Unexpected beneficial effects of drugs: an analysis of cases in the Dutch spontaneous reporting system
Discussion  and conclusionThe analysis showed a diverse spectrum of reported reactions and drugs with some categories of unexpected beneficial effects of drugs mentioned multiple times for certain drug classes on the 4th ATC level. Most of these findings are consistent with the existing literature and knowledge on the pharmacological mechanism of the drugs in question. Coding harmonization would make it possible to study these effects in international databases. (Source: European Journal of Clinical Pharmacology)
Source: European Journal of Clinical Pharmacology - September 21, 2021 Category: Drugs & Pharmacology Source Type: research

Direct oral anticoagulant safety during breastfeeding: a narrative review
AbstractPurposeThere are limited data regarding the safety of direct oral anticoagulants (DOACs) during breastfeeding. The aim of the present study is to investigate the extent of excretion of DOACs into human milk according to the available clinical and experimental studies.MethodsOn 16th January 2021, we systematically searched PubMed, Scopus, Embase, and Web of Science for all studies which investigated DOACs in breastfeeding without any time frame and language limitation. Search keywords were [breastfeeding, breast feeding, breastfed, lactation, milk secretion OR milk] AND [apixaban OR Eliquist OR rivaroxaban OR Xarelt...
Source: European Journal of Clinical Pharmacology - September 21, 2021 Category: Drugs & Pharmacology Source Type: research

Comparing the clinical outcomes across different sodium/glucose cotransporter 2 (SGLT2) inhibitors in heart failure patients: a systematic review and network meta-analysis of randomized controlled trials
ConclusionsThere were no demonstrable treatment differences across SGLT2 inhibitors across cardiovascular, renal, and metabolic outcomes, although this needs to be interpreted considering the wide confidence intervals, limited number of included studies, and heterogeneity present. Future research of different SGLT2 inhibitors in head-to-head studies is warranted to determine if there is a drug class effect. (Source: European Journal of Clinical Pharmacology)
Source: European Journal of Clinical Pharmacology - September 21, 2021 Category: Drugs & Pharmacology Source Type: research

Association between the use of hormonal contraceptives and risk of cholecystectomy in women of reproductive age
ConclusionIn this large population-based study, there was an increased risk of cholecystectomy with medroxyprogesterone acetate and intrauterine device but not other hormonal contraceptives. Additional large observational studies are required to corroborate these findings. (Source: European Journal of Clinical Pharmacology)
Source: European Journal of Clinical Pharmacology - September 21, 2021 Category: Drugs & Pharmacology Source Type: research

A phase I study assessing the safety, tolerability, immunogenicity, and low-density lipoprotein cholesterol-lowering activity of immunotherapeutics targeting PCSK9
This study aimed to investigate safety, tolerability, antibody development, and reduction of low-density lipoprotein choleste rol (LDLc) following four subcutaneous immunizations.MethodsThis phase I, single-blind, randomized, placebo-controlled study was conducted in a total of 72 healthy subjects with a mean fasting LDLc level at baseline of 117.1  mg/dL (range 77–196 mg/dL). Each cohort enrolled 24 subjects to receive three priming immunizations at weeks 0, 4, and 8 and to receive a single booster immunization at week 60 of either AT04A, AT06A, or placebo. In addition to safety (primary objective), the an...
Source: European Journal of Clinical Pharmacology - September 21, 2021 Category: Drugs & Pharmacology Source Type: research

Prognostic association of medication trajectories with 3-year mortality in heart failure and preserved ejection fraction: findings from the EPICAL2 cohort study
ConclusionIn an unselected population-based sample of HFpEF patients, the long-term stable use of the combination ACEI/ARB and BB, BB exclusively, ACEI/ARB exclusively, or the combination ACEI/ARB and BB and MRAs was associated with reduced three-year all-cause mortality. (Source: European Journal of Clinical Pharmacology)
Source: European Journal of Clinical Pharmacology - September 21, 2021 Category: Drugs & Pharmacology Source Type: research

