CEFOXITIN SODIUM
For general information on the cephalosporins including adverse effects, contraindications, overdosage, drug interactions, and monitoring parameters, refer to the monograph: Cephalosporins, General Information.
Chemistry - Actually a cephamycin, cefoxitin sodium is a semisynthetic antibiotic that is derivedfrom cephamycin C which is produced by Streptomyces lactamdurans. It occurs as a white to off-white, somewhat hygroscopic powder or granules with a slight characteristic odor. It is very solublein water and slightly soluble in alcohol. Each gram of cefoxitin sodium contains 2.3 mEq ofsodium.
After reconstitution, the solution is stable for 24 hours when kept at room temperature and from48 hours to 1 week if refrigerated. If after reconstitution the solution is immediately frozen in theoriginal container, the preparation is stable up to 30 weeks when stored at -20°C. Stability is dependent on the diluent used and the reader should refer to the package insert or other specialized references for more information. The powder or reconstituted solution may darken, but this apparently does not affect the potency of the product.
All commonly used IV fluids and the following drugs are reportedly compatible with cefoxitin:amikacin sulfate, cimetidine HCl, gentamicin sulfate, kanamycin sulfate, mannitol, metronidazole, mutivitamin infusion concentrate, sodium bicarbonate, tobramycin sulfate and vitamin B-complexwith C. Compatibility is dependent upon factors such as pH, concentration, temperature anddiluents used. It is suggested to consult specialized references for more specific information (e.g.,
Handbook on Injectable Drugs by Trissel; see bibliography).
Pharmacology/Spectrum of Activity - Although not a true cephalosporin, cefoxitin is usuallyclassified as a 2nd generation agent. Cefoxitin has activity against gram positive cocci, but less soon a per weight basis than the 1st generation agents. Unlike the first generation agents, it has goodactivity against many strains of E. coli, Klebsiella and Proteus that may be resistant to the firstgeneration agents. In human medicine, cefoxitin's activity against many strains of Bacteroidesfragilis has placed it in a significant therapeutic role. While Bacteroides fragilis has been isolatedfrom anerobic infections in veterinary patients, it may not be as significant a pathogen in veterinaryspecies as in humans.
Because 2nd generation cephalosporins exhibit specific activities against bacteria, a 30-micrograms cefoxitin disk should be used when performing Kirby-Bauer disk susceptibility tests for thisantibiotic.
Pharmacokinetics (specific) - Cefoxitin is not appreciably absorbed after oral administration andmust be given parenterally to achieve therapeutic serum levels. The absorbed drug is primarilyexcreted unchanged by the kidneys into the urine via both tubular secretion and glomerularfiltration. In humans, approximately 2% of a dose is metabolized to descarbamylcefoxitin, which isinactive. Elimination half-lives may be significantly prolonged in patients with severely diminishedrenal function.
In horses, the apparent volume of distribution at steady state is 110 ml/kg, total body clearance of4.32 ml/min/kg with a serum elimination half-life of 49 minutes.
In calves, the volume of distribution is 318 ml/kg, and has a terminal elimination half-life of 67minutes after IV dosing, and 81 minutes after IM administration. Cefoxitin is approximately 50%bound to calf plasma proteins. Probenecid (40 mg/kg) has been demonstrated to significantlyprolong elimination half-lives.
Chemistry - Actually a cephamycin, cefoxitin sodium is a semisynthetic antibiotic that is derivedfrom cephamycin C which is produced by Streptomyces lactamdurans. It occurs as a white to off-white, somewhat hygroscopic powder or granules with a slight characteristic odor. It is very solublein water and slightly soluble in alcohol. Each gram of cefoxitin sodium contains 2.3 mEq ofsodium.
Storage, Stability, Compatibility
Cefoxitin sodium powder for injection should be stored attemperatures less than 30°C and should not be exposed to temperatures greater than 50°C. Thefrozen solution for injection should be stored at temperatures no higher than -20°C.After reconstitution, the solution is stable for 24 hours when kept at room temperature and from48 hours to 1 week if refrigerated. If after reconstitution the solution is immediately frozen in theoriginal container, the preparation is stable up to 30 weeks when stored at -20°C. Stability is dependent on the diluent used and the reader should refer to the package insert or other specialized references for more information. The powder or reconstituted solution may darken, but this apparently does not affect the potency of the product.
All commonly used IV fluids and the following drugs are reportedly compatible with cefoxitin:amikacin sulfate, cimetidine HCl, gentamicin sulfate, kanamycin sulfate, mannitol, metronidazole, mutivitamin infusion concentrate, sodium bicarbonate, tobramycin sulfate and vitamin B-complexwith C. Compatibility is dependent upon factors such as pH, concentration, temperature anddiluents used. It is suggested to consult specialized references for more specific information (e.g.,
Handbook on Injectable Drugs by Trissel; see bibliography).
Pharmacology/Spectrum of Activity - Although not a true cephalosporin, cefoxitin is usuallyclassified as a 2nd generation agent. Cefoxitin has activity against gram positive cocci, but less soon a per weight basis than the 1st generation agents. Unlike the first generation agents, it has goodactivity against many strains of E. coli, Klebsiella and Proteus that may be resistant to the firstgeneration agents. In human medicine, cefoxitin's activity against many strains of Bacteroidesfragilis has placed it in a significant therapeutic role. While Bacteroides fragilis has been isolatedfrom anerobic infections in veterinary patients, it may not be as significant a pathogen in veterinaryspecies as in humans.
Because 2nd generation cephalosporins exhibit specific activities against bacteria, a 30-micrograms cefoxitin disk should be used when performing Kirby-Bauer disk susceptibility tests for thisantibiotic.
Uses, Indications
In the United States, there are no cefoxitin products approved for veterinaryspecies, but it has been used clinically in several species when an injectable second generationcephalosporin may be indicated.Pharmacokinetics (specific) - Cefoxitin is not appreciably absorbed after oral administration andmust be given parenterally to achieve therapeutic serum levels. The absorbed drug is primarilyexcreted unchanged by the kidneys into the urine via both tubular secretion and glomerularfiltration. In humans, approximately 2% of a dose is metabolized to descarbamylcefoxitin, which isinactive. Elimination half-lives may be significantly prolonged in patients with severely diminishedrenal function.
In horses, the apparent volume of distribution at steady state is 110 ml/kg, total body clearance of4.32 ml/min/kg with a serum elimination half-life of 49 minutes.
In calves, the volume of distribution is 318 ml/kg, and has a terminal elimination half-life of 67minutes after IV dosing, and 81 minutes after IM administration. Cefoxitin is approximately 50%bound to calf plasma proteins. Probenecid (40 mg/kg) has been demonstrated to significantlyprolong elimination half-lives.