Suspected adverse reactions associated with herbal products used for weight loss: spontaneous reports from the Italian Phytovigilance System
ConclusionsThe data collected confirmed the existence of safety concerns on herbal dietary supplements used for body weight control, mainly related to quality of products and their use as self-medication. In this scenario, spontaneous reports represent the only tools available to monitor safety of these products. (Source: European Journal of Clinical Pharmacology)
Source: European Journal of Clinical Pharmacology - August 19, 2019 Category: Drugs & Pharmacology Source Type: research

Insulin resistance induced by olanzapine and other second-generation antipsychotics in Chinese patients with schizophrenia: a comparative review and meta-analysis
ConclusionsExisting data suggest that olanzapine is associated with a significantly greater risk of IRI, FBG, and FINS, while other agents are associated with relatively lower risks. Thus, olanzapine is more likely to induce insulin resistance than are other SGAs in schizophrenic patients in China. (Source: European Journal of Clinical Pharmacology)
Source: European Journal of Clinical Pharmacology - August 19, 2019 Category: Drugs & Pharmacology Source Type: research

Cinnarizine/betahistine combination vs. the respective monotherapies in acute peripheral vertigo: a randomized triple-blind placebo-controlled trial
ConclusionThis study indicated the superiority of the cinnarizine/betahistine combination over the respective monotherapies in the treatment of APV.Trial registrationIRCT20130710013947N9 (Source: European Journal of Clinical Pharmacology)
Source: European Journal of Clinical Pharmacology - August 16, 2019 Category: Drugs & Pharmacology Source Type: research

Breast cancer and spironolactone: an observational postmarketing study
ConclusionThis study did not find evidence for breast cancer associated with spironolactone. (Source: European Journal of Clinical Pharmacology)
Source: European Journal of Clinical Pharmacology - August 15, 2019 Category: Drugs & Pharmacology Source Type: research

Cytochrome P450 2A6 and 2B6 polymorphisms and smoking cessation success in patients treated with varenicline
ConclusionCYP2B6 rs8109525 was associated with a higher success rate of smoking cessation with varenicline treatment. This finding may be useful in pharmacogenomic strategies for smoking cessation therapy. (Source: European Journal of Clinical Pharmacology)
Source: European Journal of Clinical Pharmacology - August 11, 2019 Category: Drugs & Pharmacology Source Type: research

CYP3A5 and CYP3A7 genetic polymorphisms affect tacrolimus concentration in pediatric patients with nephrotic range proteinuria
ConclusionsOur study demonstrated the associations between CYP3A5*3, CYP3A7 rs2257401 and rs10211, and tacrolimus concentration in pediatric patients with nephrotic range proteinuria. Children with CYP3A5*3 A, CYP3A7 rs2257401 C, and rs10211 G alleles might need a higher dose of tacrolimus. (Source: European Journal of Clinical Pharmacology)
Source: European Journal of Clinical Pharmacology - August 10, 2019 Category: Drugs & Pharmacology Source Type: research

Siponimod pharmacokinetics, safety, and tolerability in combination with the potent CYP3A4 inhibitor itraconazole in healthy subjects with different CYP2C9 genotypes
ConclusionsThe minor albeit significant reduction in plasma exposure of siponimod and its metabolites by itraconazole was unexpected. While the reason is unclear, the results suggest that coadministration of the two drugs would not cause a considerable increase of siponimod exposure independent of CYP2C9 genotype. (Source: European Journal of Clinical Pharmacology)
Source: European Journal of Clinical Pharmacology - August 7, 2019 Category: Drugs & Pharmacology Source Type: research

Dose evaluation of intravenous metamizole (dipyrone) in infants and children: a prospective population pharmacokinetic study
AbstractPurposeThe prodrug metamizole is prescribed intravenously for postoperative pain in children, including off-label use in infants
Source: European Journal of Clinical Pharmacology - August 7, 2019 Category: Drugs & Pharmacology Source Type: research

