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Zithromax Review Article

 

Zithromax, Sumamed, generic named: azithromycin, is a semi-synthetic macrolide antibiotic chemically related to erythromycin and clarithromycin also known as biaxin. It is used in treating a wide variety of bacteria organisms, such as Streptococcus pneumoniae, Hemophilus influenzae, Mycoplasma pneumoniae, Staphylococcus aureus, mycobacterium avium, and many others. Unusually, it stays in the body for quite a while, allowing for once a day dosing and for shorter treatment courses for most infections. Azithromycin, like all macrolide antibiotics, prevents bacteria from growing by interfering with their ability to make proteins. Due to the differences in the way proteins are made in bacteria and humans, the macrolide antibiotics do not interfere with humans' ability to make proteins.

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Zithromax is one of the most widely-sold antibiotics. It is a broad-spectrum antibacterial. It was discovered in 1980 by a team of researchers in a Croatian pharmaceutical company, Pliva. It is available in some parts of Europe as Sumamed, marketed by Pliva. It is available as Zithromax in USA, Australia, Asia, and the rest of Europe. FDA approved this drug in 2009.

Information
Generic Name: Azithromycin.

Product Brand Name: Zithromax in USA, Canada, UK, Australia, Malaysia, Philippines, Thailand, South Africa, Egypt, Lebanon, Belgium, Finland, Greece, Italy, and Portugal; Sumamed in Bulgaria, Croatia, Czech Republic, Hungary, Republic of Macedonia, Russian Federation, Slovakia, and Slovenia.

Product Manufacturer: Pfizer U.S. Pharmaceuticals Group

Zithromax Description
The generic name of Zithromax is azithromycin. It is derived from erythromycin though it has a somewhat different chemical structure. It is a macrolide antibiotic. This means it has a macrolide ring present in its structure. Macrolides inhibit protein biosynthesis inside the bacterial cell preventing further growth of the cell. This causes a bacteriostatic effect, though in greater concentrations it can work as bactericidal as well.

Zithromax Statistics
Azithromycin is effective against Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis, Streptococcus pyogenes, Chlamydia trachomatis, Staphylococcus aureus, Mycoplasma pneumoniae, and Chlamydophila psittaci along with many other bacteria. It is not effective against viruses. It is more effective against gram-negative bacteria than other macrolides. Azithromycin can be administered once daily, because it has a long elimination half-life. After absorption, it stays in high concentrations in some specific types of cells, such as leucocytes, monocytes, and macrophages.

It has been shown that a once-a-day administration of azithromycin lasting for three days can have the same effectiveness as a once-a-day administration of other antibacterial agents that lasts for 5 or even 10 days. Side effects of azithromycin are mainly gastrointestinal in nature and occur in less frequency than other macrolides. It has lesser drug-drug interaction than other macrolides. Shorter duration of therapy, easy administration, and lesser adverse effect also account for the better compliance of patients towards azithromycin. It is helpful for patients who cannot take erythromycin due to several contraindications. (Dunn and Barradell, 1996).

Statistics of infectious diseases
According to the World Health Organization (WHO) fact sheet, Haemophilus influenzae causes three million cases of sickness and 386,000 estimated deaths per year through influenza and pneumonia. Most of the patients are under the age of five. Meningitis leaves at least 15% of its survivors with permanent disabilities, while the total number of deaths caused by pneumonia is much higher than those caused by meningitis. Vaccines have been available for H. influenzae since the early 1990s, but even with yearly vaccinations, many children still die by H. Influenza infections .


Mechanisms of Action

Azithromycin is a semi-synthetic antibiotic and it is acid-stable. It has a bioavailability of 38% and is rapidly absorbed on an empty stomach. It reaches its highest concentration in the plasma after one to two hours following oral administration. Because of its high concentrations in specific cell types, it reaches the area of infection rapidly. It has an inhibiting effect to protein-synthesis in bacterial cells, but does not inhibit protein synthesis in human cells.

The mechanism of action is mainly similar to erythromycin from which this drug is derived. However, the mechanism is still not fully understood. Azithromycin binds to the 50S subunit of the ribosome and inhibits the process of mRNA translocation, preventing the transfer of tRNA from the acceptor site to the donor site, thus preventing protein synthesis inside the bacterial cell. As proteins are not synthesized inside the cell, important cellular functions and necessary structural processes are prevented, which causes the bacteriostatic and bactericidal effects. (Saeb-Parsy, 1999).

Dosage
Zithromax is available in three forms; namely oral suspension, powder, and oral tablets. Oral suspension comes in 300 mg, 600 mg, 900 mg, and 1200 mg of azithromycin in a bottle. Tablets come in 250 mg and 500 mg dose. Powder is available in a 1 g packet. Dose for an individual varies depending on various factors. Physician’s consult is required.

