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.

Vemurafenib en dabrafenib in combinatie met radiotherapie en het risico op verergerde radiotoxiciteit

A.H.M. de Vries Schultink a*, J. Koomen b, B. van Triest c, J.J.M.A. Hendrikx a, J.B.A.G. Haanen d, J.H. Beijnen ae en A.D.R. Huitema af

Lees abstract

Vemurafenib and dabrafenib in combination with radiotherapy and the risk of aggravated radiotoxicity

OBJECTIVE

Firstly, to evaluate radiotoxicity in a cohort with patients receiving both radiotherapy and a BRAF inhibitor (BRAFi). Secondly, to identify whether the BRAFi used, dabrafenib or vemurafenib, is related to radiotoxicity.

DESIGN

This study is a retrospective cohort study, reflecting daily clinical practice.

METHODS

In total, 119 patients were included in this analysis. Patients were treated with vemurafenib (n = 42) or dabrafenib (n = 77) in combination with radiotherapy within a time frame of two months. The incidence of induced radiotoxicity was compared between both groups with a Fisher’s exact test. A logistic regression analysis was performed to identify potential factors related to the probability of experiencing induced radiotoxicity: type of BRAFi, combination therapy with a MEK inhibitor, age, sequence of treatment and location, cumulative radiation dose and total incidences of radiotherapy.

RESULTS

Induced radiotoxicity was seen in 6.7% of all patients. In the vemurafenib group 4.8% of patients experienced induced radiotoxicity compared to 7.8% in the dabrafenib group, this difference was not significant (P = 0.71). The logistic regression analysis revealed that none of the analyzed factors were related to the probability of experiencing induced radiotoxicity.

CONCLUSION

Both vemurafenib and dabrafenib administered in combination with radiotherapy induced radiotoxicity. No preference for dabrafenib over vemurafenib exists. The induced toxicity was manageable and did not lead to fatalities in this cohort. No predictive factors could be identified.

Rubriek: Oorspronkelijk artikel
Identificatie: 2018;3:a1669
Datum: 29 maart 2018

Beloop en behandeling van een intoxicatie met baclofen

D. Mitrovic a*, A. Assendorp b, C. Bethlehem c, H. de Boer d en E. ten Hoeve e

Lees abstract

Course and treatment of baclofen intoxication

INTRODUCTION

The number of reports on baclofen intoxication has increased in recent years. This is related to the increasing use of baclofen in the treatment of alcohol and gamma-hydroxybutyric acid withdrawal and as recreative drug.

DESCRIPTION

A 27-year-old man with a history of psychiatric comorbidity and an addiction problem was brought to the emergency department (ED) in an unresponsive state (EMV score 3) after an attempted suicide with medication. After heteroanamnesis, he was diagnosed with an intoxication of 850 mg baclofen, 2.5 liters’ beer and an unknown amount of heroine. He was intubated because of respiratory failure. Besides, activated charcoal in combination with a laxative was administered. Morphine and midazolam were administered to prevent withdrawal symptoms. The EMV score improved 30 hours after admission and he was detubated 60 hours after admission.

DISCUSSION AND CONCLUSION

The treatment of a baclofen intoxication consists of supportive care. This case demonstrates the importance of keeping a baclofen intoxication in mind in the differential diagnoses when a comatose or confused patient with addiction problems is brought in at the ED. Baclofen levels cannot be determined with standard drug screening so considering specific laboratory testing is necessary to detect baclofen intoxication.

Rubriek: Casuïstische mededeling
Identificatie: 2018;3:a1670
Datum: 28 maart 2018

De invloed van SGLT-2-remmers op de nierfunctie en cardiovasculaire risico’s

Harm Geers ab*

Lees abstract

The influence of SGLT-2 inhibitors on kidney function and cardiovascular risks

BACKGROUND

SGLT-2 inhibitors are a new treatment option in type 2 diabetes mellitus. The EMPA-REG OUTCOME study showed improved outcomes in mortality and cardiovascular disease in patients treated with empagliflozine. A subanalysis on microvascular outcomes showed that empagliflozine protected renal function by lowering the intraglomerular pressure. In June 2016 the FDA issued a warning for acute kidney injury associated with canagliflozine and dapagliflozine use.

