterial susceptibility and resistance[edit]
Chlamydia pneumoniae, Chlamydia trachomatis, Eikenella corrodens, Escherichia coli, Haemophilus influenzae, Moraxella catarrhalis, Mycobacterium chelonae, Mycoplasma fermentans, Neisseria gonorrhoeae and Ureaplasma urealyticum are generally susceptible to azithromycin dihydrate, while Pseudomonas aeruginosa, Staphylococcus aureus, and Streptococcus pyogenes are resistant to azithromycin dihydrate. Furthermore, some Brevibacterium spp., Corynebacterium amycolatum, Haemophilus influenzae and Mycobacterium abscessus have developed resistance to azithromycin dihydrate to varying degrees.[20]
Pharmacokinetics[edit]
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This section does not cite any references or sources. (May 2012) |
Unlike erythromycin, azithromycin is acid-stable, so it can be taken orally with no need of protection from gastric acids. It is readily absorbed, but its absorption is greater on an empty stomach. Time to peak concentration in adults is 2.1 to 3.2 hours for oral dosage forms and one to two hours after a dose. 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,[citation needed] due to ion trapping and its high lipid solubility (volume of distribution is too high).
Azithromycin's half-life allows a large single dose to be administered and yet maintain bacteriostatic levels in the infected tissue for several days.
Metabolism[edit]
According to Davis' Drug Guide for Nurses, following a single 500 mg dose, the half-life of azithromycin is 11–14 h. The longer half-life of 68 h is achieved only when multiple doses are consumed. Biliary excretion of azithromycin, predominantly unchanged, is a major route of elimination. Over the course of a week, approximately 6% of the administered dose appears as unchanged drug in urine.
Etymology[edit]
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This section does not cite any references or sources. (May 2012) |
The name Azithromycin is derived from the azane-substituent and erythromycin.
History[edit]
A team of researchers at the Yugoslav (now Croatian) 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 of Sumamed in 1988. Pfizer launched azithromycin under Pliva's license in other markets under the brand name Zithromax in 1991.[21] Pfizer's exclusive rights have since lapsed and Pliva-manufactured azithromycin is also marketed in the United States by generic drug maker Teva Pharmaceuticals (which now owns Pliva).
After several years, the U.S. Food and Drug Administration (FDA) approved AzaSite, an ophthalmic formulation of azithromycin, for the treatment of eye infections. AzaSite is marketed in the U.S. and Canada by Inspire Pharmaceuticals, a wholly owned subsidiary of Merck.[22]
Available forms[edit]
Azithromycin is commonly administered in tablet or oral suspension (a one-dose version was made available in 2005). It is also available for intravenous injection and in a 1% ophthalmic solution. Tablets come in doses of 250 mg and 500 mg. Oral suspension comes in strengths of 100 mg/5 ml and 200 mg/5 ml. The 250-mg tablets are often dispensed in packages of six and commonly referred to as a "Z-Pak," whereas the 500-mg tablets are commonly available commercially in a pack of three tablets, or "Tri-Pak," intended as a three-day treatment. A common dose of oral azithromycin therapy consists of a "double dose" of medication on the first day of treatment and subsequent treatment for four or five additional days. With the "Z-Pak", this means two 250-mg tablets (a total of 500 mg) on the first day and one 250-mg tablet once daily for the next four days.
Pfizer brand name, i.e. Zithromax, azithromycin tablets are mottled pink, unscored, film-coated, modified oval-shaped tablets containing azithromycin monohydrate and the following inactive ingredients: butylated hydroxytoluene, calcium phosphate, carmine, colloidal silicon dioxide, FD&C red # 40 lake, FD&C yellow # 6 lake, hypromellose (2910, 15cP), lactose monohydrate, magnesium stearate, pregelatinized starch, sodium lauryl sulfate, talc, titanium dioxide, and triacetin. In Colombia (South America), it is marketed under the name Zaret from Laboratorios Bussié. In Bangladesh, it is marketed under the name Azithin from Chemist Laboratories Ltd., and Penalox from Rephco Pharmaceuticals Limited. In Canada azithromycin is marketed by Sandoz.
References[edit]
- ^ [1][dead link]
- ^ "Azythromycin: A world best-selling antibiotic - Pliva". Case Studies. World Intellectual Property Organization (WIPO).
