AZACTAM (aztreonam injection)inGALAXY Plastic Container (PL 2040) for Intravenous Use

Toreduce the development of drug-resistant bacteria and maintain the effectivenessof AZACTAM and other antibacterial drugs, AZACTAMshould be used only to treat or prevent infections that are proven or stronglysuspected to be caused by bacteria.

AZACTAM (aztreonaminjection) contains the active ingredient aztreonam, a monobactam. It wasoriginally isolated from Chromobacterium violaceum. It isa synthetic bactericidal antibiotic.

The monobactams,having a unique monocyclic beta-lactam nucleus, are structurally differentfrom other beta-lactam antibiotics (eg, penicillins, cephalosporins, cephamycins).The sulfonic acid substituent in the 1-position of the ring activates thebeta-lactam moiety; an aminothiazolyl oxime side chain in the 3-position anda methyl group in the 4-position confer the specific antibacterial spectrumand beta-lactamase stability.

Aztreonam is designatedchemically as (Z)-2-[[[(2-amino-4-thiazolyl)[[(2S,3S)-2-methyl-4-oxo-1-sulfo-3-azetidinyl]carbamoyl]methylene]amino]oxy]-2-methylpropionicacid. Structural formula:

AZACTAM in the GALAXY plastic container (PL 2040) is afrozen, iso-osmotic, sterile, sodium-free, nonpyrogenic intravenous solution.Each 50 mL of solution contains 1 g, or 2 g aztreonam with approximately 1.7g, or 700 mg dextrose hydrous, USP added to adjust osmolality,and approximately 780 mg, or 1.6 g of arginine added for pH adjustment, respectively.Thawed solutions have a pH in the range of 4.5 to 7.5. The solution is forintravenous administration following thawing at room temperature or underrefrigeration.

This GALAXY container is fabricatedfrom a specially designed multilayer plastic (PL 2040). Solutions are in contactwith the polyethylene layer of this container and can leach out certain chemicalcomponents of the plastic in very small amounts within the expiration period.The suitability of the plastic has been confirmed in tests in animals accordingto the USP biological tests for plastic containers as well as by tissue culturetoxicity studies.

Single 30-minute intravenous infusionsof 500 mg, 1 g, and 2 g doses of AZACTAM in healthy subjects produced aztreonampeak serum levels of 54 mcg/mL, 90 mcg/mL, and 204 mcg/mL,respectively, immediately after administration; at 8 hours, serum levels were1 mcg/mL, 3 mcg/mL, and 6 mcg/mL, respectively(Figure 1). Single 3-minute intravenous injections of the same doses resultedin serum levels of 58 mcg/mL, 125 mcg/mL, and 242 mcg/mL at 5 minutes followingcompletion of injection.

Serum concentrations of aztreonamfollowing completion of single intravenous infusions of 500 mg, 1 g, and 2g doses are depicted in Figure 1.

The serum levels of aztreonam following single 500 mg,1 g, or 2 g intravenous doses of AZACTAM exceed the MIC for Neisseria sp., Haemophilusinfluenzae, and most genera of the Enterobacteriaceae for8 hours (for Enterobacter sp., the 8-hour serum levels exceedthe MIC for 80% of strains). For Pseudomonas aeruginosa, asingle 2 g intravenous dose produces serum levels that exceedthe MIC for approximately 4 to 6 hours. All of theabove doses of AZACTAM result in average urine levels of aztreonam that exceedthe MIC for the same pathogens for up to 12 hours.

Whenaztreonam pharmacokinetics were assessed for adult and pediatric patients,they were found to be comparable (down to 9 months old). The serum half-lifeof aztreonam averaged 1.7 hours (1.5-2.0) in subjects with normal renal function,independent of the dose. In healthy subjects, based on a 70 kg person, theserum clearance was 91 mL/min and renal clearance was 56 mL/min; the apparentmean volume of distribution at steady-state averaged 12.6 liters, approximatelyequivalent to extracellular fluid volume.

In elderlypatients, the mean serum half-life of aztreonam increased and the renal clearancedecreased, consistent with the age-related decrease in creatinine clearance. Thedosage of AZACTAM should be adjusted accordingly (see DOSAGEAND ADMINISTRATION: Renal Impairment in Adult Patients ).

