Hypersensitivity: Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients receiving beta-lactam or cephalosporin therapy, including cefoperazone. These reactions are more apt to occur in individuals with a history of hypersensitivity reactions to multiple allergens.
Before therapy with cefoperazone is instituted, careful inquiry should be made to determine whether the patient has had previous hypersensitivity reactions to cephalosporins, penicillins or other drugs. This product should be given cautiously to penicillin-sensitive patients.
Antibiotics should be administered with caution to any patient who has demonstrated some form of allergy, particularly to drugs.
If an allergic reaction occurs, the drug should be discontinued and the appropriate therapy instituted. Serious anaphylactoid reactions require immediate emergency treatment with adrenaline. Oxygen, intravenous steroids, and airway management, including intubation, should be administered as indicated.
Severe and occasionally fatal skin reactions such as toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome (SJS), and dermatitis exfoliative have been reported in patients on cefoperazone therapy. If a severe skin reaction occurs cefoperazone should be discontinued and appropriate therapy should be initiated (see Adverse Reactions).
Use in Hepatic Dysfunction: Cefoperazone is extensively excreted in bile. The serum half-life of cefoperazone is usually prolonged and urinary excretion of the drug increased in patients with hepatic diseases and/or biliary obstruction. Even with severe hepatic dysfunction, therapeutic concentrations of cefoperazone are obtained in bile and only a 2 to 4 fold increase in half-life seen (see Dosage & Administration).
General: Serious hemorrhage cases, including fatalities, have been reported with cefoperazone. As with other antibiotics, Vitamin K deficiency resulting in coagulopathy has occurred in patients treated with cefoperazone. The mechanism may possibly be related to the suppression of gut flora which normally synthesize this vitamin. Those at risk include patients with poor diet, malabsorption states (e.g. cystic fibrosis) and patients on prolonged intravenous alimentation regimens. Prothrombin time should be monitored in these patients and exogenous vitamin K administered as indicated. Discontinue cefoperazone if there is persistent bleeding and no alternative explanations are identified.
As with other antibiotics, overgrowth of non-susceptible organisms may occur during prolonged use of cefoperazone. Patients should be observed carefully during treatment. As with any potent systemic agent, it is advisable to check periodically for organ system dysfunction during extended therapy; this includes renal, hepatic, and hematopoietic systems. This is particularly important in neonates, especially when premature, and other infants.
Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including cefoperazone, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.
C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.
Usage in Infancy: Cefoperazone has been effectively used in infants. It has not been extensively studied in premature infants and neonates. Therefore in treating premature infants and neonates potential benefits and possible risks involved should be considered before instituting therapy (see Pharmacology: Toxicoloy: Preclinical Safety Data under Actions).
In neonates with kernicterus, cefoperazone does not displace bilirubin from plasma protein binding sites.
Effects on ability to drive and use machines: Clinical experience with cefoperazone indicates that it is unlikely to impair a patient's ability to drive or use machinery.