Each vial contains: Azithromycin Dihydrate USP. Eq. to Azithromycin Anhydrous 500 mg.
Each ampoule contains: Sterile water for Injection BP 5mL.
Pharmacology: The mode of action of Azithromycin is inhibition of protein synthesis in bacteria by binding to the 50's ribosomal subunit and preventing translocation of peptides.
Pharmacokinetics: Absorption: After oral administration in humans, Azithromycin is widely distributed throughout the body, and its bioavailability is approximately 37%. The administration of Azithromycin capsules after a substantial meal reduces bioavailability.
Peak plasma levels are reached after 2-3 hours. The terminal plasma elimination half-life closely reflects the elimination half-life from tissues of 2-4 days.
In patients hospitalized with Community-Acquired Pneumonia treated with a daily single intravenous infusion of 500 mg azithromycin, over one hour, in a solution with a concentration of 2 mg/mL, for 2 days to 5 days, the mean Cmax ± D achieved was of 3.63 ± 1.60 μg/mL, while the trough levels concentration at 24 hours was 0.20 ± 0.15 μg/mL and the AUC24 of 9.60 ± 4.80 μg.h/mL.
Mean Cmax, trough levels concentration at 24 hours and AUC24 values were of 1.14 ± 0.14 μg/mL, 0.18 ± 0.02 μg/mL and 8.03 ± 0.86 μg.h/mL, respectively, in normal volunteers receiving intravenous infusion of 500 mg Azithromycin at a concentration of 1 mg/mL, for 3 hours.
Distribution: In animal tests, high concentrations of Azithromycin have been found in phagocytes. It has also been established that during active phagocytosis, higher concentrations of Azithromycin are released from inactive phagocytes. In animal models this results in high concentrations of Azithromycin being delivered to the site of infection.
In pharmacokinetic studies, it has been demonstrated that the concentrations of Azithromycin measured in tissues are noticeably higher (as much as 50 times that those measured in plasma), which indicates that the agent strongly binds to tissues. Concentrations in target tissues such as lung, tonsil, and prostate exceed the MIC90 for likely pathogen agents after a single dose of 500 mg. High Azithromycin concentrations were detected in gynecological tissue 96 hours after a single dose of 500 mg Azithromycin.
Biotransformation/Elimination: In a multiple-dose study in 12 normal volunteers using a 500 mg (1 mg/mL) one-hour intravenous dosage regimen for five days, the amount of administered azithromycin dose excreted in urine in 24 hours was about 11% after the 1st dose and 14% after the 5th dose. These values are higher than the reported 6% as being excreted unchanged in urine after oral administration of azithromycin. Biliary excretion is a major route of elimination for unchanged drug. Also in bile, ten (10) metabolites were detected, which were formed through N-demethylation and O-demethylation hydrolyzation of desosamine and aglycone rings cleavage of cladinose conjugate. Comparison of the results HPLC (high pressure liquid chromatography) and microbiological analyses carried out in tissues suggest that the metabolites do not contribute to Azithromycin microbiological activity.
Pharmacokinetics in special patient groups: Renal insufficiency: Following a single oral dose of Azithromycin 1 g, mean Cmax and AUC0-120 increased by 5.1% and 4.2% respectively, in subjects with mild to moderate renal impairment (glomerular filtration rate of 10-80 mL/min) compared with normal renal function (GFR >80 mL/min). In subjects with severe renal impairment, the mean Cmax and AUC0-120 increased 61% and 35% respectively compared to normal.
Hepatic insufficiency: In patients with mild to moderate hepatic impairment, there is no evidence of a marked change in serum pharmacokinetics of azithromycin compared to normal hepatic function. In these patients, urinary recovery of Azithromycin appears to increase perhaps to compensate for reduced hepatic clearance.
Elderly: The pharmacokinetics of Azithromycin in elderly men was similar to that of young adults; however, in elderly women, although higher peak concentrations (increased by 30-50%) were observed, no significant accumulation occurred. In elderly volunteers (>65 years), higher (29%) AUC values were always observed after a 5-day course than in younger volunteers (<45 years). However, these differences are not considered to be clinically relevant; no dosage adjustment is therefore recommended.
