14 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

("drug-induced" OR "drug-related") AND ("adverse events" OR "side effects" OR "side-effects")

These pubmed results were generated on 2019/04/17

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

13 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

("drug-induced" OR "drug-related") AND ("adverse events" OR "side effects" OR "side-effects")

These pubmed results were generated on 2019/04/17

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

[Appropriate Use of Medicine and Polypharmacy in Older Patients].

Yakugaku Zasshi. 2019;139(4):571-574

Authors: Ooi K

Abstract
In Japan, the population aged 65 years and older exceeds 28% of the total population. Since the birth rate is also declining, aging of the population is likely to continue. According to a patient survey conducted by the Ministry of Health, Labour and Welfare in 2014, the number of outpatients aged ≥65 years was higher by approximately 1.8 million since the previous survey in 2011. Drug therapy for the elderly is, thus, a matter of rapidly growing importance. The older generation has poorer physiological functions than younger adults. Therefore they are more likely to experience variable efficacy of drugs administered. The incidence of adverse effects is known higher in elderly people, and multidrug regimens are often unavoidable, especially when patients have more than one disease. In elderly patients, chronic lifestyle-related diseases are usually associated with geriatric syndrome. Given these circumstances, the potential area to be covered by pharmacists is very broad, and they should be involved in drug treatment of elderly people from hospital to home. We therefore propose the establishment of a new scientific field of geriatric pharmacology. We will consider novel approaches to geriatric pharmacotherapy from the viewpoints of basic science and clinical practice, deliberating the role that pharmacists should play in the provision of polypharmacy in older patients.

PMID: 30930390 [PubMed - indexed for MEDLINE]

[Establishing Evidence for Appropriate Drug Use during Pregnancy and Lactation].

Yakugaku Zasshi. 2019;139(4):565-570

Authors: Nakajima K

Abstract
When considering the use of pharmaceutical drugs during pregnancy and lactation, two concerns must be weighed against each other: the potential deleterious effects on the fetus and the possibility that treatment necessary for the woman but risky for the fetus either cannot be administered or else the woman must give up the pregnancy or give up nursing. The main roadblock to weighing these two concerns is a lack of evidence about what drugs are harmful to the fetus. Establishing this evidence is important to implementing the "Choosing Wisely" policy. In 2005, Japan established the Japan Drug Information Institute in Pregnancy (JDIIP), which addresses issues regarding treatments with pharmaceutical drugs during pregnancy and lactation. The JDIIP has analyzed data regarding the pregnancy results of patients who have received counseling and has conducted a registration survey, analyzed post-marketing survey data from pharmaceutical companies, and measured drug concentrations in breast milk. Currently, the JDIIP is increasing the number of targeted drugs about which it is collecting evidence. In addition, it is re-evaluating the published literature and implementing a project to revise drug packaging inserts. Pharmacists are expected to implement the "Choosing Wisely" policy regarding pharmaceutical treatment during pregnancy and lactation and to contribute to the collection of new evidence.

PMID: 30930389 [PubMed - indexed for MEDLINE]

Real world evidence on gemcitabine and nab-paclitaxel combination chemotherapy in advanced pancreatic cancer.

BMC Cancer. 2019 Jan 08;19(1):40

Authors: Blomstrand H, Scheibling U, Bratthäll C, Green H, Elander NO

Abstract
BACKGROUND: In the recent phase III trial MPACT the combination of gemcitabine and nab-paclitaxel (Gem/NabP) showed increased overall survival compared to gemcitabine alone in the treatment of advanced pancreatic ductal adenocarcinoma (aPDA). Until now there has been limited information on the clinical benefit and toxicity of the combination regimen in a real world setting. In addition the value for patients with locally advanced rather than metastatic aPDA has been unclear, since the former category of patients was not included in the MPACT trial.
METHODS: A multicentre retrospective observational study in the South Eastern Region of Sweden was performed, with the first 75 consecutive patients diagnosed with aPDA (both locally advanced and metastatic disease) who received first-line treatment with Gem/NabP.
RESULTS: In the overall population median progression free survival (PFS) and overall survival (OS) were 5.2 (3.4-7.0 95% CI) and 10.9 (7.8-14.0 95% CI) months, respectively. Patients with metastatic disease displayed a median OS of 9.4 (4.9-13.9) and a median PFS of 4.5 (3.3-5.7) months whereas the same parameters in the locally advanced subgroup were 17.1 (7.6-26.6) and 6.8 (5.2-8.4) months, respectively. Grade 3-4 hematologic toxicity was recorded: Neutropenia, leukopenia, thrombocytopenia, and anaemia were observed in 23, 20, 5, and 4% of patients, respectively. Dose reductions were performed in 80% of the patients.
CONCLUSION: This study confirms the effectiveness and safety of first-line Gem/NabP in both locally advanced and metastatic PDA in a real world setting.

