Presentation
Zibac™ IV Injection: Each vial contains sterile lyophilized Azithromycin EP equivalent to 500 mg Azithromycin.

Description
Azithromycin is derived from erythromycin; Azithromycin is an azalide antibiotic active against Gram-positive and Gram-negative organism. The mode of action of Azithromycin is inhibition of protein synthesis in bacteria by binding to the 50S ribosomal subunit and preventing translocation of peptides. Nucleic acid synthesis is not affected.

Indications
Community-acquired pneumonia due to Chlamydia pneumoniae, Haemophilus influenzae, Legionella pneumophila, Moraxella catarrhalis, Mycoplasma pneumoniae, Staphylococcus aureus, or Streptococcus pneumoniae in patients who require initial intravenous therapy. Pelvic inflammatory disease due to Chlamydia trachomatis, Neisseria gonorrhoeae, or Mycoplasma hominis in patients who require initial intravenous therapy. If anaerobic microorganisms are suspected of contributing to the infection, an antimicrobial agent with anaerobic activity should be administered in combination with ZIBAC. ZIBAC INJECTION SHOULD BE FOLLOWED BY ZIBAC BY THE ORAL ROUTE AS REQUIRED.

Dosage and Administrations
Community-acquired pneumonia: 500 mg as a single daily dose by the intravenous route for at least two days. Intravenous therapy should be followed by Azithromycin by the oral route at a single, daily dose of 500 mg, administered as two 250-mg tablets to complete a 7- to 10-day course of therapy. The timing of the switch to oral therapy should be done at the discretion of the physician and in accordance with clinical response. Pelvic inflammatory diseas: 500 mg as a single daily dose by the intravenous 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 the switch 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 agent with anaerobic activity should be administered in combination with ZIBAC. Renal Insufficiency: No dosage adjustment is recommended for subjects with renal impairment (GFR<80 mL/min). Caution should be exercised when Azithromycin is administered to subjects with severe renal impairment. Hepatic Insufficiency: No dose adjustment recommendations can be made in patients with impaired hepatic function. No dosage adjustment is recommended based on age or gender.

THE INFUSATE CONCENTRATION AND RATE OF INFUSION FOR ZIBAC INJECTION SHOULD BE EITHER 1 mg/mL OVER 3 HOURS OR 2 mg/mL OVER 1 HOUR. ZIBAC INJECTION SHOULD NOT BE GIVEN AS A BOLUS OR AS AN INTRAMUSCULAR INJECTION.

Preparation of the solution for intravenous administration is as follows: Reconstitution
Prepare the initial solution of ZIBAC injection by adding 4.8 mL of Sterile Water For Injection to the 500 mg vial and shaking the vial until all of the drug is dissolved. 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 For Injection is dispensed. Each mL of reconstituted solution contains 100 mg Azithromycin. Reconstituted solution is stable for 24 hours when stored below 30°C or 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. Dilution: To provide Azithromycin over a concentration range of 1.0-2.0 mg/mL, transfer 5 mL of the 100 mg/mL Azithromycin solution into the appropriate amount of any of the diluents listed below: Normal Saline (0.9% Sodium chloride), 1/2 Normal Saline (0.45% Sodium chloride), 5% Dextrose in Water Lactated Ringer's Solution, 5% Dextrose in 1/2 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 in 1/2 Normal Saline (0.45% Sodium chloride).

 

Final Infusion Solution Concentration (mg/ml)	Amount of Diluent (ml)
1.0 mg/ml	500 ml
2.0 mg/ml	250 ml

It is recommended that a 500-mg dose of ZIBAC injection, diluted as above,be infused over a period of not less than 60 minutes. ZIBAC INJECTIONSHOULD NOT BE GIVEN AS A BOLUS OR AS AN INTRAMUSCULAR INJECTION. Other intravenous substances, additives, or medications should not be added to ZIBAC injection, or infused simultaneously through the same intravenous line.

Side Effects
Most of the reported side effects were mild to moderate in severity and were reversible upon discontinuation of the drug. Azithromycin in studies of community-acquired pneumonia were related to the gastrointestinal system with diarrhea/loose stools, nausea, abdominal pain, and vomiting being the most frequently reported. Approximately 12% of patients experienced a side effect related to the intravenous infusion; most common were pain at the injection site (6.5%) and local inflammation (3.1%). The most common side effects associated with treatment in adult women who received I.V./P.O. Azithromycin in studies of pelvic inflammatory disease were related to the gastrointestinal system. Diarrhea and nausea were most commonly reported, followed by vaginitis, abdominal pain, anorexia, rash and pruritus.

Contraindications
Azithromycin is contraindicated in patients with known hypersensitivity to Azithromycin, Erythromycin, or any macrolide antibiotic.

Drug Interactions
Concurrent use of macrolides and Warfarin in clinical practice has been associated with increased anticoagulant effects. When used in therapeutic doses, Azithromycin had a modest effect on the pharmacokinetics of Atorvastatin, Carbamazepine, Cetirizine, Didanosine, Efavirenz, Fluconazole, Indinavir, Midazolam, Rifabutin, Sildenafil, Theophylline (intravenous and oral), Triazolam, Trimethoprim/Sulfamethoxazole or Zidovudine. Co-administration with Efavirenz or Fluconazole had a modest effect on the pharmacokinetics of Azithromycin. No dosage adjustment of either drug is recommended when Azithromycin is coadministered with any of these agents. When Azithromycin and these drugs are used concomitantly, careful monitoring of patients is advised: Digoxin, Ergotamine or Dihydroergotamine, Terfenadine, Cyclosporine, Hexobarbital and Phenytoin. Pregnancy: Azithromycin is pregnancy Category B. Nursing Mothers: 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. Pediatric Use: Safety and effectiveness of Azithromycin for injection in children or adolescents under 16 years have not been established.

Precautions
Serious allergic reactions, including angioedema, anaphylaxis, and dermatologic reactions including Stevens Johnson Syndrome and toxic epidermal necrolysis have been reported rarely in patients on Azithromycin therapy. Although rare, fatalities have been reported. If an allergic reaction occurs, the drug should be discontinued and appropriate therapy should be instituted. Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including ZIBAC injection, and may range in severity from mild diarrhea to fatal colitis. 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. ZIBAC INJECTION SHOULD BE RECONSTITUTED AND DILUTED AS DIRECTED AND ADMINISTERED AS AN INTRAVENOUS INFUSION OVER NOT LESS THAN 60 MINUTES. 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 caution should be exercised when prescribing Azithromycin in these patients.

Overdosage
There are no data on overdosage of intravenous Azithromycin.

Pharmaceutical Precautions
Store in a cool dry place protected from light. Keep out of reach of children.

Commercial Pack
Zibac™ IV Injection: Each combipack contains 1 vial and 1 ampoule.