Pharmacodynamics properties
Azithromycin is an azalide, a sub-class of the macrolide broad-spectrum antibiotics. The drug is bactericidal by binding to ribosomes of pathogenic bacteria, preventing protein synthesis. However, azithromycin demonstrates cross-resistance with erythromycin; so azithromycin should be used with careful consideration due to spread of macrolide-resistant bacteria in Vietnam.
Azithromycin is active against Gram-positive bacteria, including Streptococcus, Pneumococcus, Staphylococcus aureus. Studies in Vietnam showed that these bacteria are resistant to macrolides with a rate of 40%. Thus, use of azithromycin is decreased and limited more and less. Some other strains are also susceptible to azithromycin, such as Corynebacterium diphtheriae, Clostridium perfringens, Peptostreptococcus and Propionibacterium acnes. It should always be remembered that erythromycin-resistant microorganisms are resistant to both azithromycin and Gram-positive species, including Enterococci. Most methicillin-resistant staphylococci are completely resistant to azithromycin.
Azithromycin is active against Gram-negative bacteria, including Haemophilus influenzae, H. parainfluenzae, H.ducreyi, Moraxella catamhalis, Acinetobacter, Yersinia, Legionella pneumophila, Bordetella pertussis and parapertussis, Neisseria gonorrhoeae and Campylobacter spp. In addition, azithromycin also is active against Listeria monocytogenes, Mycobacterium avium, Mycoplasma pneumoniae and hominis, Ureaplasma urealyticum, Toxoplasma gondii, Chlamydia trachomatis and Chlamydia pneumoniae, Treponema pallidum and Borrellia burgdorferi. Azithromycin is moderately active against Gram-negative bacteria, including E.coli, Salmonella typhi, Enterobacter, Acromonas hydrophilia, Klebsiella. Azithromycin-resistant negative-gram bacteria include Proteus, Serralia, Pseudomonas aeruginosa và Morganella.
Azithromycin generally is less active against Gram-positive bacteria than erythromycin, but more active against some Gram-negative bacteria including Haemophilus.
Pharmacokinetic properties
Azithromycin appears to be distributed throughout the entire body after oral administration. The biological availability of azithromycin is approximately 40%. Food reduces the absorption of azithromycin by about 50%. Peak plasma levels are achieved 2-3 hours after taking the medicinal product. Azithromycin is mainly distributed into tissues, such as lungs, tonsil, prostate, granulocyte, and macrophages. Studies have shown clearly higher azithromycin levels in the tissues than in the plasma (up to 50 times the maximum observed concentration in plasma). However, CNS azithromycin concentrations is very low. An amount of azithromycin is de-methylated in the liver and is excreted in bile as unchanged and partly as metabolites. Approximately 6% of the oral dose is excreted in the urine within 72 hours as unchanged. The half-life is 2-4 days.
Indications
Macromax SK is indicated for the treatment of the following infections, when caused by microorganisms sensitive to azithromycin:
- Lower respiratory tract infections: acute and chronic bronchitis, pneumonia (including community-acquired pneumonia and typical or atypical pneumonia), bronchitis.
- Upper respiratory tract infections: pharyngitis, otic infections, rhinitis, sinusitis, otitis media and tonsillitis.
- Skin and soft tissue infections: pimples, poisonous boil, hair folliculitis, cellulitis, and infectious injuries or ulcers, abscesses and impetigo.
- Urinary tract infections and sexually transmitted diseases: vaginitis, vulvitis, cervicitis, cystitis, pyelitis, ovary inflammation. Azithromycin is particularly effective in the treatment of Chlamydia trichomatis and H.ducreyi, and non-resistant Neisseeria gonorrhoeae.
Contraindications
Hypersensitivity to azithromycin or to any of the excipients.
Precautions
- Azithromycin and other macrolides should be used with caution because of allergic reactions, including angioedema and anaphylaxis (very dangerous but rarely), superinfection caused by susceptible bacteria.
- Dosage adjustment is appropriate for patients with renal disease who have abnormal creatinine clearance (<40 ml/min).
- Caution should be exercised in patients with severe hepatic disease because the drug is excreted primarily by the liver.
Pregnancy and lactation
Safety of oral azithromycin in pregnancy and lactation has been adequately determined. There are no reports of drug excretion through breast milk.
Effects on ability to drive and use machines
No found.
Interactions:
- Although no reports have been given, drug interactions with ergotamine, digoxin, triazolam, phenytoin and hexobarbital should be monitored.
- Azithromycin absorption is not affected by concurrent use of azithromycin and cimetidin, theophylline, warfarin, carbamazepine, methyl prednisolone and zidovudine.
- Aluminum- and magnesium-containing antacids reduce the rate but does not limit the absorption of azithromycin.
Dosage
- Lower respiratory tract infections, ENT infections, skin and soft tissue infections:
Macromax SK (azithromycin) should be taken as a single dose on an empty stomach (at least 1 hour before or 2 hours after a meal).
Adults: 2 capsules (500 mg) daily for 3 days. Or 2 capsules (500 mg) given as a single dose on the first day of therapy, followed by 1 capsule (250 mg) on days 2 to 5. Total cumulative dose is 1.5 g.
Children: 10mg/kg/day for 3 days. Or 10 mg/kg/day on the first day of therapy, followed by 5 mg/kg/day on days 2 to 5.
The latest recommended dose for the treatment of pharyngitis, tonsillitis is 12 mg/kg/day for 5 days.
- Urinary tract infections and sexually transmitted infections: 1 g single dose.
Undesirable effects
Macromax®SK (azithromycin) generally is well tolerated in most age groups.
- The most frequent adverse effects of azithromycin involve the GI tract (3-5%) i.e., nausea, vomiting, diarrhea, abdominal pain and dyspepsia.
- Less frequent adverse effects (that occurred with a frequency of <1%) include headache, dizziness, vertigo, fatigue, palpitations, chest pain, vaginitis, nephritis, jaundice, cholestasis and allergic reactions (rash, angioedema), photosensitivity.
Most adverse effects were mild in severity and were reversible upon discontinuance of the drug.
Changes in test parameters for azithromycin treatment were rare and were transient and reversible (if any).
Inform your doctor about any side effects that may occur during the treatment.
Overdose
- Limited information is available on the acute toxicity of azithromycin. Typical symptoms of overdose of macrolide antibiotics are usually decreased hearing, nausea, vomiting and diarrhea.
- Treatment: gastric lavage and supportive treatment.
Shelf-life: 36 months from the manufacturing date.
Storage: Store in cool dry places, below 30oC, protect from direct light.
Specifications: Manufacturer’s.
Registration number: VD-15166-11