A cross-sectional study of chemotherapy-related AKI
This study aims to detail the characteristics of chemotherapy-related acute kidney injury (CR-AKI) and investigate its effect on patient outcomes.MethodsThis is a multicenter cross-sectional study of cancer patients with CR-AKI screened from hospital-acquired adult AKI patients based on a nationwide AKI survey in China.ResultsOf the 3468 patients with hospital-acquired AKI, 258 cases of CR-AKI were identified. Of the patients, 20.1% (52/258) were ≥ 70 years old. Among the 258 CR-AKI cases, 61 (23.6%) reached AKI stage 3, and 75 (29.1%) reached AKI stage 2. The remaining 122 (47.3%) remained at AKI stage 1. A total of 41...
Source: European Journal of Clinical Pharmacology - September 21, 2021 Category: Drugs & Pharmacology Source Type: research

Uptake of biosimilar trastuzumab in Denmark compared with other European countries: a comparative study and discussion of factors influencing implementation and uptake of biosimilars
ConclusionThe implementation of biosimilar trastuzumab in Denmark was rapid and achieved high overall uptake compared with other EU countries. The switch from one biosimilar to another was also achieved quickly and thoroughly. We believe that the rapid dissemination of information and involvement of all stakeholders — administrators, pharmacies, prescribers, nurses, and patients — constitute the backbone of the Danish success. A similar strategy is recommend for biosimilar implementation in other countries. (Source: European Journal of Clinical Pharmacology)
Source: European Journal of Clinical Pharmacology - September 21, 2021 Category: Drugs & Pharmacology Source Type: research

Causality assessment between reported fatal cerebral haemorrhage and suspected drugs: developing a new algorithm based on the analysis of the Japanese Adverse Event Report (JADER) database and literature review
ConclusionIn this study, the information considered necessary for causality assessment between drugs and fatal cerebral haemorrhage was reviewed and an assessment algorithm was developed. Future studies are needed to validate the usefulness of this method. (Source: European Journal of Clinical Pharmacology)
Source: European Journal of Clinical Pharmacology - September 21, 2021 Category: Drugs & Pharmacology Source Type: research

The efficacy and safety of rivaroxaban in coronary artery disease patients with heart failure and sinus rhythm: a systematic review and meta-analysis
ConclusionsIn SR patients with CAD and HF, the rates of MI and stroke associated with rivaroxaban combined with APT were lower than those associated with APT alone, and the two treatments had similar rates of all-cause death and major bleeding. (Source: European Journal of Clinical Pharmacology)
Source: European Journal of Clinical Pharmacology - September 21, 2021 Category: Drugs & Pharmacology Source Type: research

Trends and patterns in EU(7)-PIM prescribing to elderly patients in Germany
AbstractPurposeThe aim of this study was to explore patterns and long-term development in prescribing potentially inappropriate medication (PIM) according to the EU(7)-PIM list to elderly patients in Germany.MethodsWe analysed anonymized German claims data. The study population comprised 6.0 million insured individuals at least 65  years old, including all their prescriptions reimbursed in 2019. For the analysis of long-term development, we used data for the years 2009–2019. Factors associated with PIM prescribing were considered from two perspectives: patient-oriented analysis was performed with logistic regres...
Source: European Journal of Clinical Pharmacology - September 21, 2021 Category: Drugs & Pharmacology Source Type: research

Drug-drug interactions between vitamin K antagonists and statins: a systematic review
ConclusionThe anticoagulant effect of statin initiation in patients treated with VKA is likely to be of limited clinical relevance but should be evaluated individually. (Source: European Journal of Clinical Pharmacology)
Source: European Journal of Clinical Pharmacology - September 21, 2021 Category: Drugs & Pharmacology Source Type: research

Effectiveness of fondaparinux vs unfractionated heparin following percutaneous coronary intervention in survivors of out-of-hospital cardiac arrest due to acute myocardial infarction
ConclusionsThe present analysis suggests that fondaparinux is safer than UFH in the management of OHCA due to AMI by reducing early bleeding complications at one month. (Source: European Journal of Clinical Pharmacology)
Source: European Journal of Clinical Pharmacology - September 21, 2021 Category: Drugs & Pharmacology Source Type: research

