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Romiplostim preparation and distribution in ready to administer weekly syringes to patients

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European Statement

Production and Compounding

Author(s)

BELEN SANCHEZ PASCUAL, IRENE SALVADOR LLANA, ANA MARIA MARTIN DE ROSALES CABRERA, MONTSERRAT PEREZ ENCINAS

Why was it done?

Romiplostim should be administered once weekly as a subcutaneous injection. The initial dose is 1µg/kg. According to platelet response (PR) the dose should be increased until the patient achieves platelet count over 50,000 platelets/µL(maximum dose=10µg/kg). In order to maintain durable PR, weekly doses of romiplostim are prescribed and adjusted every 4-6weeks. Although patients could be trained for the injection preparation, many had reported difficulties to understand instructions and calculations of concentrations/volume. Romiplostim vials have a significant overdose to ensure the extraction of the declared amount. The actual content of the 250µg vial was found to be 360 µg (110µg excess). The 500µg vial contents 600µg. In addition, patients should discard the unused part. The aim is to centralise the preparation/distribution of individualised weekly doses of romiplostim for each patient in RtA syringes that allows them to receive the correct dose and to maximise the use of vials.

What was done?

We develop a procedure for the preparation and distribution of individualised weekly doses of romiplostim prepared in the sterile preparation area in prefilled syringes Ready to Administer (RtA) by the patient.

How was it done?

The Pharmacy service (PS) prepares the individualised doses in syringes RtA in a laminar-flow cabinet. The waste of the vial is kept to be reused.
The main obstacle is the increase in the volume of daily preparations in the PS due to dose individualisation. This obstacle is overcome with fluid communication with the Haematology service that reports prescriptions with a duration of up to 21 days (if the patient´s control is adequate).

What has been achieved?

From the past 3 years (2019-2021), we prepared individualised syringes for 36 patients. The centralised preparation reduces unused romiplostin waste allowing a cost saving of near 50% of drug spending. Specifically, in this 3-year period, €385,759.00 were saved.

What next?

Preparation of RtA syringes of romiplostim under sterile conditions in a laminar-flow cabinet helps patient’s auto-administration (since is an easier dispositive) and allows for greater use and significant economic savings. It is a process that can be easily extrapolated to any PS. Next step would be to carry out stability studies in order to be able to work further in advance and allow to space out hospital visits of well-controlled patients.

Implementation of a multidisciplinary personalised medicine unit for pharmacogenetic testing

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European Statement

Clinical Pharmacy Services

Author(s)

Jorge Fernández-Fradejas, Matías Morín-Rodríguez, Eva Delgado-Silveira, Miguel Ángel Moreno-Pelayo, Ana María Álvarez-Díaz

Why was it done?

There is an increasing number of gene-drug interactions that have the potential to predict patient response. Although the study of some genetic variants can be a useful tool to achieve a safer and more effective pharmacotherapy, the integration of personalised medicine in clinical practice has been challenging over the years, mainly due to prescriber’s scepticism and lack of clinical guidelines and protocols.

What was done?

We have implemented a multidisciplinary Personalised Medicine Unit (PMU) at a third- level hospital to facilitate preemptive pharmacogenetic testing.

How was it done?

The PMU provides its service with the involvement of Pharmacy and Genetics Department according to the following workflow:
1. Physicians order the pharmacogenetic test in the first contact with a patient expected to be treated with a drug with an available pharmacogenetic test.
2. A peripheral blood sample is drawn for DNA extraction and analysed by the Genetics Department.
3. An integrated pharmacogenetics report is generated and uploaded to the patient’s electronic medical record. This report contains the molecular information and its interpretation (responsibility of Genetics Department) and the clinical pharmacotherapeutic recommendation according to the results obtained (responsibility of Pharmacy Department). Dose adjustment recommendations follow the Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines and Dutch Pharmacogenomics Working Group (DPWG) guidelines.
4. Pharmacy Department follows up pharmacotherapeutic recommendation acceptance and clinical outcomes.

What has been achieved?

Since July 2021 we have implemented pharmacogenetic testing for seven drug-gene interactions:
July 2021. CYP2C9 – Siponimod.
November 2021. DPYD – Fluoropyrimidines (capecitabine, fluorouracil, tegafur).
April 2022. UGT1A1 – Irinotecan, liposomal pegylated irinotecan, sacituzumab govitecan.
Three hundred and seventy patients have benefited from pharmacogenetics testing. These tests have been requested by three different clinical departments and had a mean turnaround time of less than 10 days, preventing any potential treatment delays. An integrated Pharmacy-Genetics report with individualised pharmacotherapeutic recommendations was generated for every patient. These recommendations had an acceptance rate of 100%.

What next?

Since the creation of the PMU, we have been able to implement pharmacogenetic testing in clinical practice with a high level of acceptance. Our next challenges are introducing next- generation sequencing for the study of new gene-drug interactions in the unit portfolio and achieve a deeper integration of pharmacogenetic information in clinical decision support systems.

Determination of dihydropyrimidine dehydrogenase genotypes to guide physicians in the dosing of fluoropyrimidines

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European Statement

Clinical Pharmacy Services

Author(s)

Aina Oliver Noguera, Luis Pérez de Amezaga Tomáss, Margarita Nigorra Caro, Fernando Do Pazo Oubiña, Esther Falcó Ferrer, Teresa Fernández Rodriguez, Maria Fiorella Sarubbo, Antònia Obrador de Hevia, Montserrat Vilanova Boltó

Why was it done?

Treatment with fluoropyrimidine produces severe toxicity in about 30% of the patients. This toxicity has been related to a reduction in the activity of DPD, the rate-limiting enzyme for fluoropyrimidine catabolism. This is due to certain genetic variants of DPYD, the gene encoding DPD. For this reason, regulatory agencies such as the European Medicines Agency (EMA) recommend determining DPD deficiency in all patients who are candidates for treatment with fluoropyrimidines.

What was done?

Design of a protocol for the Implementation of dihydropyrimidine dehydrogenase (DPD) genotype tests in our hospital so that the results can be clinically interpreted by the pharmacists, and then used to guide physicians in the dosing of fluoropyrimidines (5-fluorouracil/capecitabine). The project was done with the collaboration of the Genetic and Genomic Laboratory (GGL) located in the reference hospital of our territory.

How was it done?

The elaboration of the protocol took place as follows, coordinated by the oncology pharmacist:
– Informatics. They created a formulary at the electronic prescription programme (HP-HCIS®) for the inclusion of the patients in the testing protocol.
– Oncologists and nursing service. They were trained in the implementation of this new determination, as well as in the procedure for obtaining and sending samples to the GGL.
– GGL. They conducted the DPYD genotype tests and report the results to the oncology pharmacist.
– Oncology pharmacist. They did the clinical interpretation of the result based on the following European Society for Medical Oncology (ESMO) recommendations for heterozygous DPYD variant allele carriers:
-DPYD*2A (rs3918290): dose reduction of 50%
-c.1679T>G (rs55886062): 50%
-c.2846A>T (rs67376798): 25%
-c.1236G>A/HapB3 (rs56038477): 25%

What has been achieved?

Since the implementation of the protocol, 73 determinations of DPYD polymorphisms have been performed (November 202 to August 2022). Three patients (4.1%) were found to be heterozygous DPYD gene variant carriers (two DPYD*2A and one c.2846A>T).
The average time for obtaining the results was 17.5 days. For this reason, in most cases the treatment was started before the result was obtained.

What next?

We are working on the implementation of a new fluorescence technique that will allow us to shorten the time of obtaining the genotype result.

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