Patient Reporting of Adverse Drug Reactions: An International Survey of National Competent Authorities ’ Views and Needs
ConclusionsMost countries accept ADR reports from patients by an official reporting system designed for patients or through the existing system for healthcare professionals. The main reasons for not having a PRS is financial restraints and a lack of information/education of patients. Attitudes toward a PRS are positive, but some countries fear that they will not be able to handle an increase in reports. (Source: Drug Safety)
Source: Drug Safety - August 31, 2016 Category: Drugs & Pharmacology Source Type: research

Drug –Drug Interactions, Effectiveness, and Safety of Hormonal Contraceptives in Women Living with HIV
AbstractFamily planning options, including hormonal contraceptives, are essential for improving reproductive health among the more than 17  million women living with HIV worldwide. For these women, prevention of unintended pregnancy decreases maternal and child mortality, as well as reduces the risk of perinatal HIV transmission. Similarly, treatment of HIV with antiretroviral therapy (ART) is essential for reducing morbidity and mort ality among HIV-positive individuals, as well as preventing HIV transmission between sexual partners or from mother to child. Importantly, despite the benefits of hormonal contraceptives...
Source: Drug Safety - August 25, 2016 Category: Drugs & Pharmacology Source Type: research

National ADR Monitoring System in China
AbstractIt has been more than 25  years since an adverse drug reaction (ADR) monitoring agency was first established in China. In the past few years, the National ADR Monitoring System (NADRMS) has developed rapidly in the country. However, this system has not been reviewed in detail in the literature. Our aim was to demonstrate h ow individual case safety reports (ICSRs) are reported and evaluated and how data quality control is achieved in China. We also aimed to discuss the present status and future of NADRMS. We reviewed the relevant regulations and literature around ADR reporting in China. ADR report collection t...
Source: Drug Safety - August 22, 2016 Category: Drugs & Pharmacology Source Type: research

Pattern of Onset and Risk Factors for Peripheral Oedema During Vildagliptin Use: Analysis from the Vildagliptin Prescription –Event Monitoring Study in England
This study was a per-protocol supplementary analysis to investigate the pattern of onset and effect of vildagliptin combination therapy on PO risk.MethodsThe PMS used an observational cohort design. OAD exposure, selected risk factors and outcome data were collected from general practitioners in England regarding vildagliptin users for the 6-month period after starting treatment. Data analysis comprised univariate case/non-case analysis, time-to-onset analysis and Cox proportional hazard models to estimate hazard ratios (HR) of PO adjusting for selected patients ’ baseline characteristics.ResultsThe study cohort incl...
Source: Drug Safety - August 17, 2016 Category: Drugs & Pharmacology Source Type: research

Neuropsychiatric Effects of HIV Antiviral Medications
AbstractThe development of antiretroviral therapy (ART) has dramatically increased the lifespan of HIV patients but treatment is complicated by numerous adverse effects and toxicities. ART complications include neuropsychiatric, metabolic, gastrointestinal, cardiac, and numerous other toxicities, and clinicians often have to choose one toxicity over another to offer the best medication regimen for a patient. Some antiviral drugs cause significant neuropsychiatric complications, including depression, cognitive impairment, and sleep disturbance. Even in careful studies, it may be difficult to determine which effects are rela...
Source: Drug Safety - August 17, 2016 Category: Drugs & Pharmacology Source Type: research

Tyrosine Kinase Inhibitor-Induced Interstitial Lung Disease: Clinical Features, Diagnostic Challenges, and Therapeutic Dilemmas
AbstractSince the approval of the first molecularly targeted tyrosine kinase inhibitor (TKI), imatinib, in 2001, TKIs have heralded a new era in the treatment of many cancers. Among their innumerable adverse effects, interstitial lung disease (ILD) is one of the most serious, presenting most frequently with dyspnea, cough, fever, and hypoxemia, and often treated with steroids. Of the 28 currently approved TKIs, 16 (57 %) are reported to induce ILD with varying frequency and/or severity. The interval from drug administration to onset of ILD varies between patients and between TKIs, with no predictable time course. Its incid...
Source: Drug Safety - August 17, 2016 Category: Drugs & Pharmacology Source Type: research

