DOSAGE AND ADMINISTRATION
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.
Table 4: Azactam Dosage Guidelines for Adults*
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 1 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.)
Table 5: Azactam Dosage Guidelines for Pediatric Patients*
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.
Constituted solutions are not for multiple-dose use; should the entire volume
in the container not be used for a single dose, the unused solution must be
discarded.
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 room temperature
or 7 days under refrigeration. Ampicillin sodium admixtures with aztreonam
in Sodium Chloride Injection, USP 0.9% are stable for 24 hours at room temperature
and 48 hours under refrigeration; stability in Dextrose Injection, USP 5%
is 2 hours at room temperature and 8 hours under refrigeration.
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 room temperature.
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 contents of an AZACTAM 15 mL capacity vial should
be constituted with 6 to 10 mL Sterile Water for Injection, USP.
For
Infusion: If the contents of a 15 mL capacity vial 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 contents of an AZACTAM 15 mL capacity
vial 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 (59°F-86°F/15°C-30°C)
or within 7 days if refrigerated (36°F-46°F/2°C-8°C).
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 or within 7 days if refrigerated.
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.
Intramuscular Administration
The dose should be given by deep injection
into a large muscle mass (such as the upper outer quadrant of the gluteus
maximus or lateral part of the thigh). Aztreonam is well tolerated and should
not be admixed with any local anesthetic agent.
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