cefoxitin sodium
Mefoxin

Available forms
Available by prescription only
Infusion: 1 g, 2 g in 50-ml containers
Injection: 1 g, 2 g

Indications and dosages
 Serious respiratory, GU, gynecologic, skin, soft-tissue, bone, joint, blood, and intra-abdominal infections caused by susceptible organisms. Adults: 1 to 2 g I.V. q 6 to 8 hours for uncomplicated forms of infection. Up to 12 g daily in life-threatening infections.
Children older than age 3 months: 80 to 160 mg/kg I.V. daily given in four to six equally divided doses. Don’t exceed 12 g daily.
  Total daily dose is same for I.M. and I.V. administration and depends on susceptibility of organism and severity of infection. Inject cefoxitin deep into a large muscle mass, such as the gluteus or lateral aspect of the thigh.
 Perioperative prophylaxis, use in contaminated surgery ◇. Adults: 2 g I.V. 30 to 60 minutes before surgery; then 2 g I.V. q 6 hours for 24 hours postoperatively.
Children older than age 3 months: 30 to 40 mg/kg I.V. 30 to 60 minutes before surgery; then 30 mg/kg I.V. q 6 hours for 24 hours postoperatively. For contaminated surgery, 1 to 2 g I.V. q 6 hours with or without I.V. gentamicin (1.5 mg/kg q 8 hours) for 5 days.
 Uncomplicated gonorrhea ◇. Adults: Give 2 g I.M. as a single dose with 1 g probenecid P.O. at the same time or up to 30 minutes beforehand.
 Pelvic inflammatory disease. Adults: 2 g I.V. q 6 hours. (If Chlamydia trachomatis is suspected, give additional antichlamydial coverage.)
≡ Dosage adjustment. For patients with impaired renal function, doses or frequency of administration must be modified based on degree of renal impairment, severity of infection, and susceptibility of organism. To prevent toxic accumulation, reduced dosage may be required in patients with creatinine clearance less than 50 ml/minute.

Creatinine clearance (ml/min) Adult dosage 30-50 1-2 g q 8-12 hr 10-29 1-2 g q 12-24 hr 5-9 500 mg-1 g q 12-24 hr < 5 500 mg-1 g q 24-48 hr

Pharmacodynamics
Antibacterial action: Cefoxitin is primarily bactericidal; it also may be bacteriostatic. Activity depends on the organism, tissue penetration, dosage, and rate of organism multiplication. It acts by adhering to bacterial penicillin-binding proteins, thereby inhibiting cell wall synthesis.
  Cefoxitin is active against many gram-positive organisms and enteric gram-negative bacilli, including Escherichia coli and other coliform bacteria, Staphylococcus aureus (penicillinase- and non-penicillinase-producing), Staphylococcus epidermidis, streptococci, Klebsiella, Haemophilus influenzae, and Bacteroides species (including B. fragilis). Enterobacter, Pseudomonas, and Acinetobacter species are resistant to cefoxitin.

Pharmacokinetics
Absorption: Administered I.V. and I.M.
Distribution: Distributed widely into most body tissues and fluids, including the gallbladder, liver, kidneys, bone, sputum, bile, and pleural and synovial fluids; CSF penetration is poor. Cefoxitin crosses the placental barrier and is 50% to 80% protein-bound.
Metabolism: About 2% of a cefoxitin dose is metabolized.
Excretion: Excreted primarily in urine by renal tubular secretion and glomerular filtration; small amounts of drug appear in breast milk. Elimination half-life is about 0.7 to 1.1 hours in patients with normal renal function; half-life is prolonged in patients with severe renal dysfunction to 6.3 to 21.5 hours. Cefoxitin can be removed by hemodialysis but not by peritoneal dialysis.

Contraindications and precautions
Contraindicated in patients hypersensitive to drug or other cephalosporins. Use cautiously in breast-feeding women and patients with impaired renal function or penicillin allergy.

Interactions
Drug-drug. Bacteriostatic drugs (chloramphenicol, erythromycin, tetracyclines): May impair bactericidal activity of cefoxitin. Avoid use together.
Loop diuretics, nephrotoxic drugs (aminoglycosides, colistin, polymyxin B, vancomycin): May increase risk of nephrotoxicity. Monitor patient closely.
Probenecid: Competitively inhibits renal tubular secretion of cephalosporins, resulting in higher, prolonged serum levels of these drugs. Monitor patient closely.

Adverse reactions
CV: hypotension, thrombophlebitis.
GI: pseudomembranous colitis, nausea, vomiting, diarrhea.
GU: acute renal failure.
Hematologic: transient neutropenia, eosinophilia, hemolytic anemia, anemia, thrombocytopenia, leukopenia, bone marrow suppression.
Respiratory: dyspnea with I.V. injection.
Skin: maculopapular and erythematous rash, toxic epidermal necrolysis, urticaria, pruritus, exfoliative dermatitis, pain, induration, sterile abscesses, tissue sloughingat injection site.
Other: hypersensitivity reactions (serum sickness, anaphylaxis), elevated temperature.

Effects on lab test results
• May increase ALT, AST, alkaline phosphatase, bilirubin, and LDH levels and BUN and creatinine levels.
• May increase eosinophil count. May decrease hemoglobin and neutrophil, WBC, and platelet counts.

Overdose and treatment
Overdose may cause neuromuscular hypersensitivity. Seizures may follow high CNS levels.
 Cefoxitin may be removed by hemodialysis.

Special considerations
 ALERT Names of some cephalosporins are similar. Use caution when prescribing.
• For I.V. use, reconstitute 1 g of cefoxitin with at least 10 ml of sterile water for injection, or 2 g of cefoxitin with 10 to 20 ml. Solutions of D₅W and normal saline solution for injection can also be used.
• For I.M. injection, reconstitute with 0.5% to 1% lidocaine hydrochloride (without epinephrine) to minimize pain at injection site; or with sterile water for injection.
• Administer cefoxitin I.M. deep into a large muscle mass. Aspirate before injecting to prevent inadvertent injection into a blood vessel, and rotate sites to prevent tissue damage.
• After reconstituting, shake vial and then let stand until clear to ensure complete drug dissolution. Solution is stable for 24 hours at room temperature, for 1 week if refrigerated, or 26 weeks if frozen.
• Solution may range from colorless to light amber and may darken during storage. Slight color change doesn’t indicate loss of potency.
• Cefoxitin injection contains 2.3 mEq of sodium per gram of drug.
• Cefoxitin causes false-positive results in urine glucose tests using cupric sulfate (Benedict’s reagent or Clinitest); use glucose oxidase tests (Chemstrip uG, Diastix, or glucose enzymatic test strip) instead. Cefoxitin also causes false elevations in serum or urine creatinine levels in tests using Jaffe reaction. May cause positive Coombs’ test results.
• Cefoxitin has been linked to thrombophlebitis. Frequently assess I.V. site for signs of infiltration or phlebitis.
• If patient has renal impairment, monitor renal function before and during therapy.
Pregnant patients
• Use only when clearly needed.
Breast-feeding patients
• Drug appears in breast milk; use cautiously in breast-feeding women.
Pediatric patients
• Dosage may need to be reduced in infants younger than age 3 months. Safety hasn’t been established.
Geriatric patients
• Dosage reduction may be needed in patients with diminished renal function.

Patient education
• Inform patient of potential adverse reactions.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use