No

Antibiotic, Cephalosporin (Third Generation)

Treatment of susceptible bacterial infection; mainly respiratory tract, skin and skin structure, bone and joint, urinary tract and gynecologic as well as septicemia. Active against a variety of gram-negative bacilli, some gram-positive cocci, and has some activity against Pseudomonas aeruginosa.

B

Hypersensitivity to cefoperazone or any component or cephalosporins

Modify dosage in patients with severe renal or hepatic impairment; prolonged use may result in superinfection; although rare, cefoperazone may interfere with hemostasis via destruction of vitamin K-producing intestinal bacteria, prevention of activation of prothrombin by the attachment of a methyltetrazolethiol side chain, and by an immune-mediated thrombocytopenia; use with caution in patients with a history of penicillin allergy especially IgE-mediated reactions (eg, anaphylaxis, urticaria); may cause antibiotic-associated colitis or colitis secondary to C. difficile

Contains MTT side chain which may lead to increased risk of hypoprothrombinemia and bleeding.

Dermatologic: Rash (maculopapular or erythematous) (2%)

Gastrointestinal: Diarrhea (3%)

Hematologic: Decreased neutrophils (2%), decreased hemoglobin or hematocrit (5%), eosinophilia (10%)

Hepatic: Increased transaminases (5% to 10%)

<1%: Hypoprothrombinemia, bleeding, pseudomembranous colitis, nausea, vomiting, elevated BUN, elevated creatinine, pain at injection site, induration at injection site, phlebitis, drug fever

Other reactions with cephalosporins include anaphylaxis, seizures, Stevens-Johnson syndrome, toxic epidermal necrolysis, renal dysfunction, toxic nephropathy, cholestasis, aplastic anemia, hemolytic anemia, pancytopenia, agranulocytosis, colitis, superinfection

Symptoms of overdose include neuromuscular hypersensitivity, convulsions especially with renal insufficiency; many beta-lactam antibiotics have the potential to cause neuromuscular hyperirritability or seizures

Hemodialysis may be helpful to aid in the removal of the drug from the blood, otherwise most treatment is supportive or symptom directed

Disulfiram-like reaction has been reported when taken within 72 hours of alcohol consumption

Increased nephrotoxicity: Aminoglycosides, furosemide

Reconstituted solution and I.V. infusion in NS or D₅W solution are stable for 24 hours at room temperature, 5 days when refrigerated or 3 weeks, when frozen; after freezing, thawed solution is stable for 48 hours at room temperature or 10 days when refrigerated

Inhibits bacterial cell wall synthesis by binding to one or more of the penicillin-binding proteins (PBPs) which in turn inhibits the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls, thus inhibiting cell wall biosynthesis. Bacteria eventually lyse due to ongoing activity of cell wall autolytic enzymes (autolysins and murein hydrolases) while cell wall assembly is arrested.

Distribution: Widely distributed in most body tissues and fluids; highest concentrations in bile; low penetration in CSF; variable when meninges are inflamed; crosses placenta; small amounts into breast milk

Half-life: 2 hours, higher with hepatic disease or biliary obstruction

Time to peak serum concentration: I.M.: Within 1-2 hours

Elimination: Principally in bile (70% to 75%); 20% to 30% recovered unchanged in urine within 6-12 hours

I.M., I.V.:

Adults: 2-4 g/day in divided doses every 12 hours; up to 12 g/day

Dosing adjustment in hepatic impairment: Reduce dose 50% in patients with advanced liver cirrhosis; maximum daily dose: 4 g

Cefoperazone may decrease vitamin K synthesis by suppressing GI flora; vitamin K deficiency may occur and result in an increased risk of hemorrhage; patients at risk include those with malabsorption states (eg, cystic fibrosis) or poor nutritional status; monitor prothrombin time and administer vitamin K as needed

Monitor for coagulation abnormalities and diarrhea; observe for signs and symptoms of anaphylaxis during first dose

Positive direct Coombs', false-positive urinary glucose test using cupric sulfate (Benedict's solution, Clinitest®, Fehling's solution), false-positive serum or urine creatinine with Jaffé reaction

May cause nervousness; case reports of euphoria, delusion, illusions, and depersonalization with cephalosporins

May rarely cause neutropenia; use caution with clozapine and carbamazepine

No information available to require special precautions

No effects or complications reported

This drug is administered I.M. or I.V. Drink 2-3 L fluid/day. Avoid alcohol during therapy and for 72 hours after last dose (may cause severe disulfiram-like reactions). If diarrhea occurs, yogurt or buttermilk may help. May cause false-positive test with Clinitest®; use another form of testing. May interfere with oral contraceptives; additional contraceptive measures are necessary. Report severe, unresolved diarrhea; vaginal itching or drainage; sores in mouth; blood, pus, or mucus in stool or urine; easy bleeding or bruising; unusual fever or chills; rash; or respiratory difficulty. Breast-feeding precautions: Consult prescriber if breast-feeding.

Do not admix with aminoglycosides in same bottle/bag

Injection, as sodium, premixed (frozen): 1 g (50 mL); 2 g (50 mL)

Powder for injection, as sodium: 1 g, 2 g

Deeter RG, Weinstein MP, Swanson KA, et al, "Crossover Assessment of Serum Bactericidal Activity and Pharmacokinetics of Five Broad-Spectrum Cephalosporins in the Elderly," Antimicrob Agents Chemother, 1990, 34(6):1007-13.

Donowitz GR and Mandell GL, "Beta-Lactam Antibiotics," N Engl J Med, 1988, 318(7):419-26 and 318(8):490-500.

Klein NC and Cunha BA, "Third-Generation Cephalosporins," Med Clin North Am, 1995, 79(4):705-19.

Marshall WF and Blair JE, "The Cephalosporins," Mayo Clin Proc, 1999, 74(2):187-95.

Meyers BR, Mendelson MN, Deeter RG, et al, "Pharmacokinetics of Cefoperazone in Ambulatory Elderly Volunteers Compared With Young Adults," Antimicrob Agents Chemother, 1987, 31(6):925-9.

Naber K, Adam D, Schalkhauser K, et al, "Pharmacokinetics of Cefoperazone in Geriatric Patients and Concentrations in Different Tissues of the Urinary Tract," Excerpta Medica, 1982, 114.