Description: Azithromycin tablets contain the active ingredient azithromycin, an azalide, a subclass of macrolide antibiotics, for oral administration. Azithromycin has the chemical name (2R,3S,4R,5R,8R,10R, 11R,12S,13S,14R) -13-[(2,6-dideoxy-3-C-methyl-3-O-methyl-α-L- ribo-hexopyranosyl)oxy]-2-ethyl-3,4,10-trihydroxy-3,5,6,8,10,12,14-heptamethyl-11-[[3,4,6-trideoxy-3-(dimethylamino)-β-D-xylo-hexopyranosyl]oxy]-1-oxa-6-azacyclopentadecan-15-one. Azithromycin is derived from erythromycin; however, it differs chemically from erythromycin in that a methyl-substituted nitrogen atom is incorporated into the lactone ring. Its molecular formula is CHNO, and its molecular weight is 749. Each azithromycin tablet, intended for oral administration, contains azithromycin monohydrate equivalent to 250 mg or 500 mg of azithromycin. In addition, each tablet contains the following inactive ingredients: colloidal silicon dioxide, lecithin, magnesium stearate, microcrystalline cellulose, polyvinyl alcohol, pregelatinized starch, sodium lauryl sulfate, sodium starch glycolate, talc, titanium dioxide and xanthan gum.
Pharmacological effects: Azithromycin of barriers to bacterial peptide process, thereby inhibiting bacterial protein synthesis. In vitro tests proved right azithromycin many common clinical pathogens effectively, including Gram-positive aerobes: Staphylococcus aureus, Streptococcus pyogenes (group A β - hemolytic streptococcus), pneumonia (chain) cocci, α - hemolytic streptococcus (Streptococcus Green Grass) and other streptococcus, diphtheria (ROD) bacilli. Azithromycin for erythromycin-resistant Gram-positive bacteria, including fecal streptococcus (enterococci), and methicillin-resistant Staphylococcus aureus strains showed a variety of cross-resistance. Gram-negative aerobes: influenza (Haemophilus) bacteria, parainfluenza (Haemophilus) bacteria, cards he (quietly) bacteria, Acinetobacter is, Yersinia species, Legionella pneumophila, pertussis bacteria, vice pertussis bacteria, Shigella species, genus Pasteur, Huo chaos Vibrio vice hemolytic bacteria, like Shigella bacteria topiramate Plesiomonas. Anaerobes: Bacteroides fragilis, Bacteroides is, Clostridium bacteria, Streptococcus digest necrosis fusobacterium, of Propionibacterium acnes.Sexually transmitted disease microorganisms: Chlamydia trachomatis, dense spiral of syphilis, gonorrhea, Duke (Haemophilus) bacilli. Other microorganisms include: Charles borrow spiral of (Lyme pathogens) (Lyme diseaseagent), Mycoplasma pneumoniae, Mycoplasma hominis, Ureaplasma body of the original, Pneumocystis carinii, Mycobacterium is a bird, bending genus, mononucleosis and Lee de bacilli. Following Gram-negative bacteria is usually resistant: Proteus is a Shara genus, Morgan bacteria, green pus (PSEUDOMONAS) bacilli. Animal model studies found that the materials found in phagocytic cells, and when phagocytic cells were activated, after the release of the high concentration of azithromycin. Therefore liver infection sites in a high concentration.
Pharmacokinetics: Following oral administration of a single 500 mg dose (two 250 mg tablets) to 36 fasted healthy male volunteers, the mean (SD) pharmacokinetic parameters were AUC = 4.3 (1.2) mcg•h/mL; C = 0.5 (0.2) mcg/mL; T = 2.2 (0.9) hours. With a regimen of 500 mg (two 250 mg capsules) on day 1, followed by 250 mg daily (one 250 mg capsule) on days 2 through 5, the pharmacokinetic parameters of azithromycin in plasma in healthy young adults (18 to 40 years of age) are portrayed in the chart below. C and C remained essentially unchanged from day 2 through day 5 of therapy. In a two-way crossover study, 12 adult healthy volunteers (6 males, 6 females) received 1,500 mg of azithromycin administered in single daily doses over either 5 days (two 250 mg tablets on day 1, followed by one 250 mg tablet on days 2 to 5) or 3 days (500 mg per day for days 1 to 3). Due to limited serum samples on day 2 (3-day regimen) and days 2 to 4 (5-day regimen), the serum concentration-time profile of each subject was fit to a 3-compartment model and the AUC for the fitted concentration profile was comparable between the 5-day and 3-day regimens. Median azithromycin exposure (AUC) in mononuclear (MN) and polymorphonuclear (PMN) leukocytes following either the 5-day or 3-day regimen was more than a 1000-fold and 800-fold greater than in serum, respectively. Administration of the same total dose with either the 5-day or 3-day regimen may be expected to provide comparable concentrations of azithromycin within MN and PMN leukocytes. Two azithromycin 250 mg tablets are bioequivalent to a single 500 mg tablet.
