Abstracts Eur J Hosp Pharm: first published as 10.1136/ejhpharm-2019-eahpconf.440 on 1 March 2019. Downloaded from come across with altered blood-glucose concentration in options include enzyme replacement therapy (ERT) or sub- patients on TPN feeding who require closer monitoring with strate reduction (SRT) to prevent glucocerebroside complex and dynamic treatment such as insulin. Despite such accumulation. potential benefits, insulin added to TPN is still controversial Purpose To describe the use of ERT and SRT in patients with due mainly to the potential risk of hypoglycaemia related to Gaucher disease. its biodisponibility. Material and methods Retrospective observational study of all Purpose Analyse and evaluate the efficacy and safety of fast- patients diagnosed with Gaucher disease in our area, followed acting insulin added to TPN admixtures, in patients with up in our hospital and in treatment with ERT or SRT. Respec- altered glycaemia, followed up by nutrition support pharma- tive electronic medical records and analytics were reviewed to cists (NSP). collect the following data: sex, age, symptomatology of Material and methods Observational and retrospective study Gaucher disease at the time of diagnosis, value of chitotriosi- carried out in a General Hospital for 19 months (January dase before and after starting treatment, and adverse reactions 2017 to July 2018). Data was collected from electronic clini- to it. cal records and the electronic prescribing system. Data col- Results A total of four patients (two males and two females) lected: total patients on TPN with altered blood-sugar levels with an average age of 50 years were included. All patients followed up by the pharmacy team, patients treated with fast- had type1 Gaucher disease (not neuropathic). The initial treat- acting insulin (TPN bag additive), daily (three times) blood- ment was miglustat (SRT) in three patients and velaglucerase sugar levels (BMs), patient’s demographics, hypoglycaemias (ERT) in one of them. The value of chitotriosidase before the (blood-sugar levels less than 70 mg/dL) and hyperglycaemias start of treatment had a mean value of 11034 nmol/h/mL (BMs>180 mg/dL). Patients admitted to the critical care unit (7184–12777) and after treatment it was 1536 nmol/h/mL (CCU) or not followed up by the pharmacy team were (239–3973). excluded. We considered target BMs between 140–180 mg/dL. All the patients presented at the beginning with typical All insulin adjustments were done by NSP. manifestations of type 1 Gaucher disease as bone affectation Results The total number of patients on NPT with altered (three), hepatosplenomegaly (three), anaemia (two) and throm- BMs was 148, and 36 (24.3%) patients required fast-acting bopaenia (two). Regarding the safety of the SRT, treatment insulin therapy. Thirty patients were included in this study with miglustat was started in three patients. It was finished in due to six being admitted to the CCU. Patients included: 20 two cases due to bone progression and in one case due to were males (66.6%), average age 67 years (range 45–91). poor tolerance (paresthaesia, diarrhoea, tremor and weight Twenty-five (83.3%) patients had hyperglycaemia loss) and the TES was switched to imiglucerase or velaglucer-

(1BMs>180 mg/dL) of whom 17 (56.6%) required fast-act- ase, which were well tolerated in all patients. All the patients copyright. ing insulin therapy on the TPN bag. Average NPT duration presented improvement in the symptoms of Gaucher disease on fast-acting insulin-treated patients was 10 days (range 3– when starting ERT. 36). Average days BMs>180 mg/dL:4.5 (range 1–11). Average Conclusion TRS with miglustat is a convenient option due to BMs>180 mg/dL: 242 mg/dL (range 181–427 mg/dL; mode: its oral administration, although in three patients who were 220 mg/dL). One patient had hypoglycaemia non-insulin- initially administered, it had to be suspended due to poor tol- related. None treated with fast-acting insulin had erance or progression. ERT has been shown to be effective hypoglycaemia. and safe, and, despite not being curative, an improvement and Conclusion Despite more than half of the patients treated even remission of certain symptoms of the disease has been with fast-acting insulin therapy having hyperglycaemia, none proven.

of them had hypoglycaemia. On the other hand, a cautious http://ejhp.bmj.com/ use of the fast-acting insulin TPN bag added could boost REFERENCES AND/OR ACKNOWLEDGEMENTS hyperglycaemias in our patients. Administering insulin along https://ejhp.bmj.com/content/21/Suppl_1/A38.1 with TPN continuously appeared to be a safe method, provid- No conflict of interest. ing a smoother glycaemic profile.

