Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2023 Publisher: Bristol-Myers Squibb Pharmaceuticals Unlimited Company, Plaza 254, Blanchardstown Corporate Park 2, Dublin 15, Dublin, D15 T867
The treatment of the following infections caused by susceptible aerobic Gram-negative micro-organisms:
Urinary tract infections: including pyelonephritis and cystitis (initial and recurrent) and asymptomatic bacteriuria, including those due to pathogens resistant to the aminoglycosides, cephalosporins or penicillins.
Gonorrhoea: acute uncomplicated urogenital or anorectal infections due to beta-lactamase producing or non-producing strains of N. gonorrhoeae.
Lower respiratory tract infections: including pneumonia, bronchitis and lung infections in patients with cystic fibrosis.
Bacteraemia/septicaemia.
Meningitis caused by Haemophilus influenzae or Neisseria meningitidis. Since Azactam provides only Gram negative cover, it should not be given alone as initial blind therapy, but may be used with an antibiotic active against Gram positive organisms until the results of sensitivity tests are known.
Bone and joint infections.
Skin and soft tissue infections: including those associated with postoperative wounds, ulcers and burns.
Intra-abdominal infections: peritonitis.
Gynaecological infections: pelvic inflammatory disease, endometritis and pelvic cellulitis.
Azactam is indicated for adjunctive therapy to surgery in the management of infections caused by susceptible organisms, including abscesses, infections complicating hollow viscus perforations, cutaneous infections and infections of serous surfaces.
Bacteriological studies to determine the causative organism(s) and their sensitivity to aztreonam should be performed. Therapy may be instituted prior to receiving the results of sensitivity tests.
In patients at risk of infections due to non-susceptible pathogens, additional antibiotic therapy should be initiated concurrently with Azactam to provide broad-spectrum coverage before identification and susceptibility testing results of the causative organism(s) are known. Based on these results, appropriate antibiotic therapy should be continued.
Patients with serious Pseudomonas infections may benefit from concurrent use of Azactam and an aminoglycoside because of their synergistic action. If such concurrent therapy is considered in these patients, susceptibility tests should be performed in vitro to determine the activity in combination. The usual monitoring of serum levels and renal function during aminoglycoside therapy applies.
Intramuscular or intravenous injection, or intravenous infusion.
Azactam is given by deep injection into a large muscle mass, such as the upper quadrant of the gluteus maximus or the lateral part of the thigh.
The dose range of Azactam is 1 to 8 g daily in equally divided doses. The usual dose is 3 to 4 g daily. The maximum recommended dose is 8 g daily. The dosage and route of administration should be determined by the susceptibility of the causative organisms, severity of infection and the condition of the patient.
Dosage Guide: Adults (see table below):
| Type of Infection1 | Dosage | Frequency (hours) | Route |
|---|---|---|---|
| Urinary tract infections | 500 mg or 1 g | 8 or 12 | IM or IV |
| Gonorrhoea/cystitis | 1 g | single dose | IM |
| Cystic fibrosis | 2 g | 6-8 | IV |
| Moderately severe systemic infections | 1 g or 2 g | 8 or 12 | IM or IV |
| Severe systemic or life-threatening infections | 2 g | 6 or 8 | IM or IV |
| Other infections either or | 1 g 2 g | 8 12 | IM or IV IV |
1 Because of the serious nature of infections due to Pseudomonas aeruginosa, a dose of 2 g every 6 or 8 hours is recommended, at least for initial 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 septicaemia, localised parenchymal abscess (e.g. intra-abdominal abscess), peritonitis, meningitis or other severe systemic or life-threatening infections.
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.
Elderly patients normally have a creatinine clearance in excess of 30 mL/min and therefore would receive the normal recommended dose. If renal function is below this level, the dosage schedule should be adjusted (see Renal Impairment).
Prolonged serum levels of aztreonam may occur in patients with transient or persistent renal insufficiency. Therefore, after an initial usual dose, the dosage of aztreonam should be halved in patients with estimated creatinine clearances between 10 and 30 mL/min/1.73 m².
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 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.
A dose reduction of 20-25% is recommended for long-term treatment of patients with chronic liver disease with cirrhosis, especially in cases of alcoholic cirrhosis and when renal function is also impaired.
