Carbenicillin indanyl sodium warnings and precautions

# Warnings and Precautions

## Warnings
Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients on oral penicillins therapy. Although anaphylaxis is more frequent following parenteral therapy, it has occurred in patients on oral penicillins. These reactions are more apt to occur in individuals with a history of penicillin hypersensitivity and/or a history of sensitivity to multiple allergens.
There have been reports of individuals with a history of penicillin hypersensitivity who have experienced severe hypersensitivity reactions when treated with a cephalosporin, and vice versa. Before initiating therapy with a penicillins, careful inquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins, or other allergens. If an allergic reaction occurs, the drug 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 GEOCILLIN(carbenicillin indanyl sodium ), 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
As with any penicillin preparation, an allergic response, including anaphylaxis, may occur particularly in a hypersensitive individual.
Long term use of Geocillin may result in the overgrowth of nonsusceptible organisms. If superinfection occurs during therapy, appropriate measures should be taken.
Since carbenicillin is primarily excreted by the kidney, patients with severe renal impairment (creatinine clearance of less than 10 ml/min) will not achieve therapeutic urine levels of carbenicillin.
In patients with creatinine clearance of 1020 ml/min it may be necessary to adjust dosage to prevent accumulation of drug.
Prescribing Geocillin 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 Geocillin should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When Geocillin 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 Geocillin 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.

## Laboratory Tests
As with other penicillins, periodic assessment of organ system function including renal, hepatic, and hematopoietic systems is recommended during prolonged therapy.

## Drug Interactions
Geocillin (carbenicillin indanyl sodium) blood levels may be increased and prolonged by concurrent administration of probenecid.

## Carcinogenesis, Mutagenesis, Impairment Of Fertility
There are no long-term animal or human studies to evaluate carcinogenic potential. Rats fed 2501000 mg/kg/day for 18 months developed mild liver pathology (e.g., bile duct hyperplasia) at all dose levels, but there was no evidence of drug-related neoplasia. Geocillin administered at daily doses ranging to 1000 mg/kg had no apparent effect on the fertility or reproductive performance of rats.

## Pregnancy Category B
Reproduction studies have been performed at dose levels of 1000 or 500 mg/kg in rats, 200 mg/kg in mice, and at 500 mg/kg in monkeys with no harm to fetus due to Geocillin. 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
It is not known whether the use of Geocillin 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
Carbenicillin class antibiotics are excreted in milk although the amounts excreted are unknown; therefore, caution should be exercised if administered to a nursing woman.

## Pediatric Use
Since only limited clinical data is available to date in children, the safety of Geocillin administration in this age group has not yet been established.