COVID-19 outbreak: An experience to reappraise the role of hospital at home in the anti-cancer drug injection.

BACKGROUND: The COVID-19 outbreak has posed considerable challenges to the health care system worldwide, especially for cancer treatment. We described the activity and the care organisation of the Hospitalisation At Home (HAH) structure during the pandemic for treating patients with anti-cancer injections. METHODS: We report the established organisation, the eligibility criteria, the patient characteristics, the treatment schemes and the stakeholders' role during two 5-week periods in 2020, before and during the French population's lockdown. RESULTS: The increase of activity during the lockdown (+32% of treated patients, +156% of new patients and +28% of delivered preparations) concerned solid tumour, mainly breast cancer, even if haematological malignancies remained the most frequent. Thirty different drugs were delivered, including three new drugs administered in HAH versus 19 during the routine period (p < 0.01). For those clinical departments accustomed to using HAH, the usual organisation was kept, but with adjustments. Five clinical departments increased the number of patients treated at home and widened the panel of drugs prescribed. Three oncology departments and one radiotherapy department for the first time solicited HAH for anti-cancer injections, mainly for immunotherapy. We adjusted the HAH organisation with additional human resources and allowed to prescribe drugs with an infusion time of <30 min only for the new prescribers. CONCLUSION: HAH allowed for the continuation of anti-cancer injections without postponement during the pandemic, and for a decrease in unnecessary patient travel to hospital with its concomitant COVID-19 transmission risk. Often left out of guidelines, the place of HAH in treating cancer patients should be reappraised, even more so during a pandemic.

Comparative analysis of methods for real-time analytical control of chemotherapies preparations.

Control of chemotherapies preparations are now an obligation in France, though analytical control is compulsory. Several methods are available and none of them is presumed as ideal. We wanted to compare them so as to determine which one could be the best choice. We compared non analytical (visual and video-assisted, gravimetric) and analytical (HPLC/FIA, UV/FT-IR, UV/Raman, Raman) methods thanks to our experience and a SWOT analysis. The results of the analysis show great differences between the techniques, but as expected none us them is without defects. However they can probably be used in synergy. Overall for the pharmacist willing to get involved, the implementation of the control for chemotherapies preparations must be widely anticipated, with the listing of every parameter, and remains according to us an analyst's job.

Compatibility and stability of binary mixtures of acetaminophen, nefopam, ketoprofen and ketamine in infusion solutions.

BACKGROUND AND OBJECTIVE: Administering various combinations of acetaminophen, ketoprofen, nefopam and ketamine, though sometimes discussed, is expected to provide superior pain relief and reduce opioid analgesic-related side effects. However, some studies have indicated that multimodal analgesia has limited efficacy. We studied the stability of various binary combinations of these four drugs. PATIENTS AND METHODS: The drugs were studied at 25 degrees C. Binary mixtures of acetaminophen, ketoprofen, nefopam and ketamine were produced. Each drug concentration was assessed using a specific high-performance liquid chromatographic technique. Measurements were carried out at T0, +1, +2, +4, +6 and +24 h. A 5% loss of initial concentration was considered to be significant. The changes with time of the concentrations were analysed using linear regression analysis. A P value of less than 0.05 was significant. RESULTS: The four drugs tested in the binary mixtures were stable, showing neither loss of concentration nor degradation products (P > or = 0.05). CONCLUSION: Physicochemical negative interaction is not likely to account for the limited clinical efficacy sometimes reported with binary combinations of these drugs. Coadministration of binary mixtures of acetaminophen, nefopam, ketoprofen and ketamine from the same bottle or infusion bag using the same venous line is demonstrated to be feasible.

Stability of antineoplastic agents in use for home-based intravenous chemotherapy.

