Safety Profile

Most common adverse reactions

The most frequently reported adverse reactions occurring in ≥2% of patients treated with ZAYNICH^™ were diarrhea, hypertension, headache, and hypokalemia.

*Hypertension includes blood pressure inadequately controlled and hypertension.

Trial 1 was not designed to evaluate meaningful comparisons of the incidence of adverse reactions in the ZAYNICH^™ and meropenem treatment groups.

Warnings and precautions

• Hypersensitivity reactions

  Serious hypersensitivity reactions, including anaphylaxis, have been reported in patients treated with ZAYNICH^™. Serious and occasionally fatal hypersensitivity reactions and serious skin reactions have been reported in patients receiving beta-lactam antibacterial drugs.

  Before therapy with ZAYNICH^™ is instituted, carefully inquire about previous hypersensitivity reactions to cefepime, cephalosporins, penicillins, or other beta-lactams because cross-hypersensitivity among beta-lactam antibacterial drugs has been reported.

  If an allergic reaction to ZAYNICH^™ occurs, discontinue the drug and institute appropriate supportive measures.

• Neurotoxicity

  Neurotoxicity has been reported during treatment with cefepime, a component of ZAYNICH^™, including life-threatening or fatal occurrences of the following:

  • Encephalopathy (disturbance of consciousness including confusion, hallucinations, stupor, and coma)
  • Aphasia
  • Myoclonus
  • Seizures
  • Nonconvulsive status epilepticus

  Most cases occurred in patients with renal impairment who did not receive appropriate dosage adjustment. However, some cases of neurotoxicity occurred in patients receiving a dosage adjustment appropriate for their degree of renal impairment. In the majority of cases, symptoms of neurotoxicity were reversible and resolved after discontinuation of cefepime and/or after hemodialysis. If neurotoxicity associated with ZAYNICH^™ therapy occurs, discontinue ZAYNICH^™ and institute appropriate supportive measures.

• Clostridioides difficile infection

  Clostridioides difficile (C. difficile) infection (CDI) has been reported with the use of nearly all antibacterial agents including ZAYNICH^™ 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 CDI. Hypertoxin-producing isolates of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDI must be considered in all patients who present with diarrhea following antibacterial drug use. Careful medical history is necessary since CDI has been reported to occur over two months after the administration of antibacterial agents.

  If CDI 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 drug treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.

• Positive direct Coombs’ tests

  Positive direct Coombs’ tests with or without hemolysis have been reported during treatment with cefepime, a component of ZAYNICH^™. In patients who develop hemolytic anemia, discontinue the drug and institute appropriate therapy. Positive Coombs’ test may be observed in newborns whose mothers have received cephalosporin antibacterial drugs before parturition.

• Prolonged prothrombin time

  Decrease in prothrombin activity has been reported for many cephalosporins including cefepime, a component of ZAYNICH^™. Those at risk of developing prolonged prothrombin time include patients with renal or hepatic impairment or poor nutritional state, as well as patients receiving a protracted course of antimicrobial therapy. Prothrombin time should be monitored in patients at risk, and exogenous vitamin K should be administered as indicated.

• Development of drug-resistant bacteria

  Prescribing ZAYNICH^™ in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

• Interactions with urine glucose testing

  The administration of cefepime, a component of ZAYNICH^™, may result in a false-positive reaction for glucose in the urine when using some methods (e.g., Clinitest^™ tablets).