Inpatients with impaired renal function, the serum half-life of aztreonam isprolonged. (See DOSAGE AND ADMINISTRATION:Renal Impairment in Adult Patients .) The serum half-life ofaztreonam is only slightly prolonged in patients with hepatic impairment sincethe liver is a minor pathway of excretion.

Averageurine concentrations of aztreonam were approximately 1100 mcg/mL, 3500 mcg/mL,and 6600 mcg/mL within the first 2 hours following single 500 mg, 1 g, and2 g intravenous doses of AZACTAM (30-minute infusions), respectively. Therange of average concentrations for aztreonam in the 8- to 12-hour urine specimensin these studies was 25 to 120 mcg/mL. In healthysubjects, aztreonam is excreted in the urine about equally by active tubularsecretion and glomerular filtration. Approximately 60% to 70% of an intravenousdose was recovered in the urine by 8 hours. Urinary excretion of a singleintravenous dose was essentially complete by 12 hours after injection. About12% of a single intravenous radiolabeled dose was recovered in the feces.Unchanged aztreonam and the inactive beta-lactam ring hydrolysis product ofaztreonam were present in feces and urine.

Intravenousadministration of a single 500 mg or 1 g dose of AZACTAM every 8 hours for7 days to healthy subjects produced no apparent accumulation of aztreonamor modification of its disposition characteristics; serum protein bindingaveraged 56% and was independent of dose.

Renal functionwas monitored in healthy subjects given aztreonam; standard tests (serum creatinine,creatinine clearance, BUN, urinalysis, and total urinary protein excretion)as well as special tests (excretion of N-acetyl-β-glucosaminidase, alanineaminopeptidase, and β-microglobulin) were used. Noabnormal results were obtained.

Aztreonam achievesmeasurable concentrations in the following body fluids and tissues:

The concentration of aztreonam in saliva at 30 minutesafter a single 1 g intravenous dose (9 patients) was 0.2 mcg/mL; in humanmilk at 2 hours after a single 1 g intravenous dose (6 patients), 0.2 mcg/mL;in amniotic fluid at 6 to 8 hours after a single 1 g intravenous dose (5 patients),2 mcg/mL. The concentration of aztreonam in peritoneal fluid obtained 1 to6 hours after multiple 2 g intravenous doses ranged between 12 mcg/mL and90 mcg/mL in 7 of 8 patients studied.

Aztreonam givenintravenously rapidly reaches therapeutic concentrations in peritoneal dialysisfluid; conversely, aztreonam given intraperitoneally in dialysis fluid rapidlyproduces therapeutic serum levels.

Concomitant administrationof probenecid or furosemide and aztreonam causes clinically insignificantincreases in the serum levels of aztreonam. Single-dose intravenous pharmacokineticstudies have not shown any significant interaction between aztreonam and concomitantlyadministered gentamicin, nafcillin sodium, cephradine, clindamycin, or metronidazole.No reports of disulfiram-like reactions with alcohol ingestion have been noted;this is not unexpected since aztreonam does not contain a methyl-tetrazoleside chain.

Aztreonamexhibits potent and specific activity in vitro against awide spectrum of Gram-negative aerobic pathogens including Pseudomonasaeruginosa. The bactericidal action of aztreonam results from theinhibition of bacterial cell wall synthesis due to a high affinity of aztreonamfor penicillin binding protein 3 (PBP3). Aztreonam, unlike the majority ofbeta-lactam antibiotics, does not induce beta-lactamase activity and its molecularstructure confers a high degree of resistance to hydrolysis by beta-lactamases(ie, penicillinases and cephalosporinases) produced by most Gram-negativeand Gram-positive pathogens; it is, therefore, usually active against Gram-negativeaerobic microorganisms that are resistant to antibiotics hydrolyzed by beta-lactamases.It is active against many strains that are multiply-resistant to other antibiotics,such as certain cephalosporins, penicillin, and aminoglycosides. Aztreonammaintains its antimicrobial activity over a pH range of 6 to 8 invitro, as well as in the presence of human serum and under anaerobicconditions.

Aztreonam has been shown to be activeagainst most strains of the following microorganisms, both in vitro andin clinical infections as described in the INDICATIONSAND USAGE section.

Aerobic Gram-negativemicroorganisms:

The following in vitro data are available, buttheir clinical significance is unknown .

Aztreonamexhibits in vitro minimal inhibitory concentrations (MICs)of 8 mcg/mL or less against most (≥90%) strains of the following microorganisms;however, the safety and effectiveness of aztreonam in treating clinical infectionsdue to these microorganisms have not been established in adequate and well-controlledclinical trials.

Aerobic Gram-negative microorganisms:

Aztreonam and aminoglycosides have been shown to be synergistic invitro against most strains of P. aeruginosa, manystrains of Enterobacteriaceae, and other Gram-negative aerobicbacilli.

Alterations of the anaerobic intestinal floraby broad spectrum antibiotics may decrease colonization resistance, thus permittingovergrowth of potential pathogens, eg, Candida and Clostridium species.Aztreonam has little effect on the anaerobic intestinal microflora in invitro studies. Clostridium difficile and its cytotoxinwere not found in animal models following administration of aztreonam. (See ADVERSE REACTIONS: Gastrointestinal .)

Dilution Techniques: Quantitativemethods are used to determine antimicrobial minimal inhibitory concentrations(MICs). These MICs provide estimates of the susceptibility of bacteria toantimicrobial compounds. The MICs should be determined using a standardizedprocedure. Standardized procedures are based on a dilution method (brothor agar) or equivalent with standardized inoculum concentrations and standardizedconcentrations of aztreonam powder. The MIC values should be interpreted accordingto the following criteria:

A report of “Susceptible” indicates that the pathogenis likely to be inhibited if the antimicrobial compound in the blood reachesthe concentrations usually achievable. A report of “Intermediate” indicatesthat the result should be considered equivocal, and, if the microorganismis not fully susceptible to alternative, clinically feasible drugs, the testshould be repeated. This category implies possible clinical applicabilityin body sites where the drug is physiologically concentrated or in situationswhere high dosage of drug can be used. This category also provides a bufferzone which prevents small uncontrolled technical factors from causing majordiscrepancies in interpretation. A report of “Resistant” indicates that thepathogen is not likely to be inhibited if the antimicrobial compound in theblood reaches the concentrations usually achievable; other therapy shouldbe selected.

Standardized susceptibility test proceduresrequire the use of laboratory control microorganisms to control the technicalaspects of the laboratory procedures. Standard aztreonam powder should providethe following MIC values:

Diffusion Techniques: Quantitativemethods that require measurement of zone diameters also provide reproducibleestimates of the susceptibility of bacteria to antimicrobial compounds. Onesuch standardized procedure requires the use ofstandardized inoculum concentrations. This procedure uses paper disks impregnatedwith 30 mcg aztreonam to test the susceptibility of microorganisms to aztreonam.

Reportsfrom the laboratory providing results of the standard single-disk susceptibilitytest with a 30-mcg aztreonam disk should be interpreted according to the followingcriteria:

Interpretation should be as stated above for results usingdilution techniques. Interpretation involves correlation of the diameter obtainedin the disk test with the MIC for aztreonam.

As withstandardized dilution techniques, diffusion methods require the use of laboratorycontrol microorganisms that are used to control the technical aspects of thelaboratory procedures. For the diffusion technique, the 30-mcg aztreonam diskshould provide the following zone diameters in these laboratory test qualitycontrol strains.

To reduce the development of drug-resistantbacteria and maintain the effectiveness of AZACTAM (aztreonam injection) and other antibacterialdrugs, AZACTAM should be used only to treat or prevent infections that areproven or strongly suspected to be caused by susceptible bacteria. When cultureand susceptibility information are available, they should be considered inselecting or modifying antibacterial therapy. In the absence of such data,local epidemiology and susceptibility patterns may contribute to the empiricselection of therapy.

AZACTAM is indicated for thetreatment of the following infections caused by susceptible Gram-negativemicroorganisms:

Urinary Tract Infections (complicatedand uncomplicated), including pyelonephritis and cystitis (initial and recurrent)caused by Escherichia coli, Klebsiella pneumoniae, Proteusmirabilis, Pseudomonas aeruginosa, Enterobactercloacae, Klebsiella oxytoca*, Citrobacter species*,and Serratia marcescens*.

LowerRespiratory Tract Infections, including pneumonia and bronchitis causedby Escherichia coli, Klebsiella pneumoniae, Pseudomonasaeruginosa, Haemophilus influenzae, Proteusmirabilis, Enterobacter species, and Serratiamarcescens*.

Septicemia causedby Escherichia coli, Klebsiella pneumoniae, Pseudomonasaeruginosa, Proteus mirabilis*, Serratiamarcescens*, and Enterobacter species.