The potential of training specialist oncology nurses in real-life reporting of adverse drug reactions
AbstractSpecialist oncology nurses (SONs) have the potential to play a major role in monitoring and reporting adverse drug reactions (ADRs); and reduce the level of underreporting by current healthcare professionals. The aim of this study was to investigate the long term clinical and educational effects of real-life pharmacovigilance education intervention for SONs on ADR reporting. This prospective cohort study, with a 2-year follow-up, was carried out in the three postgraduate schools in the Netherlands. In one of the schools, the prescribing qualification course was expanded to include a lecture on pharmacovigilance, an...
Source: European Journal of Clinical Pharmacology - September 21, 2021 Category: Drugs & Pharmacology Source Type: research

Torsade de pointes associated with chloroquine, hydroxychloroquine, and azithromycin: a retrospective analysis of individual case safety reports from VigiBase
ConclusionsThe prescription of CQ, HCQ, and AZT should be restricted to therapeutic indications with established positive benefit/risk profile. Doctors and patients should be aware of this potential adverse reaction especially when several risk factors are present. (Source: European Journal of Clinical Pharmacology)
Source: European Journal of Clinical Pharmacology - September 21, 2021 Category: Drugs & Pharmacology Source Type: research

Correction to: Current evidence on the impact of medication optimization or pharmacological interventions on frailty or aspects of frailty: a systematic review of randomized controlled trials
(Source: European Journal of Clinical Pharmacology)
Source: European Journal of Clinical Pharmacology - September 21, 2021 Category: Drugs & Pharmacology Source Type: research

Plasma concentrations of remdesivir metabolite in a critical COVID-19 patient needing continuous venovenous haemodialysis
(Source: European Journal of Clinical Pharmacology)
Source: European Journal of Clinical Pharmacology - September 21, 2021 Category: Drugs & Pharmacology Source Type: research

Drugs and Dupuytren ’s disease: a pharmacovigilance study in VigiBase®
(Source: European Journal of Clinical Pharmacology)
Source: European Journal of Clinical Pharmacology - September 21, 2021 Category: Drugs & Pharmacology Source Type: research

Duplicate prescriptions —proposal of a clinically oriented categorisation
(Source: European Journal of Clinical Pharmacology)
Source: European Journal of Clinical Pharmacology - September 21, 2021 Category: Drugs & Pharmacology Source Type: research

Correction to: Calling for an exponential escalation scheme in vaccine development for COVID-19
A correction to this paper has been published: https://doi.org/10.1007/s00228-021-03165-2 (Source: European Journal of Clinical Pharmacology)
Source: European Journal of Clinical Pharmacology - September 21, 2021 Category: Drugs & Pharmacology Source Type: research

Correction to: Current evidence on the impact of medication optimization or pharmacological interventions on frailty or aspects of frailty: a systematic review of randomized controlled trials
(Source: European Journal of Clinical Pharmacology)
Source: European Journal of Clinical Pharmacology - September 15, 2021 Category: Drugs & Pharmacology Source Type: research

Delayed crises following benzodiazepine withdrawal: deficient adaptive mechanisms or simple pharmacokinetics? Detoxification assisted by serum-benzodiazepine elimination tracking
ConclusionsThe low-concentration detoxification stage is critical for patients ’ confrontations with recurring withdrawal symptoms. Underestimated elimination time following drug withdrawal and premature conclusions of detoxification expose patients to unassisted withdrawal crises. Concentration tracking defines proper limits for medical assistance, preventing early relapses . (Source: European Journal of Clinical Pharmacology)
Source: European Journal of Clinical Pharmacology - September 13, 2021 Category: Drugs & Pharmacology Source Type: research

Correction to: Physiologically based pharmacokinetic modelling to predict the clinical effect of CYP3A inhibitors/inducers on esaxerenone pharmacokinetics in healthy subjects and subjects with hepatic impairment
(Source: European Journal of Clinical Pharmacology)
Source: European Journal of Clinical Pharmacology - September 8, 2021 Category: Drugs & Pharmacology Source Type: research