The Patient ’s Voice in Pharmacovigilance: Pragmatic Approaches to Building a Patient-Centric Drug Safety Organization
AbstractPatient-centeredness has become an acknowledged hallmark of not only high-quality health care but also high-quality drug development. Biopharmaceutical companies are actively seeking to be more patient-centric in drug research and development by involving patients in identifying target disease conditions, participating in the design of, and recruitment for, clinical trials, and disseminating study results. Drug safety departments within the biopharmaceutical industry are at a similar inflection point. Rising rates of per capita prescription drug use underscore the importance of having robust pharmacovigilance syste...
Source: Drug Safety - August 13, 2016 Category: Drugs & Pharmacology Source Type: research

Comment on: “Safety and Tolerability of Pharmacological Treatment of Alcohol Dependence: Comprehensive Review of Evidence”
(Source: Drug Safety)
Source: Drug Safety - August 8, 2016 Category: Drugs & Pharmacology Source Type: research

Authors ’ Reply to Alain Braillon’s Comment on “Safety and Tolerability of Pharmacological Treatment of Alcohol Dependence: Comprehensive Review of Evidence”
(Source: Drug Safety)
Source: Drug Safety - August 8, 2016 Category: Drugs & Pharmacology Source Type: research

Causality Assessment in Premarketing Drug Clinical Trials: Regulatory Evolution in the USA and Ongoing Concerns
Abstract Since 1993, how to assess the causality of serious adverse events in premarketing drug clinical trials has undergone sustained regulatory evolution in the USA. In that year, an investigational drug study for chronic hepatitis B virus infection was emergently stopped after a patient suddenly exhibited hepatic failure and lactic acidosis, which later developed, along with pancreatitis and peripheral neuropathy, in several others after drug discontinuation. Five patients eventually died, including three despite emergency liver transplantation. The drug ’s multisystem toxicity was not predicted by preclinical a...
Source: Drug Safety - July 29, 2016 Category: Drugs & Pharmacology Source Type: research

Adverse-Drug-Reaction-Related Hospitalisations in Developed and Developing Countries: A Review of Prevalence and Contributing Factors
Abstract Adverse drug reactions (ADRs) are one of the leading causes of hospital admissions and morbidity in developed countries and represent a substantial burden on healthcare delivery systems. However, there is little data available from low- and middle-income countries. This review compares the prevalence and characteristics of ADR-related hospitalisations in adults in developed and developing countries, including the mortality, severity and preventability associated with these events, commonly implicated drugs and contributing factors. A literature search was conducted via PubMed, Scopus, Web of Science, Embase, ProQ...
Source: Drug Safety - July 23, 2016 Category: Drugs & Pharmacology Source Type: research

The Impact of Experiencing Adverse Drug Reactions on the Patient ’s Quality of Life: A Retrospective Cross-Sectional Study in the Netherlands
Conclusion Patients who reported possible ADRs after the Thyrax ® packaging change experienced a significant decrease in HR-QOL. This impact was highest for the domains ‘daily activities’, ‘overall health status’, and ‘mental health’ and lowest for ‘physical fitness’. (Source: Drug Safety)
Source: Drug Safety - July 22, 2016 Category: Drugs & Pharmacology Source Type: research