PMID: 30621618 [PubMed - indexed for MEDLINE]

Methadone maintenance treatment patients with a history of childhood trauma succeed more in a cognitive paradigm that is associated with a negative reward.

Psychiatry Res. 2019 01;271:381-388

Authors: Weiss O, Levy-Gigi E, Adelson M, Peles E

Abstract
Previously we showed that methadone maintenance treatment (MMT) patients displayed difficulties in generalization and reversal learning in the presence of drug-related context, compared to prolonged abstinence individuals. We now tested how history of childhood trauma, affects their reversal learning abilities. Fifty-one MMT patients were evaluated on a performance- based paradigm which assesses the ability to acquire and reverse stimulus-outcome associations in neutral and drug-related context. Patients with a history of childhood trauma (n = 32) as compared to patients without such a history showed decreased ability to learn associations with positive outcome, and had poorer performance in drug compare to neutral-related context. Most importantly, while individuals with childhood trauma history showed higher success rates in conditions of positive to negative reversals, an opposite pattern was observed in conditions of negative to positive reversal; whereas patients with trauma history preformed significantly worse than patients with no history. The results are in line with other studies which tested the effects of childhood trauma both in clinical and in healthy populations. Recognizing this trait that more disturbed by drug related context, may contribute to develop and improve personalized treatments which takes into account the difficulties as well as the strength associated with childhood trauma.

PMID: 30529875 [PubMed - indexed for MEDLINE]

The Problem With Predictive Values: Are We Using the Right Metrics for Preclinical Prediction of Drug Hepatotoxicity?

Toxicol Sci. 2018 09 01;165(1):3-4

Authors: McGill MR

PMID: 30165627 [PubMed - indexed for MEDLINE]

Clinical features of patients with homozygous complement C4A or C4B deficiency.

PLoS One. 2018;13(6):e0199305

Authors: Liesmaa I, Paakkanen R, Järvinen A, Valtonen V, Lokki ML

Abstract
INTRODUCTION: Homozygous deficiencies of complement C4A or C4B are detected in 1-10% of populations. In genome-wide association studies C4 deficiencies are missed because the genetic variation of C4 is complex. There are no studies where the clinical presentation of these patients is analyzed. This study was aimed to characterize the clinical features of patients with homozygous C4A or C4B deficiency.
MATERIAL AND METHODS: Thirty-two patients with no functional C4A, 87 patients with no C4B and 120 with normal amount of C4 genes were included. C4A and C4B numbers were assessed with genomic quantitative real-time PCR. Medical history was studied retrospectively from patients' files.
RESULTS: Novel associations between homozygous C4A deficiency and lymphoma, coeliac disease and sarcoidosis were detected. These conditions were present in 12.5%, (4/32 in patients vs. 0.8%, 1/120, in controls, OR = 17.00, 95%CI = 1.83-158.04, p = 0.007), 12.5% (4/32 in patients vs. 0%, 0/120 in controls, OR = 1.14, 95%CI = 1.00-1.30, p = 0.002) and 12.5%, respectively (4/32 in patients vs. 2.5%, 3/120 in controls, OR = 5.571, 95%CI = 1.79-2.32, p = 0.036). In addition, C4A and C4B deficiencies were both associated with adverse drug reactions leading to drug discontinuation (34.4%, 11/32 in C4A-deficient patients vs. 14.2%, 17/120 in controls, OR = 3.174, 95%CI = 1.30-7.74, p = 0.009 and 28.7%, 25/87 in C4B-deficient patients, OR = 2.44, 95%CI = 1.22-4.88, p = 0.010).
CONCLUSION: This reported cohort of homozygous deficiencies of C4A or C4B suggests that C4 deficiencies may have various unrecorded disease associations. C4 gene should be considered as a candidate gene in studying these selected disease associations.

