Ampicillin and Sulbactam (Ampicillin Sodium / Sulbactam Sodium) - Warnings and Precautions

WARNINGS

SERIOUS AND OCCASIONALLY FATAL HYPERSENSITIVITY (ANAPHYLACTIC) REACTIONS HAVE BEEN REPORTED IN PATIENTS ON PENICILLIN THERAPY. THESE REACTIONS ARE MORE APT TO OCCUR IN INDIVIDUALS WITH A HISTORY OF PENICILLIN HYPERSENSITIVITY AND/OR HYPERSENSITIVITY REACTIONS TO MULTIPLE ALLERGENS. THERE HAVE BEEN REPORTS OF INDIVIDUALS WITH A HISTORY OF PENICILLIN HYPERSENSITIVITY WHO HAVE EXPERIENCED SEVERE REACTIONS WHEN TREATED WITH CEPHALOSPORINS. BEFORE THERAPY WITH A PENICILLIN, CAREFUL INQUIRY SHOULD BE MADE CONCERNING PREVIOUS HYPERSENSITIVITY REACTIONS TO PENICILLINS, CEPHALOSPORINS, AND OTHER ALLERGENS. IF AN ALLERGIC REACTION OCCURS, AMPICILLIN AND SULBACTAM FOR INJECTION SHOULD BE DISCONTINUED AND THE APPROPRIATE THERAPY INSTITUTED.

SERIOUS ANAPHYLACTOID REACTIONS REQUIRE IMMEDIATE EMERGENCY TREATMENT WITH EPINEPHRINE. OXYGEN, INTRAVENOUS STEROIDS, AND AIRWAY MANAGEMENT, INCLUDING INTUBATION, SHOULD ALSO BE ADMINISTERED AS INDICATED.

Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including Ampicillin and Sulbactam for Injection, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.

C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.

If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.

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 Ampicillin and Sulbactam 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 Ampicillin and Sulbactam for Injection in the absence of a 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 Ampicillin and Sulbactam for Injection should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When Ampicillin and Sulbactam for Injection 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 Ampicillin and Sulbactam for Injection 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 Ampicillin and Sulbactam 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 Ampicillin and Sulbactam and allopurinol administered concurrently. Ampicillin and Sulbactam and aminoglycosides should not be reconstituted together due to the in vitro inactivation of aminoglycosides by the ampicillin component of Ampicillin and Sulbactam.

Drug/Laboratory Test Interactions

Administration of Ampicillin and Sulbactam 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 Ampicillin and Sulbactam.

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 Ampicillin and Sulbactam. 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.)

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 Ampicillin and Sulbactam 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 Ampicillin and Sulbactam is administered to a nursing woman.

Pediatric Use

The safety and effectiveness of Ampicillin and Sulbactam for Injection have been established for pediatric patients one year of age and older for skin and skin structure infections as approved in adults. Use of Ampicillin and Sulbactam for Injection 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 Ampicillin and Sulbactam for Injection have not been established for pediatric patients for intra-abdominal infections.