Cefotetan warnings and precautions

# WARNINGS
BEFORE THERAPY WITH CEFOTAN IS INSTITUTED, CAREFUL INQUIRY SHOULD BE MADE TO DETERMINE WHETHER THE PATIENT HAS HAD PREVIOUS HYPERSENSITIVITY REACTIONS TO CEFOTETAN DISODIUM, CEPHALOSPORINS, PENICILLINS, OR OTHER DRUGS. IF THIS PRODUCT IS TO BE GIVEN TO PENICILLIN-SENSITIVE PATIENTS, CAUTION SHOULD BE EXERCISED BECAUSE CROSS-HYPERSENSITIVITY AMONG BETA-LACTAM ANTIBIOTICS HAS BEEN CLEARLY DOCUMENTED AND MAY OCCUR IN UP TO 10% OF PATIENTS WITH A HISTORY OF PENICILLIN ALLERGY. IF AN ALLERGIC REACTION TO CEFOTAN OCCURS, DISCONTINUE THE DRUG. SERIOUS ACUTE HYPERSENSITIVITY REACTIONS MAY REQUIRE TREATMENT WITH EPINEPHRINE AND OTHER EMERGENCY MEASURES, INCLUDING OXYGEN, INTRAVENOUS FLUIDS, INTRAVENOUS ANTIHISTAMINES, CORTICOSTEROIDS, PRESSOR AMINES, AND AIRWAY MANAGEMENT, AS CLINICALLY INDICATED.
AN IMMUNE MEDIATED HEMOLYTIC ANEMIA HAS BEEN OBSERVED IN PATIENTS RECEIVING CEPHALOSPORIN CLASS ANTIBIOTICS. SEVERE CASES OF HEMOLYTIC ANEMIA, INCLUDING FATALITIES, HAVE BEEN REPORTED IN ASSOCIATION WITH THE ADMINISTRATION OF CEFOTETAN. SUCH REPORTS ARE UNCOMMON. THERE APPEARS TO BE AN INCREASED RISK OF DEVELOPING HEMOLYTIC ANEMIA ON CEFOTETAN RELATIVE TO OTHER CEPHALOSPORINS OF AT LEAST 3 FOLD. IF A PATIENT DEVELOPS ANEMIA ANYTIME WITHIN 2-3 WEEKS SUBSEQUENT TO THE ADMINISTRATION OF CEFOTETAN, THE DIAGNOSIS OF A CEPHALOSPORIN ASSOCIATED ANEMIA SHOULD BE CONSIDERED AND THE DRUG STOPPED UNTIL THE ETIOLOGY IS DETERMINED WITH CERTAINTY. BLOOD TRANSFUSIONS MAY BE CONSIDERED AS NEEDED (See CONTRAINDICATIONS).
PATIENTS WHO RECEIVE COURSES OF CEFOTETAN FOR THE TREATMENT OR PROPHYLAXIS OF INFECTIONS SHOULD HAVE PERIODIC MONITORING FOR SIGNS AND SYMPTOMS OF HEMOLYTIC ANEMIA INCLUDING A MEASUREMENT OF HEMATOLOGICAL PARAMETERS WHERE APPROPRIATE.
Pseudomembranous colitis has been reported with nearly all antibacterial agents, including cefotetan, and may range in severity from mild to life-threatening. Therefore, it is important to consider this diagnosis in patients who present with diarrhea subsequent to the administration of antibacterial agents.
Treatment with antibacterial agents alters the normal flora of the colon and may permit overgrowth of clostridia. Studies indicate that a toxin produced byClostridium difficile is a primary cause of antibiotic-associated colitis.
After the diagnosis of pseudomembranous colitis has been established, appropriate therapeutic measures should be initiated. Mild cases of pseudomembranous colitis usually respond to drug discontinuation alone. In moderate to severe cases, consideration should be given to management with fluids and electrolytes, protein supplementation, and treatment with an antibacterial drug clinically effective against Clostridium difficile colitis. (SeeADVERSE REACTIONS.)
In common with many other broad-spectrum antibiotics, CEFOTAN may be associated with a fall in prothrombin activity and, possibly, subsequent bleeding. Those at increased risk include patients with renal or hepatobiliary impairment or poor nutritional state, the elderly, and patients with cancer. Prothrombin time should be monitored and exogenous vitamin K administered as indicated.

