Azactam Drug Information
Generic name: AZTREONAM
Monobactam Antibacterial [EPC]
Uses of Azactam
To reduce the development of drug-resistant bacteria and maintain the effectiveness of AZACTAM (aztreonam for injection, USP) and other antibacterial drugs, AZACTAM 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.
AZACTAM is indicated for the treatment of the following infections caused by susceptible Gram-negative microorganisms: Urinary Tract Infections (complicated and uncomplicated), including pyelonephritis and cystitis (initial and recurrent) caused by Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, Enterobacter cloacae, Klebsiella oxytoca *, Citrobacter species*, and Serratia marcescens *. Lower Respiratory Tract Infections, including pneumonia and bronchitis caused by Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Haemophilus influenzae, Proteus mirabilis, Enterobacter species, and Serratia marcescens *. Septicemia caused by Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Proteus mirabilis *, Serratia marcescens *, and Enterobacter species. Skin and Skin-Structure Infections, including those associated with postoperative wounds, ulcers, and burns, caused by Escherichia coli, Proteus mirabilis, Serratia marcescens, Enterobacter species, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Citrobacter species*. Intra-abdominal Infections, including peritonitis caused by Escherichia coli, Klebsiella species including K. pneumoniae, Enterobacter species including E. cloacae *, Pseudomonas aeruginosa, Citrobacter species* including C. freundii *, and Serratia species* including S. marcescens *. Gynecologic Infections, including endometritis and pelvic cellulitis caused by Escherichia coli, Klebsiella pneumoniae *, Enterobacter species* including E. cloacae *, and Proteus mirabilis *. 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. AZACTAM is effective against most of the commonly encountered Gram-negative aerobic pathogens seen in general surgery. ------------------------------- * Efficacy for this organism in this organ system was studied in fewer than 10 infections.
Concurrent Therapy Concurrent initial therapy with other antimicrobial agents and AZACTAM is recommended before the causative organism(s) is known in seriously ill patients who are also at risk of having an infection due to Gram-positive aerobic pathogens. If anaerobic organisms are also suspected as etiologic agents, therapy should be initiated using an anti-anaerobic agent concurrently with AZACTAM (see DOSAGE AND ADMINISTRATION ). Certain antibiotics (eg, cefoxitin, imipenem) may induce high levels of beta-lactamase in vitro in some Gram-negative aerobes such as Enterobacter and Pseudomonas species, resulting in antagonism to many beta-lactam antibiotics including aztreonam. These in vitro findings suggest that such beta-lactamase-inducing antibiotics not be used concurrently with aztreonam.
Following identification and susceptibility testing of the causative organism(s), appropriate antibiotic therapy should be continued.
Dosage & Administration of Azactam
| * Maximum recommended dose is 8 g per day. | |
|---|---|
| Urinary tract infections | 500 mg or 1 g |
| Moderately severe systemic infections | 1 g or 2 g |
| Severe systemic or life-threatening infections | 2 g |
Side Effects of Azactam
Local reactions such as phlebitis/thrombophlebitis following intravenous administration, and discomfort/swelling at the injection site following intramuscular administration occurred at rates of approximately 1.9% and 2.4%, respectively. Systemic reactions (considered to be related to therapy or of uncertain etiology) occurring at an incidence of 1% to 1.3% include diarrhea, nausea and/or vomiting, and rash. Reactions occurring at an incidence of less than 1% are listed within each body system in order of decreasing severity: Hypersensitivity —anaphylaxis, angioedema, bronchospasm Hematologic —pancytopenia, neutropenia, thrombocytopenia, anemia, eosinophilia, leukocytosis, thrombocytosis Gastrointestinal —abdominal cramps; rare cases of C. difficile –associated diarrhea, including pseudomembranous colitis, or gastrointestinal bleeding have been reported.
Onset of pseudomembranous colitis symptoms may occur during or after antibiotic treatment. (See WARNINGS.) Dermatologic —toxic epidermal necrolysis (see WARNINGS ), purpura, erythema multiforme, exfoliative dermatitis, urticaria, petechiae, pruritus, diaphoresis Cardiovascular —hypotension, transient ECG changes (ventricular bigeminy and PVC), flushing Respiratory —wheezing, dyspnea, chest pain Hepatobiliary —hepatitis, jaundice Nervous System —seizure, confusion, encephalopathy, vertigo, paresthesia, insomnia, dizziness Musculoskeletal —muscular aches Special Senses —tinnitus, diplopia, mouth ulcer, altered taste, numb tongue, sneezing, nasal congestion, halitosis Other —vaginal candidiasis, vaginitis, breast tenderness Body as a Whole —weakness, headache, fever, malaise Pediatric Adverse Reactions Of the 612 pediatric patients who were treated with AZACTAM in clinical trials, less than 1% required discontinuation of therapy due to adverse events. The following systemic adverse events, regardless of drug relationship, occurred in at least 1% of treated patients in domestic clinical trials: rash (4.3%), diarrhea (1.4%), and fever (1.0%). These adverse events were comparable to those observed in adult clinical trials. In 343 pediatric patients receiving intravenous therapy, the following local reactions were noted: pain (12%), erythema (2.9%), induration (0.9%), and phlebitis (2.1%). In the US patient population, pain occurred in 1.5% of patients, while each of the remaining 3 local reactions had an incidence of 0.5%. The following laboratory adverse events, regardless of drug relationship, occurred in at least 1% of treated patients: increased eosinophils (6.3%), increased platelets (3.6%), neutropenia (3.2%), increased AST (3.8%), increased ALT (6.5%), and increased serum creatinine (5.8%). In US pediatric clinical trials, neutropenia (absolute neutrophil count less than 1000/mm 3 ) occurred in 11.3% of patients (8/71) younger than 2 years receiving 30 mg/kg every 6 hours.
