cefoperazone sodium
Cefobid

Available forms
Available by prescription only
Infusion: 1 g, 2 g piggyback
Parenteral: 1 g, 2 g

Indications and dosages
 Serious respiratory tract, intra-abdominal, gynecologic, skin, skin-structure, urinary tract, and enterococcal infections; bacterial septicemia caused by susceptible organisms; perioperative prophylaxis ◇. Adults: Usual dosage is 1 to 2 g q 12 hours I.M. or I.V. In severe infections or infections caused by less sensitive organisms, the dose may be increased up to 16 g daily in certain situations.
≡ Dosage adjustment. No dosage adjustment is usually needed in patients with renal impairment. However, give doses of 4 g daily cautiously to patients with hepatic disease. Adults with impaired hepatic and renal function shouldn’t receive more than 1 g (base) daily without serum determinations. In patients receiving hemodialysis, schedule a dose to follow treatment.

Pharmacodynamics
Antibacterial action: Cefoperazone is primarily bactericidal; it also may be bacteriostatic. Activity depends on the organism, tissue penetration, dosage, and rate of organism multiplication. Drug acts by adhering to bacterial penicillin-binding proteins, thereby inhibiting cell wall synthesis. Third-generation cephalosporins appear to be more active against some beta-lactamase-producing gram-negative organisms.
Cefoperazone is active against some gram- positive organisms and many enteric gram-negative bacilli, including Streptococcus pneumoniae and Streptococcus pyogenes, Staphylococcus aureus (penicillinase- and non- penicillinase-producing), Staphylococcus epidermidis, Escherichia coli, Klebsiella, Haemophilusinfluenzae, Enterobacter, Citrobacter, Proteus, some Pseudomonas species (including Pseudomonasaeruginosa), and Bacteroides fragilis. Acinetobacter and Listeria usually are resistant. Cefoperazone is less effective than cefotaxime or ceftizoxime against Enterobacteriaceae but is slightly more active than those drugs against Pseudomonas aeruginosa.

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 occurs in patients with inflamed meninges. It crosses the placental barrier. Protein-binding is dose-dependent and decreases as serum levels rise; average is 82% to 93%.
Metabolism: Not substantially metabolized.
Excretion: Excreted primarily in bile; some drug is excreted in urine by renal tubular secretion and glomerular filtration; and small amounts in breast milk. Elimination half-life is about 1 1/2 to 2 1/2 hours in patients with normal hepatorenal function; biliary obstruction or cirrhosis prolongs half-life to about 3 1/2 to 7 hours. Hemodialysis removes cefoperazone.

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

Interactions
Drug-drug. Aminoglycosides: Produces synergistic activity against P. aeruginosa and Serratia marcescens; slightly increases risk of nephrotoxicity. Use together cautiously.
Anticoagulants: May increase risk of bleeding. Use together cautiously.
Probenecid: Competitively inhibits renal tubular secretion of cephalosporins, causing prolonged serum levels of these drugs. Use together cautiously.
Drug-lifestyle. Alcohol use: May cause disulfiram-like reaction. Discourage alcohol use.

Adverse reactions
CV: phlebitis, thrombophlebitis with I.V. injection.
GI: pseudomembranous colitis, nausea, vomiting, diarrhea.
Hematologic: transient neutropenia, eosinophilia, anemia, hypoprothrombinemia, bleeding.
Skin: maculopapular and erythematous rashes, urticaria; pain, induration, sterile abscesses, temperature elevation, tissue sloughingat injection site.
Other: hypersensitivity reactions (serum sickness, anaphylaxis); drug fever with I.V. injection.

Effects on lab test results
• May increase ALT, AST, alkaline phosphatase, bilirubin, GGT, and LDH levels.
• May increase INR and eosinophil count. May decrease hemoglobin, hematocrit, and neutrophil count. May increase or decrease PT.

Overdose and treatment
  Overdose may cause neuromuscular hypersensitivity. Seizures may follow high CNS levels. Hypoprothrombinemia and bleeding may occur.
  Hypoprothrombinemia and bleeding may require treatment with vitamin K or blood products. Hemodialysis removes cefoperazone.

Special considerations
• Diarrhea may be more common with drug than with other cephalosporins because of high degree of biliary excretion.
• Patients with biliary disease may need lower doses.
• For patients on sodium restriction, note that cefoperazone injection contains 1.5 mEq of sodium per gram of drug.
• To prepare I.M. injection, use the appropriate diluent, including sterile water for injection or bacteriostatic water for injection. Follow manufacturer’s recommendations for mixing drug with sterile water for injection and lidocaine 2% injection. Final solution for I.M. injection will contain 0.5% lidocaine and will be less painful upon administration (recommended for concentrations of 250 mg/ml or greater). Inject cefoperazone deep into a large muscle mass, such as the gluteus or the lateral aspect of the thigh.
• Store drug in refrigerator and away from light before reconstituting.
• Allow solution to stand after reconstituting to allow foam to dissipate and solution to clear. Solution can be shaken vigorously to ensure complete drug dissolution.
• After reconstitution, solution is stable for 24 hours at a controlled room temperature or 3 days if refrigerated. Protecting drug from light is unnecessary.
• Because cefoperazone is dialyzable, patients undergoing treatment with hemodialysis may require dosage adjustment.
• Cephalosporins cause false-positive results in urine glucose tests using cupric sulfate (Benedict’s reagent or Clinitest); use glucose oxidase (Chemstrip uG, Diastix, or glucose enzymatic test strip) instead. Cefoperazone may cause positive Coombs’ test results.
• Monitor INR regularly. Vitamin K promptly reverses bleeding if it occurs.
• In patient with renal impairment, monitor renal function before and during therapy.
Pregnant patients
• Use during pregnancy only when clearly needed.
Breast-feeding patients
• Drug appears in breast milk; use cautiously in breast-feeding women.
Pediatric patients
• Safety and effectiveness in children younger than age 12 haven’t been established.
Geriatric patients
• Hypoprothrombinemia and bleeding have been reported more frequently in elderly patients. Use cautiously, and monitor PT and INR and check for signs of abnormal bleeding.

Patient education
• Inform patient of potential adverse reactions.
• Tell patient to report discomfort at I.V. site.

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