Drug Detail:Azactam (injection) (Aztreonam (injection) [ az-tree-oh-nam ])
Generic Name: aztreonam 1g
Dosage Form: injection, powder, for solution
Drug Class: Miscellaneous antibiotics
Dosage in Adult Patients
AZACTAM may be administered intravenously or by intramuscular injection. Dosage and route of administration should be determined by susceptibility of the causative organisms, severity and site of infection, and the condition of the patient.
| Type of Infection | Dose | Frequency (hours) |
|---|---|---|
| * Maximum recommended dose is 8 g per day. | ||
|
Urinary tract infections |
500 mg or 1 g |
8 or 12 |
|
Moderately severe systemic infections |
1 g or 2 g |
8 or 12 |
|
Severe systemic or life-threatening infections |
2 g |
6 or 8 |
Because of the serious nature of infections due to Pseudomonas aeruginosa, dosage of 2 g every six or eight hours is recommended, at least upon initiation of therapy, in systemic infections caused by this organism.
The intravenous route is recommended for patients requiring single doses greater than 1 g or those with bacterial septicemia, localized parenchymal abscess (eg, intra-abdominal abscess), peritonitis, or other severe systemic or life-threatening infections.
The duration of therapy depends on the severity of infection. Generally, AZACTAM should be continued for at least 48 hours after the patient becomes asymptomatic or evidence of bacterial eradication has been obtained. Persistent infections may require treatment for several weeks. Doses smaller than those indicated should not be used.
Renal Impairment in Adult Patients
Prolonged serum levels of aztreonam may occur in patients with transient or persistent renal insufficiency. Therefore, the dosage of AZACTAM should be halved in patients with estimated creatinine clearances between 10 and 30 mL/min/1.73 m2 after an initial loading dose of 1g or 2 g.
When only the serum creatinine concentration is available, the following formula (based on sex, weight, and age of the patient) may be used to approximate the creatinine clearance (Clcr). The serum creatinine should represent a steady state of renal function.
weight (kg) × (140−age)
Males: Clcr = ———————————————
72 × serum creatinine (mg/dL)
Females: 0.85 × above value
In patients with severe renal failure (creatinine clearance less than 10 mL/min/1.73 m2), such as those supported by hemodialysis, the usual dose of 500 mg, 1 g, or 2 g should be given initially. The maintenance dose should be one-fourth of the usual initial dose given at the usual fixed interval of 6, 8, or 12 hours. For serious or life-threatening infections, in addition to the maintenance doses, one-eighth of the initial dose should be given after each hemodialysis session.
Dosage in the Elderly
Renal status is a major determinant of dosage in the elderly; these patients in particular may have diminished renal function. Serum creatinine may not be an accurate determinant of renal status. Therefore, as with all antibiotics eliminated by the kidneys, estimates of creatinine clearance should be obtained and appropriate dosage modifications made if necessary.
Dosage in Pediatric Patients
AZACTAM should be administered intravenously to pediatric patients with normal renal function. There are insufficient data regarding intramuscular administration to pediatric patients or dosing in pediatric patients with renal impairment. (See PRECAUTIONS: Pediatric Use.)
| Type of Infection | Dose | Frequency (hours) |
|---|---|---|
| * Maximum recommended dose is 120 mg/kg/day. | ||
|
Mild to moderate infections |
30 mg/kg |
8 |
|
Moderate to severe infections |
30 mg/kg |
6 or 8 |
CLINICAL STUDIES
A total of 612 pediatric patients aged 1 month to 12 years were enrolled in uncontrolled clinical trials of aztreonam in the treatment of serious Gram-negative infections, including urinary tract, lower respiratory tract, skin and skin-structure, and intra-abdominal infections.
Preparation of Parenteral Solutions
General
Upon the addition of the diluent to the container, contents should be shaken immediately and vigorously. Use constituted solution immediately. Discard any remaining unused constituted solution.
Depending upon the concentration of aztreonam and diluent used, constituted AZACTAM yields a colorless to light straw yellow solution which may develop a slight pink tint on standing (potency is not affected). Parenteral drug products should be inspected visually for particulate matter and discoloration whenever solution and container permit.