AST and ALT elevations to greater than 3 times the upper limit of normal were noted in 15% to 20% of patients aged 2 years or above receiving 50 mg/kg every 6 hours. The increased frequency of these reported laboratory adverse events may be due to either increased severity of illness treated or higher doses of AZACTAM administered. Adverse Laboratory Changes Adverse laboratory changes without regard to drug relationship that were reported during clinical trials were: Hepatic —elevations of AST (SGOT), ALT (SGPT), and alkaline phosphatase; signs or symptoms of hepatobiliary dysfunction occurred in less than 1% of recipients (see above). Hematologic —increases in prothrombin and partial thromboplastin times, positive Coombs’ test.
Renal —increases in serum creatinine.
Warnings & Cautions for Azactam
Both animal and human data suggest that AZACTAM (aztreonam for injection, USP) is rarely cross-reactive with other beta-lactam antibiotics and weakly immunogenic. Treatment with aztreonam can result in hypersensitivity reactions in patients with or without prior exposure. (See CONTRAINDICATIONS.) Careful inquiry should be made to determine whether the patient has any history of hypersensitivity reactions to any allergens. While cross-reactivity of aztreonam with other beta-lactam antibiotics is rare, this drug should be administered with caution to any patient with a history of hypersensitivity to beta-lactams (eg, penicillins, cephalosporins, and/or carbapenems). Treatment with aztreonam can result in hypersensitivity reactions in patients with or without prior exposure to aztreonam.
If an allergic reaction to aztreonam occurs, discontinue the drug and institute supportive treatment as appropriate (eg, maintenance of ventilation, pressor amines, antihistamines, corticosteroids). Serious hypersensitivity reactions may require epinephrine and other emergency measures. (See ADVERSE REACTIONS.) Clostridium difficile –associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including AZACTAM, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile. C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin-producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy.
CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over 2 months after the administration of antibacterial agents. If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued.
Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated. Rare cases of toxic epidermal necrolysis have been reported in association with aztreonam in patients undergoing bone marrow transplant with multiple risk factors including sepsis, radiation therapy, and other concomitantly administered drugs associated with toxic epidermal necrolysis.
Pregnancy Safety for Azactam
Pregnancy In pregnant women, aztreonam crosses the placenta and enters the fetal circulation. Developmental toxicity studies in pregnant rats and rabbits with daily doses of aztreonam up to 1800 and 1200 mg/kg, respectively, revealed no evidence of embryotoxicity or fetotoxicity or teratogenicity. These doses, based on body surface area, are 2.2- and 2.9-fold greater than the MRHD for adults of 8 g per day.
A peri/postnatal study in rats revealed no drug-induced changes in any maternal, fetal, or neonatal parameters. The highest dose used in this study, 1800 mg/kg/day, is 2.2 times the MRHD based on body surface area. There are no adequate and well-controlled studies of aztreonam on human pregnancy outcomes.
Because animal reproduction studies are not always predictive of human response, aztreonam should be used during pregnancy only if clearly needed.
Pediatric Use of Azactam
Pediatric Use The safety and effectiveness of intravenous AZACTAM have been established in the age groups 9 months to 16 years. Use of AZACTAM in these age groups is supported by evidence from adequate and well-controlled studies of AZACTAM in adults with additional efficacy, safety, and pharmacokinetic data from noncomparative clinical studies in pediatric patients. Sufficient data are not available for pediatric patients under 9 months of age or for the following treatment indications/pathogens: septicemia and skin and skin-structure infections (where the skin infection is believed or known to be due to H. influenzae type b). In pediatric patients with cystic fibrosis, higher doses of AZACTAM may be warranted. (See CLINICAL PHARMACOLOGY, DOSAGE AND ADMINISTRATION, and CLINICAL STUDIES.)
Contraindications for Azactam
This preparation is contraindicated in patients with known hypersensitivity to aztreonam or any other component in the formulation.
Overdosage Information for Azactam
If necessary, aztreonam may be cleared from the serum by hemodialysis and/or peritoneal dialysis.
Clinical Studies of Azactam
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. 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.
Drug information sourced from the FDA. This content is for informational purposes only and does not constitute medical advice. Consult a healthcare professional before making any medication decisions.
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