Het Nederlands Platform voor Farmaceutisch Onderzoek (NPFO) presenteert onderzoek in de farmaceutische wetenschappen. De nadruk ligt op klinische toepassing zoals medicatieveiligheid, patiëntenzorg, formulering, analyse, farmacologie en casuïstiek.
Hiv therapy in the year 2019
BACKGROUND and METHODS
HIV infection has become a chronic infection due to the high efficacy and good tolerability of combination antiretroviral therapy (cART). In contrast to earlier days, cART is now recommended to all HIV-positive persons, for their own health and to prevent transmission of the virus to other persons (“treatment as prevention”).
RESULTS
More recently introduced anti-hiv agents have more favorable pharmacokinetics than older ones. First line regimens usually consist of a backbone of two nucleoside reverse transcriptase inhibitors to which an integrase inhibitor is added as a third drug. Pre-exposure prophylaxis by using two antiretroviral agents (tenofovir DF/emtricitabine) is receiving increased interest for use in hiv-negative people who are at risk for hiv infection.
CONCLUSION
Generic forms of widely-used antiretroviral agents have been introduced in the Netherlands, and make considerable cost savings possible. Drug-drug interactions remain an important safety risk for hiv-positive patients on cART.
Safely prescribing drugs in patients with cirrhosis: a survey among general practitioners
BACKGROUND
Cirrhosis can impact drug pharmacokinetics and pharmacodynamics which increases the risk of adverse drug reactions. In 2016, a website (https://www.drugsinlivercirrhosis.org/) was published with recommendations on safe prescribing of drugs in patients with cirrhosis.
OBJECTIVE
We studied the knowledge of general practitioners (GPs) about the classification for severity of cirrhosis and the website with prescribing recommendations. Also, to assess their expertise in prescribing analgesics and antibiotics in these patients.
DESIGN and METHODS
In May and June 2017, a questionnaire was distributed among GPs in Groningen and surroundings. GPs were asked if they knew the Child-Pugh classification and the website (https://www.drugsinlivercirrhosis.org/). Two cases were presented and we asked the GPs to indicate which analgesic and antibiotic they would prescribe.
RESULTS
Of the 133 GPs invited to participate, 65 returned the questionnaire (49%). One quarter of GPs (26%) knew the Child-Pugh classification and 3% knew the website with recommendations. Most GPs (92%) consulted the Farmacotherapeutisch Kompas before prescribing in cirrhosis. The pharmacist (40%) and gastroenterologist (31%) were also often consulted.
In a patient with cirrhosis and mild pain, most GPs would prescribe paracetamol (56%, n = 33) or non-steroidal anti-inflammatory drugs (NSAIDs; 24%, n = 14). Two thirds of GPs (68%) would act differently for a patient with viral hepatitis B infection when cirrhosis was also present.
CONCLUSION
Most GPs in our study were not familiar with the severity classification of cirrhosis, nor the website with prescribing recommendations. GPs knew that caution is needed when prescribing drugs for cirrhosis patients, but did not always choose for the safest analgesic.
Deprescribing in newly admitted psychogeriatric nursing facility patients
OBJECTIVE
To determine whether advised changes as a result of structured medication reviews in psychogeriatric patients were implemented and implemented changes were maintained.
DESIGN
We performed a prospective cohort study in three nursing homes in The Netherlands.
METHODS
After admission, newly admitted psychogeriatric residents were subjected to a structured medication review – performed by a pharmacist and physician – resulting in a treatment plan, which was approved by the patient’s legal representative and effectuated. Main outcome measures were the percentage of advised changes approved (= approval rate) and the percentage of implemented medication changes still present 90 days after approval (= 90-day implementation rate).
RESULTS
A total of 45 patients were included who used a total number of 333 drugs (mean ± SD = 7.4 ± 3.3 drugs). Changes were advised for 159 medications used by 42 patients. Of these changes 150 were approved (approval rate = 94.3%). Finally, 105 were implemented and 89 were still implemented after 90 days (90-day implementation rate = 84.8%). Overall, 59.7% of the advised changes concerned deprescribing, 22.6% concerned an adjustment of a drug (dose, pharmaceutical form, administration time, frequency of dosing or a combination) and 11.9% concerned starting a drug. The proportion of advised changes implemented was similar for symptom-modifying and risk-modifying drugs, namely, almost 85%. Overall, 55.3% of the recommended changes to deprescribe or reduce dose concerned 10 drug groups.
CONCLUSION
Medication could be successfully deprescribed from psychogeriatric patients after structured medication reviews, performed by pharmacists and nursing home physicians. More than 50% of the advised changes to deprescribe or reduce dose involved 10 drug groups, which raises the question whether the structured medication review can be performed more efficiently by focusing on the most common problems.
The optimal dosage for continuous infusion of flucloxacillin in non-critically ill patients
BACKGROUND
Flucloxacillin is approved for intermittent dosing. The antibacterial activity of flucloxacillin is time dependent so continuous infusion is probably more effective. Furthermore, for some patients continuous dosing can have practical benefits. Currently, the optimal flucloxacillin dosage for continuous infusion is unknown.
OBJECTIVE
To determine the optimal dosage for continuous flucloxacillin infusion in non-critically ill patients.
METHODS
Unbound flucloxacillin levels of 30 patients receiving intravenous flucloxacillin were analysed using non-linear mixed effects modelling. A Monte-Carlo simulation was used to assess the dosage needed to treat bacteria with a MIC of 0.25-2 mg/L in > 90% of the population.
RESULTS
A dosage of 4 g/24 hours was sufficient for 93.4% of the population to obtain a target of 100% fT > MIC of 0.5 mg/L. In 88.9% of the population a dosage of 12 g/24 hours was sufficient for a MIC of 2 mg/L, being the clinical breakpoint for S. aureus.
CONCLUSION
This simulation study showed that 4 g/24 hours is sufficient to reach unbound flucloxacillin levels exceeding 0.5 mg/L, the most common MICs found for S. aureus, in non-critically ill patients. In case of toxicity or if patients are not responding to a regular dosage, we advise to alter the dosage based on unbound flucloxacillin levels and the MIC.