ZOSYN (piperacillin and tazobactam) Injection

ZOSYN (piperacillin and tazobactam) Injection
Indications and Important Risk Information

Indications

ZOSYN Injection is a combination of piperacillin, a penicillin-class antibacterial and tazobactam, a beta-lactamase inhibitor, indicated for the treatment of:

• Intra-abdominal infections in adult and pediatric patients 2 months of age and older
• Nosocomial pneumonia in adult and pediatric patients 2 months of age and older
• Skin and skin structure infections in adults
• Female pelvic infections in adults
• Community-acquired pneumonia in adults

To reduce the development of drug-resistant bacteria and maintain the effectiveness of ZOSYN Injection and other antibacterial drugs, ZOSYN Injection should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria.

Important Risk Information

• Contraindications: ZOSYN Injection is contraindicated in patients with a history of allergic reactions to any of the penicillins, cephalosporins, or beta-lactamase inhibitors.
• Hypersensitivity Adverse Reactions: Serious and occasionally fatal hypersensitivity (anaphylactic/anaphylactoid) reactions (including shock) have been reported in patients receiving therapy with ZOSYN Injection. These reactions are more likely to occur in individuals with a history of penicillin, cephalosporin, or carbapenem hypersensitivity or a history of sensitivity to multiple allergens. If an allergic reaction occurs, ZOSYN Injection should be discontinued and appropriate therapy instituted.
• Severe Cutaneous Adverse Reactions: ZOSYN Injection may cause severe cutaneous adverse reactions, such as Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms, and acute generalized exanthematous pustulosis. If patients develop a skin rash they should be monitored closely and ZOSYN Injection discontinued if lesions progress.
• Hemophagocytic Lymphohistiocytosis (HLH): Cases of HLH have been reported in pediatric and adult patients treated with ZOSYN Injection. Signs and symptoms of HLH may include fever, rash, lymphadenopathy, hepatosplenomegaly and cytopenia. If HLH is suspected, discontinue ZOSYN Injection immediately and institute appropriate management.
• Rhabdomyolysis: Rhabdomyolysis has been reported with the use of piperacillin and tazobactam. If signs or symptoms of rhabdomyolysis such as muscle pain, tenderness or weakness, dark urine, or elevated creatine phosphokinase are observed, discontinue ZOSYN Injection and initiate appropriate therapy.
• Hematologic Adverse Reactions: Bleeding manifestations have occurred in some patients receiving beta-lactam drugs, including piperacillin. These reactions have sometimes been associated with abnormalities of coagulation tests such as clotting time, platelet aggregation and prothrombin time, and are more likely to occur in patients with renal failure. If bleeding manifestations occur, ZOSYN Injection should be discontinued and appropriate therapy instituted. The leukopenia/neutropenia associated with ZOSYN Injection administration appears to be reversible and most frequently associated with prolonged administration. Periodic assessment of hematopoietic function should be performed, especially with prolonged therapy, i.e., ≥ 21 days.
• Central Nervous System Adverse Reactions: As with other penicillins, ZOSYN Injection may cause neuromuscular excitability or seizures. Patients receiving higher doses, especially patients with renal impairment may be at greater risk for central nervous system adverse reactions. Closely monitor patients with renal impairment or seizure disorders for signs and symptoms of neuromuscular excitability or seizures.
• Nephrotoxicity in Critically Ill Patients: The use of ZOSYN Injection was found to be an independent risk factor for renal failure and was associated with delayed recovery of renal function as compared to other beta-lactam antibacterial drugs in critically ill patients. Alternative treatment options should be considered in the critically ill population. If alternative treatment options are inadequate or unavailable, monitor renal function during treatment with ZOSYN Injection.
• Clostridioides difficile-associated diarrhea (CDAD): CDAD has been reported with use of nearly all antibacterial agents, including ZOSYN Injection, and may range in severity from mild diarrhea to fatal colitis. 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.
• Adverse Reactions: The most common adverse reactions (incidence >5%) are diarrhea, constipation, nausea, headache, and insomnia.
• Renal Impairment: In patients with creatinine clearance ≤ 40 mL/min and dialysis patients (hemodialysis and CAPD), the intravenous dose of ZOSYN Injection should be reduced to the degree of renal function impairment.

• Drug Interactions:

  • ZOSYN Injection administration can significantly reduce tobramycin concentrations in hemodialysis patients. Monitor tobramycin concentrations in these patients.
  • Probenecid prolongs the half-lives of piperacillin and tazobactam and should not be co-administered with ZOSYN Injection unless the benefit outweighs the risk.
  • Co-administration of ZOSYN Injection with vancomycin may increase the incidence of acute kidney injury. Monitor kidney function in patients receiving ZOSYN Injection and vancomycin.
  • Monitor coagulation parameters in patients receiving ZOSYN Injection and heparin or oral anticoagulants.
  • ZOSYN Injection may prolong the neuromuscular blockade of vecuronium and other non-depolarizing neuromuscular blockers. Monitor for adverse reactions related to neuromuscular blockade.

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