PMID: 29928053 [PubMed - indexed for MEDLINE]

Fast Screening Technology for Drug Emergency Management: Predicting Suspicious SNPs for ADR with Information Theory-based Models.

Comb Chem High Throughput Screen. 2018;21(2):93-99

Authors: Liang Z, Liu J, Huang JX, Zeng X

Abstract
OBJECTIVE: The genetic polymorphism of Cytochrome P450 (CYP 450) is considered as one of the main causes for adverse drug reactions (ADRs). In order to explore the latent correlations between ADRs and potentially corresponding single-nucleotide polymorphism (SNPs) in CYP450, three algorithms based on information theory are used as the main method to predict the possible relation.
METHODS: The study uses a retrospective case-control study to explore the potential relation of ADRs to specific genomic locations and single-nucleotide polymorphism (SNP). The genomic data collected from 53 healthy volunteers are applied for the analysis, another group of genomic data collected from 30 healthy volunteers excluded from the study are used as the control group. The SNPs respective on five loci of CYP2D6*2,*10,*14 and CYP1A2*1C, *1F are detected by the Applied Biosystem 3130xl. The raw data is processed by ChromasPro to detect the specific alleles on the above loci from each sample. The secondary data are reorganized and processed by R combined with the reports of ADRs from clinical reports. Three information theory based algorithms are implemented for the screening task: JMI, CMIM, and mRMR. If a SNP is selected by more than two algorithms, we are confident to conclude that it is related to the corresponding ADR. The selection results are compared with the control decision tree + LASSO regression model.
RESULTS: In the study group where ADRs occur, 10 SNPs are considered relevant to the occurrence of a specific ADR by the combined information theory model. In comparison, only 5 SNPs are considered relevant to a specific ADR by the decision tree + LASSO regression model. In addition, the new method detects more relevant pairs of SNP and ADR which are affected by both SNP and dosage. This implies that the new information theory based model is effective to discover correlations of ADRs and CYP 450 SNPs and is helpful in predicting the potential vulnerable genotype for some ADRs.
CONCLUSION: The newly proposed information theory based model has superiority performance in detecting the relation between SNP and ADR compared to the decision tree + LASSO regression model. The new model is more sensitive to detect ADRs compared to the old method, while the old method is more reliable. Therefore, the selection criteria for selecting algorithms should depend on the pragmatic needs.

PMID: 29336255 [PubMed - indexed for MEDLINE]

[Pharmacovigilance of Chinese medicine: practice of cognition, application, prevention and rescue of drug toxicity].

Zhongguo Zhong Yao Za Zhi. 2017 May;42(10):2017-2020

Authors: Zhang B, Lin ZJ, Zhang XM

Abstract
Toxicity of traditional Chinese medicine(TCM) is the core of pharmacovigilance of Chinese medicine, whose initiation, development and practice revolves around the toxicity of TCM. Toxicity of TCM has rich meanings, and are influenced by three factors: drug composition, clinical use and patient constitution. With the increasingly deep understanding of toxicity of TCM, the cognition of clinicians is more objective, and the application, prevention and rescue are more complete. Therefore, based on the analysis of large numbers of ancient books, we put forward the whole pharmacovigilance theoretical frame that is formed by cognition, application, prevention and rescue of drug toxicity, which comprehensively reflects the academic Characteristics of safety medication in TCM.

PMID: 29090566 [PubMed - indexed for MEDLINE]

Safety and efficacy of canagliflozin in elderly patients with type 2 diabetes mellitus: a 1-year post-marketing surveillance in Japan.