Hepatic Safety of Atypical Antipsychotics: Current Evidence and Future Directions
Abstract The newer atypical antipsychotic agents (AAPs) represent an attractive therapeutic option for a wide range of psychotic disorders, including schizophrenia and bipolar mania, because of the reduced risk of disabling extrapyramidal symptoms. However, their growing use has raised questions about their tolerability over the endocrine, metabolic, and cardiovascular axes. Indeed, atypical antipsychotic drugs are associated, to differing extents, with mild elevation of aminotransferases related to weight gain, AAP-induced metabolic syndrome, and nonalcoholic fatty liver disease. Although the hepatic safety of new AAPs s...
Source: Drug Safety - July 22, 2016 Category: Drugs & Pharmacology Source Type: research

Drug Interactions of Direct-Acting Oral Anticoagulants
Abstract In recent years, new direct-acting oral anticoagulants (DOACs) have been introduced into clinical practice that specifically inhibit either factor Ia or Xa. These drugs have, to a large extent, replaced warfarin for the treatment of venous thrombosis, pulmonary embolism, and non-valvular atrial fibrillation. They have potential advantages over warfarin in providing more stable anticoagulation and the lack of a need for regular venesection to monitor activity. They also have the promise of less drug and food interactions. All of these drugs are substrates for the permeability glycoprotein (P-gp) excretion ...
Source: Drug Safety - July 19, 2016 Category: Drugs & Pharmacology Source Type: research

Benefit –Risk Assessment of Fish Oil in Preventing Cardiovascular Disease
Abstract Cardiovascular disease (CVD) is a preventable disease, which combines two general processes: chronic vascular inflammation and acute thrombosis. Both are amplified with positive feedback signals by n-6 eicosanoids derived from food-based n-6 highly unsaturated fatty acids (n-6 HUFA). This amplification is lessened by competing actions of n-3 HUFA. Death results from fatal interactions of the vascular wall with platelets and clotting proteins. The benefits of fish oil interventions are confounded by complex details in pharmacokinetics, pharmacodynamics, adverse events, timescale factors, topology, financial incent...
Source: Drug Safety - July 13, 2016 Category: Drugs & Pharmacology Source Type: research

Benefit–Risk Assessment of Fish Oil in Preventing Cardiovascular Disease
Abstract Cardiovascular disease (CVD) is a preventable disease, which combines two general processes: chronic vascular inflammation and acute thrombosis. Both are amplified with positive feedback signals by n-6 eicosanoids derived from food-based n-6 highly unsaturated fatty acids (n-6 HUFA). This amplification is lessened by competing actions of n-3 HUFA. Death results from fatal interactions of the vascular wall with platelets and clotting proteins. The benefits of fish oil interventions are confounded by complex details in pharmacokinetics, pharmacodynamics, adverse events, timescale factors, topology, financia...
Source: Drug Safety - July 13, 2016 Category: Drugs & Pharmacology Source Type: research

Patient-Reported Safety Information: A Renaissance of Pharmacovigilance?
Abstract The role of patients as key contributors in pharmacovigilance was acknowledged in the new EU pharmacovigilance legislation. This contains several efforts to increase the involvement of the general public, including making patient adverse drug reaction (ADR) reporting systems mandatory. Three years have passed since the legislation was introduced and the key question is: does pharmacovigilance yet make optimal use of patient-reported safety information? Independent research has shown beyond doubt that patients make an important contribution to pharmacovigilance signal detection. Patient reports provide fir...
Source: Drug Safety - July 5, 2016 Category: Drugs & Pharmacology Source Type: research

Pharmacokinetics, Efficacy, and Safety of Hepatitis  C Virus Drugs in Patients with Liver and/or Renal Impairment
Abstract Hepatitis C virus (HCV)-infected patients often suffer from liver cirrhosis, which can be complicated by renal impairment. Therefore, in this review we describe the treatment possibilities in HCV patients with hepatic and renal impairment. Cirrhosis alters the structure of the liver, which affects drug-metabolizing enzymes and drug transporters. These modifications influence the plasma concentration of substrates of drugs metabolized/transported by these enzymes. The direct-acting antivirals (DAAs) are substrates of, for example, cytochrome P450 enzymes in the liver. Most DAAs are not studied in HCV-infected indi...
Source: Drug Safety - July 1, 2016 Category: Drugs & Pharmacology Source Type: research