Use of Zithromax
Zithromax is used to treat various types of infections in adults and children.
1. Respiratory tract infections such as acute sinusitis, chronic obstructive pulmonary disease due to bacterial infection, community-acquired pneumonia, and Legionnaires' disease. It is also used for prophylaxis of whooping cough.
2. Ear infection/acute otitis media.
3. Pharyngitis and tonsillitis.
4. GI infections such as symptomatic enteric infection caused by Campylobacter jejuni; cryptosporidiosis in HIV-infected people; traveller’s diarrhoea; shigellosis; diarrhoea and dysentery caused by E. coli; typhoid; and salmonellosis.
5. A few types of skin infection.
6. Parasitic diseases such as malaria, babesiosis, toxoplasmosis.
7. Genital ulcers, urethritis, cervicitis, Chlamydia infection in pregnant woman, chlamydial pneumonia and conjunctivitis in newborns, psittacosis, and syphilis in non-pregnant woman.
8. Mycobacterium avium complex infections.
9. Meningitis.
10. Pelvic inflammatory disease.
11. Bacterial endocarditis.
12. Prophylaxis in sexual assault victims.

Side Effects
The following side effects can be seen with long-term or short-term use of Zithromax.
1. Nausea, vomiting, loss of taste, loss of appetite, jaundice, stomachache, watery or bloody diarrhoea, dark-coloured stool, and constipation.
2. Irregular heartbeat and chest pain.
3. Fever, chills, and sore throat.
4. Skin rash, skin itching, skin discoloration, blistering and peeling of the skin, and swelling of the face and tongue.
5. Hearing problem, ringing in the ears, and decreased sense of smell.
6. Headache, dizziness, tiredness, and sleep disturbance.
7. Vaginal itching.

Caution
Administration of Zithromax is contraindicated in the following cases.
1. Zithromax is contraindicated if the patient is allergic to azithromycin, erythromycin, or any other broad-spectrum antibiotic.
2. If the patient has a history of liver disease, kidney disease, or myasthenia gravis, Zithromax should not be administered.
3. If after taking Zithromax patient feels palpitation or a change in heart rhythm, this should be immediately reported to a physician.

Drug interactions
Though Zithromax has fewer drug interactions than other macrolides, a total of 259 drugs are known to interact with it, among which 33 have major interactions. All the drugs, which are substrates of the enzyme CYP450, are contraindicated for coadministration with Zithromax, as the plasma concentration levels of these drugs can rise acutely, causing various side effects. Some of the 259 drugs are anti-arrhythmic, like amiodarone, dofetilide, ibutilide, and sotalol; others are anti-psychotic like haloperidone, and clozapine; others are calcium channel blockers, and some are HMC CoA inhibitors (King and Brucker, 2009).

Conclusion
So far, studies have not shown any contraindications of Azithromycin for pregnant women. It is still not known if it can be transferred from a mother to a baby through breast milk. This drug has a legal status of prescription only.


References:


Dunn, CJ, Barradell, LB, 1996, Azithromycin. A review of its pharmacological properties and use as 3-day therapy in respiratory tract infections, Drugs;51(3):483-505.

Kanoh S, Rubin BK, 2010, Mechanisms of action and clinical application of macrolides as immunomodulatory medications, Clin Microbiol Rev. Jul;23(3):590-615.

King, TL, Brucker, MC, 2009, Pharmacology for Women's Health, Jones & Bartlett Learning, page 267-268

Nguyen D, Emond MJ, Mayer-Hamblett N, Saiman L, Marshall BC, Burns JL., 2007, Clinical response to azithromycin in cystic fibrosis correlates with in vitro effects on Pseudomonas aeruginosa phenotypes, Pediatr Pulmonol.;42(6):533-41.

Retsema, J, Girard, A, Schelkly, W, Manousos, M, Anderson, M, Bright, G, Borovoy, R, Brennan, L, Mason, R, 1987, Spectrum and mode of action of azithromycin (CP-62,993), a new 15-membered-ring macrolide with improved potency against gram-negative organisms, Antimicrob Agents Chemother.; 31(12): 1939–1947.

Saeb-Parsy, K, 1999, Instant pharmacology, John Wiley and Sons.

Chang AB, Grimwood K, White AV, Maclennan C, Sloots TP, Sive A, McCallum GB, Mackay IM, Morris PS, 2011, Randomized placebo-controlled trial on azithromycin to reduce the morbidity of bronchiolitis in Indigenous Australian infants: rationale and protocol, Trials. 2011 Apr 14;12:94.
byKourosh Saeb-Parsy; John Wiley and Sons, 1999


 

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