Curr Med Res Opin. 2018 02;34(2):319-327

Authors: Goda M, Yamakura T, Sasaki K, Tajima T, Ueno M

Abstract
OBJECTIVE: To evaluate the safety and efficacy of canagliflozin in elderly patients with type 2 diabetes mellitus (T2DM) in clinical settings.
METHODS: The authors conducted a 1-year post-marketing surveillance (PMS) of canagliflozin in almost all the elderly patients (≥65 years old) with T2DM who began taking canagliflozin during the first 3 months after its launch in Japan. The main outcomes included the incidences of adverse drug reactions (ADRs), serious ADRs, and the changes of laboratory tests as well as efficacy variables.
RESULTS: An ADR was reported in 9.09% (125 of 1375 patients) in the safety analysis set. The main ADRs were dehydration, constipation, thirst, pollakiuria, dizziness, cystitis, eczema, pruritus, and rash. The incidence of serious ADRs was 1.02% (14 patients), which included urinary tract infection, dehydration, hypoglycemia, and cerebral infarction (two patients each). ADRs of special interest that had been reported in clinical trials of SGLT2 inhibitors, such as hypoglycemia, volume depletion-related events, genital/urinary tract infection, polyuria/pollakiuria, and ketone body increased were also observed in this PMS. The safety profiles were similar to the results of a previous clinical study of canagliflozin, and new safety concerns were not identified in this survey. The mean change in HbA1c was -0.77% after 12 months of treatment in the efficacy analysis set.
CONCLUSION: In this PMS, the safety and efficacy profiles of canagliflozin in elderly patients with T2DM were obtained in the clinical settings in Japan and the drug was well tolerated and effective in improving glycemic control.

PMID: 29025285 [PubMed - indexed for MEDLINE]

Gentamicin as empirical treatment in hemodialysis patients: safety, pharmacokinetics and pharmacodynamics.

Ther Apher Dial. 2019 Apr 13;:

Authors: Guisado-Gil AB, Herrera-Hidalgo L, Santos-Rubio MD, Gil-Sacaluga L, Molina Gil-Bermejo J, Lepe-Jiménez JA, Camacho-Martínez P, Gil-Navarro MV

Abstract
The aim was to describe safety profile and pharmacokinetic/pharmacodynamic parameters in end-stage renal disease patients who received gentamicin as empirical treatment in catheter related bacteremia when they showed infection signs, regardless timing of next hemodialysis. Patients received gentamicin 3 mg/kg before blood culture extraction when they showed infection signs and regardless timing of next hemodialysis. Serum concentrations were collected after the gentamicin administration (peak level) and before the next hemodialysis (trough level). Toxicities and adverse drug events were registered. The main pharmacokinetic/pharmacodynamic goal for gram-negative infections was peak:MIC≥10. Sixteen patients were included. Nephrotoxicity was not assessed in this population and no ototoxicity was found. According to microbial isolation and gentamicin susceptibility, the values of peak:MIC was 5.4±2.0. The administration of gentamicin in these conditions was safe. Estimated pharmacokinetic values were consistent with previous studies and appropriate according to peak:MIC goal for gram-negative organisms with MIC≤1 mg/L. This article is protected by copyright. All rights reserved.

PMID: 30980613 [PubMed - as supplied by publisher]

14 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

("drug-induced" OR "drug-related") AND ("adverse events" OR "side effects" OR "side-effects")

These pubmed results were generated on 2019/04/13

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Paradoxical Skin Reactions to Biologics in Patients With Rheumatologic Disorders.

Front Pharmacol. 2019;10:282

Authors: Garcovich S, De Simone C, Genovese G, Berti E, Cugno M, Marzano AV

Abstract
Targeted immune-modulating treatment with biological agents has revolutionized the management of immune-mediated inflammatory diseases, including rheumatologic conditions. The efficacy and tolerability of biological agents, from the initial tumour necrosis factor (TNF)-α inhibitors to the new anti-cytokine monoclonal antibodies, have dramatically changed the natural history of debilitating conditions such as rheumatoid arthritis and seronegative spondyloarthropathies. The widening use of biologics across several rheumatologic diseases has been associated with a new class of adverse events, the so-called paradoxical reactions. These events are inflammatory immune-mediated tissue reactions, developing paradoxically during treatment of rheumatologic conditions with targeted biologics that are commonly used for treating the idiopathic counterparts of these drug-induced reactions. The skin is frequently involved, and, even if considered rare to uncommon, these cutaneous manifestations are an important cause of biologic agent discontinuation. TNF-α antagonist-induced psoriasis, which can manifest de novo or as exacerbation of a pre-existing form, is the prototypic and most frequent paradoxical skin reaction to biologics while other reactions, such as eczematous and lichenoid eruptions, hidradenitis suppurativa, pyoderma gangrenosum, Sweet's syndrome and granulomatous skin diseases, occur much more rarely. Management of these reactions consists of topical or systemic skin-directed therapies, depending on the severity and extension of the cutaneous picture, and it is generally associated with switching over to other disease-modifying regimens for treating the underlying rheumatologic condition. Here, we review in detail the current concepts and controversies on classification, pathogenesis and clinical management of this new class of cutaneous adverse events induced by biologics in rheumatologic patients.