- ^ Hahn DL (October 1995). "Treatment of Chlamydia pneumoniae infection in adult asthma: a before-after trial". The Journal of Family Practice 41 (4): 345–51. PMID 7561707.
- ^ Klausner JD, Passaro D, Rosenberg J, Thacker WL, Talkington DF, Werner SB, Vugia DJ (January 1998). "Enhanced control of an outbreak of Mycoplasma pneumoniae pneumonia with azithromycin prophylaxis". Journal of Infectious Diseases 177 (1): 161–6. doi:10.1086/513818. PMID 9419183.
- ^ a b monograph
- ^ Paul Auwaerter, M.D. (2011-02-11). "Johns Hopkins Guides: Haemophilus species". Hopkinsguides.com. Retrieved 2013-01-06.
- ^ Chisholm SA, Neal TJ, Alawattegama AB, Birley HD, Howe RA, Ison CA (August 2009). "Emergence of high-level azithromycin resistance in Neisseria gonorrhoeae in England and Wales". Journal of Antimicrobial Chemotherapy 64 (2): 353–8. doi:10.1093/jac/dkp188. PMID 19468025.
- ^ Hansen, CR; Pressler T, Hoiby N, Johansen HK (January 2009). "Long-term, low-dose azithromycin treatment reduces the incidence but increases macrolide resistance in Staphylococcus aureus in Danish CF patients". Journal of Cystic Fibrosis 8 (1): 58–62. doi:10.1016/j.jcf.2008.09.001. PMID 18849202.
- ^ Noedl, H.; Krudsood, S.; Chalermratana, K. et al. (November 2006). "Azithromycin combination therapy with artesunate or quinine for the treatment of uncomplicated Plasmodium falciparum malaria in adults: a randomized, phase 2 clinical trial in Thailand". Clinical Infectious Diseases 43 (10): 1264–71. doi:10.1086/508175. PMID 17051490.
- ^ Toh, S.; Mitchell, AA; Anderka, M; de Jong-van den Berg, LT & Hernandez-Diaz, S. (2011). "Antibiotics and oral contraceptive failure- a case-crossover study". Contraception 83 (5): 418–25. PMID 21477683.
- ^ "How to Give a Child Azithromycin". eHow.co.uk. Retrieved 2013-01-06.
- ^ Tilelli, J. A.; Smith, K. M.; Pettignano, R. (2006). "Life-threatening bradyarrhythmia after massive azithromycin overdose". Pharmacotherapy 26 (1): 147–150. PMID 16506357.
- ^ Baselt, R. (2008). Disposition of Toxic Drugs and Chemicals in Man (8th ed.). Foster City, CA: Biomedical Publications. pp. 132–133.
- ^ Denise Grady (May 16, 2012). "Popular Antibiotic May Raise Risk of Sudden Death". The New York Times. Retrieved May 18, 2012.
- ^ Ray WA, Murray KT, Hall K, Arbogast PG, Stein CM (May 2012). "Azithromycin and the risk of cardiovascular death". N. Engl. K. Bel. 366 (20): 1881–90. doi:10.1056/NEJMoa1003833. PMID 22591294.
- ^ FDA Statement regarding azithromycin (Zithromax, Azithrocin) and the risk of cardiovascular death
- ^ Zithromax (azithromycin): FDA Statement on risk of cardiovascular death
- ^ FDA Drug Safety Communication: Azithromycin (Zithromax or Zmax) and the risk of potentially fatal heart rhythms
- ^ "azithromycin (Zithromax, Zmax, Z-Pak) - Side Effects, Drug Interactions". MedicineNet. Retrieved 2013-01-06.
- ^ "Azithromycin Dihydrate spectrum of bacterial susceptibility and Resistance". Retrieved 1 May 2012.
- ^ Banić Tomišić, Z. (2011). "The Story of Azithromycin". Kemija u industriji 60 (12): 603–617. ISSN 00229830.
- ^ "Merck Completes Acquisition of Inspire Pharmaceuticals, Inc." (Press release). Merck.
External links[edit]
- "azithromycin" at medicinenet.com
- "Azithromycin". Drug Information Portal. United States National Library of Medicine (NLM).
- Azithromycin PubMed Health
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