Cefotetan

To reduce the development of drug-resistant bacteria and maintain the effectiveness of CEFOTAN ® and other antibacterial drugs, CEFOTAN ® should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy. Treatment CEFOTAN® (Cefotetan for Injection, USP) is indicated for the therapeutic treatment of the following infections when caused by susceptible strains of the designated organisms: Urinary Tract Infections caused by E. coli , Klebsiella spp (including K. pneumoniae ), Proteus mirabilis , Proteus vulgaris , Providencia rettgeri , and Morganella morganii . Lower Respiratory Tract Infections caused by Streptococcus pneumoniae , Staphylococcus aureus (methicillin susceptible), Haemophilus influenza e, Klebsiella species (including K. pneumoniae ), E. coli , Proteus mirabilis , and Serratia marcescens .* Skin and Skin Structure Infections due to Staphylococcus aureus (methicillin-susceptible), Staphylococcus epidermidis (methicillin susceptible), Streptococcus pyogenes , Streptococcus species, Escherichia coli , Klebsiella pneumoniae , Peptococcus niger *, Peptostreptococcus species. Gynecologic Infections caused by Staphylococcus aureus (methicillin susceptible), Staphylococcus epidermidis (methicillin susceptible, Streptococcus species, Streptococcus agalactiae , E. coli , Proteus mirabilis , Neisseria gonorrhoeae , Bacteroides fragilis , Prevotella melaninogenica Bacteroides vulgatus , Fusobacterium species*, and gram-positive anaerobic cocci (including Peptococcus niger and Peptostreptococcus species). Cefotetan, like other cephalosporins, has no activity against Chlamydia trachomatis. Therefore, when cephalosporins are used in the treatment of pelvic inflammatory disease, and C. trachomatis is one of the suspected pathogens, appropriate antichlamydial coverage should be added. Intra-abdominal Infections caused by E. coli , Klebsiella species (including K. pneumoniae ), Streptococcus species, Bacteroides fragilis , Prevotella melaninogenica , Bacteroides vulgatus and Clostridium species (other than Clostridium difficile [see WARNINGS ])*. Bone and Joint Infections caused by Staphylococcus aureus (methicillin susceptible)*. * Efficacy for this organism in this organ system was studied in fewer than ten infections in clinical studies Specimens for bacteriological examination should be obtained in order to isolate and identify causative organisms and to determine their susceptibilities to cefotetan. Therapy may be instituted before results of susceptibility studies are known; however, once these results become available, the antibiotic treatment should be adjusted accordingly. In cases of confirmed or suspected gram-positive or gram-negative sepsis or in patients with other serious infections in which the causative organism has not been identified, it is possible to use CEFOTAN® concomitantly with an aminoglycoside. Cefotetan combinations with aminoglycosides have been shown to be synergistic in vitro against many Enterobacteriaceae and also some other gram-negative bacteria. The dosage recommended in the labeling of both antibiotics may be given and depends on the severity of the infection and the patient's condition. NOTE : 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. Prophylaxis The preoperative administration of CEFOTAN® may reduce the incidence of certain postoperative infections in patients undergoing surgical procedures that are classified as clean contaminated or potentially contaminated (e.g., cesarean section, abdominal or vaginal hysterectomy, transurethral surgery, biliary tract surgery, and gastrointestinal surgery). If there are signs and symptoms of infection, specimens for culture should be obtained for identification of the causative organism so that appropriate therapeutic measures may be initiated.

Treatment CEFOTAN® (Cefotetan for Injection, USP) is indicated for the therapeutic treatment of the following infections when caused by susceptible strains of the designated organisms: Urinary Tract Infections caused by E. coli , Klebsiella spp (including K. pneumoniae ), Proteus mirabilis , Proteus vulgaris , Providencia rettgeri , and Morganella morganii . Lower Respiratory Tract Infections caused by Streptococcus pneumoniae , Staphylococcus aureus (methicillin susceptible), Haemophilus influenza e, Klebsiella species (including K. pneumoniae ), E. coli , Proteus mirabilis , and Serratia marcescens .* Skin and Skin Structure Infections due to Staphylococcus aureus (methicillin-susceptible), Staphylococcus epidermidis (methicillin susceptible), Streptococcus pyogenes , Streptococcus species, Escherichia coli , Klebsiella pneumoniae , Peptococcus niger *, Peptostreptococcus species. Gynecologic Infections caused by Staphylococcus aureus (methicillin susceptible), Staphylococcus epidermidis (methicillin susceptible, Streptococcus species, Streptococcus agalactiae , E. coli , Proteus mirabilis , Neisseria gonorrhoeae , Bacteroides fragilis , Prevotella melaninogenica Bacteroides vulgatus , Fusobacterium species*, and gram-positive anaerobic cocci (including Peptococcus niger and Peptostreptococcus species). Cefotetan, like other cephalosporins, has no activity against Chlamydia trachomatis. Therefore, when cephalosporins are used in the treatment of pelvic inflammatory disease, and C. trachomatis is one of the suspected pathogens, appropriate antichlamydial coverage should be added. Intra-abdominal Infections caused by E. coli , Klebsiella species (including K. pneumoniae ), Streptococcus species, Bacteroides fragilis , Prevotella melaninogenica , Bacteroides vulgatus and Clostridium species (other than Clostridium difficile [see WARNINGS ])*. Bone and Joint Infections caused by Staphylococcus aureus (methicillin susceptible)*. * Efficacy for this organism in this organ system was studied in fewer than ten infections in clinical studies Specimens for bacteriological examination should be obtained in order to isolate and identify causative organisms and to determine their susceptibilities to cefotetan. Therapy may be instituted before results of susceptibility studies are known; however, once these results become available, the antibiotic treatment should be adjusted accordingly. In cases of confirmed or suspected gram-positive or gram-negative sepsis or in patients with other serious infections in which the causative organism has not been identified, it is possible to use CEFOTAN® concomitantly with an aminoglycoside. Cefotetan combinations with aminoglycosides have been shown to be synergistic in vitro against many Enterobacteriaceae and also some other gram-negative bacteria. The dosage recommended in the labeling of both antibiotics may be given and depends on the severity of the infection and the patient's condition. NOTE : 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.