Evaluation of pharmacogenomics and hepatic nuclear imaging –related covariates by population pharmacokinetic models of irinotecan and its metabolites
ConclusionThe identified UGT1A3_c.31  T >  C and ABCB1_c.3435C >  T variants, from wild type to homozygous, were included in the final model for SN38 clearance. (Source: European Journal of Clinical Pharmacology)
Source: European Journal of Clinical Pharmacology - September 4, 2021 Category: Drugs & Pharmacology Source Type: research

Pharmacokinetic interaction between atorvastatin and fixed-dose combination of sofosbuvir/ledipasvir in healthy male Egyptian volunteers
ConclusionAfter concurrent administration of FDCSL with atorvastatin, the AUC0 −∞ of both atorvastatin and sofosbuvir were increased. Caution should be taken with close monitoring for possible side effects after co-administration of atorvastatin and FDCSL in clinical practice. (Source: European Journal of Clinical Pharmacology)
Source: European Journal of Clinical Pharmacology - September 1, 2021 Category: Drugs & Pharmacology Source Type: research

Essentials in saline pharmacology for nasal or respiratory hygiene in times of COVID-19
ConclusionsSaline interacts at various levels relevant to nasal or respiratory hygiene (nasal irrigation, gargling or aerosol). If used from the onset of common cold symptoms, it may represent a useful add-on to first-line interventions for COVID-19. Formal evaluation in mild COVID-19 is desirable as to establish efficacy and optimal treatment regimens. (Source: European Journal of Clinical Pharmacology)
Source: European Journal of Clinical Pharmacology - September 1, 2021 Category: Drugs & Pharmacology Source Type: research

S-warfarin limited sampling strategy with a population pharmacokinetic approach to estimate exposure and cytochrome P450 (CYP) 2C9 activity in healthy adults
This study evaluated S-warfarin limited sampling strategy with a population pharmacokinetic (PK) approach to estimate CYP2C9 activity in healthy adults.MethodsIn 6 previously published studies, a single oral dose of warfarin 10  mg was administered alone or with a CYP2C9 inducer to 100 healthy adults. S-warfarin concentrations were obtained from adults during conditions when subjects were not on any prescribed medications. A population PK model was developed using non-linear mixed effects modeling. Limited sampling models (LSMs) using single- or 2-timepoint concentrations were compared with full PK profiles from inten...
Source: European Journal of Clinical Pharmacology - September 1, 2021 Category: Drugs & Pharmacology Source Type: research

Evaluation of the effects of atazanavir-ritonavir on the pharmacokinetics of lumefantrine in patients living with HIV in Lagos University Teaching Hospital, South-Western Nigeria
ConclusionATVr increased drug exposure and day 7 plasma concentration of lumefantrine. AL is therefore considered effective for the treatment of malaria in patients taking ATVr-based regimen. However, the safety associated with the interaction requires further elucidation.Trial registrationClinClinicalTrials.gov Identifier: NCT04531072, August 27, 2020. “Retrospectively registered” (Source: European Journal of Clinical Pharmacology)
Source: European Journal of Clinical Pharmacology - September 1, 2021 Category: Drugs & Pharmacology Source Type: research

Medication incident recovery and prevention utilising an Australian community pharmacy incident reporting system: the QUMwatch study
ConclusionIncident reporting provided insights on the human and organisational factors involved in the recovery of MIs in community pharmacy. Optimising existing safeguards and redesigning certain structures and processes may enhance the resilience of the medication use system in primary care. (Source: European Journal of Clinical Pharmacology)
Source: European Journal of Clinical Pharmacology - September 1, 2021 Category: Drugs & Pharmacology Source Type: research

Global prevalence and types of complementary and alternative medicines use amongst adults with diabetes: systematic review and meta-analysis
ConclusionsA wide variation in prevalence of CAM use by patients with diabetes was identified. Healthcare professionals should be aware of their patients ’ use of CAM to ensure treatment optimization, avoid herb–drug interactions and promote medication adherence in diabetes. Diabetic reviews and clinical guidelines should incorporate exploration of patient use of CAM as many patients do not proactively disclose the use of CAM to their healthcare professionals.RegistrationThe protocol for this study was registered with the Centre for Review and Dissemination (CRD). Protocol registration number CRD42019125036. (S...
Source: European Journal of Clinical Pharmacology - September 1, 2021 Category: Drugs & Pharmacology Source Type: research

