AZTREONAM Adverse Reactions

(aztreonam for injection, USP)

ADVERSE REACTIONS

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 aztreonam for injection 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 1,000/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 aztreonam for injection 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.

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Adverse Reactions

ADVERSE REACTIONS

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 aztreonam for injection 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 1,000/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 aztreonam for injection 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.

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