Skinand Skin-Structure Infections, including those associated with postoperativewounds, ulcers, and burns caused by Escherichia coli, Proteusmirabilis, Serratia marcescens, Enterobacter species, Pseudomonasaeruginosa, Klebsiella pneumoniae, and Citrobacter species*.

Intra-abdominalInfections, including peritonitis caused by Escherichia coli, Klebsiella speciesincluding K. pneumoniae, Enterobacter speciesincluding E. cloacae*, Pseudomonas aeruginosa, Citrobacter species*including C. freundii*, and Serratia species*including S. marcescens*.

GynecologicInfections, including endometritis and pelvic cellulitis caused by Escherichiacoli, Klebsiella pneumoniae*, Enterobacter species*including E. cloacae*, and Proteus mirabilis*.

AZACTAM is indicated for adjunctive therapy to surgery in themanagement 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 thecommonly encountered Gram-negative aerobic pathogens seen in general surgery.

Concurrent initial therapy with otherantimicrobial agents and AZACTAM is recommended before the causative organism(s)is known in seriously ill patients who are also at risk of having an infectiondue to Gram-positive aerobic pathogens. If anaerobic organisms are also suspectedas etiologic agents, therapy should be initiated using an anti-anaerobic agentconcurrently with AZACTAM (see DOSAGE AND ADMINISTRATION ).Certain antibiotics (eg, cefoxitin, imipenem) may induce high levels of beta-lactamase invitro 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-lactamaseinducing antibiotics not be used concurrently with aztreonam. Following identificationand susceptibility testing of the causative organism(s), appropriate antibiotictherapy should be continued.

This preparation is contraindicatedin patients with known hypersensitivity to aztreonam or any other componentin the formulation.

Both animal and human data suggest thatAZACTAM (aztreonam injection) is rarely cross-reactive with other beta-lactamantibiotics and weakly immunogenic. Treatment with aztreonam can result inhypersensitivity reactions in patients with or without prior exposure. (See CONTRAINDICATIONS .)

Carefulinquiry should be made to determine whether the patient has any history ofhypersensitivity reactions to any allergens.

Whilecross-reactivity of aztreonam with other beta-lactam antibiotics is rare,this drug should be administered with caution to any patient with a historyof hypersensitivity to beta-lactams (eg, penicillins, cephalosporins, and/orcarbapenems). Treatment with aztreonam can result in hypersensitivity reactionsin patients with or without prior exposure to aztreonam. If an allergic reactionto aztreonam occurs, discontinue the drug and institute supportive treatmentas appropriate (eg, maintenance of ventilation, pressor amines, antihistamines,corticosteroids). Serious hypersensitivity reactions may require epinephrineand other emergency measures. (See ADVERSE REACTIONS .)

Clostridiumdifficile associated diarrhea (CDAD) has been reported with use ofnearly all antibacterial agents, including AZACTAM, and may range in severityfrom mild diarrhea to fatal colitis. Treatment with antibacterial agents altersthe normal flora of the colon leading to overgrowth of C. difficile.

C.difficile produces toxins A and B which contribute to the developmentof CDAD. Hypertoxin-producing strains of C. difficile causeincreased morbidity and mortality, as these infections can be refractory toantimicrobial therapy and may require colectomy. CDAD must be considered inall patients who present with diarrhea following antibiotic use. Careful medicalhistory is necessary since CDAD has been reported to occur over two monthsafter the administration of antibacterial agents.

IfCDAD is suspected or confirmed, ongoing antibiotic use not directed against C.difficile may need to be discontinued. Appropriate fluid and electrolytemanagement, protein supplementation, antibiotic treatment of C. difficile,and surgical eva luation should be instituted as clinically indicated.

Rarecases of toxic epidermal necrolysis have been reported in association withaztreonam in patients undergoing bone marrow transplant with multiple riskfactors including sepsis, radiation therapy, and other concomitantly administereddrugs associated with toxic epidermal necrolysis.

PrescribingAZACTAM in the absence of a proven or strongly suspected bacterial infectionor a prophylactic indication is unlikely to provide benefit to the patientand increases the risk of the development of drug-resistant bacteria.

Inpatients with impaired hepatic or renal function, appropriate monitoring isrecommended during therapy.