Comparison of the effect of direct-acting antiviral with and without ribavirin on cyclosporine and tacrolimus clearance values: results from the ANRS CO23 CUPILT cohort
ConclusionOur study demonstrated that liver transplant patients with a recurrence of hepatitis C who are initiating ribavirin combined with a sofosbuvir-daclatasvir direct-acting antiviral regimen may be at risk of lower tacrolimus concentrations because of probable ribavirin-induced anaemia and higher fibrosis score, although there are no effects on cyclosporine levels.Trial registrationNCT 01944527 (Source: European Journal of Clinical Pharmacology)
Source: European Journal of Clinical Pharmacology - August 5, 2019 Category: Drugs & Pharmacology Source Type: research

m-TOR inhibitors and risk of Pneumocystis pneumonia after solid organ transplantation: a systematic review and meta-analysis
This study aimed to examine the association between m-TOR inhibitors and the risk of developing PCP in solid organ transplant (SOT) recipients.MethodsA comprehensive search was performed to find the eligible studies that investigated the incidence of PCP in patients treated with mTOR inhibitors after SOT. Random effect model was applied for meta-analysis.ResultsCombination of 15 effect sizes showed a significant positive association between mTOR inhibitor administration and the risk of PCP (OR  = 1.90, 95%CIs = 1.44, 2.75). There was no heterogeneity between studies (I2 = 3.5%). Subg...
Source: European Journal of Clinical Pharmacology - August 3, 2019 Category: Drugs & Pharmacology Source Type: research

Sodium-glucose cotransporter 2 inhibitors for type 2 diabetes —cardiovascular and renal benefits in patients with chronic kidney disease
ConclusionsDespite minimal glycaemic benefits in patients with type 2 diabetes and stage 3 CKD, the cardiovascular and renal benefits of these agents are preserved in this group of patients. Whether these agents have cardiovascular and renal benefits in patients with stage 4 CKD and patients with non-diabetic CKD needs further research. (Source: European Journal of Clinical Pharmacology)
Source: European Journal of Clinical Pharmacology - August 3, 2019 Category: Drugs & Pharmacology Source Type: research

Meta-analysis on vitamin C and the common cold in children may be misleading
(Source: European Journal of Clinical Pharmacology)
Source: European Journal of Clinical Pharmacology - August 3, 2019 Category: Drugs & Pharmacology Source Type: research

Breast milk concentration of hydroxychloroquine in Chinese lactating women with connective tissue diseases
ConclusionOur study found that HCQ has very low concentrations in breast milk. It is probably safe for the patients to give breastfeeding during HCQ therapy period. (Source: European Journal of Clinical Pharmacology)
Source: European Journal of Clinical Pharmacology - August 2, 2019 Category: Drugs & Pharmacology Source Type: research

Effectiveness of using STOPP/START criteria to identify potentially inappropriate medication in people aged ≥ 65 years with chronic kidney disease: a randomized clinical trial
ConclusionsThe intervention with the STOPP/START criteria identified a high prevalence of inappropriate medications  in the elderly with advanced CKD and reduced the number of PPOs. However, there was no detectable impact of the intervention on medication adherence or HRQoL. (Source: European Journal of Clinical Pharmacology)
Source: European Journal of Clinical Pharmacology - July 29, 2019 Category: Drugs & Pharmacology Source Type: research

Is vancomycin clearance really correlated with hemoglobin? Arguments that it ’s not
(Source: European Journal of Clinical Pharmacology)
Source: European Journal of Clinical Pharmacology - July 27, 2019 Category: Drugs & Pharmacology Source Type: research

Polypharmacy patterns in the last year of life in patients with dementia
ConclusionsDementia patients are prescribed high levels of medication, many potentially inappropriate, during their last year of life, with reductions occurring relatively late. Improvements to medication optimisation guidelines are needed to inform decision-making around deprescribing of long-term medications in patients with limited life-expectancy. (Source: European Journal of Clinical Pharmacology)
Source: European Journal of Clinical Pharmacology - July 25, 2019 Category: Drugs & Pharmacology Source Type: research

Response to: Is vancomycin clearance really correlated with hemoglobin? Arguments that it ’s not
(Source: European Journal of Clinical Pharmacology)
Source: European Journal of Clinical Pharmacology - July 24, 2019 Category: Drugs & Pharmacology Source Type: research

