PHARMACEUTICAL INTERVENTION TO IMPROVE DOSE CALCULATION OF 4 MABS S. Machado1, A. Rebelo 1, N. Landeira 1, M. Pereira 1 1 Hospital Espírito Santo Évora- EPE, Pharmacy Department, Évora, Portugal

INTRODUCTION METHODS Antibody-based therapy for cancer has become established over the past 15 years and is now one of the most successful and important strategies for treating All patients (a) with Bevacizumab, patients with haematological malignancies and solid tumours.1 Cetuximab, Trastuzumab, Panitumumab Monoclonal antibodies (mAb) market has grown significantly in the past years. prescriptions , from may to august 2016 By 2020 combined worldwide sales will be nearly $125 billion.2 Pharmacist calculates weight’s based dose (according to Summary of Product Cetuximab, Trastuzumab, Bevacizumab and Panitumumab were the mAbs most Characteristics) used on our Hospital, which represents 35,25% of oncology service total CALCULATED DOSE (CD) expenditures in 2015. The initially Prescribed Dose (PD) by the oncologist was only revised when the protocol was changed, toxicity occurred or disease CALCULATED DOSE administrated to the progression. patient (after authorization by Head’s department) OBJECTIVES 1) To calculate doses based on patient’s weight, presented at the day of CALCULATED DOSES vs. PRESCRIBED treatment, of the mAbs most used: Cetuximab, Trastuzumab, Bevacizumab and DOSES Panitumumab – Calculated Dose(CD) 2) To compare CD with PD and assess economic impact and cost savings when PD > CD (a) Patients with reduced dose due to adverse reactions or previous toxicity were excluded

RESULTS The mAb doses were calculated for 367 administrations, which corresponds to 77 patients (n=367). The PD was equal to CD only in 24% of total treatments (88 out of 367). Treatments with PD

Table 1: CD vs. PD analysis 9% Trastu- Panitu- Bevaci- Cetuxi- 20% Total zumab mumab zumab mab No. of patients 25 10 29 13 77 49% No. Drug 119 39 140 69 367 58% 33% Administrations No. Administrations 11 8 25 44 88 31% DP = DC No. Adminstrations 39 12 52 9 112 DP > DC No. Administrations 69 19 63 16 170 Bevacizumab Cetuximab DP < DC

18% 23% Table 2: Costs associated when DP > DC Trastu- Panitu- Bevaci- Cetuxi- 45% Total zumab mumab zumab mab 13% Sum of difference 64% between DP and DC 1201mg 767,8mg 942,8mg 128 mg 37%

Estimated value € 4 143 € 2 793 € 2 367 € 224 € 9 527 €

*value based on mean cost of the drugs PD=CD PD>CD PD

Figure 1: PD vs CD in total drug administrations

CONCLUSIONS o Deviations from the recommended dose were not very significant. The study time may not have been enough to weight changes might impact on dose. o The mAb with a smaller difference between PD and CD was Cetuximab possibly because the dose is calculated based on body surface area. o We extrapolated cost savings in about 9527€. The amount of € 9527 is an estimate value. This cost-review should have been done assessing the number of vials consumed per patient. This was not possible because our institution has a policy of using one vial for more than one patient. o Some analysis show that the weight / pharmacodynamic-kinetic relationship is not always proportional4. Wang et al found no significant difference in weight-adjusted vs. fixed-dose doses, with the latter showing advantages in the preparation, costs and error minimization.4 This might be a future approach.

BIBLIOGRAPHY 1Scott, A; Wolchok, JD; Old, L- Antibody therapy of cancer. Nature Reviews Cancer. Vol12(2012), p.278-287 PS-049 2Ecker,D; Jones,S; Levine,H - The therapeutic monoclonal antibody market. mAbs. Vol7(2015),p.9-14 3Wang,W; Wang,E; Balthasar,J - Monoclonal antibody pharmacokinetics and pharmacodynamics. Clinical Pharmacology & Therapeutics. Vol84(2008), p.1532-6535 L01 - Cytostatics 4Wang,DD et al. - Fixed Dosing Versus Body Size-Based Dosing of Monoclonal Antibodies in Adult Clinical Trials. The Journal of Clinical Pharmacology. Vol 49(2009), p.1552-4604