# PRECAUTIONS

## General:
Prescribing CEFOTANin the absence of a proven or strongly suspected bacterial infection of a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.
As with other broad-spectrum antibiotics, prolonged use of CEFOTAN may result in overgrowth of nonsusceptible organisms. Careful observation of the patient is essential. If superinfection does occur during therapy, appropriate measures should be taken.
CEFOTAN should be used with caution in individuals with a history of gastrointestinal disease, particularly colitis.

## Information for Patients:
Patients should be counseled that antibacterial drugs, including CEFOTAN, should only be used to treat bacterial infections. They do not treat viral infections (eg, the common cold). When CEFOTANis 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 CEFOTANor other antibacterial drugs in the future.
As with some other cephalosporins, a disulfiram-like reaction characterized by flushing, sweating, headache, and tachycardia may occur when alcohol (beer, wine, etc.) is ingested within 72 hours after CEFOTAN administration. Patients should be cautioned about the ingestion of alcoholic beverages following the administration of CEFOTAN.

## Drug Interactions:
Increases in serum creatinine have occurred when CEFOTAN was given alone. If CEFOTAN and an aminoglycoside are used concomitantly, renal function should be carefully monitored, because nephrotoxicity may be potentiated.

## Drug/Laboratory Test Interactions:
The administration of CEFOTAN may result in a false positive reaction for glucose in the urine using Clinitest, Benedict's solution, or Fehling's solution. It is recommended that glucose tests based on enzymatic glucose oxidase be used.
As with other cephalosporins, high concentrations of cefotetan may interfere with measurement of serum and urine creatinine levels by Jaffe  reaction and produce false increases in the levels of creatinine reported.

## Carcinogenesis, Mutagenesis, Impairment of Fertility:
Although long-term studies in animals have not been performed to evaluate carcinogenic potential, no mutagenic potential of cefotetan was found in standard laboratory tests.
Cefotetan has adverse effects on the testes of prepubertal rats. Subcutaneous administration of 500 mg/kg/day (approximately 8-16 times the usual adult human dose) on days 6-35 of life (thought to be developmentally analogous to late childhood and prepuberty in humans) resulted in reduced testicular weight and seminiferous tubule degeneration in 10 of 10 animals. Affected cells included spermatogonia and spermatocytes; Sertoli and Leydig cells were unaffected. Incidence and severity of lesions were dose-dependent; at 120 mg/kg/day (approximately 2-4 times the usual human dose) only 1 of 10 treated animals was affected, and the degree of degeneration was mild.
Similar lesions have been observed in experiments of comparable design with other methylthiotetrazole-containing antibiotics and impaired fertility has been reported, particularly at high dose levels. No testicular effects were observed in 7-week-old rats treated with up to 1000 mg/kg/day SC for 5 weeks, or in infant dogs (3 weeks old) that received up to 300 mg/kg/day IV for 5 weeks. The relevance of these findings to humans is unknown.

## Pregnancy:
Teratogenic Effects: Pregnancy Category B:
Reproduction studies have been performed in rats and monkeys at doses up to 20 times the human dose and have revealed no evidence of impaired fertility or harm to the fetus due to cefotetan. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproductive studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

## Nursing Mothers:
Cefotetan is excreted in human milk in very low concentrations. Caution should be exercised when cefotetan is administered to a nursing woman.

## Pediatric Use:
Safety and effectiveness in children have not been established.

## Geriatric Use:
Of the 925 subjects who received cefotetan in clinical studies, 492 (53%) were 60 years and older, while 76 (8%) were 80 years and older. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and the other reported clinical experience has not identified differences in responses between elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
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. (See DOSAGE AND ADMINISTRATION Impaired Renal Function).