2015 Beers Criteria and STOPP v2 for detecting potentially inappropriate medication in community-dwelling older people: prevalence, profile, and risk factors
ConclusionsThe 2015 AGS BC showed high sensitivity and good applicability to the European older patients. Both updated tools identified some pharmacological groups (benzodiazepines, PPIs, and opioids, among others) and certain health problems (insomnia, psychological disorders, and osteoarticular diseases) as factors of influence on PIM. Based on these findings, interventions aimed at promoting appropriate use of medications should be developed. (Source: European Journal of Clinical Pharmacology)
Source: European Journal of Clinical Pharmacology - July 24, 2019 Category: Drugs & Pharmacology Source Type: research

Evaluation of a non-parametric modelling for meropenem in critically ill patients using Monte Carlo simulation
ConclusionsThis study proposed different dosing regimens depending on renal clearance strata and the MIC of the germ targeted. (Source: European Journal of Clinical Pharmacology)
Source: European Journal of Clinical Pharmacology - July 23, 2019 Category: Drugs & Pharmacology Source Type: research

Premedication with intravenous steroids does not influence the incidence of infusion reactions following infliximab infusions in pediatric inflammatory bowel disease patients —a case-control study
ConclusionThe incidence of IR was low, and premedication with steroids did not decrease the incidence of IR in this cohort of PIBD patients receiving IFX. Our results indicate that PM with steroids is not indicated in PIBD to prevent IR. (Source: European Journal of Clinical Pharmacology)
Source: European Journal of Clinical Pharmacology - July 22, 2019 Category: Drugs & Pharmacology Source Type: research

Effects of PDE4 gene polymorphisms on efficacy and adverse drug events of ritodrine therapy in preterm labor patients: a prospective observational study
ConclusionsThis pharmacogenomic study suggested thatPDE4 genetic polymorphisms impact individual susceptibility to β2-adrenergic receptor targeted therapy in patients with preterm labor. (Source: European Journal of Clinical Pharmacology)
Source: European Journal of Clinical Pharmacology - July 19, 2019 Category: Drugs & Pharmacology Source Type: research

UK medical students ’ perspectives on practical prescribing teaching and learning provisions: a cross-sectional survey
ConclusionsUK medical students reported a variety of methods utilised in the teaching and learning of practical prescribing. However, methods they perceived to be very effective (simulation and pre-prescribing) do not appear to be widely available or are only reserved for the final year of study. Combining such methods with involvement of professional groups perceived to be most effective should be explored. (Source: European Journal of Clinical Pharmacology)
Source: European Journal of Clinical Pharmacology - July 18, 2019 Category: Drugs & Pharmacology Source Type: research

Dose rationale and pharmacokinetics of dexmedetomidine in mechanically ventilated new-borns: impact of design optimisation
ConclusionsThe use of optimal design in conjunction with simulation scenarios improved the accuracy and precision of the estimates of the parameters of interest, taking into account protocol deviations, which are often unavoidable in this event-prone population. (Source: European Journal of Clinical Pharmacology)
Source: European Journal of Clinical Pharmacology - July 16, 2019 Category: Drugs & Pharmacology Source Type: research

Letter to the Editor: Clinically relevant drug –drug interactions among elderly people with dementia
(Source: European Journal of Clinical Pharmacology)
Source: European Journal of Clinical Pharmacology - July 16, 2019 Category: Drugs & Pharmacology Source Type: research

Disproportionality analysis for identification of drug safety signals in a database shared by the Norwegian network of drug information centres (RELIS)
(Source: European Journal of Clinical Pharmacology)
Source: European Journal of Clinical Pharmacology - July 12, 2019 Category: Drugs & Pharmacology Source Type: research

Risk estimation of fetal adverse effects after short-term second trimester exposure to non-steroidal anti-inflammatory drugs: a literature review
ConclusionsBased on these results, short-term use of NSAIDs as analgesics or antipyretics in the 2nd trimester does not appear to pose a substantial risk for fetal adverse effects. Long-term use in the late 2nd trimester, however, should always be monitored. (Source: European Journal of Clinical Pharmacology)
Source: European Journal of Clinical Pharmacology - July 4, 2019 Category: Drugs & Pharmacology Source Type: research

