Expert Opinion on Drug Safety

Description

Impact factor 2.74

  • 5-year impact
    2.43
  • Cited half-life
    4.10
  • Immediacy index
    0.66
  • Eigenfactor
    0.00
  • Article influence
    0.74
  • ISSN
    1744-764X

Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: Introduction: Rheumatoid arthritis (RA) is a chronic inflammatory disease that is associated with increased cardiovascular (CV) morbidity and mortality. This increased CV burden is the result of an enhanced prevalence of traditional CV risk factors, the effects of treatments given for RA but also systemic inflammation. In this setting, the control of inflammation by the current therapeutic approach may improve the overall CV prognosis of RA.Areas covered: This paper analyses the impact of TNFα inhibitors on the different CV risk factors with a special emphasis on lipid profile and body composition. The lipid profile under TNFα inhibitors changes, an increase in total and high density lipoprotein (HDL) cholesterol is observed but the atherogenic index and low density lioprotein cholesterol are unaffected. In parallel, TNFα inhibitors induce an accumulation of fat in the abdominal/visceral region. Analysis of cohort and registry studies indicates that CV events are reduced under this treatment.Expert opinion: Overall, the favourable CV effect under TNFα inhibitors does not seem to be explained by the changes in traditional CV risk factors, but rather by the improvement in systemic inflammation. Alternatively, the changes in body composition raise the question of their effect on long-term CV safety.
    Expert Opinion on Drug Safety 01/2015;
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    ABSTRACT: The epidemiology, natural history and efficacy of treatment for chronic hepatitis C in children are presented. An increase in the number of vertical infections of this etiology is suggested. In children, especially in those vertically infected, spontaneous elimination of hepatitis C virus (HCV) is observed more often than it is in adults. The most common HCV genotype detected in children is genotype 1, but Italian researchers have described an increase of infection with genotypes 3 and 4 HCV in children in recent years. In the context of recent opinions suggesting a more rapid progression of HCV 3 genotype infection, treatment of these children should begin immediately. The high efficacy (sustained viral response > 50%), safety (few adverse events with less intensity as compared to adults) and good tolerance of therapy with pegylated IFN α-2a and ribavirin have been revealed in children. The differences in the efficacy and tolerability of HCV treatment between children and adults are described. A recommendation for inclusion and monitoring parameters of children's physical and mental development during HCV treatment is presented. Regarding new anti-HCV therapies with very high efficacy, including IFN-free treatment, the introduction of these therapies to children is recommended.
    Expert Opinion on Drug Safety 01/2015;
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    ABSTRACT: Introduction: Cystic fibrosis (CF) is an autosomal recessive disease and is the most commonly seen monogenetic disease in Caucasians. The disease has various manifestations resulting from the abnormal thick secretions, most common being chronic lung infection and airway obstruction. Many new promising drugs have appeared on the horizon over the years. This review here is an attempt to bring together the various treatments being used to prolong and enhance the quality of life of CF patients. Areas covered: A literature review of published as well as ongoing clinical trials, meta-analysis and systematic reviews regarding the drugs used in CF management was carried out using PubMed and Ovid databases. Expert opinion: New concepts have been formed and some positive results in this direction have already led to the approval of cystic fibrosis transmembrane conductance regulator potentiator drug. Gene therapy and stem cell therapy are under development. The current therapies such as dornase alfa and pancreatic enzymes targeting the symptoms continue to evolve as they play an important complementary role. Development of new simple and cost-effective markers, which help assess the efficacy and safety of these constantly emerging new drugs, is also being investigated.
    Expert Opinion on Drug Safety 01/2015;
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    ABSTRACT: Introduction: Umeclidinium bromide (UM) with vilanterol (VI) is the first once-daily long-acting muscarinic antagonist/long-acting β2 agonist (LAMA/LABA) combination approved for use in the treatment of chronic obstructive pulmonary disease (COPD) in the USA. Prior to this, only combinations of short-acting bronchodilators and short-acting muscarinic antagonists were available in the USA as a single inhaler and they required frequent dosing. LAMA or LABA therapy is the recommended first choice for moderate-to-very severe COPD with combination therapy added if monotherapy fails to control patients’ symptoms. This allows lower dosing of individual medications, which may limit adverse effects. It could also have the additional benefit of improving patient compliance by making medication regimens less laboring.Areas covered: A comprehensive literature search of journal articles and abstracts looking for trials that evaluated both the efficacy and the safety of UM/VI revealed that UM/VI improves patients’ lung function and overall health status, while maintaining excellent safety and tolerability profiles compared to placebo and other bronchodilators.Expert opinion: Given the clinical efficacy, favorable safety profile and ease of use, clinicians may recommend UM/VI to patients with moderate-to-very severe COPD – a shift that could have significant impact on the management of COPD.
    Expert Opinion on Drug Safety 01/2015; 14(2).
