Real-World Nivolumab Wastage and Leftover Drug Stability Assessment to Facilitate Drug Vial Optimization for Cost Savings

Abstract

PURPOSE: Nivolumab dosage was initially selected on the basis of body weight, often resulting in leftover drug after sterile compounding. This study sought to investigate the real-world wastage of nivolumab and assess the long-term stability of leftover nivolumab within vials to facilitate drug vial optimization (DVO). METHODS: We collected all discarded vials after preparation from 17 regional hospitals in Japan over a 6-month period preceding the adoption of a fixed dose of 240 mg per administration. The actual amount of waste was measured for each preparation. Stability assessment was performed under different storage conditions. RESULTS: A total of 2,789 100-mg vials and 4,069 20-mg vials were collected. Overall, the drug cost associated with the expenditure of nivolumab alone was $12.1 million, whereas the total cost due to drug wastage was $0.735 million (rate of wastage, 6.1%). Furthermore, the immunoglobulin G concentrations of nivolumab remaining within vials, as well as binding activity to programmed death-1 protein, did not change significantly over 4 weeks of storage at either 4°C or room temperature. CONCLUSION: Significant drug wastage occurs during sterile preparation of nivolumab according to body weight–based dosing. Although nivolumab dosing has been changed to a fixed dose in Japan, body weight–based dosing is still applied in some other countries, as well as in combination therapy with ipilimumab. Our findings regarding the long-term stability of leftover nivolumab within the vials should motivate hospitals to implement DVO for cost savings.

Nivolumab vs Pembrolizumab for Treatment of US Patients With Platinum-Refractory Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

“… 6 , 7 , 11 , 19 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 Given the amount of leftover nivolumab resulting from the weight-based administration, a rate of 6.1% for the real-world wastage of nivolumab was considered. 42 We acquired the costs of administration, immunohistochemical tests, and follow-up from the 2020 Medicare physician fee schedule and Medicare fee-for-service payment. 33 , 34 Best supportive care and terminal care costs were estimated based on the Surveillance, Epidemiology, and End Results–Medicare data.…”

“…The adverse events associated with utility decrements were obtained from the literature 11,[24][25][26][27][28][29][30] 1). 6,7,11,19,[24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43] Given the amount of leftover nivolumab resulting from the weight-based administration, a rate of 6.1% for the real-world wastage of nivolumab was considered. 42 We acquired the costs of administration, immunohistochemical tests, and follow-up from the 2020 Medicare physician fee schedule and Medicare fee-for-service payment.…”

Evolution of preclinical characterization and insights into clinical pharmacology of checkpoint inhibitors approved for cancer immunotherapy

“…Most of the approved anti‐PD‐1/L1 agents are thus administered at a flat dose, and many agents under development are evaluating flat dosing in ongoing clinical trials. 58 …”

“…Most of the approved anti-PD-1/L1 agents are thus administered at a flat dose, and many agents under development are evaluating flat dosing in ongoing clinical trials. 58 The PKs of the approved CPIs are similar to that of endogenous immunoglobulin G (IgG). The typical volume of distribution of mAbs is comparable to their plasma volume (i.e., 2-4 L).…”

“…This eliminates drug waste, reduces dosing errors, and eliminates the need for on‐site compounding—all advantages over body‐weight‐based dosing. Most of the approved anti‐PD‐1/L1 agents are thus administered at a flat dose, and many agents under development are evaluating flat dosing in ongoing clinical trials 58 …”