Therapeutic Drug Monitoring and Safety of Amikacin in Patients with Febrile Neutropenia

Abstract

Objective: To evaluate AMK TDM in hematology-oncology patients with neutropenic fever and to explore the effects of cachexia, demographic, anthropometric, and renal function variables on AMK PK parameters.

Methodology: In this prospective observational study, 68 febrile neutropenic patients aged ?13 years at the Armed Forces of Bone Marrow Transplant Centre, Rawalpindi, received daily intravenous amikacin (15 mg/kg/day). Patients were classified into cachexia (n=34) and non-cachexia (n=34) groups. Peak (Cmax) and trough (Cmin) AMK concentrations were measured at steady state, and PK parameters were calculated using a one-compartment model. Data were analyzed using SPSS.25.

Results: Patients with cachexia had low body weight, body mass index, albumin, and creatinine. More than 70% of patients achieved their therapeutic levels, and both groups' Cmax and Cmin amikacin levels were comparable. While weight-normalized PK parameters did not significantly vary, the individuals in the cachexia group's absolute clearance was significantly higher (127.8±63.66 mL/min vs. 118±53.49 mL/min, p <0.001). The cachexia group experienced a longer time to effervescence (p=0.01), while nephrotoxicity was more common in the non-cachexic group; ototoxicity was not observed in any group.

Conclusion: In neutropenic hematological populations with and without cachexia, weight based amikacin dosage with TDM is safe and effective. Individualized monitoring is still essential because cachexia causes pharmacokinetic alterations, especially in renal clearance. Larger, multi-center clinical investigations are necessary to further develop dosage methods for these patients.