Anticholinergic load and delirium in end-of-life patients
AbstractBackgroundDelirium is a neuropsychiatric syndrome associated with negative outcomes, including worsening of cognitive and functional status and an increased burden on patients and caregivers. Medications with anticholinergic effect have been associated with delirium symptoms, but the relationship is still debated.ObjectiveTo assess the relation between delirium and anticholinergic load according to the hypothesis that the cumulative anticholinergic burden increases the risk of delirium.MethodsThis retrospective cross-sectional study was conducted in a sample of end-of-life patients in a hospice or living at home be...
Source: European Journal of Clinical Pharmacology - September 1, 2021 Category: Drugs & Pharmacology Source Type: research

Randomized, placebo-controlled trial of orally administered vitamin K1 for warfarin-associated coagulopathy in Chinese patients with mechanical heart valves
ConclusionLow-dose oral vitamin K1 can be effectively administered to Chinese patients with mechanical heart valves taking warfarin to rapidly reduce elevated INR values. (Source: European Journal of Clinical Pharmacology)
Source: European Journal of Clinical Pharmacology - September 1, 2021 Category: Drugs & Pharmacology Source Type: research

Sertraline concentrations in pregnant women are steady and the drug transfer to their infants is low
ConclusionPlacental passage of sertraline to the infant is low. However, the interindividual variation in maternal concentrations during pregnancy is huge, why therapeutic drug monitoring might assist in finding the poor metabolizers at risk for adversity and increase the safety of the treatment.Trial registrationThe trial was registered atclinicaltrials.gov July 9, 2014 with TRN: NCT02185547. (Source: European Journal of Clinical Pharmacology)
Source: European Journal of Clinical Pharmacology - September 1, 2021 Category: Drugs & Pharmacology Source Type: research

Repositioning HIV protease inhibitors and nucleos(t)ide RNA polymerase inhibitors for the treatment of SARS-CoV-2 infection and COVID-19
DiscussionThis review discusses the pharmacological/clinical background and questions the rationale and study design of clinical trials with already approved HIV protease inhibitors and nucleos(t)ide RNA polymerase inhibitors which are repositioned during the SARS-CoV-2 pandemic worldwide. Proposals are made for future study design and drug repositioning of approved antiretroviral compounds. (Source: European Journal of Clinical Pharmacology)
Source: European Journal of Clinical Pharmacology - September 1, 2021 Category: Drugs & Pharmacology Source Type: research

The effect of potent CYP2D6 inhibition on the pharmacokinetics and safety of deutetrabenazine in healthy volunteers
ConclusionsParoxetine-induced increases in exposure to the active deutetrabenazine metabolites were less than those previously reported for tetrabenazine, a finding expected to reduce the burden of drug interaction. In addition, single doses of 22.5  mg deutetrabenazine, when given alone or in the presence of steady-state paroxetine (20 mg daily), were safe. (Source: European Journal of Clinical Pharmacology)
Source: European Journal of Clinical Pharmacology - September 1, 2021 Category: Drugs & Pharmacology Source Type: research

Population pharmacokinetic model of subcutaneous fentanyl in older acute care patients
AbstractPurposeSubcutaneous fentanyl injection is commonly prescribed to manage acute pain in older patients; however, there is a gap in the literature describing the pharmacokinetic parameters for this route of administration in this population. The aim of this study was to develop and evaluate a population pharmacokinetic model for subcutaneous fentanyl injection in older patients.MethodsTwenty-one patients who received subcutaneous fentanyl injections (50 to 75 μg) were recruited. Fentanyl concentrations were determined using a validated liquid chromatography/tandem mass spectrometry method. A population pharmacokine...
Source: European Journal of Clinical Pharmacology - September 1, 2021 Category: Drugs & Pharmacology Source Type: research

Strategies to prevent drug incompatibility during simultaneous multi-drug infusion in intensive care units: a literature review
ConclusionAlthough many strategies have been developed in recent years to address drug incompatibility risks, clinical data is still lacking. All studies with in vitro design were excluded although some current innovative strategies, like niosomes, should be considered and studied by means of clinical data in the future. (Source: European Journal of Clinical Pharmacology)
Source: European Journal of Clinical Pharmacology - September 1, 2021 Category: Drugs & Pharmacology Source Type: research