Pacific Island Pharmacovigilance: The Need for a Different Approach
Abstract Many Pacific Island countries (PICs) are recipients of funding support from the Global Fund to Fight AIDS, Tuberculosis and Malaria (Global Fund). However, most of these countries cannot be expected to meet Global Fund and World Health Organization (WHO) minimum requirements for a functioning pharmacovigilance (PV) system. We argue that a different approach is required to move PV forward in such countries. Although the long-term aim is to build adequate national PV capacity, we propose an approach in which resources are focused initially towards ensuring a proper system for the reporting of “problem...
Source: Drug Safety - June 30, 2016 Category: Drugs & Pharmacology Source Type: research

Innovative Digital Tools and Surveillance Systems for the Timely Detection of Adverse Events at the Point of Care: A Proof-of-Concept Study
Conclusion Mobile applications are taking data standards to the point of care, enabling clinicians to ascertain potential adverse events in the ED setting and during inpatient follow-up. Compliance with Clinical Data Interchange Standards Consortium (CDISC) data standards facilitates data interoperability according to regulatory requirements. (Source: Drug Safety)
Source: Drug Safety - June 27, 2016 Category: Drugs & Pharmacology Source Type: research

Active Surveillance versus Spontaneous Reporting for First-Line Antiretroviral Medicines in Namibia: A Cost–Utility Analysis
Conclusion Active surveillance pharmacovigilance was projected to be highly cost effective to improve treatment for HIV in Namibia. Active surveillance pharmacovigilance may be valuable to improve lives of HIV patients and more efficiently allocate health resources in Namibia. (Source: Drug Safety)
Source: Drug Safety - June 17, 2016 Category: Drugs & Pharmacology Source Type: research

Neonatal Adaptation Issues After Maternal Exposure to Prescription Drugs: Withdrawal Syndromes and Residual Pharmacological Effects
Abstract Exposure to drugs during pregnancy has the potential to harm offspring. Teratogenic effects are the most feared adverse outcomes in newborns; however, a wide spectrum of less known, usually reversible and often acute, neonatal adverse events can also occur due to drug intake by mothers during pregnancy, particularly in close proximity to delivery. This narrative review is aimed at the description of drugs and drug classes for which licit maternal use in the predelivery period has been associated with neonatal non-teratogenic disorders. For each drug class, epidemiology, clinical features, biological mecha...
Source: Drug Safety - June 11, 2016 Category: Drugs & Pharmacology Source Type: research

Targeted Spontaneous Reporting: Assessing Opportunities to Conduct Routine Pharmacovigilance for Antiretroviral Treatment on an International Scale
Conclusion We found minimal information is available about facility characteristics that may contribute to pharmacovigilance activities. Our findings, therefore, are a first step that can potentially assist implementers and facility staff to identify opportunities and leverage their existing capacities to incorporate TSR into their routine clinical programs. (Source: Drug Safety)
Source: Drug Safety - June 9, 2016 Category: Drugs & Pharmacology Source Type: research

Pregnancy Outcomes in the Tofacitinib Safety Databases for Rheumatoid Arthritis and Psoriasis
Conclusions The pregnancy outcomes reported in this small number of RA/psoriasis patients appear similar to those observed in the general population and in patients treated with biologic therapies for inflammatory diseases. However, definitive conclusions cannot be drawn, and pregnancy outcomes in patients receiving tofacitinib will continue to be monitored. (Source: Drug Safety)
Source: Drug Safety - June 9, 2016 Category: Drugs & Pharmacology Source Type: research

Drug Safety Monitoring in Children: Performance of Signal Detection Algorithms and Impact of Age Stratification
Conclusion The performance of the two tested SDAs was similar in the pediatric population. Age adjustment does not improve performance and is therefore not recommended to be performed routinely. Stratification can reveal new associations, and therefore is recommended when either drug use is age-specific or when an age-specific risk is suspected. (Source: Drug Safety)
Source: Drug Safety - June 2, 2016 Category: Drugs & Pharmacology Source Type: research

