Nederlands Platform voor Farmaceutisch Onderzoek

Het Nederlands Platform voor Farmaceutisch Onderzoek (NPFO) presenteert onderzoek in de farmaceutische wetenschappen, zoals medicatieveiligheid, patiëntenzorg, formulering, (bio)analyse, (klinische) farmacologie en casuïstiek.

Ziekenhuisfarmaciedagen, 9 en 10 november 2017

Lees abstract

De hier opgenomen abstracts vormen de mondelinge presentaties tijdens de Ziekenhuisfarmaciedagen op 9 en 10 november 2017 te Bunnik.

Rubriek: Congresabstracts
Identificatie: 2017;2:a1666
Datum: 15 december 2017

Sederende medicatie bij de geriatrische intensivecarepatiënt

Bart G.J. Dekkers ab, Bert Loef c, Marijn Boer c en Ithamar Brinkman a*

Lees abstract

Sedative drugs in the geriatric intensive care patient

BACKGROUND

The number of elderly patients admitted to Intensive Care Units (ICUs) has increased significantly in recent years. It has been demonstrated that the elderly are more prone to inadequate drug treatment and adverse drug effects.

OBJECTIVE

To perform a literature review on the effects of aging on pharmacokinetic and pharmacodynamic properties of commonly used sedative drugs in Dutch ICUs.

DESIGN AND METHODS

Literature review using PubMed.

RESULTS

Literature on the effects of aging on the pharmacology of commonly used sedative drugs in the ICU is scarce. For the general population, we found that for midazolam, propofol, fentanyl and remifentanil aging is associated with an increased susceptibility of the patients for the pharmacodynamic properties of these agents. This effect is confirmed for some of these drugs in ICU patients. In addition, a reduction in drug clearance was observed for propofol and remifentanil.

CONCLUSION

Based on these findings, we suggest to start with lower dosages for midazolam, propofol, fentanyl and remifentanil in elderly ICU patients and to re-evaluate frequently and adjust the therapy by clinical effect if necessary.

Rubriek: Overzichtsartikel
Identificatie: 2017;a1659
Datum: 15 december 2017

Afbouw TNF-alfaremmers in de dagelijkse klinische praktijk bij reumatologie

C. Lau ab, N. van Rein a, C.F. Allaart c en J. Zwaveling a*

Lees abstract

Dose tapering of TNF-alpha inhibitors in clinical daily practice based on pharmacy dispensing data

OBJECTIVE

To analyse the clinical daily practice of dose tapering of subcutaneous TNF-alpha inhibitors in patients of the Department of Rheumatology of the Leiden University Medical Centre (LUMC).

DESIGN AND METHODS

Dispensing data of the outpatient pharmacy of the LUMC from 2012-2015 were extracted. Patients of the Department of Rheumatology receiving a subcutaneous TNF-alpha inhibitor at stable dose (range 80-120%) during at least six months were included. Dose tapering was defined as receiving a dose reduction of at least 30% compared to the last stable dose after two subsequent prescriptions or as dispensing only one prescription of the TNF-alpha inhibitor over minimally 200 days.

RESULTS

Dispensing data of 235 patients were available: 66% were diagnosed with rheumatoid arthritis, and 59% of the patients were treated with etanercept. No data were available about previous or current disease activity or concomitant treatment. Of 235 patients, 46 (20%) matched the definition of receiving a dose reduction in TNF-alpha inhibitor based on dispensing data. Remarkably, 53% of all attempts to taper a TNF-alpha inhibitor seemed not successfully continued. Compared to patients who used etanercept, patients who used adalimumab were 1.4 times more likely (95% confidence interval [95% CI] = 0.8-2.4) to receive a dose reduction and 3.4 times more likely (95% CI = 1.7-6.8) to receive a dose increment. The type of rheumatic diagnosis was not associated with the frequency of dose reduction.

CONCLUSION

This study shows that dispensing data can be a useful source to analyse dose tapering of TNF-alpha inhibitors in daily clinical practice. However, factors that contribute to dose reduction or dose tapering could not be directly analysed.

Rubriek: Oorspronkelijk artikel
Identificatie: 2017;2:a1660
Datum: 15 december 2017

Evaluatie van doseerrichtlijnen en populatiefarmacokinetiek van vancomycine bij kinderen met kanker

P.S. van Egmond a*, N.K.A. van Eijkelenburg b, C.M. Zwaan cd en R.A.A. Mathôt a

Lees abstract

Evaluation of dosing guidelines and population pharmacokinetics of vancomycin in children with cancer

BACKGROUND

Vancomycin is standard therapy in pediatric oncology patients with neutropenic fever. In a previous study we showed that with a starting dose of 60 mg/kg/day in four doses 58% of patients had inadequate trough levels. As a result the starting dose was increased to 90 mg/kg/day.

OBJECTIVE

To determine whether a starting dose of 90 mg/kg/day in four doses leads to a higher percentage therapeutic trough levels compared to 60 mg/kg/day in four doses. Furthermore, population pharmacokinetics were described in pediatric oncology patients.

DESIGN AND METHODS

Prospective data from the VANCOPOP study were combined with retrospective data from the Academisch Medisch Centrum, Amsterdam. The percentage therapeutic trough levels (10-15 mg/L) in the first three days of therapy was the primary endpoint. As a secondary endpoint, renal toxicity was evaluated. Population pharmacokinetics were described using nonlinear mixed-effects modelling.

RESULTS

Data was available from 53 and 22 patients receiving 60 and 90 mg/kg/day, respectively. The percentages therapeutic trough concentrations were comparable in both groups (21% and 23%, respectively). The percentages sub- (68% and 41%, respectively) and supratherapeutic concentrations (12% and 36%, respectively) were different between dosing groups (p < 0.05). The population pharmacokinetics of vancomycin were described by a two-compartment model with creatinine clearance significantly affecting clearance. Based on Monte Carlo simulations the following doses were proposed: younger than two years 90 mg/kg/day, two till six years 80 mg/kg/day, six till twelve years 70 mg/kg/day and twelve till eighteen years 60 mg/kg/day, all in four doses.

CONCLUSION

Vancomycin clearance is age-dependent and highly variable in pediatric oncology patients. A prospective study is necessary to evaluate the proposed dosing guidelines for different age groups.

Rubriek: Korte bijdrage
Identificatie: 2017;2:a1658
Datum: 10 november 2017

Minder accidentele overdoseringen en intoxicaties met Thyrax bij kleine kinderen door wijziging van flacon naar blisterverpakking

T.E. van Riemsdijk *, A.J.H.P. van Riel, C.C. Hunault en I. de Vries

Lees abstract

Less accidental overdoses and intoxications with Thyrax in little children because of change from bottle to blister packaging

OBJECTIVE

In December 2013, the largest manufacturer of levothyroxine for the Dutch market (brand Thyrax) started packaging their product from glass bottles into blisters to protect it from environmental influences. We investigated whether this change in the primary packaging influenced the frequency and severity of accidental levothyroxine overdose in young children.

DESIGN AND METHODS

Telephone inquiries to our Dutch Poisons Information Center concerning children under seven years of age exposed to Thyrax were registered between January 2010 and December 2015. The ingested amount of levothyroxine in mg/kg body weight was recorded and the severity of the overdoses was estimated. An unknown dose or an ingested dose of more than 0.05 mg/kg of levothyroxine was defined as a toxic dose. Information about the actual manner of packaging was collected in 2014 and 2015. The number of telephone inquiries before and after the change in the primary packaging were compared using interrupted time series analyses. The decrease in proportions of cases exposed to a toxic dose were compared using a Z-test.

RESULTS

The monthly average number of Thyrax overdose cases decreased from 12.1 per month before the change in the primary packaging to 6.4 after (P = 0.04). Furthermore, this decrease was proportionally larger among children exposed to a toxic dose than among children exposed to a non-toxic dose: –66% versus –38%, respectively (P = 0.002). However, in 2015 still 21% of the children with an overdose took these Thyrax tablets out of a bottle.

CONCLUSION

Blister packaging has significantly reduced the number and severity of accidental intake of Thyrax by young children. However, this preventive effect is hampered by parents removing the medication from the blister well before use.

Rubriek: Oorspronkelijk artikel
Identificatie: 2017;2:a1656
Datum: 10 november 2017

Prevalentie en aard van bloedingen en tromboses en geassocieerde risicofactoren tijdens de ziekenhuisopname bij patiënten die anticoagulantia gebruiken

A.R. Dreijer ab*, J. Diepstraten b, M.J.H.A. Kruip c, R. Brouwer d, F.W.G. Leebeek c en P.M.L.A. van den Bemt a

Lees abstract

Prevalence and nature of bleedings and thrombotic events and associated risk factors during hospitalization of patients that use anticoagulants

OBJECTIVE

Primary aim: to determine the prevalence of bleedings and thrombotic events in anticoagulants users during hospitalization. Secondary aims: to determine the type and location and the potential risk factors that are associated with bleedings and thrombotic events.

DESIGN

Prospective, observational, multicenter cohort study.

METHODS

The study was performed at the Erasmus MC, Rotterdam and the Reinier de Graaf hospital, Delft. Patients who were treated with anticoagulants were included in the study. Exclusion criteria were hospitalization of less than 24 hours, admission to the intensive care unit without admission to another, regular hospital department, and patients treated with low-molecular-weight heparins only for thrombosis prophylaxis.

RESULTS

We included 942 patients. The prevalence of in-hospital bleeding events was 8.8%, of which 44% were surgical site bleedings. The prevalence of thrombotic events during hospitalization was 0.7%. Multivariate logistic regression analysis indicated that female gender (odds ratio [OR] 1.82; 95% confidence interval [95% CI] 1.11-2.99), age 70 years or older (OR 1.73; 95% CI 1.03-2.89), hospitalization of five days or longer (OR 2.86; 95% CI 1.43-5.72), admission to the academic hospital (OR 1.93; 95% CI 1.12-3.34) and admission to surgical wards (OR 1.98; 95% CI 1.20-3.73) were associated with more bleeding events. We found no potential risk factors associated with thrombotic events, as the number of cases was very small.

CONCLUSION

Bleeding events occurred in 8.8%, thrombotic events in 0.7% of anticoagulants users during hospitalization. Female gender, age 70 years or older, hospitalization of 5 days or longer, admission to the academic hospital and admission to surgical wards seem to be risk factors.

Rubriek: Korte bijdrage
Identificatie: 2017;2:a1652
Datum: 8 november 2017

De rol van klinische presentatie, comorbiditeit en behandeling bij multipel myeloom-patiënten op overlevingsduur

Ciske van den Oever

Rubriek: Referaat
Identificatie: 2017;2:e1644
Datum: 23 oktober 2017

Effecten van kortdurend vasten op systemisch cytochroom P450-gemedieerd geneesmiddelmetabolisme

Ciske van den Oever

Rubriek: Referaat
Identificatie: 2017;2:e1643
Datum: 23 oktober 2017

Bio-equivalentie van een vermalen tablet elvitegravir + cobicistat + emtricitabine + tenofovir (Stribild) in combinatie met een gestandaardiseerd ontbijt of sondevoeding

Mieke Jongbloed-de Hoon ab*, Angela Colbers a, Kirsten Velthoven-Graafland a, Marjolijn Duisenberg-van Essenberg b, Martine Kruijssen a, Evertine Abbink c, Reinout van Crevel a en David Burger a

Lees abstract

Pharmacokinetics of crushed elvitegravir combination tablet given with or without enteral nutrition

We investigated whether a fixed-dose combination tablet of elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil (Stribild) can be crushed and combined with enteral nutrition without influencing pharmacokinetics. This was an open-label, 3-period, single-dose, randomized, crossover trial in 24 healthy volunteers. Subjects received Stribild whole tablet with breakfast (reference), crushed/suspended Stribild + breakfast, crushed/suspended Stribild + enteral nutrition. Crushed/suspended Stribild + enteral nutrition was bioequivalent (90% confidence interval between 80% and 125%) with a whole Stribild tablet. Crushed/suspended Stribild + breakfast showed bioequivalence for the area under the curve (AUC032), but not for maximum concentration (Cmax) (considered not clinically relevant). Patients with swallowing difficulties or an enteral feeding tube can use crushed and suspended Stribild tablets.