Prescription prevalence of psychotropic drugs in children and adolescents: an analysis of international data
ConclusionsThe study provides global estimates of paediatric psychotropic drug prevalence and its trends. Systematic monitoring is lacking in most countries, and very heterogeneous reporting is common across studies. (Source: European Journal of Clinical Pharmacology)
Source: European Journal of Clinical Pharmacology - July 4, 2019 Category: Drugs & Pharmacology Source Type: research

Fluoroquinolones and the risk of tendon injury: a systematic review and meta-analysis
AbstractPurposeTendinopathy is a known adverse reaction associated to fluoroquinolones, but a meta-analysis was not yet published. The aim of this study was to conduct a systematic review and a meta-analysis of the scientific evidence evaluating the risk of tendon injury associated with fluoroquinolones.MethodsA literature search was conducted to identify observational studies which reported results on the risk of Achilles tendon rupture (ATR), risk of Achilles tendinitis (AT), or risk of any tendon disorders (ATD). A meta-analysis was performed by pooling odds ratios (ORs) with their 95% confidence intervals (CIs).Results...
Source: European Journal of Clinical Pharmacology - July 4, 2019 Category: Drugs & Pharmacology Source Type: research

No effects of Hypericum -containing complex on dolutegravir plasma trough concentrations: a case report
(Source: European Journal of Clinical Pharmacology)
Source: European Journal of Clinical Pharmacology - July 1, 2019 Category: Drugs & Pharmacology Source Type: research

Correction to: Adverse drug reaction causality assessment tools for drug-induced Stevens-Johnson syndrome and toxic epidermal necrolysis: room for improvement
The correct name of the 9th Author is David J. Margolis. The original article was corrected. (Source: European Journal of Clinical Pharmacology)
Source: European Journal of Clinical Pharmacology - June 29, 2019 Category: Drugs & Pharmacology Source Type: research

Pharmacokinetic study of imrecoxib in patients with renal insufficiency
AbstractObjectiveRenal insufficiency may influence the pharmacokinetics of drugs. We have investigated the pharmacokinetic parameters of imrecoxib and its two main metabolites in individuals with osteoarthritis (OA) with normal renal function and renal insufficiency, respectively.MethodsThis was a prospective, parallel, open, matched-group study in which 24 subjects were enrolled (renal insufficiency group,n = 12; healthy control group, n = 12). Blood samples of subjects administered 100 mg imrecoxib were collected at different time points and analyzed. Plasma concentrations of imrecoxib an...
Source: European Journal of Clinical Pharmacology - June 27, 2019 Category: Drugs & Pharmacology Source Type: research

Influence of the aldehyde dehydrogenase 2 polymorphism on the vasodilatory effect of nitroglycerin in infants with congenital heart disease and pulmonary arterial hypertension
ConclusionsThese data suggest that the ALDH2 gene polymorphism influences the pharmacokinetics and haemodynamics of GTN in human subjects. (Source: European Journal of Clinical Pharmacology)
Source: European Journal of Clinical Pharmacology - June 27, 2019 Category: Drugs & Pharmacology Source Type: research

‘Engagement’ of patients and healthcare professionals in regulatory pharmacovigilance: establishing a conceptual and methodological framework
ConclusionCapturing all three dimensions of engagement is vital to develop valid understandings of what works and why, thus informing engagement interventions of patients and healthcare professionals to given regulatory pharmacovigilance scenarios. (Source: European Journal of Clinical Pharmacology)
Source: European Journal of Clinical Pharmacology - June 25, 2019 Category: Drugs & Pharmacology Source Type: research

Adherence to psychotropic medication in completed suicide in Sweden 2006 –2013: a forensic-toxicological matched case-control study
ConclusionAfter adjustment for the need of treatment, biochemically verified incomplete adherence to antipsychotic pharmacotherapy was associated with markedly increased risks of completed suicide. (Source: European Journal of Clinical Pharmacology)
Source: European Journal of Clinical Pharmacology - June 19, 2019 Category: Drugs & Pharmacology Source Type: research

Non-commercial trials on medicines submitted to the Ethics Committee of the University Hospital of Bologna (Italy) along 8  years of activity: time to update rules and recommendations
ConclusionsOur results show a not negligible industrial influence on non-commercial trials through additional support, mostly to those of phase II. An update of the present legislation on this matter is desirable, adopting clearer rules on the relations sponsor-industry. (Source: European Journal of Clinical Pharmacology)
Source: European Journal of Clinical Pharmacology - June 18, 2019 Category: Drugs & Pharmacology Source Type: research