Infections from respiratory pathogens (e.g., S. pyogenes, S. pneumoniae, M. catarrhalis, C. trachomatis, Legionella sp., Mycoplasma pneumoniae, S. aureus, and H. influenzae); C. pneumoniae and M. avium infection; uncomplicated chlamydial urethritis, cervicitis or pharyngitis; alternative drug for multi-resistant Salmonella typhi infection outside the Central Nervous System (CNS).
For the treatment of granuloma inguinale, an initial dose of 1 g followed by 500 mg daily may be given.
For uncomplicated genital infections due to Chlamydia trachomatis, 1 g of Azithromycin is given as single dose of 2 g has been given for uncomplicated gonorrhea.
For prophylaxis of disseminated MAC infections, Azithromycin 1.2 g may be given once weekly.
Azithromycin dihydrate may also be given initially by intravenous infusion in dose equivalent to 500 mg of Azithromycin at a single daily dose in the treatment Community-Acquired Pneumonia and Pelvic Inflammatory Disease. It may be given either in a solution containing 2 mg/mL over 1 hour.
For the treatment of adult patients with CAP due to the indicated organisms, the recommended dose of intravenous Azithromycin is 500 mg as single dose by the IV route for at least two days. Intravenous therapy should be followed by oral Azithromycin at a single dose of 500 mg to complete a 7 to 10 days course of therapy. The timing of the conversion to oral therapy should be done at the discretion of the physician and in accordance with clinical response.
For the treatment of adult patient with PID due to the indicated organisms, the recommended dose of intravenous Azithromycin is 500 mg as a single dose by the IV route for one or two days. Intravenous therapy should be followed by Azithromycin by the oral route at a single daily dose of 250 mg to complete a 7 day course of therapy. The timing of conversion to oral therapy should be done at the discretion of the physician and in accordance with clinical response.
If anaerobic microorganisms are suspected of contributing to the infection, an antimicrobial anaerobic agent may be administered in combination with Azithromycin. Intravenous administration: After reconstitution and dilution, the recommended route of administration for intravenous Azithromycin is by IV infusion only. It is not recommended for administration as an intravenous bolus or an intramuscular injection.
Azithromycin tablets is contraindicated in patients with known hypersensitivity to Azithromycin, or any macrolides or ketolide antibiotic.
Animal reproduction studies have demonstrated that Azithromycin crosses the placenta, but have revealed no evidence of harm to the fetus. There are no data on secretion in breastmilk. Safety for use in human pregnancy and lactation has not been established. Azithromycin should only be in pregnant and lactating women where adequate alternatives are not available.
Abdominal or stomach cramps or pain (severe); abdominal tenderness; diarrhea (watery and severe, which may be bloody); difficulty in breathing; fever, joint pain, skin rash, swelling of face, mouth, neck hands and feet; diarrhea (mild); nausea; stomach pain or discomfort, dizziness; headache.
Azithromycin has not been studied in pregnant women. However, Azithromycin has not been shown to cause birth defects or other problems in animal studies.
It is not known whether Azithromycin is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when azithromycin is administered to a nursing woman.
This medicine has been tested in a limited number of children up to the age of 16. In effective doses, the medicine has not been shown to cause different side effects or problems than it does in adults.
This medicine has not been tested in a limited number of elderly patients and has not been shown to cause different effects or problems in older people that it does in younger adults.
Antacids: In a pharmacokinetic study investigating the effects of simultaneous administration of antacid with azithromycin, no effect on overall bioavailability was seen, although peak serum concentrations were reduced approximately by 24%. In patients receiving both azithromycin and antacids, the drugs should not be taken simultaneously.
Cetirizine: In healthy volunteers, co-administration of a 5-day regimen of azithromycin with 20 mg cetirizine at steady-state resulted in no pharmacokinetic interaction and no significant changes in the QT interval.