REFERENCES AND/OR ACKNOWLEDGEMENTS 5PSQ-007 SEBELIPASE ALFA AS ENZYME REPLACEMENT https://doi.org/10.1177/0148607117722750 THERAPY IN THREE PAEDIATRIC PATIENTS on September 26, 2021 by guest. Protected http://dx.doi.org/10.1136/ejhpharm-2018-eahpconf.136 No conflict of interest. C Jimenez Nunez*, J Alvarez Criado, T Perez Robles, P Gabaldon Garnica, C Jimenez Vicente, M Moreno Palomino, P Lucena Martinez, A Herrero Ambrosio. Hospital Universitario la Paz, Hospital Pharmacy, Madrid, Spain

5PSQ-006 USE OF SUBSTITUTE ENZYMATIC TREATMENT AND 10.1136/ejhpharm-2019-eahpconf.440 SUBSTRATE REDUCTION IN GAUCHER DISEASE Background Lysosomal acid lipase deficiency (LALD) is a rare V González Rosa*, MI Sierra Torres, S Fernández Espínola, M Zaragoza Rascón, M Pajares lysosomal disorder characterised by clinical with dyslipidaemia Alonso. Hospital Serrania Ronda, Servicio de Farmacia, Ronda Málaga, Spain and steatohepatitis. Sebelipase-alfa is a recombinant human 10.1136/ejhpharm-2019-eahpconf.439 LAL, recently approved for clinical use in LALD. Purpose Evaluation of the effectiveness and safety of sebeli- Background Gaucher disease is included within lipidosis that pase-alfa as enzyme replacement therapy in paediatric patients occur due to mutations in the gene encoding the enzyme ß- with LALD. glucosidase. As a result of this, a fatty substance accumu- Material and methods Observational, retrospective study lates, the glucocerebroside that is the cause of disease mani- included three patients treated with sebelipase-alfa. From festations such as anaemia, thrombocytopaenia, clinical history the following data were obtained: age, sex, hepatosplenomegaly and bone injuries. Available therapeutic diagnosis, values of total cholesterol, low-density lipoprotein

A204 EJHP 2019;26(Suppl 1):A1–A311 Abstracts Eur J Hosp Pharm: first published as 10.1136/ejhpharm-2019-eahpconf.440 on 1 March 2019. Downloaded from

(LDL), high density lipoprotein (HDL), triglycerides (TG), allele. The primary endpoint was the occurrence of athero- alanine- aminotransferase (ALT) and aspartate aminotransfer- thrombotic ischaemic events, diagnosed by ultrasound imaging, ase (AST), liver size and fibrosis before and during treat- during 12 months’ follow-up. Furthermore, we collected data ment with sebelipase alfa, and adverse events. From the about clinical parameters (age, sex, ethnicity), co-medication outpatient programme were obtained dose, administrations during follow-up, vascular risk factors and surgical parameters. and weeks of treatment. The efficacy was evaluated by nor- We tested the association between carrying LOF or GOF malising the analytical values of the lipidic and liver profiles alleles and the primary endpoint in a univariate analysis, and in three patients who participated in the clinical trial until multivariate analysis including those clinical parameters previ- April 2018. ously related to clopidogrel response. OR and HR were calcu- Results Three male brothers 12, 15 and 17 years’ old diag- lated and P-values<0.05 were considered statistically nosed with LALD before 5 years, heterozygous for mutation significant. in the LIPA gene c.894G>A, c.256C>T. Before the trial, Results Seventy-two patients were recruited, mean age 67.4 patients presented abnormal analytical values (except TG), ±9.4 years, 22.2 females and 100% were caucasians. Carrying hepatomegaly and fibrosis. Patients received continuous treat- CYP2C19 LOF alleles was significantly associated with the pri- ment with sebelipase-alfa at a dose of 1 mg/kg/2 weeks intra- mary endpoint in the single analysis (OR=4.49; 95% CI: 1.45 venously. Preparation of the medication was carried out by to 13.84; p=0.009), in the multivariate analysis (OR=4.89; the hospital pharmacy service. In April 2018, after 225, 183 95% CI: 1.32 to 12.83; p=0.018). This association remains and 114 weeks of treatment respectively, all three patients significant if we perform a survival analysis (HR=4.07; maintained the values analysed in the range of normality 95% CI: 1.80 to 9.20; p£0.001). On the other hand, carrying (except HDL in two and TG in one patient). Hepatomegaly CYP2C19 GOF alleles was not related to the primary reversed in all patients. The means of the values and of the endpoint. percentages of variation to the basal were: cholesterol 150.66 Conclusion CYP2C19 LOF polymorphisms show a higher ±22.89 mg/dL (34.19%), LDL 89.33±12.20 mg/dL effect on clopidogrel response in PAD patients than that pro- (46.90%), HDL 35.66±6.35 mg/dL (+1.55%), AST 30.66 vided in acute coronary syndrome patients. These SNPs may ±4.04 IU/L (64.88%), ALT 21.33±4.93 mg/dL (65.99%) be used as genetic markers of clopidogrel response in PAD and TG 130±85.91 mg/dL (+2.12%). Concerning safety, two patients. Clopidogrel treatment may be guided by CYP2C19 patients who suffered diarrhoea, and adverse effects related to genotyping, although further analysis should be performed. the infusion were not reported. Conclusion LALD is a rare disease, and sebelipase-alfa is the REFERENCES AND/OR ACKNOWLEDGEMENTS first drug authorised for its treatment. The response to treat- Thanks to all the patients participating in this study and all copyright. ment with sebelipase-alfa has been favourable from the begin- the people working in our hospital who took part in this ning, with an improvement in the studied variables and a project. good safety profile in the reported cases. No conflict of interest.

