Veterinary Drug Handbook (VDH) is the reference veterinarians turn to when they want an independent source of information on the drugs that are used in veterinary medicine today.

CEFOPERAZONE SODIUM

Chemistry - A third generation cephalosporin, cefoperazone sodium contains a piperazine sidechain giving it antipseudomonal activity. It occurs as white, crystalline powder and is freely solublein water and poorly soluble in alcohol. At room temperature, cefoperazone sodium has a maximumsolubility in compatible IV solutions of 475 mg/ml (at concentrations >333 mg/ml vigorous andprolonged shaking may be required). Reconstituted solutions of the drug have a pH from 4.5 - 6.5.
One gram contains 1.5 mEq of sodium.

Storage, Stability, Compatibility

The sterile powder for injection should be stored at temperatures less than 25°C and protected from light. Once reconstituted, solutions do not need to be protected from light.
After reconstitution, cefoperazone sodium is generally stable for 24 hours at room temperature and5 days when refrigerated in a variety of IV solutions (e.g., sterile or bacteriostatic water for injection, dextrose in water/saline/LRS solutions, lactated Ringer's injection, Normasol R, and saline IVsolutions). When frozen at -2 to -10°C in dextrose, sodium chloride or sterile water for injection, cefoperazone sodium is stable for 3 weeks (dextrose solutions) to 5 weeks (water or salinesolutions).
Cefoperazone sodium is reportedly compatible with cimetidine HCl, clindamycin phosphate, furosemide and heparin sodium, acyclovir sodium, cyclophosphamide, esmolol HCl, famotidine, hydromorphone HCl, magnesium sulfate, and morphine sulfate. It is reportedly incompatible withsome TPN mixtures, doxapram HCl, gentamicin sulfate, hetastarch, labetolol HCl, meperidine HCl, odansetron HCl, perphenazine, promethazine, and sargostim. Compatibility is dependent uponfactors such as pH, concentration, temperature and diluents used. It is suggested to consultspecialized references (e.g., Handbook on Injectable Drugs by Trissel; see bibliography) for morespecific information.

Pharmacology - CEFOPERAZONE SODIUM

Cefoperazone is a third generation injectable cephalosporin agent. For more information, refer to the monograph: Cephalosporins, General Information.
Uses, Indications - Cefoperazone is used to treat serious infections, particularly against susceptible
Enterobacteriaceae not susceptible to other less expensive agents or when aminoglycosides are notindicated (due to their potential toxicity).

Pharmacokinetics - CEFOPERAZONE SODIUM

Cefoperazone is not absorbed after oral administration and must be givenparenterally. It is widely distributed throughout the body; CSF levels are low if meninges are notinflamed. Cefoperazone crosses the placenta and enters maternal milk in low concentrations; nodocumented adverse effects to offspring have been noted. Unlike most cephalosporins, cefopera-zone is principally excreted in the bile and elimination half-lives are approximately 2 hours in humans. Dosage adjustments generally are not required for patients with renal insufficiency.

Contraindications, Precautions, Reproductive Safety

Only prior allergic reaction tocephalosporins contraindicates cefoperazone's use. In humans documented hypersensitive topenicillin, up to 16% may also be allergic to cephalosporins. The veterinary significance of this isunclear. Because cefoperazone is excreted in the bile, patients with significant hepatic disease orbiliary obstruction may have their serum half-lives increase 2 - 4 times above normal. Dosageadjustment may be necessary. Cefoperazone should be used with caution in patients with preexisting bleeding disorders. It contains a thiomethyltetrazole side-chain which has been associatedwith causing coagulation abnormalities.
No teratogenic effects were demonstrated in studies in pregnant mice, rats, and monkeys given upto 10 times labeled doses of cefoperazone.

Adverse Effects, Warnings

Cefoperazone is a relatively safe agent. Rarely, hypersensitivity reactions could potentially occur in animals. Because of its thiomethyltetrazole side-chain it may alsorarely cause hypoprothrombinemia. Diarrhea secondary to changes in gut flora have been reported.
Some human patients demonstrate mild, transient increases in liver enzymes, serum creatinine and BUN. Clinical significance of these effects is in doubt. If administered via the IM route, pain at theinjection site has also been noted.

Overdosage, Acute Toxicity

No specific antidotes are available. Overdoses should be monitoredand treated symptomatically and supportively if required.

Drug Interactions

A disulfiram-like reaction (anorexia, nausea, vomiting) has been reported inhumans who have ingested alcohol with 48-72 hours of receiving beta-lactam antibiotics with athiomethyltetrazole side-chain (e.g., cefamandole, cefoperazone, moxalactam, cefotetan). Becausethese antibiotics have been associated with bleeding, they should be used cautiously in patientsreceiving oral anticoagulants.
Synergism against some Enterobacteriaceae (e.g., Pseudomonas aeruginosa) may be attained ifusing cefoperazone with a beta-lactamase inhibitor such as clavulanic acid or with an aminoglycoside (e.g., gentamicin, amikacin). Do not mix cefoperazone in same syringe or IV bag with aminoglycosides as inactivation may occur. Synergy may be unpredictable however andalthough there have been no reports of additive nephrotoxicity with cefoperazone, some cephalosporins may increase the nephrotoxic potential of aminoglycosides. Probenecid does not have an effect on cefoperazone elimination.
Laboratory Considerations - When using Kirby-Bauer disk diffusion procedures for testingsusceptibility, a specific 75 micrograms cefoperazone disk should be used. A cephalosporin-classdisk containing cephalothin should not be used to test for cefoperazone susceptibility. An inhibitionzone of 21 mm or more indicates susceptibility; 16-20 mm, intermediate; and 15 mm or less, resistant.
When using a dilution susceptibility procedure, an organism with a MIC of 16 micrograms/ml orless is considered susceptible and 64 micrograms/ml or greater is considered resistant. With eithermethod, infections caused by organisms with intermediate susceptibility may be effectively treated ifthe infection is limited to tissues where the drug is concentrated (e.g., urine, bile) or if a higher thannormal dose is used.
In some human patients receiving cefoperazone, a positive direct antiglobulin (Coombs') test hasbeen reported.
Cefoperazone, like most other cephalosporins, may cause a false-positive urine glucose determination when using the cupric sulfate solution test (e.g., Clinitest®).
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