Zithromax Injection (Azithromycin Injection) - Indications and Dosage

INDICATIONS AND USAGE

ZITHROMAX (azithromycin for injection) is indicated for the treatment of patients with infections caused by susceptible strains of the designated microorganisms in the conditions listed below. As recommended dosages, durations of therapy, and applicable patient populations vary among these infections, please see DOSAGE AND ADMINISTRATION for dosing recommendations.

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 ZITHROMAX.

ZITHROMAX^® (azithromycin for injection) should be followed by ZITHROMAX by the oral route as required. (See DOSAGE AND ADMINISTRATION.)

Appropriate culture and susceptibility tests should be performed before treatment to determine the causative microorganism and its susceptibility to azithromycin. Therapy with ZITHROMAX may be initiated before results of these tests are known; once the results become available, antimicrobial therapy should be adjusted accordingly.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of ZITHROMAX (azithromycin) and other antibacterial drugs, ZITHROMAX (azithromycin) should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

DOSAGE AND ADMINISTRATION

(See INDICATIONS AND USAGE and CLINICAL PHARMACOLOGY.)

The recommended dose of ZITHROMAX (azithromycin for injection) for the treatment of adult patients with community-acquired pneumonia due to the indicated organisms is: 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.

The recommended dose of ZITHROMAX (azithromycin) for the treatment of adult patients with pelvic inflammatory disease due to the indicated organisms is: 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 ZITHROMAX.

RENAL INSUFFICIENCY:

No dosage adjustment is recommended for subjects with renal impairment (GFR </= 80 mL/min). The mean AUC_0-120 was similar in subjects with GFR 10-80 mL/min compared to subjects with normal renal function, whereas it increased 35% in subjects with GFR <10 mL/min compared to subjects with normal renal function. Caution should be exercised when azithromycin is administered to subjects with severe renal impairment. (See CLINICAL PHARMACOLOGY, Special Populations, Renal Insufficiency.)

HEPATIC INSUFFICIENCY:

The pharmacokinetics of azithromycin in subjects with hepatic impairment have not been established. No dose adjustment recommendations can be made in patients with impaired hepatic function (See CLINICAL PHARMACOLOGY, Special Populations, Hepatic Insufficiency.)

No dosage adjustment is recommended based on age or gender. (See CLINICAL PHARMACOLOGY, Special Populations.)

The infusate concentration and rate of infusion for ZITHROMAX (azithromycin for injection) should be either 1 mg/mL over 3 hours or 2 mg/mL over 1 hour.

PREPARATION OF THE SOLUTION FOR INTRAVENOUS ADMINISTRATION IS AS FOLLOWS:

Reconstitution

Prepare the initial solution of ZITHROMAX (azithromycin for 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. Since ZITHROMAX (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 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.

Dilute this solution further prior to administration as instructed below.

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)

Normosol^® -M in 5% Dextrose

Normosol^® -R in 5% Dextrose

When used with the Vial-Mate™ drug reconstitution device, please reference the Vial-Mate™ instructions for assembly and reconstitution.

It is recommended that a 500-mg dose of ZITHROMAX (azithromycin for injection), diluted as above, be infused over a period of not less than 60 minutes.

ZITHROMAX (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 ZITHROMAX (azithromycin for injection), or infused simultaneously through the same intravenous line.

Storage

When diluted according to the instructions (1.0 mg/mL to 2.0 mg/mL), ZITHROMAX (azithromycin for injection) is stable for 24 hours at or below room temperature (30°C or 86°F), or for 7 days if stored under refrigeration (5°C or 41°F).

HOW SUPPLIED

ZITHROMAX^® (azithromycin for injection) is supplied in lyophilized form under a vacuum in a 10-mL vial equivalent to 500 mg of azithromycin for intravenous administration. Each vial also contains sodium hydroxide and 413.6 mg citric acid.

These are packaged as follows:

   10 vials of 500 mg                                                      NDC 0069-3150-83

   10 vials of 500 mg with

     1 Vial-Mate™ Adaptor each                                   NDC 0069-3150-14

CLINICAL STUDIES

COMMUNITY-ACQUIRED PNEUMONIA

In a controlled study of community-acquired pneumonia performed in the U.S., azithromycin (500 mg as a single daily dose by the intravenous route for 2-5 days, followed by 500 mg/day by the oral route to complete 7-10 days therapy) was compared to cefuroxime (2250 mg/day in three divided doses by the intravenous route for 2-5 days followed by 1000 mg/day in two divided doses by the oral route to complete 7-10 days therapy), with or without erythromycin. For the 291 patients who were evaluable for clinical efficacy, the clinical outcome rates, i.e., cure, improved, and success (cure + improved) among the 277 patients seen at 10-14 days post-therapy were as follows:

In a separate, uncontrolled clinical and microbiological trial performed in the U.S., 94 patients with community-acquired pneumonia who received azithromycin in the same regimen were evaluable for clinical efficacy. The clinical outcome rates, i.e., cure, improved, and success (cure + improved) among the 84 patients seen at 10-14 days post-therapy were as follows:

Microbiological determinations in both trials were made at the pre-treatment visit and, where applicable, were reassessed at later visits. Serological testing was done on baseline and final visit specimens. The following combined presumptive bacteriological eradication rates were obtained from the evaluable groups:

The presumed bacteriological outcomes at 10-14 days post-therapy for patients treated with azithromycin with evidence (serology and/or culture) of atypical pathogens for both trials were as follows:

ANIMAL TOXICOLOGY

Phospholipidosis (intracellular phospholipid accumulation) has been observed in some tissues of mice, rats, and dogs given multiple doses of azithromycin. It has been demonstrated in numerous organ systems (e.g., eye, dorsal root ganglia, liver, gallbladder, kidney, spleen, and pancreas) in dogs treated with azithromycin at doses which, expressed on the basis of mg/m², are approximately equal to the recommended adult human dose, and in rats treated at doses approximately one-sixth of the recommended adult human dose. This effect has been shown to be reversible after cessation of azithromycin treatment. Phospholipidosis has been observed to a similar extent in the tissues of neonatal rats and dogs given daily doses of azithromycin ranging from 10 days to 30 days. Based on the pharmacokinetic data, phospholipidosis has been seen in the rat (30 mg/kg dose) at observed C_max value of 1.3 µg/mL (six times greater than the observed C_max of 0.216 µg/mL at the pediatric dose of 10 mg/kg). Similarly, it has been shown in the dog (10 mg/kg dose) at observed C_max value of 1.5 µg/mL (seven times greater than the observed same C_max and drug dose in the studied pediatric population). On a mg/m² basis, 30 mg/kg dose in the neonatal rat (135 mg/m²) and 10 mg/kg dose in the neonatal dog (79 mg/m²) are approximately 0.45 and 0.3 times, respectively, the recommended dose in the pediatric patients with an average body weight of 25 kg. Phospholipidosis, similar to that seen in the adult animals, is reversible after cessation of azithromycin treatment. The significance of these findings for animals and for humans is unknown.