Artesunate/Amodiaquine-Induced Acute Extrapyramidal Reactions in Children and Younger Adults: Case Series Assessment
Abstract Introduction Several studies conducted in African countries reported the artesunate and amodiaquine (AS/AQ) tablet as a safe and well-tolerated anti-malarial drug in children and younger adults. The aim of this case series assessment was to assess the causal relationship between the AS/AQ tablet and extrapyramidal reactions in children and younger adults and to investigate the factor(s) predisposing to the adverse drug reactions. Methods The causal relationship of all the cases was first assessed individually using the Naranjo Probability Scale ...
Source: Drug Safety - May 20, 2016 Category: Drugs & Pharmacology Source Type: research

Benefit and Risk of Tofacitinib in the Treatment of Rheumatoid Arthritis: A Focus on Herpes Zoster
Abstract The biologics have revolutionized the treatment of rheumatoid arthritis (RA). However, there are still patients that are difficult to control and a cure is still not achievable. Tofacitinib, a Janus kinase (JAK) inhibitor is an orally available, new-in-class, disease-modifying anti-rheumatic drug with similar efficacy to biologics. JAK is activated by multiple cytokines involved in the pathology of RA, and affects non-immune and immune cells, mainly the lymphocytes. Besides its anti-rheumatic effect, the recent focus has been on adverse events. As with other biologics, serious infections have been observe...
Source: Drug Safety - May 18, 2016 Category: Drugs & Pharmacology Source Type: research

Risk of Liver Injury Associated with Green Tea Extract in SLIMQUICK ® Weight Loss Products: Results from the DILIN Prospective Study
Conclusions SLIMQUICK® products can lead to severe acute hepatocellular liver injury, which may result in transplantation. Given the frequency of GTE as a component in weight loss products, this ingredient should be studied further as a possible cause for liver injury. (Source: Drug Safety)
Source: Drug Safety - May 17, 2016 Category: Drugs & Pharmacology Source Type: research

The Impact of Experiencing Adverse Drug Reactions on the Patient’s Quality of Life: A Retrospective Cross-Sectional Study in the Netherlands
The objective of this study was to explore the impact of ADRs on HR-QOL in patients who reported a possible ADR to Lareb in relation to the change in the packaging of the drug Thyrax®. A secondary objective was to explore factors correlated with change in HR-QOL. Methods Patients who reported an ADR in relation to the Thyrax® packaging change were included in this study. A web-based adapted version of the COOP/WONCA questionnaire was sent to explore the HR-QOL before versus during the ADR, expressed on a 5-point scale from no impact (1) to high impact (5). Multivariable linea...
Source: Drug Safety - May 4, 2016 Category: Drugs & Pharmacology Source Type: research

Drug-Induced Liver Injury: Highlights from a Review of the 2015 Literature
Abstract Numerous publications contributed to the expanding knowledge base about drug-induced liver injury (DILI) in 2015. New findings from the US Drug Induced Liver Injury Network (DILIN) in their most recently updated registry include a 1- to 3-week delay in the appearance of acute DILI from short-course antibiotics such as cefazolin. They corroborated the finding that acute DILI in patients with underlying liver disease was far more severe and potentially fatal than in patients without liver disease. The only drug that seemed to have an increased risk of hepatotoxicity in these patients was azithromycin. While...
Source: Drug Safety - May 3, 2016 Category: Drugs & Pharmacology Source Type: research

