Drug Class Description
Monobactams.

Generic Name
Aztreonam

Drug Description
Azactam for Injection vials contain 500mg, 1g or 2g aztreonam.

Presentation
Powder for solution for injection or infusion.

Indications
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 influenza 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.

Adult Dosage
Intramuscular or intravenous injection, or intravenous infusion.Adults:The dose range of Azactam is 1 to 8g daily in equally divided doses. The usual dose is 3 to 4g daily. The maximum recommended dose is 8g 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 Infection1Dosage (g)Frequency (hr)RouteUrinary tract0.5-18-12IM or IVGonorrhoea / cystitis1single doseIMCystic fibrosis26-8IVSevere or life-threatening infections26-8IVOther infections either18IM or IVor212IV1 Because of the serious nature of infections due to Pseudomonas aeruginosa , a dose of 2g 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 1g, or those with bacterial septicaemia, localised parenchymal abscess (e.g. intra-abdominal abscess), peritonitis, meningitis or other severe systemic or life-threatening infections.ReconstitutionAzactam for Injection is supplied in 15ml 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 intramuscular injection: For each gram of aztreonam add at least 3ml 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 Added0.5g 1.5ml1.0g 3.0mlAzactam 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.For intravenous injection: To the contents of the vial add 6 to 10ml of Water for Injections Ph. Eur. and shake well. Slowly inject directly into the vein over a period of 3 to 5 minutes.For intravenous infusion:Vials: For each gram of aztreonam add at least 3ml 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 50ml 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.

Child Dosage
The usual dosage for patients older than one week is 30mg/kg/dose every 6 or 8 hours. For severe infections in patients 2 years of age or older, 50mg/kg/dose every 6 or 8 hours is recommended. The total daily dose should not exceed 8g. Dosage information is not yet available for new-borns less than 1 week old.

Elderly Dosage
In the elderly, renal status is the major determinant of dosage. Estimated creatinine clearance should be used to determine appropriate dosage, since serum creatinine is not an accurate measurement of renal function in these patients.Elderly patients normally have a creatinine clearance in excess of 30ml/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).Renal Impairment:In patients with impaired renal function, the normal recommended initial dose should be given. This should be followed by maintenance doses as shown in the following table:Estimated Creatinine Clearance (ml/min) Maintenance Dose10 - 30 Half the initial doseLess than 10 One quarter of the initial doseThe normal dose interval should not be altered.In patients on haemodialysis, a supplementary one eighth of the initial dose should be given after each dialysis.

Contra Indications
Patients with a known hypersensitivity to aztreonam and L-arginine.Aztreonam is contraindicated in pregnancy. Aztreonam crosses the placenta and enters the foetal circulation.

Special Precautions
Specific studies have not shown significant cross-reactivity between Azactam and antibodies to penicillins or cephalosporins. The incidence of hypersensitivity to Azactam in clinical trials has been low but caution should be exercised in patients with a history of hypersensitivity to beta-lactam antibiotics until further experience is gained.Experience in patients with impaired hepatic function is limited. Appropriate liver function monitoring in these patients is recommended.Concurrent therapy with other antimicrobial agents and Azactam is recommended as initial therapy in patients who are at risk of having an infection due to pathogens that are not susceptible to aztreonam.As with other antibiotics, in the treatment of acute pulmonary exacerbations in patients with cystic fibrosis, while clinical improvement is usually noted, lasting bacterial eradications may not be achieved.Therapy with Azactam may result in overgrowth of nonsusceptible organisms which may require additional antimicrobial therapy. In comparative studies, the number of patients treated for superinfections was similar to that of the control drugs used.It is recommended that prothrombin times should be monitored if the patient is on concomitant anticoagulant therapy

Interactions
Single-dose pharmacokinetic studies have not shown any significant interaction between aztreonam and gentamicin, cephradine, clindamycin or metronidazole.Unlike broad spectrum antibiotics, aztreonam produces no effects on the normal anaerobic intestinal flora. No disulfuram-like reactions with alcohol ingestion have been reported.

Adverse Reactions
The following side effects have been reported with Azactam therapy:Dermatological: rash, pruritus, urticaria, erythema, petechia, exfoliative dermatitis, flushing; very rarely toxic epidermal necrolysis.Haematological: eosinophilia, increases in prothrombin and partial thromboplastin time have occurred. There have been isolated reports of thrombocytopenia, neutropenia, anaemia, bleeding and pancytopenia.Hepatobiliary: Jaundice and hepatitis: transient elevations of hepatic transaminases and alkaline phosphatase (without overt signs or symptoms of hepatobiliary dysfunction).Hypersensitivity: anaphylaxis, angioedema, bronchospasam.Gastrointestinal: Diarrhoea, very rarely pseudomembranous colitis or gastrointestinal bleeding, nausea and/or vomiting, abdominal cramps, mouth ulcer and altered taste.Local reactions: phlebitis and discomfort at the i.v. injection site: discomfort at the i.m. injection site.Rare instances of the following events have been reported:-vaginitis, candidosis, seizures, dyspnoea, hypotension, weakness, confusion, dizziness, vertigo, sweating, headache, breast tenderness, halitosis, muscle aches, fever, malaise, sneezing and nasal congestion; transient increases in serum creatinine.

Manufacturer
Bristol-Myers Squibb

Drug Availability
(POM)

Updated
26 June 2009