OBJECTIVE

To find an explanation for the mechanisms behind renal protection, reduced cardiovascular events and mechanisms that may cause acute kidney failure in SGLT-2 inhibitors.

METHODS

Literature was reviewed to find information about the possible mechanisms for renal protection and renal injury. Human, animal as well as in vitro studies that elucidated possible pharmacological mechanisms behind the effects of SGLT-2 inhibitors on renal function, the cardiovascular system, or the cause of renal injury were considered eligible for this study.

RESULTS

A possible pharmacological explanation for the effect of SGLT-2 inhibitors on renal protection was found in several studies. It was also possible to explain effects of the cardiovascular system and two possible causes of renal injury were found.

CONCLUSION

Based on the mechanism of action of SGLT-2 inhibitors, it was possible to make a recommendation for pharmacists to avoid combination of SGLT-2 inhibitors and drugs that decrease renal function, especially the combination of diuretics and/or nonsteroidal anti-inflammatory drugs with SGLT-2 inhibitors. The combination of SGLT-2 inhibitors with ACE inhibitors may also reduce renal function but is beneficial in patients with (micro)albuminuria.

Rubriek: Oorspronkelijk artikel
Identificatie: 2018;3:a1657
Datum: 28 maart 2018

Onderzoek naar zelfmanagement bij astma en goed geneesmiddelengebruik (SMARAGD-studie): een pilotonderzoek

Esther Kuipers ab*, Michel Wensing ac, Peter de Smet ad en Martina Teichert ae

Lees abstract

Self-management research of asthma and good drug use (SMARAGD study): a pilot trial

BACKGROUND

Community pharmacists play an important role in supporting patients for optimal drug use.

OBJECTIVE

To assess the effectiveness of monitoring in asthma patients with inhaled corticosteroids (ICS) on disease control.

DESIGN

Asthma patients using ICS were invited from two intervention (IG) and two control pharmacies (CG).

METHODS

Participating patients completed questionnaires at the study start and at 6-month follow-up, including the Control of Allergic Rhinitis and Asthma Test (CARAT) questionnaire. IG patients completed the CARAT questionnaire every two weeks and received counselling on disease management, ICS adherence, and inhalation technique when scores were suboptimal, deteriorating, or absent. For Turbuhaler users, additional electronic monitoring (EMI) was available, with daily alerts for ICS intake. As the primary outcome, CARAT scores at follow-up were compared between IG and CG using linear regression. As secondary outcome, refill adherence was compared using logistic regression.

RESULTS

From March to July 2015, we enrolled 39 IG and 41 CG patients. At follow-up, CARAT scores did not differ between IG and CG (-0.19; 95% confidence interval [95% CI], -2.57 to 2.20), neither did patient numbers with ICS adherence > 80% (0.82; 95% CI, 0.28-2.37). Among EMI users, CARAT scores did not differ, but ICS adherence > 80% showed a 4.52-fold increase (95% CI, 1.56-13.1) compared with EMI nonusers.

CONCLUSION

Among community-dwelling asthma patients, pharmacist monitoring did not affect CARAT scores, but EMI use showed improved ICS refill adherence.

Rubriek: Oorspronkelijk artikel
Identificatie: 2018;3:a1667
Datum: 8 maart 2018

De ziekenhuisapotheker als behandelaar bij intoxicaties: evaluatie van het zorgpad intoxicaties

Manon Bakker *, Douwe van der Meer, Daphne Bertholee en Peter ter Horst

Lees abstract

The hospital pharmacist as a member of the multidisciplinary team in the treatment of the intoxicated patient

OBJECTIVE

To investigate the role of the hospital pharmacist as a member of the multidisciplinary team in the treatment of intoxicated patients.

DESIGN AND METHODS

This study is a retrospective observational study. Electronic patient records of all patients admitted to the Isala hospital in Zwolle with an intoxication in 2016 were analysed. We determined the number of cases in which the hospital pharmacist was consulted and if this was recorded in the patient record. Furthermore, the influence of drug-specific local treatment protocols on the number of consultations was assessed. The Emergency Department (ED) doctors were questioned about their experiences regarding the consultation of the hospital pharmacist.

