FDA label e829fead-587e-423f-afc9-a3cf06ef7da4

WARNINGS Hypersensitivity Reactions SERIOUS AND OCCASIONALLY FATAL HYPERSENSITIVITY (ANAPHYLACTIC) REACTIONS HAVE BEEN REPORTED IN PATIENTS RECEIVING BETA-LACTAM ANTIBACTERIALS, INCLUDING CEFOPERAZONE. THESE REACTIONS ARE MORE APT TO OCCUR IN INDIVIDUALS WITH A HISTORY OF HYPERSENSITIVITY REACTIONS TO MULTIPLE ALLERGENS. BEFORE THERAPY WITH CEFOBID IS INSTITUTED, CAREFUL INQUIRY SHOULD BE MADE TO DETERMINE WHETHER THE PATIENT HAS HAD PREVIOUS HYPERSENSITIVITY REACTIONS TO CEPHALOSPORINS, PENICILLINS, CARBAPENEMS OR OTHER DRUGS. IF AN ALLERGIC REACTION OCCURS, CEFOPERAZONE SHOULD BE DISCONTINUED AND APPROPRIATE THERAPY INSTITUTED. Severe and occasionally fatal skin reactions such as toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome (SJS), and exfoliative dermatitis have been reported in patients on CEFOBID therapy. If a severe skin reaction occurs CEFOBID should be discontinued and appropriate therapy should be initiated (see ADVERSE REACTIONS ). Clostridioides difficile -Associated Diarrhea Clostridioides difficile -associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including CEFOBID, 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 antibacterial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibacterial drug use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents. If CDAD is suspected or confirmed, ongoing antibacterial drug use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibacterial treatment of C. difficile , and surgical evaluation should be instituted as clinically indicated. Hemorrhage Serious hemorrhage cases, including fatalities, have been reported with cefoperazone. Monitor for signs of bleeding, thrombocytopenia, and coagulopathy. Discontinue CEFOBID if there is persistent bleeding and no alternative explanations are identified. Encephalopathy Encephalopathy (including decreased consciousness, delirium, seizures) has been reported with the use of CEFOBID. Most cases occurred in patients with renal impairment. The adverse reactions resolved after discontinuation of CEFOBID and/or hemodialysis/continuous veno‑venous hemofiltration. If encephalopathy occurs, consider discontinuing CEFOBID and institute supportive measures.

ADVERSE REACTIONS Clinical Trials Experience In clinical studies the following adverse effects were observed and were considered to be related to CEFOBID therapy or of uncertain etiology: Hypersensitivity As with all cephalosporins, hypersensitivity manifested by skin reactions (1 patient in 45), drug fever (1 in 260), or a change in Coombs' test (1 in 60) has been reported. These reactions are more likely to occur in patients with a history of allergies, particularly to penicillin. Hematology As with other beta-lactam antibacterial drugs, reversible neutropenia may occur with prolonged administration. Slight decreases in neutrophil count (1 patient in 50) have been reported. Decreased hemoglobins (1 in 20) or hematocrits (1 in 20) have been reported, which is consistent with published literature on other cephalosporins. Transient eosinophilia has occurred in 1 patient in 10. Hepatic Of 1285 patients treated with cefoperazone in clinical trials, one patient with a history of liver disease developed significantly elevated liver function enzymes during CEFOBID therapy. Clinical signs and symptoms of nonspecific hepatitis accompanied these increases. After CEFOBID therapy was discontinued, the patient's enzymes returned to pre-treatment levels and the symptomatology resolved. As with other antibacterial drugs that achieve high bile levels, mild transient elevations of liver function enzymes have been observed in 5–10% of the patients receiving CEFOBID therapy. The relevance of these findings, which were not accompanied by overt signs or symptoms of hepatic dysfunction, has not been established. Gastrointestinal Diarrhea or loose stools has been reported in 1 in 30 patients. Most of these experiences have been mild or moderate in severity and self-limiting in nature. In all cases, these symptoms responded to symptomatic therapy or ceased when cefoperazone therapy was stopped. Nausea and vomiting have been reported rarely. Symptoms of pseudomembranous colitis can appear during or for several weeks subsequent to antibacterial therapy (see WARNINGS ). Renal Function Tests Transient elevations of the BUN (1 in 16) and serum creatinine (1 in 48) have been noted. Local Reactions CEFOBID is well tolerated following intramuscular administration. Occasionally, transient pain (1 in 140) may follow administration by this route. When CEFOBID is administered by intravenous infusion some patients may develop phlebitis (1 in 120) at the infusion site. Post-Marketing Experience The following adverse reactions have been identified during post-approval use of CEFOBID. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Blood and Lymphatic System Disorders: Coagulopathy, thrombocytopenia, hypoprothrombinaemia (see PRECAUTIONS ) Immune System disorders: Anaphylactic reaction including shock and fatal cases (see WARNINGS ), acute myocardial ischemia with or without myocardial infarction may occur as part of an allergic reaction. Hepatobiliary Disorders: Jaundice, hepatic dysfunction Skin and Subcutaneous Tissue Disorders: Toxic epidermal necrolysis, Stevens-Johnson syndrome, exfoliative dermatitis, pruritus Vascular Disorders: Hemorrhage (see WARNINGS ) Nervous System Disorders: Encephalopathy (including decreased consciousness, delirium, seizures) (see WARNINGS )