The usual dosage for patients older than one week is 30 mg/kg/dose every 6 or 8 hours. For severe infections in patients 2 years of age or older, 50 mg/kg/dose every 6 or 8 hours is recommended. The recommended dose for all patients in the treatment of infections due to P. aeruginosa is 50 mg/kg every six to eight hours.
The maximum daily paediatric dose should not exceed the maximum recommended dose for adults.
Dosage information is not yet available for new-borns less than 1 week old.
For instructions on dilution of the product before administration, see section 6.6.
Use of beta-lactam containing therapies, including aztreonam, can cause encephalopathy (e.g. confusion, impairment of consciousness, epilepsy, movement disorders); particularly in patients with renal impairment and in association with beta-lactam overdose.
There have been no reported cases of overdosage. If necessary, aztreonam may be cleared from the serum by hemodialysis and/or peritoneal dialysis. Aztreonam has been shown to be cleared from the serum by continuous arteriovenous hemofiltration.
a) Product unopened: 3 years.
b) Reconstituted product: 24 hours (2-8°C).
a) Product unopened:
Storage before reconstitution: Do not store above 25°C.
b) Reconstituted product:
Stability after reconstitution: Store at 2-8°C for not more than 24 hours.
Discard any unused solution.
Type III clear molded glass vials, closed with silicone grey butyl rubber closure, and sealed with aluminium seal with flip off plastic button:
1 g glass vials: pack of 1 × 15 mL
2 g glass vials: pack of 1 × 15 mL
Azactam for Injection 1 g or 2 g Vial are supplied in 15 mL vials.
Upon the addition of the diluent the contents should be shaken immediately and vigorously. Vials of reconstituted Azactam are not intended for multi-dose use, and any unused solution from a single dose must be discarded. Depending on the type and amount of diluent, the pH ranges from 4.5 to 7.5, and the colour may vary from colourless to light straw-yellow, which may develop a slight pink tint on standing; however this does not affect the potency.
For each gram of aztreonam add at least 3 mL Water for Injections Ph. Eur. or 0.9% Sodium Chloride Injection B.P. and shake well.
| Single Dose Vial Size | Volume of Diluent to be Added |
|---|---|
| 0.5 g | 1.5 mL |
| 1.0 g | 3.0 mL |
To the contents of the vial add 6 to 10 mL of Water for Injections Ph. Eur. and shake well. Slowly inject directly into the vein over a period of 3 to 5 minutes.
Vials: For each gram of aztreonam add at least 3 mL of Water for Injections Ph. Eur. and shake well.
Dilute this initial solution with an appropriate infusion solution to a final concentration less than 2% w/v (at least 50 mL solution per gram of aztreonam). The infusion should be administered over 20-60 minutes.
Appropriate infusion solutions include:
0.9% Sodium Chloride Injection B.P.
5% Glucose Intravenous Infusion B.P.
5% or 10% Mannitol Intravenous Infusion B.P.
Sodium Lactate Intravenous Infusion B.P.
0.9%, 0.45% or 0.2% Sodium Chloride and 5% Glucose Intravenous Infusion B.P.
Compound Sodium Chloride Injection B.P.C. 1959 (Ringer’s Solution for Injection)
Compound Sodium Lactate Intravenous Infusion B.P. (Hartmann’s Solution for Injection).
A volume control administration set may be used to deliver the initial solution of Azactam into a compatible infusion solution being administered. With use of a Y-tube administration set, careful attention should be given to the calculated volume of Azactam solution required so that the entire dose will be infused.
Reconstitution:
Intravenous infusion solutions of Azactam for Injection prepared with 0.9% Sodium Chloride Injection B.P. or 5% Glucose Intravenous B.P., in PVC or glass containers, to which clindamycin phosphate, gentamicin sulphate, tobramycin sulphate, or cephazolin sodium have been added at concentrations usually used clinically, are stable for up to 24 hours in a refrigerator (2-8°C). Ampicillin sodium admixtures with aztreonam in 0.9% Sodium Chloride Injection B.P. are stable for 24 hours in a refrigerator (2-8°C); stability in 5% Glucose Intravenous Infusion B.P. is eight hours under refrigeration.
If aztreonam and metronidazole are to be used together, they should be administered separately as a cherry red colour has been observed after storage of solutions containing combinations of the two products.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
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