PMID: 30971924 [PubMed]

Effects of sodium-glucose cotransporter (SGLT) inhibitors in addition to insulin therapy on glucose control and major safety outcomes in adults with type 1 diabetes: a meta-analysis of randomized controlled trials.

Diabetes Metab Res Rev. 2019 Apr 11;:e3169

Authors: Lu J, Tang L, Meng H, Zhao J, Liang Y

Abstract
Sodium-glucose cotransporter (SGLT) inhibitors added to insulin therapy have been proposed as a treatment strategy for type 1 diabetes (T1D). We thus conducted a meta-analysis of randomized controlled trials (RCTs) to assess the efficacy and adverse effects of this combination in T1D. We searched the PubMed, EMBASE, and Cochrane Library databases and ClinicalTrials.gov for RCTs. Statistical analyses were performed using STATA 15. Ten eligible placebo-controlled trials involving 5961 patients were included. Compared with placebo, SGLT inhibitors were associated with a reduction in HbA1c of -0.39% (95% CI -0.43 to -0.36), an improved mean amplitude of glucose excursion (MAGE) of -14.81 mg/dL (95% CI -19.08 to -10.54) and a reduction in body weight of -3.47% (95% CI -3.78 to -3.16), as well as no increased relative risk of hypoglycemia (1.01; 95% CI 0.99 to 1.02) or severe hypoglycemia (0.91; 95% CI 0.77 to 1.07). SGLT inhibitors decreased fasting plasma glucose and insulin requirement but increased the risk of genital infection (3.57; 95% CI 2.97 to 4.29) and diabetic ketoacidosis (3.11; 95% CI 2.11 to 4.58). However, the very low dose empagliflozin 2.5 mg did not increase the risk of diabetic ketoacidosis (RR 0.67; 95% CI 0.11 to 3.95). SGLT inhibitors had no effects on overall adverse events, urinary tract infection or bone fracture but slightly increased the risk of serious adverse events (1.35; 95% CI 1.16 to 1.58), severe adverse events (1.84; 95% CI 1.20 to 2.84), adverse events leading to discontinuation (1.50; 95% CI 1.22 to 1.84), drug-related adverse events (1.78; 95% CI 1.44 to 2.19), and diarrhea (1.54; 95% CI 1.15 to 2.05). Although adverse events exist, the available data provide evidence that the combination of SGLT inhibitors with basal insulin treatment is beneficial in patients with T1D.

PMID: 30974510 [PubMed - as supplied by publisher]

Treatment patterns and steroid dose for adult minimal change disease relapses: A retrospective cohort study.

PLoS One. 2018;13(6):e0199228

Authors: Ozeki T, Ando M, Yamaguchi M, Katsuno T, Kato S, Yasuda Y, Tsuboi N, Maruyama S