Pharmacokinetics, Efficacy, and Safety of Hepatitis C Virus Drugs in Patients with Liver and/or Renal Impairment
Abstract Hepatitis C virus (HCV)-infected patients often suffer from liver cirrhosis, which can be complicated by renal impairment. Therefore, in this review we describe the treatment possibilities in HCV patients with hepatic and renal impairment. Cirrhosis alters the structure of the liver, which affects drug-metabolizing enzymes and drug transporters. These modifications influence the plasma concentration of substrates of drugs metabolized/transported by these enzymes. The direct-acting antivirals (DAAs) are substrates of, for example, cytochrome P450 enzymes in the liver. Most DAAs are not studied in HCV-infec...
Source: Drug Safety - April 20, 2016 Category: Drugs & Pharmacology Source Type: research

Neurocognitive Adverse Effects of Anesthesia in Adults and Children: Gaps in Knowledge
Abstract Numerous preclinical and clinical studies investigating the neurodevelopmental and neurocognitive effects of exposure to anesthesia and the combination of anesthesia and surgery have demonstrated histopathological and both temporary and long-term cognitive and behavioral effects at the extremes of the human age spectrum. Increasing coverage in the lay press for both our youngest and oldest patient populations has led to heightened concerns regarding the potential harmful side effects of almost all commonly used anesthetic drug regimens. Although the majority of information regarding anesthetic risks in th...
Source: Drug Safety - April 20, 2016 Category: Drugs & Pharmacology Source Type: research

The Patient’s Voice in Pharmacovigilance: Pragmatic Approaches to Building a Patient-Centric Drug Safety Organization
Abstract Patient-centeredness has become an acknowledged hallmark of not only high-quality health care but also high-quality drug development. Biopharmaceutical companies are actively seeking to be more patient-centric in drug research and development by involving patients in identifying target disease conditions, participating in the design of, and recruitment for, clinical trials, and disseminating study results. Drug safety departments within the biopharmaceutical industry are at a similar inflection point. Rising rates of per capita prescription drug use underscore the importance of having robust pharmacovigil...
Source: Drug Safety - April 20, 2016 Category: Drugs & Pharmacology Source Type: research

Diagnosis and Management of Drug-Induced Liver Injury (DILI) in Patients with Pre-Existing Liver Disease
Abstract The relationship between drugs and pre-existing liver disease is complex, particularly when increased liver tests (LTs) or new symptoms emerge in patients with pre-existing liver disease during drug therapy. This requires two strategies to assess whether these changes are due to drug-induced liver injury (DILI) as a new event or due to flares of the underlying liver disease. Lacking a valid diagnostic biomarker, DILI is a diagnosis of exclusion and requires causality assessment by RUCAM, the Roussel Uclaf Causality Assessment Method, to establish an individual causality grading of the suspected drug(s). F...
Source: Drug Safety - April 18, 2016 Category: Drugs & Pharmacology Source Type: research

Age at First Rotavirus Vaccination and Risk of Intussusception in Infants: A Public Health Modeling Analysis
Abstract Introduction The epidemiology of naturally occurring intussusception is known to increase significantly between the ages of 3 and 8 months. Post-licensure studies have reported a fivefold and twofold increase in intussusception in the first week after the first dose and second dose, respectively, of current rotavirus vaccines (RVs). Purpose We carried out a public health risk analysis to model the impact of age at first vaccination in relation to rotavirus vaccination and risk of intussusception in infants. Met...
Source: Drug Safety - April 11, 2016 Category: Drugs & Pharmacology Source Type: research

Is Earlier Signal Detection Always Better?
(Source: Drug Safety)
Source: Drug Safety - April 11, 2016 Category: Drugs & Pharmacology Source Type: research

Contemporary Reflections on the Safety of Long-Term Aspirin Treatment for the Secondary Prevention of Cardiovascular Disease
Abstract Aspirin has been the cornerstone of therapy for the secondary prevention treatment of patients with cardiovascular disease since landmark trials were completed in the late 1970s and early 1980s that demonstrated the efficacy of aspirin for reducing the risk of ischemic events. Notwithstanding the consistent benefits demonstrated with aspirin for both acute and chronic cardiovascular disease, there are a number of toxicities associated with aspirin that have been showcased by recent long-term clinical trials that have included an aspirin monotherapy arm. As an inhibitor of cyclooxygenase (COX), aspirin imp...
Source: Drug Safety - March 30, 2016 Category: Drugs & Pharmacology Source Type: research

