Clarifying the contraindications and special population considerations for Zaynich is essential to avoid serious risks and ensure individualized treatment safety.
I. Absolute Contraindications
1. Contraindicated in patients with severe allergy history
(1) Zaynich is absolutely contraindicated in patients with a history of severe hypersensitivity reactions to any component of the formulation (cefepime or zidebactam).
(2) It is also contraindicated in patients who have experienced severe hypersensitivity reactions to other beta‑lactam antibacterial agents (e.g., penicillins, cephalosporins, carbapenems) due to the risk of cross‑hypersensitivity.
2. Contraindicated in patients with previous severe cutaneous adverse reactions
Zaynich should not be used in patients who have experienced severe skin reactions such as Stevens‑Johnson syndrome or toxic epidermal necrolysis during prior beta‑lactam therapy.
II. Use in Special Physiological Conditions
1. Pregnancy
(1) There are no adequate clinical studies of Zaynich in pregnant women to clearly assess the risk of major birth defects, miscarriage, or other adverse maternal/fetal outcomes.
(2) Zaynich should be used during pregnancy only if the anticipated benefit clearly outweighs the potential risk, and under close medical supervision.
2. Lactation
A decision should be made whether to discontinue breastfeeding or to discontinue the drug, taking into account the benefit of breastfeeding to the infant, the mother’s need for treatment, and the potential risk to the infant.
3. Pediatric use
The safety and efficacy of Zaynich in pediatric patients have not been established; use is not recommended in individuals under 18 years of age.
4. Geriatric use
(1) Renal function declines with age, and severe cefepime‑related neurotoxicity (e.g., encephalopathy, myoclonus, seizures) has been reported in elderly patients who did not receive dose adjustments based on renal function.
(2) No dose adjustment is required solely based on age; however, dosing must be individualized according to renal function assessment, with dynamic monitoring of renal function during therapy.
III. Use in Patients with Underlying Diseases
1. Patients with renal impairment
(1) Both cefepime and zidebactam are primarily excreted renally; reduced renal function leads to drug accumulation and elevated plasma concentrations.
(2) When eGFR is < 60 mL/min, dose reduction or prolongation of dosing intervals is mandatory, with specific regimens based on eGFR categories.
(3) For patients on intermittent hemodialysis, the dose should be administered after dialysis on dialysis days, and at 24‑hour intervals on non‑dialysis days.
(4) Renal function may change during therapy; eGFR should be re‑evaluated periodically and doses adjusted accordingly.
2. Patients with hepatic impairment
Both components undergo minimal hepatic metabolism (< 10%), and systemic clearance is not significantly affected by hepatic function; therefore, dose adjustment is usually not required in hepatic impairment, though monitoring of coagulation parameters is advisable.
3. Patients receiving concomitant nephrotoxic drugs
(1) Coadministration with aminoglycosides increases the risk of nephrotoxicity and ototoxicity; renal function and hearing‑related symptoms should be closely monitored.
(2) Concomitant use with potent diuretics such as furosemide may increase the risk of renal injury; urine output and serum creatinine should be monitored concurrently.
4. Patients with coagulation risk or poor nutritional status
Cephalosporins may prolong prothrombin time. In patients with hepatic or renal impairment, malnutrition, or prolonged therapy, coagulation parameters should be monitored and vitamin K supplementation considered if needed.
5. Patients with diabetes mellitus
(1) Blood glucose monitoring is advised during treatment, as hyperglycemia has been reported.
(2) For urine glucose testing, glucose oxidase methods should be used; traditional copper reduction methods may produce false‑positive results and interfere with glycemic management decisions.