RESULTS

A total of 367 intoxicated patients were admitted to the ED. In 300 of these cases the patients were intoxicated with another agent than alcohol. In 40% of these cases the hospital pharmacist was consulted, which was recorded in the electronic patient record in 71% of these cases. Four patients died as a result of their intoxication. The presence of a drug-specific local treatment protocol had no effect on the number of consultations of the hospital pharmacist. The ED doctors were satisfied with the hospital pharmacist as a member of the multidisciplinary team. The hospital pharmacist actively participates in advising about the appropriate treatment of the individual intoxicated patient.

CONCLUSION

Hospital pharmacists are valued by the ED doctors as a member of the multidisciplinary team in the treatment of intoxicated patients.

Rubriek: Oorspronkelijk artikel
Identificatie: 2018;3:a1668
Datum: 8 maart 2018

Dankbetuiging

Rubriek: Redactionele mededeling
Identificatie: 2018;3:e1661
Datum: 6 februari 2018

Dried blood spot-methode voor nilotinib

Jacqueline Hugtenburg

Rubriek: Referaat
Identificatie: 2018;3:e1650
Datum: 6 februari 2018

Factoren geassocieerd met therapieontrouw van antihypertensiva

Jacqueline Hugtenburg

Rubriek: Referaat
Identificatie: 2018;3:e1649
Datum: 6 februari 2018

Interactie tussen valproïnezuur en meropenem: waarde van de vrije concentratie

J.Y.M.N. Derijks-Engwegen a* en L.J.J. Derijks b

Lees abstract

Interaction between valproic acid and meropenem: significance of the free concentration

INTRODUCTION

Meropenem (MER) is a carbapenem antibiotic used in The Netherlands in critically ill patients. A clinically relevant interaction with valproic acid (VPA) has been described, potentially resulting in subtherapeutic levels of VPA. The combination is therefore discouraged.

DESCRIPTION

A 50-year-old patient in the intensive care unit was treated with intravenous (i.v.) VPA 800 mg twice daily and MER 1000 mg three times a day. Phenytoin 75 mg i.v. twice daily was added to prevent therapeutic failure due to interaction of MER and VPA. A sharp decline in total VPA levels to < 0.5 mg/ml was seen. After stopping MER, total VPA levels remained subtherapeutic and VPA dose was increased. No convulsions occurred during subtherapeutic anti-epileptic levels. Retrospectively, we measured unbound VPA concentrations in remaining samples. Free VPA levels after cessation of MER were all therapeutic or above.

DISCUSSION

The mechanism of interaction between carbapenems and VPA is unclear. Although declines in total blood levels of VPA have been seen, these did not always result in therapeutic failure. In most reports, no information is given on free VPA concentrations or albumin levels. Here we show that in hypoalbuminaemia, total VPA levels are misleading in evaluating the combination of MER and VPA and this may inadvertently lead to overdosing of VPA.

CONCLUSION

Due to hypoalbuminaemia in critically ill patients, VPA and its interaction with MER should be monitored based on free concentrations, to prevent overdosing of VPA or unnecessary switching to other anti-epileptics.

Rubriek: Casuïstische mededeling
Identificatie: 2018;3:a1665
Datum: 5 februari 2018

Groene verkleuring van de urine bij een intensivecarepatiënt

Kelly L. Niggebrugge-Mentink *, Charlotte van Kesteren, Serife Ozkal en Marieke M. Beex-Oosterhuis

Lees abstract

Green discolouration of urine from an intensive care patient

INTRODUCTION

Several case reports describe a green discolouration of urine during the use of the anaesthetic propofol. This side effect of propofol is described in the summary of product characteristics and is classified as very rare. For diagnosis, an overview of all possible causes of green discolouration would be useful. Since this is not available in literature, we provide it here.

DESCRIPTION

We describe a 29 year old man who was treated at our intensive care unit and whose urine turned green after four days of treatment with propofol. An overview of the possible causes of urine turning green is presented here.

DISCUSSION

We performed a literature search including several relevant terms and after selecting the articles we screened the references. In summary, we found endogenous and exogenous agents that could cause green urine. Rare cases describe microbiological or other causes. In addition, the propofol infusion syndrome and the relation with green urine is discussed.