Didanosine (Dideoxyinosine): Co-administration of 1200 mg/day azithromycin with 400 mg/day didanosine in six HIV-positive subjects did not appear to affect the steady-state pharmacokinetics of didanosine as compared to placebo.
Digoxin: Some of the macrolide antibiotics have been reported to impair the microbial metabolism of digoxin in the gut in some patients. In patients receiving concomitant azithromycin, a related azalide antibiotic, and digoxin the possibility of raised digoxin levels should be borne in mind.
Zidovudine: Single 1000 mg doses and multiple 1200 mg or 600 mg doses of azithromycin had little effect on the plasma pharmacokinetics or urinary excretion of zidovudine or its glucuronide metabolite. However, administration of azithromycin increased the concentrations of phosphorylated zidovudine, the clinically active metabolite, in peripheral blood mononuclear cells. The clinical significance of this finding is unclear, but it may be of benefit to patients.
Azithromycin does not interact significantly with the hepatic cytochrome P450 system. It is not believed to undergo the pharmacokinetic drug interactions as seen with erythromycin and other macrolides. Hepatic cytochrome P450 induction or inactivation via cytochrome-metabolite complex does not occur with azithromycin.
Ergot derivatives: Due to the theoretical possibility of ergotism, the concurrent use of azithromycin with ergot derivatives is not recommended.
Pharmacokinetic studies have been conducted between azithromycin and the following drugs known to undergo significant cytochrome P450 mediated metabolism.
Atorvastatin: Co-administration of atorvastatin (10 mg daily) and azithromycin (500 mg daily) did not alter the plasma concentrations of atorvastatin (based on a HMG CoA-reductase inhibition assay).
Carbamazepine: In a pharmacokinetic interaction study in healthy volunteers, no significant effect was observed on the plasma levels of carbamazepine or its active metabolites in patients receiving concomitant azithromycin.
Cimetidine: In a pharmacokinetic study investigating the effects of a single dose of cimetidine, given 2 hours before azithromycin, on the pharmacokinetics of Azithromycin, no alteration of azithromycin pharmacokinetics was seen.
Coumarin-type oral anticoagulants: In a pharmacokinetic interaction study, azithromycin did not alter the anticoagulant effect of a single dose of 15 mg warfarin administered to healthy volunteers. There have been reports received in the post-marketing period of potentiated anti-coagulation subsequent to co-administration of azithromycin and coumarin-type oral anticoagulants. Although a causal relationship has not been established, consideration should be given to the frequency of monitoring prothrombin time when azithromycin is used in patients receiving coumarin-type oral anticoagulants.
Ciclosporin: In a pharmacokinetic study with healthy volunteers who were administered a 500 mg/day oral dose of azithromycin for 3 days and were then administered a single 10 mg/kg oral dose of ciclosporin, the resulting ciclosporin Cmax and AUC0-5 were found to be significantly elevated (by 24% and 21% respectively), however no significant changes were seen in AUC0-∞. Consequently, caution should be exercised before considering concurrent administration of these drugs. If co-administration of these drugs is necessary, ciclosporin levels should be monitored and the dose adjusted accordingly.
Efavirenz: Co-administration of a single dose of 600 mg azithromycin and 400 mg efavirenz daily for 7 days did not result in any clinically significant pharmacokinetic interactions.
Fluconazole: Co-administration of a single dose of 1200 mg azithromycin did not alter the pharmacokinetics of a single dose of 800 mg fluconazole. Total exposure and half-life of azithromycin were unchanged by the co-administration of fluconazole, however, a clinically significant decrease in Cmax (18%) of azithromycin was observed.
Indinavir: Co-administration of a single-dose of 1200 mg azithromycin had no statistically significant effect on the pharmacokinetics of indinavir administered as 800 mg three times daily for 5 days.
Methylprednisolone: In a pharmacokinetic interaction study in healthy volunteers, azithromycin had no significant effect on the pharmacokinetics of methylprednisolone.
