Cefoxitin

INDICATIONS AND USAGE: Treatment: CEFOXITIN FOR INJECTION, USP is indicated for the treatment of serious infections caused by susceptible strains of the designated microorganisms in the diseases listed below. (1) Lower respiratory tract infections , including pneumonia and lung abscess, caused by Streptococcus pneumoniae , other streptococci (excluding enterococci, e.g., Enterococcus faecalis [formerly Streptococcus faecalis ]), Staphylococcus aureus (including penicillinase-producing strains), Escherichia coli, Klebsiella species, Haemophilus influenzae , and Bacteroides species. (2) Urinary tract infections caused by Escherichia coli, Klebsiella species, Proteus mirabilis, Morganella morganii , Proteus vulgaris and Providencia species (including P. rettgeri ). (3) Intra-abdominal infections , including peritonitis and intra-abdominal abscess, caused by Escherichia coli, Klebsiella species, Bacteroides species including Bacteroides fragilis , and Clostridium species. (4) Gynecological infections , including endometritis, pelvic cellulitis, and pelvic inflammatory disease caused by Escherichia coli , Neisseria gonorrhoeae (including penicillinase-producing strains), Bacteroides species including B. fragilis , Clostridium species, Peptococcus niger , Peptostreptococcus species, and Streptococcus agalactiae. CEFOXITIN FOR INJECTION, USP, like cephalosporins, has no activity against Chlamydia trachomatis . Therefore, when CEFOXITIN FOR INJECTION, USP is used in the treatment of patients with pelvic inflammatory disease and C. trachomatis is one of the suspected pathogens, appropriate anti-chlamydial coverage should be added. (5) Septicemia caused by Streptococcus pneumoniae, Staphylococcus aureus (including penicillinase-producing strains), Escherichia coli , Klebsiella species, and Bacteroides species including B. fragilis . (6) Bone and joint infections caused by Staphylococcus aureus (including penicillinase-producing strains). (7) Skin and skin structure infections caused by Staphylococcus aureus (including penicillinase-producing strains), Staphylococcus epidermidis , Streptococcus pyogenes and other streptococci (excluding enterococci e.g., Enterococcus faecalis [formerly Streptococcus faecalis ]), Escherichia coli, Proteus mirabilis , Klebsiella species, Bacteroides species including B. fragilis , Clostridium species, Peptococcus niger, and Peptostreptococcus species. Appropriate culture and susceptibility studies should be performed to determine the susceptibility of the causative organisms to CEFOXITIN FOR INJECTION, USP. Therapy may be started while awaiting the results of these studies. In randomized comparative studies, CEFOXITIN FOR INJECTION, USP and cephalothin were comparably safe and effective in the management of infections caused by gram-positive cocci and gram-negative rods susceptible to the cephalosporins. CEFOXITIN FOR INJECTION, USP has a high degree of stability in the presence of bacterial beta-lactamases, both penicillinases and cephalosporinases. Many infections caused by aerobic and anaerobic gram-negative bacteria resistant to some cephalosporins respond to CEFOXITIN FOR INJECTION, USP. Similarly, many infections caused by aerobic and anaerobic bacteria resistant to some penicillin antibiotics (ampicillin, carbenicillin, penicillin G) respond to treatment with CEFOXITIN FOR INJECTION, USP. Many infections caused by mixtures of susceptible aerobic and anaerobic bacteria respond to treatment with CEFOXITIN FOR INJECTION, USP. Prevention: CEFOXITIN FOR INJECTION, USP is indicated for the prophylaxis of infection in patients undergoing uncontaminated gastrointestinal surgery, vaginal hysterectomy, abdominal hysterectomy, or cesarean section. If there are signs of infection, specimens for culture should be obtained for identification of the causative organism so that appropriate treatment may be instituted. To reduce the development of drug-resistant bacteria and maintain the effectiveness of CEFOXITIN FO …