Pharmacokinetic Parameters (Mean) Total (n = 12) Day 1 Day 5
Cmax (mcg/mL) 0.41 0.24
Tmax (h) 2.5 3.2
AUC0-24 (mcg•h/mL) 2.6 2.1
Cmin (mcg /mL) 0.05 0.05
Urinary Excret. (% dose) 4.5 6.5
PharmacokineticParameter [mean (SD)] 3-Day Regimen 5-Day Regimen
Day 1 Day 3 Day 1 Day 5
Cmax(serum,mcg/mL) 0.44 (0.22) 0.54 (0.25) 0.43 (0.2) 0.24 (0.06)
Serum AUC0-∞(mcg•hr/mL) 17.4 (6.2)Total AUC for the entire 3-day and 5-day regimens 14.9 (3.1)
Serum T1/2 71.8 hr 68.9 hr
The absolute bioavailability of azithromycin 250 mg capsules is 38%. In a two-way crossover study in which 12 healthy subjects received a single 500 mg dose of azithromycin (two 250 mg tablets) with or without a high fat meal, food was shown to increase C by 23% but had no effect on AUC.
When azithromycin suspension was administered with food to 28 adult healthy male subjects, C increased by 56% and AUC was unchanged. The AUC of azithromycin was unaffected by co-administration of an antacid containing aluminum and magnesium hydroxide with azithromycin capsules; however, the C was reduced by 24%. Administration of cimetidine (800 mg) two hours prior to azithromycin had no effect on azithromycin absorption. The serum protein binding of azithromycin is variable in the concentration range approximating human exposure, decreasing from 51% at 0.02 mcg /mL to 7% at 2 mcg /mL.
Indications: Azithromycin tablets are indicated for the treatment of patients with mild to moderate infections caused by susceptible strains of the designated microorganisms in the specific conditions listed below. As recommended dosages, durations of therapy and applicable patient populations vary among these infections.
Precautions: Because azithromycin is principally eliminated via the liver, caution should be exercised when azithromycin is administered to patients with impaired hepatic function. Due to the limited data in subjects with GFR <10 mL/min, caution should be exercised when prescribing azithromycin in these patients. Prolonged cardiac repolarization and QT interval, imparting a risk of developing cardiac arrhythmia and torsades de pointes, have been seen in treatment with other macrolides. A similar effect with azithromycin cannot be completely ruled out in patients at increased risk for prolonged cardiac repolarization.Exacerbation of symptoms of myasthenia gravis and new onset of myasthenic syndrome have been reported in patients receiving azithromycin therapy. Prescribing azithromycin in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.
Adverse reaction: In clinical trials, most of the reported side effects were mild to moderate in severity and were reversible upon discontinuation of the drug. Potentially serious side effects of angioedema and cholestatic jaundice were reported rarely. Approximately 0.7% of the patients (adults and pediatric patients) from the 5-day multiple-dose clinical trials discontinued azithromycin therapy because of treatment-related side effects. In adults given 500 mg/day for 3 days, the discontinuation rate due to treatment-related side effects was 0.6%. In clinical trials in pediatric patients given 30 mg/kg, either as a single dose or over 3 days, discontinuation from the trials due to treatment-related side effects was approximately 1%. Most of the side effects leading to discontinuation were related to the gastrointestinal tract, e.g., nausea, vomiting, diarrhea, or abdominal pain.