The effect of simvastatin on warfarin anticoagulation: a Swedish register-based nationwide cohort study
ConclusionsIn conclusion, initiation of simvastatin resulted in moderately increased INR values and subsequent dose decreases in patients already on warfarin. In order to avoid the increased risk of bleeding, the initiation of simvastatin may be accompanied by closer INR monitoring. (Source: European Journal of Clinical Pharmacology)
Source: European Journal of Clinical Pharmacology - June 14, 2019 Category: Drugs & Pharmacology Source Type: research

Interaction between paracetamol and lamotrigine: new insights from the FDA Adverse Event Reporting System (FAERS) database
(Source: European Journal of Clinical Pharmacology)
Source: European Journal of Clinical Pharmacology - June 14, 2019 Category: Drugs & Pharmacology Source Type: research

Tailored P2Y 12 inhibitor treatment in patients undergoing non-urgent PCI —the POPular Risk Score study
AbstractPurposeThe POPular Risk Score was developed for the selective intensification of P2Y12 inhibitor treatment with prasugrel instead of clopidogrel in patients undergoing non-urgent percutaneous coronary intervention (PCI) with stent implantation. This score is based on platelet reactivity (VerifyNow P2Y12 assay), CYP2C19 genotyping, and clinical risk factors. Our aim was to determine if the use of this score in clinical practice is associated with a reduction in thrombotic events without increasing bleeding events.MethodsIn a single-center prospective cohort study, patients with a high risk score were treated with pr...
Source: European Journal of Clinical Pharmacology - June 14, 2019 Category: Drugs & Pharmacology Source Type: research

Association between adherence to antihypertensive medications and health outcomes in middle and older aged community dwelling adults; results from the Irish longitudinal study on ageing
ConclusionsGood adherence to AHTM was associated with less self-reported GP visits in this population, suggesting improved overall health status. However, the impact of medication non-adherence on the other self-reported healthcare utilisation outcomes (ED, outpatient visits and hospitalisations) was not evident in this study. (Source: European Journal of Clinical Pharmacology)
Source: European Journal of Clinical Pharmacology - June 12, 2019 Category: Drugs & Pharmacology Source Type: research

Mortality among patients due to adverse drug reactions that occur following hospitalisation: a meta-analysis
ConclusionADRIn is an important cause of mortality. Age groups and study wards have important influence on prevalence of fatal ADRIn and its heterogeneity across studies. Few class drugs contribute to sizable proportion of ADRIn-related mortality. (Source: European Journal of Clinical Pharmacology)
Source: European Journal of Clinical Pharmacology - June 11, 2019 Category: Drugs & Pharmacology Source Type: research

Individualized dosing of oral targeted therapies in oncology is crucial in the era of precision medicine
ConclusionsIn order to realize the full potential of personalized medicine in oncology, patients should not only be treated with the right drug, but also at the right dose. TDM could be a suitable tool to achieve this. (Source: European Journal of Clinical Pharmacology)
Source: European Journal of Clinical Pharmacology - June 7, 2019 Category: Drugs & Pharmacology Source Type: research

A population pharmacokinetic model for simvastatin and its metabolites in children and adolescents
ConclusionThe model developed describes the pharmacokinetics of simvastatin and its metabolites in children/adolescents capturing the effects of both c.521T>C and age on variability in exposure in this patient population. This joint simvastatin metabolite model is envisaged to facilitate optimisation of simvastatin dosing in children/adolescents. (Source: European Journal of Clinical Pharmacology)
Source: European Journal of Clinical Pharmacology - June 6, 2019 Category: Drugs & Pharmacology Source Type: research

Limited sampling strategy to predict mycophenolic acid area under the curve in pediatric patients with nephrotic syndrome: a retrospective cohort study
ConclusionsThe most useful equations included C0, C1, C3 and C0, C1, C2 time points; however, the most precise included C1, C3, C6 time points because of MPA enterohepatic recirculation. Better results were obtained for bootstrap validation due to greater number of patients. Validated LSS should be used only in the population for which it was developed. As there is growing evidence that underexposure of MPA is associated with insufficient treatment response, we recommend the introduction of therapeutic drug monitoring for MPA in children with nephrotic syndrome. (Source: European Journal of Clinical Pharmacology)
Source: European Journal of Clinical Pharmacology - June 6, 2019 Category: Drugs & Pharmacology Source Type: research