Is there association between clinically relevant toxicities of pazopanib and sunitinib with the use of weak CYP3A4 and P-gp inhibitors?
(Source: European Journal of Clinical Pharmacology)
Source: European Journal of Clinical Pharmacology - September 1, 2021 Category: Drugs & Pharmacology Source Type: research

SGLT2 inhibitors and euglycemic diabetic ketoacidosis
(Source: European Journal of Clinical Pharmacology)
Source: European Journal of Clinical Pharmacology - September 1, 2021 Category: Drugs & Pharmacology Source Type: research

Quality, efficacy, safety —it is not enough!
AbstractThere is a need of comparative studies to understand the differences in term of efficacy and safety of drugs with different mechanisms of action but similar therapeutic indications. This requires changes in the European Legislation of criteria for drug approval (Source: European Journal of Clinical Pharmacology)
Source: European Journal of Clinical Pharmacology - September 1, 2021 Category: Drugs & Pharmacology Source Type: research

Are adverse drug reactions to anti-diabetic drugs more common in patients whose treatment do not adhere to diabetes management clinical guidelines? Comments on a study report
(Source: European Journal of Clinical Pharmacology)
Source: European Journal of Clinical Pharmacology - September 1, 2021 Category: Drugs & Pharmacology Source Type: research

Correction to: Essentials in saline pharmacology for nasal or respiratory hygiene in times of COVID-19
A correction to this paper has been published: https://doi.org/10.1007/s00228-021-03141-w (Source: European Journal of Clinical Pharmacology)
Source: European Journal of Clinical Pharmacology - September 1, 2021 Category: Drugs & Pharmacology Source Type: research

The effect of potent CYP2D6 inhibition on the pharmacokinetics and safety of deutetrabenazine in healthy volunteers
ConclusionsParoxetine-induced increases in exposure to the active deutetrabenazine metabolites were less than those previously reported for tetrabenazine, a finding expected to reduce the burden of drug interaction. In addition, single doses of 22.5  mg deutetrabenazine, when given alone or in the presence of steady-state paroxetine (20 mg daily), were safe. (Source: European Journal of Clinical Pharmacology)
Source: European Journal of Clinical Pharmacology - September 1, 2021 Category: Drugs & Pharmacology Source Type: research

Restrictions on the use of placebo in new COVID-19 vaccine trials
(Source: European Journal of Clinical Pharmacology)
Source: European Journal of Clinical Pharmacology - August 30, 2021 Category: Drugs & Pharmacology Source Type: research

To establish a model for the prediction of initial standard and maintenance doses of warfarin for the Han Chinese population based on gene polymorphism: a multicenter study
ConclusionThe genetic and non-genetic factors affecting warfarin dose in Chinese Han population were studied systematically in this study. The pharmacogenomic dose prediction model constructed in this study can predict anticoagulant efficacy of warfarin and has potential application value in clinical practice. (Source: European Journal of Clinical Pharmacology)
Source: European Journal of Clinical Pharmacology - August 28, 2021 Category: Drugs & Pharmacology Source Type: research

CYP2D6 genetic variation in Ugandans
(Source: European Journal of Clinical Pharmacology)
Source: European Journal of Clinical Pharmacology - August 27, 2021 Category: Drugs & Pharmacology Source Type: research

Response/comments to maternal paracetamol intake and fetal ductus arteriosus closure: adding pieces to the scenery —Karel Allegaert, Michael Ceulemans, John van den Anke
(Source: European Journal of Clinical Pharmacology)
Source: European Journal of Clinical Pharmacology - August 26, 2021 Category: Drugs & Pharmacology Source Type: research

Correction to: Calling for an exponential escalation scheme in vaccine development for COVID-19
A correction to this paper has been published: https://doi.org/10.1007/s00228-021-03165-2 (Source: European Journal of Clinical Pharmacology)
Source: European Journal of Clinical Pharmacology - August 24, 2021 Category: Drugs & Pharmacology Source Type: research