Abstract
BACKGROUND: In patients with adult minimal change disease (MCD), proteinuria relapse is a problem to solve. However, the optimal relapse treatment regimen remains unclear regarding steroid dose. We described the treatment pattern of adult MCD patients and evaluated the appropriate steroid dose for relapse treatment.
METHODS: This retrospective multicenter cohort study included 192 patients with adult biopsy-proven MCD from 14 hospitals in Japan. The prescription pattern of immunosuppressive drugs in relapse was reviewed. To assess the association between steroid dose used for relapse and subsequent outcomes, data of patients with tapered prednisolone (PSL) dosage to <10 mg/day before the first relapse in whom the dose was subsequently increased to ≥10 mg/day were extracted and assigned to the High-PSL or Low-PSL groups, based on the median dose of 20 mg/day. Multivariate Cox proportional hazard model and propensity score analysis with multiple imputations were conducted to compare their clinical course.
RESULTS: During a median observation period of 37.6 months, 186/192 (96.9%) patients achieved complete remission (CR) and 100 (52.1%) relapsed. The median urinary protein level at the first relapse was 3.12 g/gCr or g/day. The proportion of non-steroidal immunosuppressant use increased with relapses; cyclosporine was the most common. No significant differences were found in the second relapse, frequent relapses, or adverse events between High-PSL (n = 34) and Low-PSL (n = 36) groups. A multivariate Cox proportional hazard model revealed that the hazard ratios adjusted with propensity score for the second relapse were 0.94 (High-PSL vs. Low-PSL; 95% confidence interval, 0.42-2.10; P = 0.88) and 0.82 (PSL dose per 10 mg/day; 95% confidence interval, 0.58-1.16; P = 0.25).
CONCLUSIONS: Among patients in CR with PSL dose <10 mg/day, higher steroid dose (PSL >20 mg/day) was not associated with favorable outcomes after the first relapse as compared to lower dose (10-20 mg/day).

PMID: 29912938 [PubMed - indexed for MEDLINE]

Phase IV Studies: Some Insights, Clarifications, and Issues.

Curr Clin Pharmacol. 2018;13(1):14-20

Authors: Cesana BM, Biganzoli EM

Abstract
BACKGROUND: There is an increasing need to face regulatory aspects as well as ethics and scientific ones in the pharmaceutical research phase after the authorization of a drug. Traditionally, Phase IV studies, after the authorization of a drug to be marketed by the Competent Authority like the Food and Drug Administration (FDA) (in Europe, European Medicine Agency - EMA- through National Procedures or Community Procedures) have been considered mainly aimed to the assessment of the new drug safety profile. However, the sample size calculation for such aim is still an open issue. Moreover, the benefit/risk assessment is a compelling global need.
METHODS: This editorial aims to give a fairly exhaustive overview of the main topics currently present in the pharmaceutical research phase after the authorization of a drug. FDA and EMA guidelines are considered under a comparative perspective with a focus on the perspective of "Post Authorization Safety Studies (PASS)" and "Post Authorization Efficacy Studies (PAES)" with critical considerations. Then, the approach of "Explanatory Trials" and "Pragmatic Trials" is proposed under the horizon of Health Technology Assessment (HTA).
CONCLUSION: Critical remarks are raised against the pure commercial perspective in the proposal of PASS and PAES and on the design of registries which should be planned with relevant objectives to be pursued by appropriate statistical analyses reported in the Statistical Analysis Plan (SAP) of the study protocol. Finally, a particular focus is placed on the work of the Ethical Committees regarding the approval of the observational studies on the safety and the efficacy of the drugs in their pragmatic clinical use.

PMID: 29651962 [PubMed - indexed for MEDLINE]

Knowledge, Attitudes, and Practices of Pharmacovigilance and ADRs Spontaneous Reporting Among Pediatricians and Pediatric Residents in Jordan.

Curr Clin Pharmacol. 2018;13(1):45-54

Authors: Mukattash TL, Alwadi MW, Abu-Farha RK, Jarab AS, Al-Zubiedi SA, Alwedyan T

Abstract
INTRODUCTION: Pharmacovigilance (PV) is the science responsible for ADRs reporting and accordingly medication safety. Pediatrics age group is a special concern as they have a higher risk of developing ADRs; this put more burden on pediatricians for early detection and reporting of ADRs. The present study aims to explore pediatricians' knowledge, attitude, and practices of pharmacovigilance.
METHOD: A structured validated questionnaire was designed to achieve the study goals. A convenient sample of 142 pediatricians took part in the study.
RESULTS: The majority of pediatricians had a poor knowledge score about pharmacovigiliance and ADRs reporting. On the other hand, 71% of respondents had a good attitude score towards reporting ADRs. When exploring their own practice, pediatricians have a low reporting rate.
CONCLUSION: The results of the present study reveal that pediatricians lack knowledge of PV and ADRs reporting. However, they have a good attitude towards ADRs reporting and enhancing their PV practice. This is still not reflected in their own practice. Further training and education about ADRs reporting are very important to move toward safer medications in children.