DOSAGE AND ADMINISTRATION: Treatment: Adults: The usual adult dosage range is 1 gram to 2 grams every 6 to 8 hours. Dosage should be determined by susceptibility of the causative organisms, severity of infection, and the condition of the patient (see Table 1 for dosage guidelines). If C. trachomatis is a suspected pathogen, appropriate anti-chlamydial coverage should be added, because cefoxitin sodium has no activity against this organism. CEFOXITIN FOR INJECTION may be used in patients with reduced renal function with the following dosage adjustments: In adults with renal insufficiency , an initial loading dose of 1 gram to 2 grams may be given. After a loading dose, the recommendations for maintenance dosage ( Table 2 ) may be used as a guide. When only the serum creatinine level is available, the following formula (based on sex, weight, and age of the patient) may be used to convert this value into creatinine clearance. The serum creatinine 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 above value In patients undergoing hemodialysis , the loading dose of 1 gram to 2 grams should be given after each hemodialysis, and the maintenance dose should be given as indicated in Table 2 . Antibiotic therapy for group A beta-hemolytic streptococcal infections should be maintained for at least 10 days to guard against the risk of rheumatic fever or glomerulonephritis. In staphylococcal and other infections involving a collection of pus, surgical drainage should be carried out where indicated. Pediatric Patients: The recommended dosage in pediatric patients 3 months of age and older is 80 to 160 mg/kg of body weight per day divided into four to six equal doses. The higher dosages should be used for more severe or serious infections. The total daily dosage should not exceed 12 grams. At this time no recommendation is made for pediatric patients from birth to 3 months of age (see PRECAUTIONS ). In pediatric patients with renal insufficiency, the dosage and frequency of dosage should be modified consistent with the recommendations for adults (see Table 2 ). Prevention: Effective prophylactic use depends on the time of administration. CEFOXITIN FOR INJECTION usually should be given one-half to one hour before the operation, which is sufficient time to achieve effective levels in the wound during the procedure. Prophylactic administration should usually be stopped within 24 hours since continuing administration of any antibiotic increases the possibility of adverse reactions but, in the majority of surgical procedures, does not reduce the incidence of subsequent infection. For prophylactic use in uncontaminated gastrointestinal surgery, vaginal hysterectomy, or abdominal hysterectomy, the following doses are recommended: Adults: 2 grams administered intravenously just prior to surgery (approximately one-half to one hour before the initial incision) followed by 2 grams every 6 hours after the first dose for no more than 24 hours. Pediatric Patients (3 Months and Older): 30 to 40 mg/kg doses may be given at the times designated above. Cesarean Section Patients: For patients undergoing cesarean section, either a single 2 gram dose administered intravenously as soon as the umbilical cord is clamped OR a 3-dose regimen consisting of 2 grams given intravenously as soon as the umbilical cord is clamped followed by 2 grams 4 and 8 hours after the initial dose is recommended (see CLINICAL STUDIES ). Table 1. Guidelines for Dosage of CEFOXITIN FOR INJECTION * Including patients in whom bacteremia is absent or unlikely. Type of Infection Daily Dosage Frequency and Route Uncomplicated forms * of infections such as pneumonia, urinary tract infection, cutaneous infection 3 to 4 grams 1 gram every 6 to 8 hours I.V. Moderately severe or severe infections 6 to 8 grams 1 gram every 4 hours or 2 grams every 6 to 8 hours I.V. Infections commonly needing antibiotics in higher do …

CONTRAINDICATIONS: CEFOXITIN FOR INJECTION is contraindicated in patients who have shown hypersensitivity to cefoxitin and the cephalosporin group of antibiotics.

