Unasyn Drug Information

Adult Patients UNASYN is generally well tolerated. The following adverse reactions have been reported in clinical trials. Local Adverse Reactions Pain at IM injection site – 16% Pain at IV injection site – 3% Thrombophlebitis – 3% Phlebitis – 1.2% Systemic Adverse Reactions The most frequently reported adverse reactions were diarrhea in 3% of the patients and rash in less than 2% of the patients.

Additional systemic reactions reported in less than 1% of the patients were: itching, nausea, vomiting, candidiasis, fatigue, malaise, headache, chest pain, flatulence, abdominal distension, glossitis, urine retention, dysuria, edema, facial swelling, erythema, chills, tightness in throat, substernal pain, epistaxis and mucosal bleeding. Pediatric Patients Available safety data for pediatric patients treated with UNASYN demonstrate a similar adverse events profile to those observed in adult patients. Additionally, atypical lymphocytosis has been observed in one pediatric patient receiving UNASYN. Adverse Laboratory Changes Adverse laboratory changes without regard to drug relationship that were reported during clinical trials were: Hepatic: Increased AST (SGOT), ALT (SGPT), alkaline phosphatase, and LDH. Hematologic: Decreased hemoglobin, hematocrit, RBC, WBC, neutrophils, lymphocytes, platelets and increased lymphocytes, monocytes, basophils, eosinophils, and platelets.

Blood Chemistry: Decreased serum albumin and total proteins. Renal: Increased BUN and creatinine. Urinalysis: Presence of RBC's and hyaline casts in urine.

Post-marketing Experience In addition to adverse reactions reported from clinical trials, the following have been identified during post-marketing use of ampicillin sodium and sulbactam sodium or other products containing ampicillin. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. These events have been chosen for inclusion due to a combination of their seriousness, frequency, or potential causal connection to ampicillin sodium and sulbactam sodium.

Infections and Infestations: Clostridioides difficile -associated diarrhea (see WARNINGS section). Blood and Lymphatic System Disorders Hemolytic anemia, thrombocytopenic purpura, and agranulocytosis have been reported. These reactions are usually reversible on discontinuation of therapy and are believed to be hypersensitivity phenomena. Some individuals have developed positive direct Coombs Tests during treatment with UNASYN, as with other beta-lactam antibacterials.

Gastrointestinal Disorders: Abdominal pain, cholestatic hepatitis, cholestasis, hyperbilirubinemia, jaundice, abnormal hepatic function, melena, gastritis, stomatitis, dyspepsia, and black "hairy" tongue (see CONTRAINDICATIONS and WARNINGS sections). General Disorders and Administration Site Conditions: Injection site reaction Immune System Disorders: Serious and fatal hypersensitivity (anaphylactic) reactions (see WARNINGS section), Acute myocardial ischemia with or without myocardial infarction may occur as part of an allergic reaction. Metabolism and Nutrition Disorders: Hypokalemia Nervous System Disorders: Convulsion and dizziness Renal and Urinary Disorders: Tubulointerstitial nephritis Musculoskeletal and Connective Tissue Disorders: Arthralgia Respiratory, Thoracic and Mediastinal Disorders: Dyspnea Skin and Subcutaneous Tissue Disorders: Toxic epidermal necrolysis, Stevens-Johnson syndrome, drug reaction with eosinophilia and systemic symptoms (DRESS), angioedema, Acute generalized exanthematous pustulosis (AGEP), erythema multiforme, exfoliative dermatitis, urticaria (see CONTRAINDICATIONS and WARNINGS sections), and linear IgA bullous dermatosis.

Drug Interactions Probenecid decreases the renal tubular secretion of ampicillin and sulbactam. Concurrent use of probenecid with UNASYN may result in increased and prolonged blood levels of ampicillin and sulbactam. The concurrent administration of allopurinol and ampicillin increases substantially the incidence of rashes in patients receiving both drugs as compared to patients receiving ampicillin alone.

It is not known whether this potentiation of ampicillin rashes is due to allopurinol or the hyperuricemia present in these patients. There are no data with UNASYN and allopurinol administered concurrently. UNASYN and aminoglycosides should not be reconstituted together due to the in vitro inactivation of aminoglycosides by the ampicillin component of UNASYN.

Pregnancy Reproduction studies have been performed in mice, rats, and rabbits at doses up to ten times the human dose and have revealed no evidence of impaired fertility or harm to the fetus due to UNASYN. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. (see PRECAUTIONS-Drug/Laboratory Test Interactions section).

Pediatric Use The safety and effectiveness of UNASYN have been established for pediatric patients one year of age and older for skin and skin structure infections as approved in adults. Use of UNASYN in pediatric patients is supported by evidence from adequate and well-controlled studies in adults with additional data from pediatric pharmacokinetic studies, a controlled clinical trial conducted in pediatric patients and post-marketing adverse events surveillance. (see CLINICAL PHARMACOLOGY, INDICATIONS AND USAGE, ADVERSE REACTIONS, DOSAGE AND ADMINISTRATION, and CLINICAL STUDIES sections). The safety and effectiveness of UNASYN have not been established for pediatric patients for intra-abdominal infections.

The use of UNASYN is contraindicated in individuals with a history of serious hypersensitivity reactions (e.g., anaphylaxis or Stevens-Johnson syndrome) to ampicillin, sulbactam or to other beta-lactam antibacterial drugs (e.g., penicillins and cephalosporins). UNASYN is contraindicated in patients with a previous history of cholestatic jaundice/hepatic dysfunction associated with UNASYN.

Neurological adverse reactions, including convulsions, may occur with the attainment of high CSF levels of beta-lactams. Ampicillin may be removed from circulation by hemodialysis. The molecular weight, degree of protein binding and pharmacokinetics profile of sulbactam suggest that this compound may also be removed by hemodialysis.