Midazolam: In healthy volunteers, co-administration of 500 mg/day azithromycin for 3 days did not cause clinically significant changes in the pharmacokinetics and pharmacodynamics of a single dose of 15 mg midazolam.
Nelfinavir: Co-administration of azithromycin (1200 mg) and nelfinavir at steady state (750 mg three times daily) resulted in increased azithromycin concentrations. No clinically significant adverse effects were observed and no dose adjustment was required.
Rifabutin: Co-administration of azithromycin and rifabutin did not affect the serum concentrations of either drug. Neutropenia was observed in subjects receiving concomitant treatment of azithromycin and rifabutin. Although neutropenia has been associated with the use of rifabutin, a causal relationship to combination with azithromycin has not been established.
Sildenafil: In normal healthy male volunteers, there was no evidence of an effect of azithromycin (500 mg daily for 3 days) on the AUC and Cmax, of sildenafil or its major circulating metabolite.
Terfenadine: Pharmacokinetic studies have reported no evidence of an interaction between azithromycin and terfenadine. There have been rare cases reported where the possibility of such an interaction could be entirely excluded; however there was no specific evidence that such an interaction had occurred.
Theophylline: There is no evidence of a clinically significant pharmacokinetic interaction when azithromycin and theophylline are co-administered to healthy volunteers.
Triazolam: In 14 healthy volunteers, co-administration of 500 mg azithromycin on Day 1 and 250 mg on Day 2 with 0.125 mg triazolam on Day 2 had no significant effect on any of the pharmacokinetic variables for triazolam compared to triazolam and placebo.
Trimethoprim/sulfamethoxazole: Co-administration of trimethoprim/sulfamethoxazole DS (160 mg/800 mg) for 7 days with 1200 mg azithromycin on Day 7 had no significant effect on peak concentrations, total exposure or urinary excretion of either trimethoprim or sulfamethoxazole. Azithromycin serum concentrations were similar to those seen in other studies.
Direction for reconstitution:
Prepare the initial solution of Azithromycin by adding 4.8 mL of Sterilized water for injection to the 500 mg vial and shaking the vial until all of the drug is dissolved. Since Azithromycin for injection is supplied under vacuum, it is recommended that a standard 5 mL (non-automated) syringe be used to ensure that the exact amount of 4.8 mL of sterile water is dispersed. Each mL of reconstituted solution contains 100 mg Azithromycin. Reconstituted solution is stable for 24 hours when stored below 30°C (86°F). Parenteral drug products should be inspected visually for particulate matter prior to administration. If particulate matter is evident in reconstituted fluids, the drug solution should be discarded. As with all parenteral admixtures, the reconstituted or further diluted solution should be examined for change in colour, precipitation, haziness or leakage. The unused proportion should be discarded.
To provide Azithromycin solution into the appropriate amount of any of the diluents listed ad follows: Normal Saline (0.9% sodium chloride), ½ Normal Saline (0.45% sodium chloride), 5% Dextrose in Water, Lactated Ringer's Solution, 5% Dextrose in ½ Normal Saline (0.45% sodium chloride) with 20 mEq KCl, 5% Dextrose in Lactated Ringer's Solution, 5% Dextrose in 1/3 Normal Saline (0.3% sodium chloride), 5% Dextrose Normal Saline (0.45% sodium chloride). (See table.)
Click on icon to see table/diagram/image
It is recommended that a 500 mg dose of Azithcor (Azithromycin for injection), diluted as previously mentioned, be infused over a period of not less than 60 minutes.
Azithromycin for injection should not be given as a bolus or as an intramuscular injection.
Other intravenous substances, additives, or medications should not be added to Azithromycin for injection, or infused simultaneously through the same intravenous line.
Store at temperatures not exceeding 30°C.
J01FA10 - azithromycin ; Belongs to the class of macrolides. Used in the systemic treatment of infections.
Powd for inj 500 mg [10 mL (vial) + 5 mL (diluent)] x 1's.