ADVERSE REACTIONS: CEFOXITIN FOR INJECTION is generally well tolerated. The most common adverse reactions have been local reactions following intravenous injection. Other adverse reactions have been encountered infrequently. Local Reactions: Thrombophlebitis has occurred with intravenous administration. Allergic Reactions: Rash (including exfoliative dermatitis and toxic epidermal necrolysis), urticaria, flushing, pruritus, eosinophilia, fever, dyspnea, and other allergic reactions including anaphylaxis, interstitial nephritis and angioedema have been noted. Cardiovascular: Hypotension. Gastrointestinal: Diarrhea, including documented pseudomembranous colitis which can appear during or after antibiotic treatment. Nausea and vomiting have been reported rarely. Neuromuscular: Possible exacerbation of myasthenia gravis. Blood: Eosinophilia, leukopenia including granulocytopenia, neutropenia, anemia, including hemolytic anemia, thrombocytopenia, and bone marrow depression. A positive direct Coombs test may develop in some individuals, especially those with azotemia. Liver Function: Transient elevations in SGOT, SGPT, serum LDH, and serum alkaline phosphatase; and jaundice have been reported. Renal Function: Elevations in serum creatinine and/or blood urea nitrogen levels have been observed. As with the cephalosporins, acute renal failure has been reported rarely. The role of CEFOXITIN FOR INJECTION in changes in renal function tests is difficult to assess, since factors predisposing to prerenal azotemia or to impaired renal function usually have been present. In addition to the adverse reactions listed above which have been observed in patients treated with CEFOXITIN FOR INJECTION, the following adverse reactions and altered laboratory test results have been reported for cephalosporin class antibiotics: Urticaria, erythema multiforme, Stevens-Johnson syndrome, serum sickness-like reactions, abdominal pain, colitis, renal dysfunction, toxic nephropathy, false-positive test for urinary glucose, hepatic dysfunction including cholestasis, elevated bilirubin, aplastic anemia, hemorrhage, prolonged prothrombin time, pancytopenia, agranulocytosis, superinfection, vaginitis including vaginal candidiasis. Several cephalosporins have been implicated in triggering seizures, particularly in patients with renal impairment when the dosage was not reduced (see DOSAGE AND ADMINISTRATION ). If seizures associated with drug therapy occur, the drug should be discontinued. Anticonvulsant therapy can be given if clinically indicated. To report SUSPECTED ADVERSE EVENTS, contact Fresenius Kabi USA, LLC at 1-800-551-7176 or FDA at 1-800-FDA-1088 or www.fda.gov .

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

Mechanism of Action: Cefoxitin is a bactericidal agent that acts by inhibition of bacterial cell wall synthesis. Cefoxitin has activity in the presence of some beta-lactamases, both penicillinases and cephalosporinases, of Gram-negative and Gram-positive bacteria.

DESCRIPTION: CEFOXITIN FOR INJECTION, USP contains cefoxitin sodium a semi-synthetic, broad-spectrum cephalosporin antibiotic for parenteral administration. It is derived from cephalosporin C, which is produced by Cephalosporium Acremonium . It is the sodium salt of 3-(hydroxymethyl)-7-methoxy-8-oxo-7-[2-(2-thienyl)acetamido]-5-thia-1-azabicyclo [4.2.0] oct-2-ene-2-carboxylate carbamate (ester). The molecular formula is C 16 H 16 N 3 NaO 7 S 2 , and the structural formula is: CEFOXITIN FOR INJECTION, USP contains approximately 53.8 mg (2.3 milliequivalents) of sodium per gram of cefoxitin activity. Solutions of CEFOXITIN FOR INJECTION, USP range from colorless to light amber in color. The pH of freshly constituted solutions usually ranges from 4.2 to 7.0. Each conventional vial contains sterile cefoxitin sodium, USP equivalent to 1 gram or 2 grams cefoxitin. Structural Formula

OVERDOSAGE: The acute intravenous LD 50 in the adult female mouse and rabbit was about 8 g/kg and greater than 1 g/kg, respectively. The acute intraperitoneal LD 50 in the adult rat was greater than 10 g/kg.

HOW SUPPLIED: CEFOXITIN FOR INJECTION, USP is a dry white to off-white powder supplied in conventional vials containing cefoxitin sodium as follows: Product Code Unit of Sale Strength Each vial PRX304125 NDC 63323-341-29 Unit of 25 Sterile cefoxitin sodium, USP equivalent to 1 gram cefoxitin NDC 63323-341-41 PRX304225 NDC 63323-342-29 Unit of 25 Sterile cefoxitin sodium, USP equivalent to 2 grams cefoxitin NDC 63323-342-41 The container closure is not made with natural rubber latex. Special storage instructions: CEFOXITIN FOR INJECTION, USP in the dry state should be stored between 2° to 25°C (36° to 77°F). Avoid exposure to temperatures above 50°C. The dry material as well as solutions tend to darken, depending on storage conditions; product potency, however, is not adversely affected.