If an aminoglycoside isused concurrently with aztreonam, especially if high dosages of the formerare used or if therapy is prolonged, renal function should be monitored becauseof the potential nephrotoxicity and ototoxicity of aminoglycoside antibiotics.

Theuse of antibiotics may promote the overgrowth of nonsusceptible organisms,including Gram-positive organisms (Staphylococcus aureus and Streptococcusfaecalis) and fungi. Should superinfection occur during therapy,appropriate measures should be taken.

Patientsshould be counseled that antibacterial drugs including AZACTAM should onlybe used to treat bacterial infections. They do not treat viral infections(eg, the common cold). When AZACTAM is prescribed to treat a bacterial infection,patients should be told that although it is common to feel better early inthe course of therapy, the medication should be taken exactly as directed.Skipping doses or not completing the full course of therapy may (1) decreasethe effectiveness of the immediate treatment and (2) increase the likelihoodthat bacteria will develop resistance and will not be treatable by AZACTAMor other antibacterial drugs in the future.

Diarrheais a common problem caused by antibiotics which usually ends when the antibioticis discontinued. Sometimes after starting treatment with antibiotics, patientscan develop watery and bloody stools (with or without stomach cramps and fever)even as late as 2 or more months after having taken the last dose of the antibiotic.If this occurs, patients should contact their physician as soon as possible.

Carcinogenicitystudies in animals have not been performed.

Genetictoxicology studies performed in vivo and in vitro withaztreonam in several standard laboratory models revealed no evidence of mutagenicpotential at the chromosomal or gene level.

Two-generationreproduction studies in rats at daily doses up to 20 times the maximum recommendedhuman dose (MRHD), prior to and during gestation and lactation, revealed noevidence of impaired fertility. There was a slightly reduced survival rateduring the lactation period in the offspring of rats that received the highestdosage, but not in offspring of rats that received 5 times the MRHD.

Aztreonam crosses the placenta and entersthe fetal circulation.

Studies in pregnant rats andrabbits, with daily doses up to 15 and 5 times, respectively, the MRHD, revealedno evidence of embryo- or fetotoxicity or teratogenicity. No drug inducedchanges were seen in any of the maternal, fetal, or neonatal parameters thatwere monitored in rats receiving 15 times the MRHD of aztreonam during lategestation and lactation.

There are no adequate andwell-controlled studies in pregnant women. Because animal reproduction studiesare not always predictive of human response, aztreonam should be used duringpregnancy only if clearly needed.

Aztreonam is excreted in human milkin concentrations that are less than 1% of concentrations determined in simultaneouslyobtained maternal serum; consideration should be given to temporary discontinuationof nursing and use of formula feedings.

The safety and effectiveness of intravenousAZACTAM have been established in the age groups 9 months to 16 years. Useof AZACTAM in these age groups is supported by evidence from adequate andwell-controlled studies of AZACTAM in adults with additional efficacy, safety,and pharmacokinetic data from noncomparative clinical studies in pediatricpatients. Sufficient data are not available for pediatric patients under 9months of age or for the following treatment indications/pathogens: septicemiaand skin and skin-structure infections (where the skin infection is believedor known to be due to H. influenzae type b). In pediatricpatients with cystic fibrosis, higher doses of AZACTAM may be warranted. (See CLINICAL PHARMACOLOGY , DOSAGEAND ADMINISTRATION , and CLINICALSTUDIES .)

Clinical studies of AZACTAM did notinclude sufficient numbers of subjects aged 65 years and over to determinewhether they respond differently from younger subjects. Other reported clinicalexperience has not identified differences in responses between the elderlyand younger patients. In general, dose selectionfor an elderly patient should be cautious, reflecting the greater frequencyof decreased hepatic, renal, or cardiac function, and of concomitant diseaseor other drug therapy.

In elderly patients, the meanserum half-life of aztreonam increased and the renal clearance decreased,consistent with the age-related decrease in creatinine clearance. Sinceaztreonam is known to be substantially excreted by the kidney, the risk oftoxic reactions to this drug may be greater in patients with impaired renalfunction. Because elderly patients are more likely to have decreased renalfunction, renal function should be monitored and dosage adjustments made accordingly(see DOSAGE AND ADMINISTRATION: Renal Impairmentin Adult Patients and Dosagein the Elderly ).

AZACTAM contains nosodium.