Safety and Tolerability of Pharmacological Treatment of Alcohol Dependence: Comprehensive Review of Evidence
Abstract Alcohol use disorders (AUD) cause significant morbidity and mortality worldwide, but pharmacological treatments for them are underused, despite evidence of efficacy. Acamprosate, naltrexone, nalmefene and disulfiram are all approved in one or more region for the treatment of AUD. Baclofen currently has a temporary indication in France. Safety considerations for using psychopharmacological treatments in this patient group include the impact of concurrent alcohol consumption at high levels; multiple physical comorbidities that may interfere with pharmacological effects, distribution and metabolism; and conc...
Source: Drug Safety - March 29, 2016 Category: Drugs & Pharmacology Source Type: research

The Safety of Metoclopramide in Children: A Systematic Review and Meta-Analysis
Abstract Introduction Metoclopramide is recommended for adults with breakthrough or refractory chemotherapy-induced nausea and vomiting (CINV) and for CINV prophylaxis in children. The drug regulatory agencies of Canada and the EU have revised the labelling of metoclopramide to contraindicate its use in children aged
Source: Drug Safety - March 22, 2016 Category: Drugs & Pharmacology Source Type: research

Linking MedDRA ® -Coded Clinical Phenotypes to Biological Mechanisms by the Ontology of Adverse Events: A Pilot Study on Tyrosine Kinase Inhibitors
Conclusion By expanding the existing OAE ontological design, our TKI use case demonstrated that the combination of OAE and MedDRA® provides a semantic framework to link clinical phenotypes of adverse drug events to biological mechanisms. (Source: Drug Safety)
Source: Drug Safety - March 22, 2016 Category: Drugs & Pharmacology Source Type: research

Ethical and Practical Considerations in Removing Black Box Warnings from Drug Labels
Abstract Boxed warnings—also known as “black box” warnings—can be a powerful tool in communicating drug risks to physicians and patients. The overall number of boxed warnings has grown in recent years as the US Food and Drug Administration (FDA) has approved more drugs on the basis of limited pre-marketing information and as new safety issues for marketed drugs have been identified. Two recent manufacturers’ petitions to remove boxed warnings on the drugs rosiglitazone (Avandia) and varenicline (Chantix) have led to divergent FDA decisions and revealed different considerations involve...
Source: Drug Safety - March 21, 2016 Category: Drugs & Pharmacology Source Type: research

Drug-Induced Mitochondrial Toxicity
Abstract The mitochondrial respiratory chain (MRC) and ATP synthase (complex V) play an essential role in cellular energy production by the process of oxidative phosphorylation. In addition to inborn errors of metabolism, as well as secondary causes from disease pathophysiology, an impairment of oxidative phosphorylation can result from drug toxicity. These ‘off-target’ pharmacological effects can occur from a direct inhibition of MRC enzyme activity, an induction of mitochondrial oxidative stress, an uncoupling of oxidative phosphorylation, an impairment of mitochondrial membrane structure or a disrup...
Source: Drug Safety - March 18, 2016 Category: Drugs & Pharmacology Source Type: research

Long-Term Outcomes of Short-Term Statin Use in Healthy Adults: A Retrospective Cohort Study
Conclusions Short-term statin use for primary prevention in this healthy cohort was associated with an increased risk of long-term diabetes and diabetic complications without cardiovascular benefits. Further study using pragmatic studies and prospective observational studies appropriately equipped to eliminate unidentified confounders are urgently needed. (Source: Drug Safety)
Source: Drug Safety - March 15, 2016 Category: Drugs & Pharmacology Source Type: research