AIM OF THE REVIEW: The aim of this work was first to define which antineoplastic agents with sufficiently long stability could be eligible in the circuit of home-based therapy (centralised preparation, transport to the patient's home and administration by nurses) and, second, to propose a standardisation of the stability data of anticancer drugs in use for home hospitalisation. METHOD: A survey carried out in six hospital pharmacies of the Assistance Publique-Hôpitaux de Paris (AP-HP) hospitals, with important activity in oncology, listed the stability data used locally by each site. The final goal is to reach a consensus for the stability of cytotoxic drugs, which was the result of an original collaboration between the pharmacists of the compounding unit and the quality control unit. These results were compared to marketing authorisation data. RESULTS: The survey showed that eight antineoplastic agents of 34 were prepared under identical conditions (infusion diluent, concentration range, protection from light, temperature) by all hospitals (3 < or = n < or = 6): the stability was identical between each site for only two cytotoxic drug preparations (fotemustine and gemcitabine) and varied by up to 168 h or 7 days for the preparations of dacarbazine, epirubicine and cisplatin. Stability validated by pharmacists and those provided by marketing authorisation ranged respectively from "extemporaneously prepared" at 1,344 h (median = 168 h) to "extemporaneously prepared" at 720 h (median = 4 h). For 11 antineoplastic drugs, no information about the stability after compounding was specified in the marketing authorisation. Of all cytotoxic drugs used in the Hospital at Home of AP-HP, stability after compounding validated by pharmacists was less than 30 h for six of them, between 30 and 78 h for four and exceeding 78 h for the remaining 24. CONCLUSION: Considering the lack of data about cytotoxic drugs stability provided by the pharmaceutical companies and the difficulties in retrieving and interpreting the literature data, a consensus on the stability of cytotoxic drug preparations is essential for the current practice. With this approach, initiated for home hospitalisation, we propose in this study an initiative of the standardisation of stability data which offers a decision support for other centres.

The application of hazard analysis and critical control points and risk management in the preparation of anti-cancer drugs.

OBJECTIVE: To apply the Hazard analysis and Critical Control Points method to the preparation of anti-cancer drugs. To identify critical control points in our cancer chemotherapy process and to propose control measures and corrective actions to manage these processes. SETTING: The Hazard Analysis and Critical Control Points application began in January 2004 in our centralized chemotherapy compounding unit. From October 2004 to August 2005, monitoring of the process nonconformities was performed to assess the method. METHODS: According to the Hazard Analysis and Critical Control Points method, a multidisciplinary team was formed to describe and assess the cancer chemotherapy process. This team listed all of the critical points and calculated their risk indexes according to their frequency of occurrence, their severity and their detectability. The team defined monitoring, control measures and corrective actions for each identified risk. Finally, over a 10-month period, pharmacists reported each non-conformity of the process in a follow-up document. RESULTS: Our team described 11 steps in the cancer chemotherapy process. The team identified 39 critical control points, including 11 of higher importance with a high-risk index. Over 10 months, 16,647 preparations were performed; 1225 nonconformities were reported during this same period. CONCLUSIONS: The Hazard Analysis and Critical Control Points method is relevant when it is used to target a specific process such as the preparation of anti-cancer drugs. This method helped us to focus on the production steps, which can have a critical influence on product quality, and led us to improve our process.

Evaluation of peracetic acid permeation during flash sterilization through pharmaceutical plastic polymers used in cytotoxic reconstitution units.

Peracetic acid (PAA) permeation in flash sterilization was studied using three different plastic infusion bags made of polypropylene and polyethylene, filled with glucose 5% or NaCl 0.9%. The pH was measured and acetic acid (AA) and PAA concentrations were made by reverse phase high-performance liquid chromatography (RP-HPLC). PAA was derivatized by oxidation of methyl tolyl sulfide (MTS) into methyl tolyl sulfoxide (MTSO) detected by ultraviolet (UV) absorbance at 230 nm. The technique has a sensitivity of 0.3 microg x L(-1) and was highly specific. Results showed that pH measurements remain constant and demonstrated the absence of PAA permeation, which was confirmed by the absence of AA permeation regardless of the brand tested, with both unwrapped and overwrapped infusion bags, when flash sterilization is applied. These results allow flash sterilization to be performed with unwrapped infusion bags without any risk of drug degradation by PAA. This makes compounding safer and easier, which improves productivity.