Local reactions (eg, phlebitis/thrombophlebitis;discomfort/swelling) following intravenous administration occurred at ratesof approximately 1.9%.

Systemic reactions (consideredto be related to therapy or of uncertain etiology) occurring at an incidenceof 1% to 1.3% include diarrhea, nausea and/or vomiting, and rash. Reactionsoccurring at an incidence of less than 1% are listed within each body systemin order of decreasing severity:

Hypersensitivity—anaphylaxis,angioedema, bronchospasm

Hematologic—pancytopenia,neutropenia, thrombocytopenia, anemia, eosinophilia, leukocytosis, thrombocytosis

Gastrointestinal—abdominal cramps; rarecases of C. difficile-associated diarrhea, including pseudomembranouscolitis, or gastrointestinal bleeding have been reported. Onset of pseudomembranouscolitis symptoms may occur during or after antibiotic treatment. (See WARNINGS .)

Dermatologic—toxicepidermal 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,vertigo, paresthesia, insomnia, dizziness

Musculoskeletal—muscularaches

Special Senses—tinnitus, diplopia,mouth ulcer, altered taste, numb tongue, sneezing, nasal congestion, halitosis

Other—vaginalcandidiasis, vaginitis, breast tenderness

Bodyas a Whole—weakness, headache, fever, malaise

Of the 612 pediatric patients who weretreated with AZACTAM in clinical trials, less than 1% required discontinuationof therapy due to adverse events. The following systemic adverse events, regardlessof drug relationship, occurred in at least 1% of treated patients in domesticclinical trials: rash (4.3%), diarrhea (1.4%), and fever (1.0%). These adverseevents were comparable to those observed in adult clinical trials.

In343 pediatric patients receiving intravenous therapy, the following localreactions were noted: pain (12%), erythema (2.9%), induration (0.9%), andphlebitis (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%.

Thefollowing laboratory adverse events, regardless of drug relationship, occurredin at least 1% of treated patients: increased eosinophils (6.3%), increasedplatelets (3.6%), neutropenia (3.2%), increased AST (3.8%), increased ALT(6.5%), and increased serum creatinine (5.8%).

In USpediatric clinical trials, neutropenia (absolute neutrophil count less than1000/mm) occurred in 11.3% of patients (8/71)younger than 2 years receiving 30 mg/kg every 6 hours. AST and ALT elevationsto 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 increasedfrequency of these reported laboratory adverse events may be due to eitherincreased severity of illness treated or higher doses of AZACTAM administered.

Adverse laboratory changes without regardto drug relationship that were reported during clinical trials were:

Hepatic—elevationsof AST (SGOT), ALT (SGPT), and alkaline phosphatase; signs or symptoms ofhepatobiliary dysfunction occurred in less than 1% of recipients (see above).

Hematologic—increasesin prothrombin and partial thromboplastin times, positive Coombs’ test.

Renal—increasesin serum creatinine.

Ifnecessary, aztreonam may be cleared from the serum by hemodialysis and/orperitoneal dialysis.

AZACTAM, an intravenous solution in GALAXYplastic containers (PL 2040), is intended for intravenous use only. Dosageshould be determined by susceptibility of the causative organisms, severityand site of infection, and the condition of the patient.

Theintravenous route is recommended for patients with bacterial septicemia, localizedparenchymal abscess (eg, intra-abdominal abscess), peritonitis, or other severesystemic or life-threatening infections.

The durationof therapy depends on the severity of infection. Generally, AZACTAM shouldbe continued for at least 48 hours after the patient becomes asymptomaticor evidence of bacterial eradication has been obtained. Persistent infectionsmay require treatment for several weeks. Doses smaller than those indicatedshould not be used.

Prolonged serum levels of aztreonam mayoccur in patients with transient or persistent renal insufficiency. Therefore,the dosage of AZACTAM should be halved in patients with estimated creatinineclearances between 10 and 30 mL/min/1.73 m after an initial loading dose of 1 or 2 g.

Whenonly the serum creatinine concentration is available, the following formula(based on sex, weight, and age of the patient) may be used to approximatethe creatinine clearance (Clcr). The serum creatinine should represent a steadystate of renal function.

                                             weight (kg) × (140−age)               Males:Clcr = ———————————————                                          72× serum creatinine (mg/dL)

               Females: 0.85 × above value

In patients with severe renalfailure (creatinine clearance less than 10 mL/min/1.73 m),such as those supported by hemodialysis, the usual dose of 500 mg, 1 g, or2 g should be given initially. The maintenance dose should be one-fourth ofthe 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 maintenancedoses, one-eighth of the initial dose should be given after each hemodialysissession.