Prophylaxis The preoperative administration of CEFOTAN® may reduce the incidence of certain postoperative infections in patients undergoing surgical procedures that are classified as clean contaminated or potentially contaminated (e.g., cesarean section, abdominal or vaginal hysterectomy, transurethral surgery, biliary tract surgery, and gastrointestinal surgery). […]

CEFOTAN® is contraindicated in patients with a known allergy to the cephalosporin group of antibiotics and in those individuals who have experienced a cephalosporin associated hemolytic anemia.

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 TO 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 TREATMENT OR PROPHYLAXIS OF INFECTIONS SHOULD HAVE PERIODIC MONITORING FOR SIGNS AND SYMPTOMS OF HEMOLYTIC ANEMIA INCLUDING A MEASUREMENT OF HEMATOLOGICAL PARAMETERS WHERE APPROPRIATE. Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including cefotetan, 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. 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.

General Prescribing CEFOTAN® 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. 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 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 CEFOTAN®, should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When CEFOTAN® 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 CEFOTAN® (Cefotetan for Injection, USP) or 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® (Cefotetan for Injection, USP) 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 Jaffé 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 0.8 times the maximum adult human dose on a body surface area basis) on days 6 to 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 (0.2 times the maximum human dose on a body surface area basis) 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 subcutaneous for 5 weeks, or in infant dogs (3 weeks old) that received up to 300 mg/kg/day intravenous for 5 weeks (both 1.6 times the maximum recommended human dose on a body surface area basis). The relevance of these findings to humans is unknown. Pregnancy Teratogenic Effects. 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. Reproduction studies have been performed in rats and monkeys at doses up to 2000 and 600 mg/kg/day (3 and 2 times the maximum recommended human dose on a body surface area basis, respectively), and have revealed no evidence of impaired fertility or harm to the fetus due to cefotetan. 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 pediatric patients 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 ).

General Prescribing CEFOTAN® 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. 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 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 CEFOTAN®, should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When CEFOTAN® 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 CEFOTAN® (Cefotetan for Injection, USP) or 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® (Cefotetan for Injection, USP) administration. […]

In clinical studies, the following adverse effects were considered related to CEFOTAN therapy. Those appearing in italics have been reported during postmarketing experience. Gastrointestinal: symptoms occurred in 1.5% of patients, the most frequent were diarrhea (1 in 80) and nausea (1 in 700); pseudomembranous colitis . Onset of pseudomembranous colitis symptoms may occur during or after antibiotic treatment or surgical prophylaxis (see WARNINGS ). Hematologic: laboratory abnormalities occurred in 1.4% of patients and included eosinophilia (1 in 200), positive direct Coombs test (1 in 250), and thrombocytosis (1 in 300); agranulocytosis, hemolytic anemia, leukopenia, thrombocytopenia, and prolonged prothrombin time with or without bleeding . Hepatic: enzyme elevations occurred in 1.2% of patients and included a rise in ALT (SGPT) (1 in 150), AST (SGOT) (1 in 300), alkaline phosphatase (1 in 700), and LDH (1 in 700). Hypersensitivity: reactions were reported in 1.2% of patients and included rash (1 in 150) and itching (1 in 700); anaphylactic reactions and urticaria . Local: effects were reported in less than 1% of patients and included phlebitis at the site of injection (1 in 300), and discomfort (1 in 500). Renal: Elevations in BUN and serum creatinine have been reported . Urogenital: Nephrotoxicity has rarely been reported . Miscellaneous: Fever In addition to the adverse reactions listed above which have been observed in patients treated with cefotetan, the following adverse reactions and altered laboratory tests have been reported for cephalosporin-class antibiotics: pruritus, Stevens-Johnson syndrome, erythema multiforme, toxic epidermal necrolysis, vomiting, abdominal pain, colitis, superinfection, vaginitis including vaginal candidiasis, renal dysfunction, toxic nephropathy, hepatic dysfunction including cholestasis, aplastic anemia, hemorrhage, elevated bilirubin, pancytopenia, and neutropenia. Several cephalosporins have been implicated in triggering seizures, particularly in patients with renal impairment, when the dosage was not reduced (see DOSAGE AND ADMINISTRATION and OVERDOSAGE ). If seizures associated with drug therapy occur, the drug should be discontinued. Anticonvulsant therapy can be given if clinically indicated. To report SUSPECTED ADVERSE REACTIONS , contact PAI Pharma at 1-800-845-8210, or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.