Azactam

Contraindications

Hypersensitivity

Cautions

CDAD has been reported with use of nearly all antibacterial agents, including aztreonam

Dose reduction required with renal impairment

Coadministration with nephrotoxic drugs increases risk of renal impairment

Prolonged use may result in superinfection

Use caution in toxic epidermal necrolysis and renal impairment

Medicines can interact with certain foods. In some cases, this may be harmful and your doctor may advise you to avoid certain foods. In the case of Azactam there are no specific foods that you must exclude from your diet when receiving Azactam.

Before taking Azactam, tell your doctor if you:

• are allergic to any antibiotics
• have liver or kidney problems
• are pregnant or plan to become pregnant
• are breastfeeding or plan to breastfeed. Talk to your doctor about the best way to breastfeed your baby if you take Azactam.

Tell your doctor about all the medicine you take, including prescription and non-prescription medicines, vitamins and herbal supplements.

Know the medicines you take. Keep a list of them to show your doctor and pharmacist when you get a new medicine.

Antibacterial; monocyclic β-lactam antibiotic; monobactam.1 42 43 44 246 253 287 306

• Monobactam antibiotic.1 42 43 44 246 253 287 306 Unlike other currently available β-lactam antibiotics, which are bicyclic and contain an adjoining ring fused to the β-lactam ring (e.g., carbapenems, cephalosporins, cephamycins, penicillins),1 3 43 57 241 246 253 287 306 monobactams are monocyclic β-lactam antibiotics.1 3 38 39 40 41 42 43 44 45 46 55 57 60 96 234 241 246 256 264 253 287 306

• Usually bactericidal,1 46 48 55 67 79 88 137 253 but not as rapidly bactericidal as some other β-lactam antibiotics (e.g., imipenem, cefotaxime, cefoxitin, ceftriaxone).137 142 247

• Like other β-lactam antibiotics, antibacterial activity results from inhibition of bacterial cell wall synthesis.1 38 46 57 59 60 247 264 253

• Narrow spectrum of activity.38 40 44 46 55 57 59 76 77 83 85 96 234 241 Active against many gram-negative aerobic bacteria, but has little or no activity against gram-positive aerobic bacteria or anaerobic bacteria.1 3 38 39 40 44 46 47 48 55 57 59 69 70 76 83 84 85 96 234 241 264 280 253 Inactive against Chlamydia,278 Mycoplasma, fungi, and viruses.276 277

• Gram-negative aerobes: Active in vitro and in clinical infections against Citrobacter (including C. freundii), Enterobacter (including E. cloacae), Escherichia coli, Haemophilus influenzae (including β-lactamase-producing strains),3 38 48 55 62 63 65 66 73 76 83 84 100 130 264 Klebsiella oxytoca, K. pneumoniae, Proteus mirabilis, and Pseudomonas aeruginosa.1 3 38 46 47 48 55 57 62 63 65 66 67 68 69 70 71 72 73 75 76 83 84 96 99 100 106 109 110 111 112 117 130 131 234 264 Also active in vitro against Aeromonas hydrophila,1 84 97 119 123 264 Moraxella catarrhalis (including β-lactamase-producing strains),100 130 Morganella morganii, Neisseria gonorrhoeae (including penicillinase-producing strains),1 3 38 48 62 65 66 76 83 84 100 102 103 130 Neisseria meningitidis,3 55 63 84 130 264 Pasteurella multocida,1 84 264 Plesiomonas shigelloides,84 Providencia rettgeri, P. stuartii, Serratia marcescens, Salmonella, Shigella, and Yersinia enterocolitica.3 46 47 48 55 57 84 96 234

• Inactive against Alcaligenes,64 70 74 234 Bordetella bronchiseptica,64 72 Brucella melitensis,125 Burkholderia (including B. cepacia, B. cenocepacia, B. gladioli, B. multivorans),3 64 65 66 69 72 74 84 100 234 311 Flavobacterium meningosepticum,64 Legionella pneumophila,120 and Stenotrophomonas maltophilia.3 64 65 66 69 72 74 84 100 131 234

• Gram-positive aerobes: May be active against some strains of Streptococcus pyogenes (group A β-hemolytic streptococci, GAS) and groups C and G streptococci, but most are resistant.3 55 57 63 73 76 83 86 99 100 117 130 S. agalactiae (group B streptococci, GBS),3 55 73 83 117 130 viridans streptococci,83 84 117 nonenterococcal group D streptococci,3 83 enterococci,3 55 63 73 76 83 86 97 100 117 130 131 234 Staphylococcus aureus,3 55 63 73 76 80 83 84 86 97 100 117 130 131 234 S. epidermidis,3 84 86 97 117 131 S. saprophyticus,73 Listeria monocytogenes,84 86 and Nocardia48 121 are resistant.

• Anaerobes: Not active against most gram-positive and -negative anaerobes, including Clostridium perfringens,84 C. difficile,84 Eubacterium,83 234 Peptococcus,83 Peptostreptococcus,83 97 Fusobacterium,63 83 Veillonella,83 Bacteroides fragilis, and Prevotella melaninogenica.63 73 76 83 97 100 234

Aztreonam is an antibiotic that is used to treat infections caused by bacteria. It works by killing bacteria or preventing their growth.

Aztreonam is used to treat bacterial infections in many different parts of the body. It is sometimes given with other antibiotics. This medicine will not work for colds, flu, or other viral infections.

This medicine is available only with your doctor's prescription.

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

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:

Hypersensitivityanaphylaxis, angioedema, bronchospasm

Hematologicpancytopenia, neutropenia, thrombocytopenia, anemia, eosinophilia, leukocytosis, thrombocytosis

Gastrointestinalabdominal 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.)

Dermatologictoxic epidermal necrolysis (see WARNINGS), purpura, erythema multiforme, exfoliative dermatitis, urticaria, petechiae, pruritus, diaphoresis

Cardiovascularhypotension, transient ECG changes (ventricular bigeminy and PVC), flushing

Respiratorywheezing, dyspnea, chest pain

Hepatobiliaryhepatitis, jaundice

Nervous Systemseizure, confusion, vertigo, paresthesia, insomnia, dizziness

Musculoskeletalmuscular aches

Special Sensestinnitus, diplopia, mouth ulcer, altered taste, numb tongue, sneezing, nasal congestion, halitosis

Othervaginal candidiasis, vaginitis, breast tenderness

Body as a Wholeweakness, 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/mm3) 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:

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

Hematologicincreases in prothrombin and partial thromboplastin times, positive Coombs’ test.

Renalincreases in serum creatinine.

If necessary, aztreonam may be cleared from the serum by hemodialysis and/or peritoneal dialysis.

Azactam® (aztreonam for injection, USP)

Single-dose 15 mL capacity vials:

Storage

Store original packages at room temperature; avoid excessive heat.

ALSO SUPPLIED AS:

Azactam® (aztreonam injection) in GALAXY plastic container (PL 2040) as a frozen, 50 mL single-dose intravenous solution as follows: