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.

Communiceren met astma/COPD-patiënten in de apotheek

Marcel Kooij

Rubriek: Referaat
Identificatie: 2017;2:e1629
Datum: 20 februari 2017

Busulfanblootstelling geassocieerd met event-vrije overleving na allogene stamceltransplantatie bij kinderen: een retrospectieve multicentrumstudie

A. Lalmohamed ab*, I.H. Bartelink c, E.M.L. van Reij a, A.C.G. Egberts ab en J.J. Boelens de

Lees abstract

Busulfan exposure associated with event-free survival in children after allogeneic haematopoietic stem cell transplantation: a retrospective multicenter cohort study

OBJECTIVE

To determine the relationship between busulfan cumulative area under the curve (AUC) and event-free survival (EFS) in children undergoing allogeneic haematopoietic stem cell transplantation (alloHCT).

DESIGN

Retrospective, multicenter cohort study.

METHODS

Children who underwent alloHCT in 15 different centres worldwide were included in this study (2000-2013). Participants had to be on intravenous busulfan and pharmacokinetic samples had to be available. Exposure of interest was the cumulative AUC of busulfan, and primary outcome was EFS (time to graft failure, relapse or all-cause mortality). Cox regression models were used to derive relative risks (RR), and the optimal busulfan AUC level was estimated using propensity adjusted Weibull models.

RESULTS

A total of 674 subjects (41% malignant, 59% non-malignant) with a median age of 4.5 years (interquartile range 1.4-10.7 years) were included in the analysis. We observed a significant U-shaped relationship between busulfan cumulative AUC and EFS (P = 0.011). The optimal target was estimated at 90 mg·h/L (78-101 mg·h/L), and was independent of any of the investigated patient characteristics. An AUC below the target increased the risk of graft failure and relapse (relative risk 1.75, P = 0.004), while transplant-related mortality was more pronounced when the AUC was too high (relative risk 2.99, P < 0.001).

CONCLUSION

This is the largest study on the relationship between busulfan and clinical outcomes in children undergoing alloHCT. Our results strongly advocate the use of therapeutic drug monitoring of busulfan, using 90 mg·h/L (78-101 mg·h/L) as a target.

Rubriek: Korte bijdrage
Identificatie: 2017;2:a1642
Datum: 20 februari 2017

Richtlijnadherentie bij het voorschrijven van direct werkende orale anticoagulantia

D. Mitrovic a*, J.A. Drost-Wijnne b, G. Jochemsen c en H. Meijerink d

Lees abstract

Guideline adherence with regard to direct acting oral anticoagulants use

OBJECTIVE

To determine guideline adherence regarding prescribing direct acting oral anticoagulants (DOACs) in daily clinical practice, distinguishing clinical and outpatient cardiology and orthopaedy patients.

DESIGN

Observational retrospective cross-sectional study.

METHODS

Four guidelines for prescribing DOACs were summarized. Medical records were used to identify patients who received rivaroxaban, dabigatran or apixaban. Baseline characteristics and adherence to the guidelines regarding interactions, CHA2DS2-VASc, HAS-BLED, dosage, renal function etc. were compared between clinical and outpatient cardiology and orthopaedy groups.

RESULTS

100 patients were included in all three groups. In four cases an interaction with possible clinical implications was found. Among almost half of the patients the CHA2DS2-VASc score was not registered. The HAS-BLED score was only determined for a handful of patients. Overtreatment was found in 3% of clinical cardiology patients and 7% of cardiology outpatients. Complications during VKA use prompted a switch to DOACs in only few cases. In 32% of orthopaedy patients and 41% of cardiology outpatients the renal function measurement was older than 60 days; in three cases the renal function was unknown. One patient with a prior cerebral haemorrhage received a DOAC without consent from a neurologist. 76% of patients in the outpatient group and 91% in the clinical cardiology group were prescribed the appropriate dose. A lower dose than appropriate was more common than a higher dose.

CONCLUSION

In general adherence to guidelines is good, but there is room for improvement. Verifying the absence of interactions, checking renal function and offering help with appropriate dosing can be performed by the hospital pharmacy. A way to improve determination and recording of CHA2DS2-VASc and HAS-BLED scores needs to be determined.

Rubriek: Oorspronkelijk artikel
Identificatie: 2017;2:a1640
Datum: 20 februari 2017

Fractuurrisico bij patiënten met COPD die intermitterend hooggedoseerde glucocorticoïden gebruiken

Kimberly N. Shudofsky ab, Andrea Burden a, Peter Vestergaard c en Frank de Vries adef*

Lees abstract

Use of high-dose intermittent glucocorticoids and the risk of fracture in patients with COPD

OBJECTIVE

To investigate the effects of high-dose intermittent glucocorticoid (GC) use on fracture risk in patients with chronic obstructive pulmonary disease (COPD).

DESIGN

Population-based retrospective case-control study.

METHODS

We conducted this study using data from the Danish National Databases. Cases were subjects ≥ 45 years with COPD, who sustained an osteoporotic fracture during the study period (1996-2011). To each case, a control without a fracture was matched by gender and year of birth. Also oral glucocorticoid use was evaluated before the index date. Associations between glucocorticoid use and fracture risk were determined using conditional logistic regression. Adjustments were made for comorbidities, drug use and disease severity.

RESULTS

Fracture risk in COPD patients currently using high-dose intermittent glucocorticoids was not increased (corrected odds ratio [ORcorr] 0.70; 95% confidence interval [CI95] 0.49-0.99). GC users with average daily dose ≥ 15 mg and cumulative dose ≥ 1 g did have a significant increased fracture risk (ORcorr 1.34, CI95 1.09-1.64). Stratification of current GC use to average daily dose did not show a clear dose-effect relationship (< 7.5 mg: ORcorr 1.08, CI95 0.99-1.17; 7.5-14.9 mg: ORcorr 1.20, CI95 1.07-1.34; 15 mg: ORcorr 1.15, CI95 0.96-1.37). For cumulative dose a trend was seen (cumulative dose 5 g: ORcorr 1.15, CI95 1.02-1.31).

CONCLUSION

COPD patients using high-dose intermittent glucocorticoids do not have an increased risk of osteoporotic fractures, regardless of disease severity. On the contrary, long-term heavy users have a clear fracture risk which is in line with guideline recommendations on fracture prevention.

Rubriek: Korte bijdrage
Identificatie: 2017;2:a1639
Datum: 7 februari 2017

Voorspelbaarheid van astma-exacerbaties bij kinderen

Marcel Kooij

Rubriek: Referaat
Identificatie: 2017;2:e1630
Datum: 7 februari 2017

Dankbetuiging

Rubriek: Redactionele mededeling
Identificatie: 2017;2:e1631
Datum: 20 januari 2017

Medisch-farmaceutische beslisregels en nierfunctiemeting in de openbare apotheek: wat levert het op?

Mette Heringa abc*, Caroline H. van de Steeg-van Gompel a en Marcel L. Bouvy ab

Lees abstract

Clinical decision rules and measuring renal function in community pharmacy: what do we get out of it?

OBJECTIVE

To investigate the frequency and management of drug therapy alerts about drug use in patients with (potential) renal impairment, to investigate the contribution of point-of-care testing (PoCT) of renal function in community pharmacy to the availability of information on renal function, and to investigate pharmacists’ experiences with drug therapy alerts and PoCT.

DESIGN AND METHODS

A clinical decision support system with clinical decision rules for eleven drugs (seven antibiotics, sotalol, digoxin, allopurinol and spironolactone) and PoCT of renal function were implemented in community pharmacies. The clinical decision rules generated an alert when dose adjustment was advised based on a registered impaired renal function, and when information on the renal function was lacking for patients over 70 years of age with a prescription for one of the selected drugs. Data registered in the clinical decision support system regarding generated alerts, renal functions and alert management were analysed retrospectively. In addition, the participating pharmacists filled out a questionnaire about their experiences.

RESULTS

336 pharmacists managed 27.307 alerts for 21.494 patients, leading to 362 dose adjustments and 65 drug replacements. For 16.208 of these patients, renal function has been registered in the clinical decision support system, including over 400 PoCT measurements. Based on PoCT, 25 cases of impaired renal function have been registered, leading to two therapy adjustments. The participating pharmacists were positive about the project.

CONCLUSION

Advanced clinical decision rules on renal function led to over 400 therapy adjustments. PoCT is a potentially useful source of information on renal function in a limited number of cases, when this information is urgently needed and not available from other sources.

Rubriek: Oorspronkelijk artikel
Identificatie: 2017;2:a1638
Datum: 9 januari 2017

Levensbedreigende bijwerking na toevoegen van DPP-4-remmer sitagliptine aan enalapril

Carina Bethlehem a*, Vincent G. Haver b en Krijn Dekens c

Lees abstract

Life-threatening side effect after adding sitagliptin to enalapril

INTRODUCTION

Angioedema is localised subcutaneous or submucosal oedema due to extravasation of fluid with a predominance for occurring in the face or airway. Because of the sudden onset with possibility of rapid progression it can be life-threatening.

DESCRIPTION

We describe the case of a patient with life-threatening angioedema after adding the dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin to enalapril. Angioedema persisted for multiple days despite treatment with H1 and H2 antihistamines and glucocorticoids. Absence of response to this therapy in combination with the history and course of the disease make a bradykinin-mediated etiology of the angioedema likely.

DISCUSSION

Inhibiting angiotensin-converting enzyme and DPP-4 inhibits two important routes to eliminate bradykinin, which can explain the development of angioedema in our patient. There are some case reports of angioedema caused by the combination of a DPP-4 inhibitor and ACE inhibition, although structured clinical evidence is weak.

CONCLUSION

We recommend to avoid the combination of DDP-4 inhibitors and ACE inhibitors in patients with previously known angioedema. Alertness to the risk of developing angioedema can prevent under-reporting of this potentially life-threatening side effect.

Rubriek: Casuïstische mededeling
Identificatie: 2017;2:a1637
Datum: 9 januari 2017

Therapeutic drug monitoring van tumornecrosefactorantagonisten bij reumatoïde artritis

Bartholomeus J.F. van den Bemt a* en Alfons A. den Broeder b

Lees abstract

Therapeutic drug monitoring of tumour necrosis factor inhibitors in rheumatoid arthritis

Therapeutic drug monitoring (TDM) of tumour necrosis factor inhibitors (TNFi) is being proposed as a useful tool for the clinician to further personalize anti-TNF treatment for patients with rheumatoid arthritis (RA). As (1) there are large interindividual differences between the pharmacokinetics of these drugs, as (2) there is an association between TNFi drug levels and clinical response on population level and as (3) dose-dependent infections and the high costs of these drugs demand for an as low as possible dosage, clinical scenarios have been proposed in which measurement of drug levels is expected to be valuable for predicting either effectiveness of a new treatment, or for identifying patients eligible for dose tapering. However, although several cross-sectional population-based studies are available, there is insufficient or contradicting evidence in RA patients that TDM-based therapies complementary to usual clinical treat-to-target care is superior to usual care with respect to better health outcomes or financial advantages.

Rubriek: Overzichtsartikel
Identificatie: 2017;2:a1630
Datum: 9 januari 2017

Zero-residual syringe als verpakkingsmateriaal voor bevacizumab als intravitreale injectie – Antwoord van de auteurs

Maartje S. Jacobs a*, Wietske L. Hemminga b, Herman J. Woerdenbag c, Marjan Bouma a en Jan Reindert Moes a

Rubriek: Correspondentie
Identificatie: 2017;2:c1604
Datum: 9 januari 2017

Zero-residual syringe als verpakkingsmateriaal voor bevacizumab als intravitreale injectie – Reactie

M. Pereboom a*, M.L. Becker a, S.L. Verweij a, R.T.M. van der Hoeven a en I.J. Mulder a

Rubriek: Correspondentie
Identificatie: 2017;2:c1603
Datum: 9 januari 2017

Het risico op hypoglykemieën bij sulfonylureumderivaten ten opzichte van metformine in relatie tot nierfunctie en metabolietgroep

Judith van Dalem abc, Martijn C.G.J. Brouwers d, Coen D.A. Stehouwer e, André Krings b, Hubert G.M. Leufkens f, Johanna H.M. Driessen acf, Frank de Vries af* en Andrea M. Burden acf

Lees abstract

Risk of hypoglycaemia in users of sulphonylureas compared with metformin in relation to renal function and sulphonylurea metabolite group

OBJECTIVE

To determine whether treatment with sulphonylureas (SUs) only in patients with renal impairment is associated with a higher risk of hypoglycaemia compared to metformin-only users.

DESIGN

Retrospective population based cohort study.

METHODS

We conducted this study using data from the Clinical Practice Research Datalink database (2004-2012). New users (N = 120,803) with at least one prescription for a non-insulin antidiabetic agent and aged over 18 were included. Associations between SU dose, renal impairment, different SUs used, and risk of hypoglycaemia were determined using Cox proportional hazard models. Adjustments were made for age, sex, life style, comorbidities and drug use.

RESULTS

The risk of hypoglycaemia in current SU-only users was significantly increased compared with current metformin-only users (adjusted hazard ratio [HRadj] 2.50; 95% confidence interval [CI95] 2.23-2.82). The risk in current SU-only users was further increased in patients with an eGFR <30 (mL/min)/(1.73m2) (HRadj 4.96; CI95 3.76-6.55). The risk of hypoglycaemia was also significantly higher in patients with a high SU dose (HRadj 3.12; CI95 2.68-3.62) and with current glibenclamide use (HRadj 7.48; CI95 4.89-11.44). Results for gliclazide, the currently recommend SU of first choice, showed a similar risk of hypoglycaemia compared to other SUs.

CONCLUSION

SU treatment in patients with an eGFR <30 (mL/min)/(1.73m2) should be considered with caution, especially the use of glibenclamide. In contrast with several guidelines, gliclazide does not seem to be superior to glimepiride, glipizide and tolbutamide.

Rubriek: Korte bijdrage
Identificatie: 2016;1:a1636
Datum: 12 december 2016

Contact

Arjan Polderman
Redacteur / secretaris

(070) 373 73 14 a.k.s.polderman@pw.nl