Admixtures with Other Antibiotics
Intravenous infusion solutions of AZACTAM not exceeding 2% w/v prepared with Sodium Chloride Injection, USP 0.9% or Dextrose Injection, USP 5%, to which clindamycin phosphate, gentamicin sulfate, tobramycin sulfate, or cefazolin sodium have been added at concentrations usually used clinically, are stable for up to 48 hours at controlled room temperature 15°C to 30°C (59°F to 86°F) or 7 days under refrigeration 2°C to 8°C (36°F to 46°F). Ampicillin sodium admixtures with aztreonam in Sodium Chloride Injection, USP 0.9% are stable for 24 hours at controlled room temperature 15°C to 30°C (59°F to 86°F) and 48 hours under refrigeration 2°C to 8°C (36°F to 46°F); stability in Dextrose Injection, USP 5% is 2 hours at controlled room temperature 15°C to 30°C (59°F to 86°F) and 8 hours under refrigeration 2°C to 8°C (36°F to 46°F).
Aztreonam-cloxacillin sodium and aztreonam-vancomycin hydrochloride admixtures are stable in Dianeal 137 (Peritoneal Dialysis Solution) with 4.25% Dextrose for up to 24 hours at controlled room temperature 15°C to 30°C (59°F to 86°F).
Aztreonam is incompatible with nafcillin sodium, cephradine, and metronidazole.
Other admixtures are not recommended since compatibility data are not available.
Intravenous Solutions
For Bolus Injection: The vial contents should be constituted with 6 mL to 10 mL Sterile Water for Injection, USP.
For Infusion: If the vial contents are to be transferred to an appropriate infusion solution, each gram of aztreonam should be initially constituted with at least 3 mL Sterile Water for Injection, USP. Further dilution may be obtained with one of the following intravenous infusion solutions:
Sodium Chloride Injection, USP, 0.9%
Ringer’s Injection, USP
Lactated Ringer’s Injection, USP
Dextrose Injection, USP, 5% or 10%
Dextrose and Sodium Chloride Injection, USP, 5%:0.9%, 5%:0.45%, or 5%:0.2%
Sodium Lactate Injection, USP (M/6 Sodium Lactate)
Ionosol® B and 5% Dextrose
Isolyte® E
Isolyte® E with 5% Dextrose
Isolyte® M with 5% Dextrose
Normosol®-R
Normosol®-R and 5% Dextrose
Normosol®-M and 5% Dextrose
Mannitol Injection, USP, 5% or 10%
Lactated Ringer’s and 5% Dextrose Injection
Plasma-Lyte M and 5% Dextrose
Intramuscular Solutions
The vial contents should be constituted with at least 3 mL of an appropriate diluent per gram aztreonam. The following diluents may be used:
Sterile Water for Injection, USP
Sterile Bacteriostatic Water for Injection, USP (with benzyl alcohol or with methyl- and propylparabens)
Sodium Chloride Injection, USP, 0.9%
Bacteriostatic Sodium Chloride Injection, USP (with benzyl alcohol)
Stability of Intravenous and Intramuscular Solutions
AZACTAM solutions for intravenous infusion at concentrations not exceeding 2% w/v must be used within 48 hours following constitution if kept at controlled room temperature 15°C to 30°C (59°F to 86°F) or within 7 days if refrigerated 2°C to 8°C (36°F to 46°F).
AZACTAM solutions at concentrations exceeding 2% w/v, except those prepared with Sterile Water for Injection, USP or Sodium Chloride Injection, USP, should be used promptly after preparation; the 2 excepted solutions must be used within 48 hours if stored at controlled room temperature 15°C to 30°C (59°F to 86°F) or within 7 days if refrigerated 2°C to 8°C (36°F to 46°F).
Intravenous Administration
Bolus Injection: A bolus injection may be used to initiate therapy. The dose should be slowly injected directly into a vein, or the tubing of a suitable administration set, over a period of 3 to 5 minutes (see next paragraph regarding flushing of tubing).
Infusion: With any intermittent infusion of aztreonam and another drug with which it is not pharmaceutically compatible, the common delivery tube should be flushed before and after delivery of aztreonam with any appropriate infusion solution compatible with both drug solutions; the drugs should not be delivered simultaneously. Any AZACTAM infusion should be completed within a 20- to 60-minute period. With use of a Y-type administration set, careful attention should be given to the calculated volume of aztreonam solution required so that the entire dose will be infused. A volume control administration set may be used to deliver an initial dilution of AZACTAM (see Preparation of Parenteral Solutions: Intravenous Solutions: For Infusion) into a compatible infusion solution during administration; in this case, the final dilution of aztreonam should provide a concentration not exceeding 2% w/v.