Herb-drug interactions: a novel algorithm-assisted information system for pharmacokinetic drug interactions with herbal supplements in cancer treatment
ConclusionsThe novel algorithm allows to transparently generate and dynamically display herb-drug interaction risks based on the available evidence from clinical and laboratory pharmacologic studies. It provides health professionals with readily available and easy updatable information about the risk of pharmacokinetic interactions between herbs and oncologic drugs. (Source: European Journal of Clinical Pharmacology)
Source: European Journal of Clinical Pharmacology - June 1, 2019 Category: Drugs & Pharmacology Source Type: research

Vancomycin population pharmacokinetics for adult patients with sepsis or septic shock: are current dosing regimens sufficient?
ConclusionsVancomycin doses ≥ 2 g every 8 h in adult patients with sepsis or septic shock with a creatinine clearance ≥ 80 mL/min/1.73 m2 are likely needed to achieve an optimal therapeutic exposure. (Source: European Journal of Clinical Pharmacology)
Source: European Journal of Clinical Pharmacology - June 1, 2019 Category: Drugs & Pharmacology Source Type: research

Intra- and inter- individual rivaroxaban concentrations and potential bleeding risk in patients with atrial fibrillation
AbstractBackgroundRoutine laboratory monitoring of rivaroxaban and dose adjustment relating to exposure is currently not recommended. However, in certain clinical situations, assessment of rivaroxaban levels is desirable.ObjectivesTo examine inter- and intra-subject plasma rivaroxaban variability in patients with atrial fibrillation (AF) and to correlate these results to clinical outcomes.Patients/methodsWe included 60 patients with AF treated with rivaroxaban: half on 20  mg daily (R20) and half on 15 mg daily (R15). Three trough and peak blood samples were collected with an interval of 6–8 weeks apar...
Source: European Journal of Clinical Pharmacology - May 28, 2019 Category: Drugs & Pharmacology Source Type: research

Regulatory characteristics and pivotal study design of US Food and Drug Administration approval of drugs for major vs. minor cancer
AbstractPurposeWe aimed to investigate the regulatory approval of drugs for cancers by the US Food and Drug Administration based on the cancer type (major vs. minor), including the use of expedited development programs and duration from Investigational New Drug application (IND) to marketing approval.MethodsFrom publicly available records and through a Freedom of Information Act request, we gathered data to evaluate regulatory characteristics and pivotal study design for 115 anticancer drug approvals between 2012 and 2017 and the data were analyzed based on cancer incidence (major vs. minor cancers) and how expedited progr...
Source: European Journal of Clinical Pharmacology - May 25, 2019 Category: Drugs & Pharmacology Source Type: research

Proton pump inhibitors: why this gap between guidelines and prescribing practices in geriatrics?
(Source: European Journal of Clinical Pharmacology)
Source: European Journal of Clinical Pharmacology - May 25, 2019 Category: Drugs & Pharmacology Source Type: research

Medication errors in hospitals in the Middle East: a systematic review of prevalence, nature, severity and contributory factors
ConclusionThere is a need to improve the quality and reporting of studies from Middle Eastern countries. A standardised approach to quantifying medication errors ’ prevalence, severity, outcomes and contributory factors is warranted. (Source: European Journal of Clinical Pharmacology)
Source: European Journal of Clinical Pharmacology - May 24, 2019 Category: Drugs & Pharmacology Source Type: research

Identification of the caffeine to trimethyluric acid ratio as a dietary biomarker to characterise variability in cytochrome P450 3A activity
ConclusionBSV in CYP3A activity was well described by caffeine/TMU ratios pre- and post-induction. The caffeine/TMU ratio may be a convenient tool to assess BSV in CYP3A activity, but assessment of caffeine/TMU ratio alone is unlikely to account for all sources of variability in CYP3A activity. (Source: European Journal of Clinical Pharmacology)
Source: European Journal of Clinical Pharmacology - May 23, 2019 Category: Drugs & Pharmacology Source Type: research