PMID: 29521246 [PubMed - indexed for MEDLINE]

Drug-induced QT Interval Prolongation in the Intensive Care Unit.

Curr Clin Pharmacol. 2017;12(4):210-222

Authors: Etchegoyen CV, Keller GA, Mrad S, Cheng S, Di Girolamo G

Abstract
BACKGROUND: The most common acquired cause of Long QT syndrome (LQTS) is drug induced QT interval prolongation. It is an electrophysiological entity, which is characterized by an extended duration of the ventricular repolarization. Reflected as a prolonged QT interval in a surface ECG, this syndrome increases the risk for polymorphic ventricular tachycardia (Torsade de Pointes) and sudden death.
METHOD: Bibliographic databases as MEDLINE and EMBASE, reports and drug alerts from several regulatory agencies (FDA, EMEA, ANMAT) and drug safety guides (ICH S7B, ICH E14) were consulted to prepare this article. The keywords used were: polymorphic ventricular tachycardia, adverse drug events, prolonged QT, arrhythmias, intensive care unit and Torsade de Pointes. Such research involved materials produced up to December 2017.
RESULTS: Because of their mechanism of action, antiarrhythmic drugs such as amiodarone, sotalol, quinidine, procainamide, verapamil and diltiazem are associated to the prolongation of the QTc interval. For this reason, they require constant monitoring when administered. Other noncardiovascular drugs that are widely used in the Intensive Care Unit (ICU), such as ondansetron, macrolide and fluoroquinolone antibiotics, typical and atypical antipsychotics agents such as haloperidol, thioridazine, and sertindole are also frequently associated with the prolongation of the QTc interval. As a consequence, critical patients should be closely followed and evaluated.
CONCLUSION: ICU patients are particularly prone to experience a QTc interval prolongation mainly for two reasons. In the first place, they are exposed to certain drugs that can prolong the repolarization phase, either by their mechanism of action or through the interaction with other drugs. In the second place, the risk factors for TdP are prevalent clinical conditions among critically ill patients. As a consequence, the attending physician is expected to perform preventive monitoring and ECG checks to control the QTc interval.

PMID: 29473523 [PubMed - indexed for MEDLINE]

Review of the Methods to Obtain Paediatric Drug Safety Information: Spontaneous Reporting and Healthcare Databases, Active Surveillance Programmes, Systematic Reviews and Meta-analyses.

Curr Clin Pharmacol. 2018;13(1):28-39

Authors: Gentili M, Pozzi M, Peeters G, Radice S, Carnovale C

Abstract
BACKGROUND: Knowledge of drugs safety collected during the pre-marketing phase is inevitably limited because the randomized clinical trials (RCTs) are rarely designed to evaluate safety. The small and selective groups of enrolled individuals and the limited duration of trials may hamper the ability to characterize fully the safety profiles of drugs. Additionally, information about rare adverse drug reactions (ADRs) in special groups is often incomplete or not available for most of the drugs commonly used in the daily clinical practice. In the paediatric setting several highimpact safety issues have emerged. Hence, in recent years, there has been a call for improved post-marketing pharmacoepidemiological studies, in which cohorts of patients are monitored for sufficient time in order to determine the precise risk-benefit ratio.
OBJECTIVE: In this review, we discuss the current available strategies enhancing the post-marketing monitoring activities of the drugs in the paediatric setting and define criteria whereby they can provide valuable information to improve the management of therapy in daily clinical practice including both safety and efficacy aspects. The strategies we cover include the signal detection using international pharmacovigilance and/or healthcare databases, the promotion of active surveillance initiatives which can generate complete, informative data sets for the signal detection and systematic review/meta-analysis.
CONCLUSION: Together, these methods provide a comprehensive picture of causality and risk improving the management of therapy in a paediatric setting and they should be considered as a unique tool to be integrated with post-marketing activities.

PMID: 29412117 [PubMed - indexed for MEDLINE]