Universal Correction for QT/RR Hysteresis
Conclusion The QT/RR hysteresis model with 95 % adaptation in 120 s is universally applicable to healthy subjects, providing small QTc variability. Supine positions do not generally stabilize heart rates in healthy subjects. Universally applicable QT/RR hysteresis correction allows clinical QT/QTc studies to include variable heart rate episodes in the time points. (Source: Drug Safety)
Source: Drug Safety - March 11, 2016 Category: Drugs & Pharmacology Source Type: research

Drug-Induced QT/QTc Interval Shortening: Lessons from Drug-Induced QT/QTc Prolongation
Abstract The review discusses safety implications of drugs found to shorten the QT/QTc interval. It uses parallels with drug-induced QT/QTc prolongation. It summarizes the evidence that increases in repolarization heterogeneity are likely more important for arrhythmia induction and maintenance than the absolute changes in the QT/QTc duration. The review further compares the direct evidence of proarrhythmia caused by QT-prolonging and -shortening drugs. At present, there is little proof of QT-shortening drugs causing ventricular fibrillation in more than rare isolated instances. Comparisons of the incidence of the ...
Source: Drug Safety - March 11, 2016 Category: Drugs & Pharmacology Source Type: research

Signal of Gastrointestinal Congenital Malformations with Antipsychotics After Minimising Competition Bias: A Disproportionality Analysis Using Data from Vigibase ®
Conclusion Confirming a first signal from spontaneous reporting data, three SDRs for antipsychotics and gastrointestinal congenital abnormalities were unmasked in VigiBase®. This signal should be further explored by ad hoc pharmacoepidemiologic studies in order to assess whether it is relevant for prescription and public health. (Source: Drug Safety)
Source: Drug Safety - March 9, 2016 Category: Drugs & Pharmacology Source Type: research

Intravitreal Bevacizumab and Cardiovascular Risk in Patients with Age-Related Macular Degeneration: Systematic Review and Meta-Analysis of Randomized Controlled Trials and Observational Studies
Conclusion Published data on IVTB in AMRD provide only a low level of evidence on its cardiovascular safety and do not support any finite conclusions. (Source: Drug Safety)
Source: Drug Safety - March 7, 2016 Category: Drugs & Pharmacology Source Type: research

Good Signal Detection Practices: Evidence from IMI PROTECT
Abstract Over a period of 5 years, the Innovative Medicines Initiative PROTECT (Pharmacoepidemiological Research on Outcomes of Therapeutics by a European ConsorTium) project has addressed key research questions relevant to the science of safety signal detection. The results of studies conducted into quantitative signal detection in spontaneous reporting, clinical trial and electronic health records databases are summarised and 39 recommendations have been formulated, many based on comparative analyses across a range of databases (e.g. regulatory, pharmaceutical company). The recommendations point to pragmati...
Source: Drug Safety - March 7, 2016 Category: Drugs & Pharmacology Source Type: research

A Pharmacovigilance Signaling System Based on FDA Regulatory Action and Post-Marketing Adverse Event Reports
Conclusions By concentrating on AE types with already demonstrated interest to FDA, we constructed a signaling system that provided focus regarding drug–AE pairs and suitable accuracy with regard to the issuance of FDA labeling changes. We suggest that focus on historical regulatory actions may increase the utility of pharmacovigilance signaling systems. (Source: Drug Safety)
Source: Drug Safety - March 5, 2016 Category: Drugs & Pharmacology Source Type: research

Medication Errors: New EU Good Practice Guide on Risk Minimisation and Error Prevention
This article describes the key concepts of the EU good practice guidance for defining, classifying, coding, reporting, evaluating and preventing medication errors. This guidance should contribute to the safe and effective use of medicines for the benefit of patients and public health. (Source: Drug Safety)
Source: Drug Safety - March 3, 2016 Category: Drugs & Pharmacology Source Type: research