Safety and hospital pharmacy implications of extended beyond-use dating for intravenous anticancer and supportive care admixtures: A systematic review and meta-analysis
Sadaf Hameed, Asma ZafarIntroduction
The stability of intravenous drug admixtures is essential for ensuring safety, efficacy, and efficient resource utilization in clinical practice. This systematic review and meta-analysis evaluated the physicochemical stability of intravenous anticancer and supportive-care admixtures and examined the influence of drug class, storage temperature, light exposure, container type, and diluent selection.
Methods
The review followed PRISMA 2020 guidelines and was registered with PROSPERO (CRD420261368183). Thirty-three studies were included. Random-effects models were used to estimate pooled stability durations, with subgroup analyses, meta-regression, and risk-of-bias assessment across six domains.
Results
The pooled mean maximum stability duration was 30.7 days (95% CI 20.1–41.3; prediction interval 1.4–60.0 days), with extreme heterogeneity (I 2 = 99.7%), limiting generalizability. Monoclonal antibodies generally showed longer stability than cytotoxic agents, particularly under refrigeration. Refrigeration was associated with modestly longer stability, while light exposure appeared to reduce stability, although evidence was limited. Container and diluent effects were variable and drug dependent. Only 12.1% of studies included microbiological assessment, and overall study quality was moderate.
Conclusions
Intravenous drug admixtures may remain physicochemically stable beyond manufacturer-defined beyond-use dates under controlled conditions. However, extended beyond-use dating should not be based on physicochemical evidence alone. Drug-specific assessment, sterility assurance, and preferably local validation are required before implementation in hospital pharmacy practice.