CONCLUSION

This case describes a very rare but benign and reversible side effect of propofol. When this phenomenon is not known by the practitioners, this could lead to excessive diagnostics and concerns. Before diagnosing propofol-induced green urine, the other possibilities of green urine should be excluded.

Rubriek: Casuïstische mededeling
Identificatie: 2018;3:a1663
Datum: 5 februari 2018

Associatie tussen HTR2C-polymorfismen en gewichtsverlies bij patiënten met obesitas

Arne J. Risselada ab*, Eibert R. Heerdink bc, Rob K. Gonera d, Toine C.G. Egberts bc en Hans Mulder ab

Lees abstract

Association between HTR2C polymorphisms and weight loss in obese patients

OBJECTIVE

To investigate whether the HTR2C rs1414334 and 759 C/T polymorphisms are associated with weight loss in an anti-obesity programme.

DESIGN AND METHODS

A longitudinal observational follow-up study was used to assess the association between HTR2C genotypes and weight loss during a nine month programme in an obesity clinic. Caucasian patients aged 18 years or older were included. Data were extracted from the patients’ medical records. In total, 128 patients were included (29 males).

RESULTS

There was a significant association between the HTR2C 759 T allele and resistance to weight loss in the first month of the programme. For each T allele present, there was 0.78% (95% confidence interval [95%-CI] 0.19-1.38; P = 0.01) less weight loss (as a percentage of the body weight at start). Patients carrying the variant HTR2C 759 T allele were also less likely to reach > 7% weight loss (odds ratio [OR] 0.23; 95%-CI 0.06-0,85; P = 0.028), and dropped out of the programme sooner (–0.78 months; 95%-CI –1.51- –0.06; P = 0.035; corrected for gender). No associations with the HTR2C rs1414334-genotype and any of the primary endpoints for weight loss or secondary endpoints were found.

CONCLUSION

Patients carrying the HTR2C 759 T allele were more resistant to weight loss and dropped out of the programme sooner. However, these effects were small and only explained a small part of a very complex puzzle. Genotyping HTR2C to predict a patient’s chance of success in an obesity clinic is therefore not warranted.

Rubriek: Oorspronkelijk artikel
Identificatie: 2018;3:a1662
Datum: 5 februari 2018

Risicofactoren voor medicatiefouten na eerdere medicatieverificatie bij electieve opnames

M.M. Ebbens abc*, K.B. Gombert-Handoko b, M. Al-Dulaimy d, P.M.L.A. van den Bemt c en E.J. Wesselink a

Lees abstract

Risk factors for medication erros at admission in preoperatively screened patients

BACKGROUND

Preoperative screening (POS) may help to reduce medication errors at admission (MEA). However, due to the time window between POS and hospital admission, unintentional medication discrepancies may still occur and thus a second medication reconciliation at hospital admission is necessary. Insight into potential risk factors associated with these discrepancies would be helpful to focus the second medication reconciliation on high risk patients.

OBJECTIVE

To determine the occurrence of MEA and to identify risk factors for MEA in preoperatively screened patients.

METHODS

This single-centre observational cross-sectional study included elective surgical patients between 26 October and 18 December 2015. Main inclusion criteria were age ≥18 years and elective non-day care admissions. Medication reconciliation took place at the preoperative screening and was repeated within 30 hours of admission. Unintended discrepancies between the first and second medication reconciliation were defined as MEA. The primary outcome was the occurrence of MEA in preoperatively screened patients. The association of this outcome with potential risk factors was analysed using multivariate logistic regression analysis.

RESULTS

Of the 183 included patients 60 (33%) patients had at least one MEA. In a multivariate model the number of medications at POS (adjusted odds ratio 1.16, 95%-confidence interval [95%-CI] 1.04-1.30), and respiratory disease (odds ratio 4.25, 95%-CI 1.52-11.83) were significantly associated with MEA.

CONCLUSION

In our study MEA occurred in 33% of preoperatively screened patients. Polypharmacy and respiratory comorbidities are risk factors for MEA in preoperatively screened patients.

Rubriek: Korte bijdrage
Identificatie: 2018;3:a1661
Datum: 9 januari 2018

Contact

Redacteur / secretaris
Arjan Polderman

(070) 373 73 14 npfo@npfo.nl