Cefoxitin warnings and precautions

# WARNINGS
BEFORE THERAPY WITH CEFOXITIN FOR INJECTION AND DEXTROSE INJECTION IS INSTITUTED, CAREFUL INQUIRY SHOULD BE MADE TO DETERMINE WHETHER THE PATIENT HAS HAD PREVIOUS HYPERSENSITIVITY REACTIONS TO CEFOXITIN, CEPHALOSPORINS, PENICILLINS, OR OTHER DRUGS. THIS PRODUCT SHOULD BE GIVEN WITH CAUTION TO PENICILLIN-SENSITIVE PATIENTS. ANTIBIOTICS SHOULD BE ADMINISTERED WITH CAUTION TO ANY PATIENT WHO HAS DEMONSTRATED SOME FORM OF ALLERGY, PARTICULARLY TO DRUGS. IF AN ALLERGIC REACTION TO CEFOXITIN FOR INJECTION AND DEXTROSE INJECTION OCCURS, DISCONTINUE THE DRUG. SERIOUS HYPERSENSITIVITY REACTIONS MAY REQUIRE EPINEPHRINE AND OTHER EMERGENCY MEASURES.
Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including Cefoxitin for Injection and Dextrose 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
Prescribing Cefoxitin for Injection and Dextrose 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.
The total daily dose should be reduced when Cefoxitin for Injection and Dextrose Injection is administered to patients with transient or persistent reduction of urinary output due to renal insufficiency (see DOSAGE AND ADMINISTRATION), because high and prolonged serum antibiotic concentrations can occur in such individuals from usual doses.
Antibiotics (including cephalosporins) should be prescribed with caution in individuals with a history of gastrointestinal disease, particularly colitis.
As with other antibiotics, prolonged use of cefoxitin may result in overgrowth of nonsusceptible organisms. Repeated evaluation of the patient's condition is essential. If superinfection occurs during therapy, appropriate measures should be taken.
As with other dextrose-containing solutions, Cefoxitin for Injection and Dextrose Injection should be prescribed with caution in patients with overt or known subclinical diabetes mellitus or carbohydrate intolerance for any reason.
If administration is controlled by a pumping device, care must be taken to discontinue pumping action before the container runs dry or air embolism may result.
Use only if solution is clear and container and seals are intact.

## Information for Patients
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.
Patients should be counseled that antibacterial drugs including Cefoxitin for Injection and Dextrose Injection should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When Cefoxitin for Injection and Dextrose 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 Cefoxitin for Injection and Dextrose Injection or other antibacterial drugs in the future.

## Laboratory Tests
As with any potent antibacterial agent, periodic assessment of organ system functions, including renal, hepatic, and hematopoietic, is advisable during prolonged therapy.

## Drug Interactions
Increased nephrotoxicity has been reported following concomitant administration of cephalosporins and aminoglycoside antibiotics.

## Drug/Laboratory Test Interactions
As with cephalothin, high concentrations of cefoxitin (>100 mcg/mL) may interfere with measurement of serum and urine creatinine levels by Jaffe reaction, and produce false increases of modest degree in the levels of creatinine reported. Serum samples from patients treated with cefoxitin should not be analyzed for creatinine if withdrawn within 2 hours of drug administration.
High concentrations of cefoxitin in the urine may interfere with measurement of urinary 17-hydroxy-corticosteroids by the Porter-Silber reaction, and produce false increases of modest degree in the levels reported.
A false-positive reaction for glucose in the urine may occur. This has been observed with CLINITEST reagent tablets.

## Carcinogenesis, Mutagenesis, Impairment of Fertility
Long term studies in animals have not been performed with cefoxitin to evaluate carcinogenic or mutagenic potential. Studies in rats treated intravenously with 400 mg/kg of cefoxitin (approximately three times the maximum recommended human dose) revealed no effects on fertility or mating ability.

## Pregnancy
Pregnancy Category B
Reproduction studies performed in rats and mice at parenteral doses of approximately one to seven and one-half times the maximum recommended human dose did not reveal teratogenic or fetal toxic effects, although a slight decrease in fetal weight was observed.
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.
In the rabbit, cefoxitin was associated with a high incidence of abortion and maternal death. This was not considered to be a teratogenic effect but an expected consequence of the rabbit's unusual sensitivity to antibiotic-induced changes in the population of the microflora of the intestine.

## Nursing Mothers
Cefoxitin is excreted in human milk in low concentrations. Caution should be exercised when cefoxitin is administered to a nursing woman.

## Pediatric Use
Safety and efficacy in pediatric patients from birth to three months of age have not yet been established. In pediatric patients three months of age and older, higher doses of cefoxitin have been associated with an increased incidence of eosinophilia and elevated SGOT.

## Geriatric Use
Of the 1,775 subjects who received cefoxitin in clinical studies, 424 (24%) were 65 and over, while 124 (7%) were 75 and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out (see CLINICAL PHARMACOLOGY).
This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function