Preparation of intravenous chemotherapy bags: evaluation of a dose banding approach in an Italian oncology hospital.

Introduction: Dose banding is an original approach that manages intravenous (IV) chemotherapy preparation by generating on a weekly basis a series of bags containing scaled dosages of the active agent. These predetermined, fixed dosage bags are intended to replace the traditional bags prepared daily that contain fully individualized dosages. Methods: Three different scenarios were examined: (1) the current method of daily preparation of individualized bags at the hospital pharmacy; (2) the weekly preparation at the hospital pharmacy of non-individualized bags containing discrete, predefined doses covering an adequate range of doses (dose banding); (3) the use of commercial ready-to-use bags based on the same approach of dose banding. The objective of this study was to compare these three different approaches in terms of cost per patient. We considered five cancer drugs (gemcitabine, oxaliplatin, paclitaxel, trastuzumab and 5-fluorouracil) that were suitable for the dose ranging approach. Appropriate dose bands for these five agents were identified. Costs were estimated for each of the three approaches. Results: A total of 13,490 fully individualized bags were studied, which corresponded to the real bags prepared at our institution for these five agents in 2018. Dose banding was predicted to determine savings ranging from €10,998 (-0.84%) for trastuzumab to €169,429.60 (-8.39%) for paclitaxel. Conclusion: The introduction of dose banding can determine economic savings along with other advantages, such as improved work conditions, management reorganization and containment of waste. The pharmaceutical industry can hopefully support these experiences by producing ready-to-use bags in predetermined dosages.

Comorbidity, Polytherapy, and Drug Interactions in a Neurological Context: An Example of a Multidisciplinary Approach to Promote the Rational Use of Drugs.

PURPOSE: A high number of adverse drug reactions (ADRs), mainly caused by drug-drug interactions (DDIs), occur in neurological wards and few data are available about incidence and prevalence of DDIs in this context. This study investigated-(1) the prevalence of drug-drug and drug-disease interactions in patients admitted to a neurological unit in Italy, (2) the risk factors for DDIs, and (3) the diseases and the drug classes mostly involved in drug-drug and drug-disease interactions. METHODS: For 2 months, we performed a retrospective, observational study in the neurological unit of St Bassiano Hospital, enrolling 79 patients who received a drug prescription at discharge. RESULTS: About half of the patients were discharged with 5 or more prescribed drugs, and 72% of patients showed potential, clinically relevant DDIs. Linear correlations were observed between age and number of prescribed drugs ( P < .01) and between age and number of interactions ( P < .01). The number of prescribed drugs was associated with the number of detected DDIs ( P < .01). The application of drug interaction alerts and the use of medication inappropriateness criteria (ie, Beers criteria) were not satisfactory in choosing the best therapy for each patient. Therefore, multidisciplinary discussions of each clinical case was required. CONCLUSION: The study demonstrated that the neurological patient, especially if elderly, has a high risk of DDI and ADRs and that many of these can be avoided by case discussion in multidisciplinary team meetings, in which the presence of a dedicated clinical pharmacist is crucial.

[Is the price of cancer drugs related to the cost of develo-pment and production or to the economic value of their clincal efficacy?]. / Il prezzo dei farmaci oncologici va correlato al costo di sviluppo e produzione o al valore economico dell'efficacia clinica?

In the past years, the expenditure for cancer drugs has quickly increased, especially for biologic agents. Pharmaceutical companies and national health systems have different approaches in handling the issue of drug reimbursement. Companies support a price based on research and development (R&D) expenditures including those for unsuccessful drug projects while national health systems generally argue that pricing should be based on the incremental benefit generated by the agent under examination (value-based pricing - VBP). Nevertheless, current oncologic drugs prices are too high and not really justified by their incremental benefits or innovation, nor can they demonstrate that higher thresholds in QALYs could bring wider societal benefits. In this article we discuss these two points of view in the light of the most recent national and international literature. In Italy, drug reimbursement is currently managed through a mixed approach between the recognition of R&D expenditures and VBP. Reimbursement is also integrated with post-marketing patient-based national registries, particularly in the field of anti-cancer agents, that provide rebates based on financial risk sharing, cost-sharing, payment by results and success fee methods.

Photoreactivity of 5-fluorouracil under UVB light: photolysis and cytotoxicity studies.

The photodegradation of the chemotherapeutic agent 5-fluorouracil (5-FU) under UVB light was studied both in aqueous and methanol solutions and in systemic and topical formulations. As monitored by HPLC, photodegradation in solution takes place in a concentration dependent manner; thus, the solution for parenteral administration (10(-1) M) showed negligible loss of the active principle. On the contrary, the commercial cream containing 5% of 5-FU showed low stability under UVB exposure. When dissolved either in water or methanol, 5-FU yields two photoproducts which have been characterized as two isomers coming from the addition of the solvent to the 5,6 double bond of the drug. As a consequence, photomodified 5-FU loses its antiproliferative activity on HCT-15 and HeLa cells. MS analysis showed that photoaddition occurred with nucleophilic amino acids, such as cysteine and serine, while susceptible amino acids (cysteine and methionine) were oxidized. In fact, high production of the superoxide anion under UVB light as well as photooxidation of BSA suggests protein photodamage as a mechanism of photosensitization. Indeed, some phototoxicity was shown in experiments on NCTC keratinocytes and MCF-7 resistant cells irradiated with UVB light. The interactions with these biological targets may contribute to skin phototoxicity and photoallergy induced by 5-FU in vivo.