Rubriek: Korte bijdrage
Identificatie: 2017;2:a1651
Datum: 23 oktober 2017

Het gebruik van risicomedicatie voor maagulcera en maagbescherming in relatie tot het ontstaan van ulcera na een bariatrische ingreep

B. Sezgi a*, M.A. Damhof a, I.F. Faneyte b, J. van der Palen c en L.L. Krens a

Lees abstract

Use of risk medication for stomach ulcers and stomach protection relating to ulcer occurrence after bariatric surgery

OBJECTIVE

To assess the influence of risk medication and proton pump inhibitor use on ulcer-free survival in patients after bariatric surgery.

DESIGN

Retrospective cohort study.

METHODS

By using a retrospective chart, review information was collected about the use of medication among 631 patients who underwent a Roux-and-Y gastric bypass, an omega-loop bypass or received a gastric sleeve. Kaplan-Meier survival estimates were calculated to study the effect of risk medication on the median time to ulcer development after bariatric surgery. The effect of the single and combined use of risk medication with or without proton pump inhibitors was evaluated by Cox proportional hazard models.

RESULTS

The median disease-free survival could not be computed because of the low incidence of ulcers (0.79%). The hazard ratios (HR) for use of any risk medication, NSAIDs, corticosteroids, antiplatelet drugs, anticoagulants and SNRIs were 1.51 (95% confidence interval [CI] 0.17-13.61, p = 0.714), 0.05 (95% CI 0.00-180,000,000, p = 0.761), 0.04 (95% CI 0.00-70,125, p = 0.668), and 4.10 (95% CI 0.68-24.66, p = 0.123), respectively. The hazard ratios for the combinations of NSAIDs with any risk medication or with SNRIs were 3.28 (95% CI 0.36-29.66, p = 0.290) and 7.74 (95% CI 0.86-69.46, p = 0.067) while the hazard ratios for the other combinations could not be calculated. The rare combination of an NSAID, an anticoagulant and an SNRI and the combination of an anticoagulant with an SNRI resulted in a statistically significant higher risk for developing an ulcer (HR 37.52 with 95% CI 4.10-343.19, p = 0.001 and 24.16 with 95% CI 4.03-144.83, p < 0.0001, respectively), despite the use of proton pump inhibitors (HR 37.52 with 95% CI 4.10-343.19, p = 0.001 and 25.45 with 95% CI 4.24-152.70, p = <0.0001, respectively).

CONCLUSION

Despite the prophylactic use of proton pump inhibitors, we found an association between the development of an ulcer and SNRI use, as well as with the combination of an SNRI and an anticoagulant with or without the use of an NSAID.

Rubriek: Korte bijdrage
Identificatie: 2017;2:a1650
Datum: 23 oktober 2017

Overdracht van CYP2D6-genotyperingsuitslagen naar huisarts en openbare apotheek

Mirjam Simoons abc, Hans Mulder ad*, Robert A. Schoevers c, Henricus G. Ruhé ce† en Eric N. van Roon bf

Lees abstract

Availability of CYP2D6 genotyping results in general practitioner and community pharmacy medical records

OBJECTIVE

To investigate the availability of CYP450–2D6 (CYP2D6) genotyping results in general practitioner (GP) and/or community pharmacy records, and the influence thereof on psychotropic CYP2D6 substrate dosing.

DESIGN

A retrospective survey with cross-sectional analysis.

METHODS

Primary outcome was the percentage of patients genotyped for CYP2D6 with their genotype/phenotype registered in GP and/or pharmacy records. Secondary outcome was the number of defined daily doses of psychotropic CYP2D6 substrates prescribed after genotyping.

RESULTS

For 216 out of 1307 eligible patients, medication overviews could be obtained. Genotyping results were available at GPs for 3.1% and at pharmacies for 5.9%. The average psychotropic CYP2D6 substrate dose was not different between any non-extensive metabolizer group and extensive metabolizer group (all P ≥ 0.486).

CONCLUSION

Valuable information for individualizing psychiatric pharmacotherapy is lost on a large scale.

Rubriek: Oorspronkelijk artikel
Identificatie: 2017;2:a1654
Datum: 13 oktober 2017

TDM bij fluorchinolonen om verworven resistentie bij tuberculose tegen te gaan

Ithamar Brinkman

Rubriek: Referaat
Identificatie: 2017;2:e1646
Datum: 12 september 2017

Contact

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Arjan Polderman

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