Renal status is a major determinant ofdosage in the elderly; these patients in particular may have diminished renalfunction. Serum creatinine may not be an accurate determinant of renal status.Therefore, as with all antibiotics eliminated by the kidneys, estimates ofcreatinine clearance should be obtained and appropriate dosage modificationsmade if necessary.

AZACTAM should be administered intravenouslyto pediatric patients with normal renal function. There are insufficient dataregarding intramuscular administration to pediatric patients or dosing inpediatric patients with renal impairment. (See PRECAUTIONS:Pediatric Use .)

Because of the serious nature of infections due to Pseudomonasaeruginosa, dosage of 2 g every 6 or 8 hours isrecommended, at least upon initiation of therapy, in systemic infections causedby this organism in adults.

A total of 612 pediatric patients aged1 month to 12 years were enrolled in uncontrolled clinical trials of aztreonamin the treatment of serious Gram-negative infections, including urinary tract,lower respiratory tract, skin and skin-structure, and intra-abdominal infections.

AZACTAM (aztreonam injection) in GALAXYplastic container (PL 2040) is to be administered as an intermittent intravenousinfusion only.

Storein a freezer capable of maintaining a temperature of –20°C (–4°F).

Thaw frozen container at room temperature,25°C (77°F) or in a refrigerator, 2° to 8°C (36°-46°F). After thawing iscomplete, invert the container to assure a well-mixed solution. (DONOT FORCE THAW BY IMMERSION IN WATER BATHS OR BY MICROWAVE IRRADIATION.)

Checkfor minute leaks by squeezing container firmly. If leaks are detected, discardsolution as sterility may be impaired.

The containershould be visually inspected. Thawed solutions should not be used unless clear;solutions will be colorless to yellow. Components of the solution may precipitatein the frozen state and will dissolve upon reaching room temperature withlittle or no agitation. If after visual inspection the solution remains discolored,cloudy, or if an insoluble precipitate is noted or if any seals or outletports are not intact, the container should be discarded.

DONOT ADD SUPPLEMENTARY MEDICATION.

The thawedsolution in GALAXY plastic container (PL 2040) remains chemically stable foreither 14 days under refrigeration (2°-8°C/36°-46°F) or for 48 hoursat room temperature (25°C/77°F). DO NOT REFREEZE THAWED ANTIBIOTICS.

Use aseptic technique.

Additives or other medication should not be added to AZACTAM(aztreonam injection) in GALAXY plastic container (PL 2040) or infused simultaneouslythrough the same intravenous line. If the same intravenous line is used forsequential infusion of several different drugs, it should be flushed beforeand after infusion of AZACTAM (aztreonam injection) in GALAXY plastic container(PL 2040) with an infusion solution compatible with AZACTAM (aztreonam injection)in GALAXY plastic container (PL 2040)* and any other drug(s) administeredvia this common line.

It is recommended that the intravenousadministration apparatus be replaced at least once every 48 hours.

CAUTION:Do not use plastic containers in series connections. Such use could resultin an embolism due to residual air being drawn from the primary containerbefore administration of the fluid from the secondary container is complete.

Infusion of AZACTAM (aztreonam injection)in GALAXY plastic container (PL 2040) should be completed within a 20- to60-minute period. The plastic container is a single-dose unit; discard anyunused portion remaining in the container.

*The followinginfusion solutions are compatible with AZACTAM (aztreonam injection) in GALAXYplastic container (PL 2040):

AZACTAM (aztreonaminjection) in GALAXY plastic container (PL 2040) is supplied as a frozen,50 mL single-dose intravenous solution as follows:

Store at or below –20°C (–4°F) [See Directions forUse of AZACTAM (aztreonam injection) in GALAXYPlastic Container (PL 2040)].

AZACTAM is a registeredtrademark of Elan Pharmaceuticals, Inc.Bristol-Myers Squibb logois a registered trademark of Bristol-Myers Squibb Company.Galaxy,Dianeal, and Plasm

Manufacturer

Elan Pharmaceuticals, Inc.

Active Ingredients

Source

• U.S. National Library of Medicine
• DailyMed
•  Last Updated: 2nd of March 2011