Cefotan

INDICATIONS AND USAGE 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 sec …

DOSAGE AND ADMINISTRATION Treatment The usual adult dosage is 1 gram (g) or 2 grams of CEFOTAN® (Cefotetan for Injection, USP) administered intravenously or intramuscularly. Proper dosage and route of administration should be determined by the condition of the patient, severity of the infection, and susceptibility of the causative organism. General Guidelines for Dosage of CEFOTAN ® (Cefotetan for Injection, USP) Type of Infection Daily Dose Frequency and Route Urinary Tract 1 g to 4 g 500 mg every 12 hours intravenous or intramuscular 1 or 2 g every 24 hours intravenous or intramuscular 1 or 2 g every 12 hours intravenous or intramuscular Skin & Skin Structure Mild - Moderate a 2 g 2 g every 24 hours intravenous 1 g every 12 hours intravenous or intramuscular Severe 4 g 2 g every 12 hours intravenous Other Sites 2 g to 4 g 1 g or 2 g every 12 hours intravenous or intramuscular Severe 4 g 2 g every 12 hours intravenous Life-Threatening 6 g b 3 g every 12 hours intravenous General Guidelines for Dosage of CEFOTAN ® (Cefotetan for Injection, USP) Type of Infection Daily Dose Frequency and Route Urinary Tract 1 to 4 grams 500 mg every 12 hours IV or IM 1 or 2 g every 24 hours IV or IM 1 or 2 g every 12 hours IV or IM Skin & Skin Structure Mild - Moderate a Severe 2 grams 2 g every 24 hours IV 1 g every 12 hours IV or IM 4 grams 2 g every 12 hours IV Other Sites 2 to 4 grams 1 or 2 g every 12 hours IV or IM Severe 4 grams 2 g every 12 hours IV Life-Threatening 6 grams b 3 g every 12 hours IV a Klebsiella pneumoniae skin and skin structure infections should be treated with 1 or 2 grams every 12 hours IV or IM. b Maximum daily dosage should not exceed 6 grams. If Chlamydia trachomatis is a suspected pathogen in gynecologic infections, appropriate antichlamydial coverage should be added, since cefotetan has no activity against this organism. Prophylaxis To prevent postoperative infection in clean contaminated or potentially contaminated surgery in adults, the recommended dosage is 1 or 2 g of CEFOTAN® (Cefotetan for Injection, USP) administered once, intravenously, 30 to 60 minutes prior to surgery. In patients undergoing cesarean section, the dose should be administered as soon as the umbilical cord is clamped. Impaired Renal Function When renal function is impaired, a reduced dosage schedule must be employed. The following dosage guidelines may be used. DOSAGE GUIDELINES FOR PATIENTS WITH IMPAIRED RENAL FUNCTION Creatinine Clearance mL/min Dose Frequency Greater than 30 Usual Recommended Dosage* Every 12 hours 10 to 30 Usual Recommended Dosage* Every 24 hours Less than 10 Usual Recommended Dosage* Every 48 hours * Dose determined by the type and severity of infection, and susceptibility of the causative organism. Alternatively, the dosing interval may remain constant at 12 hour intervals, but the dose reduced to one-half the usual recommended dose for patients with a creatinine clearance of 10 to 30 mL/min, and one-quarter the usual recommended dose for patients with a creatinine clearance of less than 10 mL/min. When only serum creatinine levels are available, creatinine clearance may be calculated from the following formula. The serum creatinine level should represent a steady state of renal function. Males: Weight (kg) x (140 - age) 72 x serum creatinine (mg/100 mL) Females: 0.85 x value for males Cefotetan is dialyzable and it is recommended that for patients undergoing intermittent hemodialysis, one-quarter of the usual recommended dose be given every 24 hours on days between dialysis and one-half the usual recommended dose on the day of dialysis. Preparation of Solution For Intravenous Use Reconstitute with Sterile Water for Injection. Shake to dissolve and let stand until clear. Vial Size Amount of Diluent Added (mL) Approximate Withdrawable Vol (mL) Approximate Average Concentration (mg/mL) 1 gram 10 10.5 95 2 gram 10 to 20 11 to 21 182 to 95 For Intramuscular Use Reconstitute with Sterile Water for Injection; Bacteriostati …

CONTRAINDICATIONS 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.

ADVERSE REACTIONS 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.

DESCRIPTION CEFOTAN ® (Cefotetan for Injection, USP), as cefotetan disodium, is a sterile, semisynthetic, broad-spectrum, beta-lactamase resistant, cephalosporin (cephamycin) antibiotic for parenteral administration. It is the disodium salt of [6 R -(6α,7α)]-7-[[[4-(2-amino-1-carboxy-2-oxoethylidene)-1,3-dithietan-2-yl]carbonyl]amino]-7-methoxy-3-[[(1-methyl-1 H -tetrazol-5-yl)thio]methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid. Structural formula: CEFOTAN ® (Cefotetan for Injection, USP) is supplied in vials containing 80 mg (3.5 mEq) of sodium per gram of cefotetan activity. It is a white to pale yellow powder which is very soluble in water. Reconstituted solutions of CEFOTAN ® (cefotetan for Injection, USP) are intended for intravenous and intramuscular administration. The solution varies from colorless to yellow depending on the concentration. The pH of freshly reconstituted solutions is usually between 4.5 to 6.5. CEFOTAN ® (Cefotetan for Injection, USP) is available in two vial strengths. Each 1 gram vial contains cefotetan disodium equivalent to 1 gram cefotetan activity. Each 2 gram vial contains cefotetan disodium equivalent to 2 grams cefotetan activity. Cefotetan Chemical Structure

OVERDOSAGE Information on overdosage with CEFOTAN® in humans is not available. If overdosage should occur, it should be treated symptomatically and hemodialysis considered, particularly if renal function is compromised.

HOW SUPPLIED CEFOTAN® (Cefotetan for Injection, USP) is a dry, white to pale yellow powder supplied in vials containing cefotetan disodium equivalent to 1 g and 2 g cefotetan activity for intravenous and intramuscular administration. The vials should be stored at 20°C to 25° C (68° to 77° F) [see USP Controlled Room Temperature] and should be protected from light. The following packages are available: NDC No. Strength Supplied 0121-0976-10 1 gram 10 mL vial, packaged in a tray of 10 0121-0977-10 2 grams 20 mL vial, packaged in a tray of 10 Vial stoppers do not contain natural rubber latex. ‡Clinitest® is a registered trademark of Siemens Healthcare Diagnostics Inc. CEFOTAN® is a registered trademark of PAI Holdings, LLC. Distributed by: PAI Pharma Greenville, SC 29605 Made in Italy I097609770723 Rev 07/2023