REFERENCES AND/OR ACKNOWLEDGEMENTS Pharmacy Hospital La Paz. 5PSQ-009 CYP2C19 SNP’S INFLUENCE ON CLOPIDOGREL No conflict of interest. RESPONSE IN CEREBROVASCULAR DISEASE PATIENTS: FINAL RESULTS 1X Díaz-Villamarín, 1CL Dávila-Fajardo, 1D Blánquez-Martínez, 1E Fernández-Gómez, CYP2C19 SNP’S http://ejhp.bmj.com/ 5PSQ-008 INFLUENCE ON CLOPIDOGREL 2A Antúnez-Rodríguez, 1ÁS Raquel*. 1Farmacia Hospital San Cecilio, Pharmacy, Granada, RESPONSE IN PERIPHERAL ARTERY DISEASE Spain; 2Genyo, Genomics Unit, Granada, Spain PATIENTS 10.1136/ejhpharm-2019-eahpconf.442 1XDíaz-Villamarín,1CL Dávila-Fajardo, 1D Blánquez-Martínez, 1E Fernández-Gómez, 2A Antúnez-Rodríguez, 1ÁS Raquel*. 1Farmacia Hospital San Cecilio, Pharmacy, Granada, Background Clopidogrel is a prodrug, which is metabolised to Spain; 2Genyo, Genomics Unit, Granada, Spain its active metabolite especially by the CYP2C19 enzyme. Car-

10.1136/ejhpharm-2019-eahpconf.441 rying some polymorphisms, contained in the DNA region on September 26, 2021 by guest. Protected encoding the CYP2C19 expression, have shown a significant Background Clopidogrel is a prodrug, metabolised to its active association with a lack of clopidogrel efficacy among coronary metabolite especially by the CYP2C19 enzyme. The effect of patients. This association had been widely researched and the CYP2C19 polymorphisms on clopidogrel efficacy in coronary clopidogrel label recommends testing the CYP2C19 loss of disease had been widely researched. The clopidogrel label rec- function alleles before the start of the treatment, even DPWG ommends testing the CYP2C19 loss of function alleles before and CPIC pharmacogenetic dosing guidelines, and recommend the start of the treatment and the DPWG and CPIC pharma- switching clopidogrel in case of carrying the CYP2C19 loss of cogenetic dosing guidelines recommend switching clopidogrel function alleles in coronary patients with stent. This remains in case of carrying the CYP2C19*2 SNP in coronary patients unstudied in cerebrovascular-disease patients. with stent. This remains unstudied in peripheral artery disease Purpose Explore the influence of CYP2C19 genetic polymor- (PAD) patients. phisms on clopidogrel response in cerebrovascular disease Purpose Explore the influence of CYP2C19 genetic polymor- patients. phisms on clopidogrel response in PAD patients. Material and methods Patients after stroke or transient ischae- Material and methods Peripheral artery disease patients treated mic event (TIA) treated with clopidogrel after hospitalisation with clopidogrel after percutaneous transluminal angioplasty were recruited. These were tested for carrying the were recruited. They were tested for carrying the CYP2C19*2, CYP2C19*2, *3 (loss of function (LOF)) and *17 (gain of *3 (loss of function (LOF)) and *17 (gain of function (GOF)) function (GOF)) alleles. As primary endpoint we considered

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