Ampicillin Sodium and Sulbactam Sodium Injection  Precautions

General

A high percentage of patients with mononucleosis who receive ampicillin develop a skin rash. Thus, ampicillin class antibiotics should not be administered to patients with mononucleosis. In patients treated with UNASYN the possibility of superinfections with mycotic or bacterial pathogens should be kept in mind during therapy. If superinfections occur (usually involving Pseudomonas or Candida), the drug should be discontinued and/or appropriate therapy instituted. 

Prescribing UNASYN in the absence of proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient  and increases the risk of the development of drug-resistant bacteria. 
Information for Patients 

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

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

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. 

Drug/Laboratory Test Interactions 

Administration of UNASYN will result in high  urine concentration of ampicillin. High urine concentrations of ampicillin may result in false positive reactions when testing  for the presence of glucose in urine using Clinitest™, Benedict's Solution  or Fehling's Solution. It is recommended that glucose tests based on enzymatic glucose oxidase reactions (such as Clinistix™ or Testape™) be used. Following administration of  ampicillin to pregnant women, a transient decrease in plasma concentration of total conjugated estriol, estriol-glucuronide, conjugated estrone  and estradiol has been noted. This effect  may also occur with UNASYN.

Carcinogenesis, Mutagenesis, Impairment of Fertility 
Long-term studies in animals have not been performed to evaluate carcinogenic or mutagenic potential. 

Pregnancy

Pregnancy Category B 

Reproduction studies have been performed in mice, rats,  and rabbits  at doses up to ten (10) 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. 

Labor and Delivery 

Studies in guinea pigs have shown that intravenous administration of ampicillin decreased the uterine tone, frequency of contractions, height of contractions, and duration of contractions. However,  it is not known whether the use of UNASYN in humans during labor  or delivery has immediate or delayed adverse effects on  the fetus, prolongs the duration of labor,  or increases  the likelihood that forceps delivery or other obstetrical intervention or resuscitation of the newborn will be necessary. 

Nursing Mothers 

Low concentrations of ampicillin and sulbactam are excreted in the milk; therefore, caution should be exercised when UNASYN  is administered to a nursing woman. 

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. The safety and effectiveness of UNASYN have  not been established  for pediatric patients for intra-abdominal infections. 

ADVERSE REACTIONS 

Adult Patients 

UNASYN is generally well tolerated. The following adverse reactions have been reported. 

Local Adverse Reactions 

• Pain at IM injection site – 16% 
• Pain at IV injection site – 3% 
• Thrombophlebitis – 3% 

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. 

The following adverse reactions have been reported with ampicillin-class antibiotics and can also occur with UNASYN. 

Gastrointestinal  

Gastritis, stomatitis, black "hairy" tongue and enterocolitis. Onset of pseudomembranous colitis symptoms may occur during  or after antibiotic treatment. 

Hypersensitivity Reactions 

Urticaria, erythema multiforme, and an occasional case of exfoliative dermatitis  have been reported. These reactions may be controlled with antihistamines and, if necessary, systemic corticosteroids. Whenever such reactions occur, the drug should be discontinued, unless the opinion of the physician dictates otherwise. Serious and occasional fatal hypersensitivity (anaphylactic) reactions can occur with a penicillin. 

Hematologic  

In addition  to the adverse laboratory changes listed above for UNASYN, agranulocytosis has been reported during  therapy with penicillins. All of 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 antibiotics. 

OVERDOSAGE  

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.