No

Antibiotic, Cephalosporin (Second Generation)

Treatment of susceptible bacterial infection; mainly respiratory tract, skin and skin structure, bone and joint, urinary tract and gynecologic, septicemia; surgical prophylaxis. Active against methicillin-sensitive staphylococci, many streptococci, and various gram-negative bacilli including E. coli, some Klebsiella, P. mirabilis, H. influenzae, and Moraxella.

B

Hypersensitivity to cefamandole nafate, any component, or cephalosporins

Modify dosage in patients with severe renal impairment; prolonged use may result in superinfection; although rare, cefamandole 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.

Gastrointestinal: Diarrhea

Local: Thrombophlebitis

<1%: Anaphylaxis, rash (maculopapular and erythematous), urticaria, pseudomembranous colitis, nausea, vomiting, elevated transaminases, cholestasis, eosinophilia, neutropenia, thrombocytopenia, increased BUN, increased creatinine, fever, prolonged PT

Reactions reported with other cephalosporins include toxic epidermal necrolysis, Stevens-Johnson syndrome, abdominal pain, superinfection, renal dysfunction, toxic nephropathy, aplastic anemia, hemolytic anemia, hemorrhage, pancytopenia, vaginitis, seizures

Symptoms of overdose include neuromuscular hypersensitivity, convulsions, especially in patients 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 cefamandole plasma levels: Probenecid

Increased nephrotoxicity: Aminoglycosides, furosemide

Hypoprothrombinemic effect increased: Warfarin and heparin

After reconstitution, CO₂ gas is liberated which allows solution to be withdrawn without injecting air; solution is stable for 24 hours at room temperature and 96 hours when refrigerated; for I.V., infusion in NS and D₅W is stable for 24 hours at room temperature, 1 week when refrigerated, or 26 weeks when frozen

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: Well throughout the body, except CSF; poor penetration even with inflamed meninges

Protein binding: 56% to 78%

Half-life: 30-60 minutes

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

Elimination: Extensive enterohepatic circulation; high concentrations in bile; majority of drug excreted unchanged in urine

I.M., I.V.:

Adults: Usual dose: 500-1000 mg every 4-8 hours; in life-threatening infections: 2 g every 4 hours may be needed

Dosing interval in renal impairment:

Cl_cr 25-50 mL/minute: 1-2 g every 8 hours

Cl_cr 10-25 mL/minute: 1 g every 8 hours

Cl_cr <10 mL/minute: 1 g every 12 hours

Hemodialysis: Moderately dialyzable (20% to 50%)

Monitor for signs of bruising or bleeding; 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 medication 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; observe for signs and symptoms of anaphylaxis during first dose

Powder for injection, as nafate: 500 mg (10 mL); 1 g (10 mL, 100 mL); 2 g (20 mL, 100 mL); 10 g (100 mL)

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

Gentry LO, Zeluff BJ, and Cooley DA, "Antibiotic Prophylaxis in Open-Heart Surgery: A Comparison of Cefamandole, Cefuroxime, and Cefazolin," Ann Thorac Surg, 1988, 46(2):167-71.

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

Mellin HE, Welling PG, and Madsen PO, "Pharmacokinetics of Cefamandole in Patients With Normal and Impaired Renal Function," Antimicrob Agents Chemother, 1977, 11:262-6.

Peterson CD, Lake KD, Arom KV, et al, "Antibiotic Prophylaxis in Open-Heart Surgery Patients: Comparison of Cefamandole and Cefuroxime," Drug Intell Clin Pharm, 1987, 21(9):728-32.