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    ABSTRACT: Introduction: The global initiative for chronic obstructive lung disease guidelines recommend maintenance therapy using long-acting bronchodilators for patients with chronic obstructive pulmonary disease (COPD) who have daily symptoms. Arformoterol is the (R, R) - enantiomer of the racemic formoterol and is more potent than (R, R/ S, S) - formoterol. Areas covered: Currently, arformoterol is one of two nebulized long-acting β-agonists on the market. It has a low incidence of cardiovascular side effects with incidence of arrhythmia and ischemia similar to placebo. β-adrenergic adverse effects are infrequent, numerically lower than formoterol, but have a quicker onset of action than salmeterol. There was no observed clinical tolerance over 12 months. arformoterol is safe in combination therapy with inhaled corticosteroids, tiotropium and rescue inhalers. A 12-month Phase IV trial found no increased risk of respiratory death or COPD exacerbation-related hospitalizations. arformoterol can potentially benefit patients with hyperinflation and low inspiratory flow rates. Expert opinion: The introduction of the centers for medicare and medicaid services penalization for COPD readmissions may boost the appeal of long-acting bronchodilators as new discharge medications. With the advent of ultra long-acting bronchodilators, its potential as a once daily agent in isolation or combination with these new therapies needs further study.
    Expert Opinion on Drug Safety 01/2015;
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    ABSTRACT: Introduction: Options for treating obesity remain limited despite it being a chronic, recurrent and morbid condition. New drugs that are proposed for its treatment encounter strong reluctance by regulatory agencies and many doctors. Areas covered: This review will focus on the safety of an older drug, orlistat (the only one still approved in the European Union) and a newer recently FDA-approved one, lorcaserin. Both are approved as long-term monotherapy for obesity in the United States of America and they have demonstrated median weight loss of nearly 3% over placebo. Expert opinion: Research, development and approval of new anti-obesity drugs are necessary for improved management of this chronic condition. Orlistat and lorcaserin are two FDA-approved drugs with limited overall efficacy. Nevertheless they are useful weapons for at least some obese individuals. Orlistat has a long and solid safety profile, whereas the safety of lorcaserin is still a matter of debate, mainly due to a lack of long-term data. However, lorcaserin's selective agonism on 5HT2c serotonin receptors diminishes concerns about valvulopathy associated with other serotonin agonists, such as fenfluramine.
    Expert Opinion on Drug Safety 01/2015;
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    ABSTRACT: Purpose: The goal of this study was to clarify the reporting patterns of self-reported adverse drug reactions (ADRs) in China. Methods: A variety of sources were searched, including the official website of China FDA, the national center for ADR monitoring center, publications from PubMed, and so on. We retrieved the relevant information and made descriptive and comparative analysis from the year 2009 to 2013. Results: The ADR reporting numbers were 638,996, 692,904, 852,799, 1,200,000 and 1,317,000 from 2009 to 2013, respectively. Healthcare professionals contributed significantly, and their proportion always exceeded 80% before 2012. The average report per million inhabitants has increased from 479 to 983 from 2009 to 2013. However, the proportion of new or serious report was always below 25%. The reports mainly concern anti-infective agents and traditional Chinese medicine (TCM), especially TCM injection. The proportion of ADR reports in geriatric patients has increased for 4 consecutive years. Conclusions: ADR report numbers and reporting rates in China are on the rise. However, the proportion of new or serious reports as well as the proportion of reports contributed by consumers and pharmaceutical companies are still quite low. More attention should be paid to the elderly, anti-infective agents and TCM, especially TCM injections.
    Expert Opinion on Drug Safety 01/2015;
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    ABSTRACT: Objective: This retrospective analysis assessed the capability of active and passive safety surveillance systems to track product-specific safety events in the USA for branded and generic enoxaparin, a complex injectable subject to immune-related and other adverse events (AEs). Methods: Analysis of heparin-induced thrombocytopenia (HIT) incidence was performed on benefit claims for commercial and Medicare supplemental-insured individuals newly treated with enoxaparin under pharmacy benefit (1 January 2009 - 30 June 2012). Additionally, spontaneous reports from the FDA AE Reporting System were reviewed to identify incidence and attribution of enoxaparin-related reports to specific manufacturers. Results: Specific, dispensed products were identifiable from National Drug Codes only in pharmacy-benefit databases, permitting sensitive comparison of HIT incidence in nearly a third of patients treated with brand or generic enoxaparin. After originator medicine's loss of exclusivity, only 5% of spontaneous reports were processed by generic manufacturers; reports attributable to specific generics were approximately ninefold lower than expected based on market share. Conclusions: Claims data were useful for active surveillance of enoxaparin generics dispensed under pharmacy benefits but not for products administered under medical benefits. These findings suggest that the current spontaneous reporting system will not distinguish product-specific safety signals for products distributed by multiple manufacturers, including biosimilars.
    Expert Opinion on Drug Safety 01/2015;
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    ABSTRACT: Introduction: Tocilizumab (TCZ), a humanized anti-IL-6 receptor (IL-6R) monoclonal antibody, has demonstrated efficacy and tolerability in several large randomized, controlled trials for the treatment of rheumatoid arthritis (RA). Areas covered: This article compares the safety profile of the newer, subcutaneous (SC) formulation of TCZ with the original intravenous (IV) formulation, in combination with traditional disease-modifying antirheumatic drugs (DMARDs) in patients with RA. Several pivotal clinical trials are included, highlighting data from: i) trials of TCZ-IV; ii) trials of TCZ-SC; and iii) trials comparing IV to SC TCZ. TCZ use in pediatric populations is beyond the scope of this review. Expert opinion: The efficacy and safety of TCZ-IV in the treatment of RA has been demonstrated in multiple clinical trials, both as monotherapy and in combination with traditional DMARDs. The data for TCZ-SC is similar, albeit with a higher frequency of injection site reactions (ISRs). With careful patient selection, the benefit: risk ratio is favorable, offering patients a rapid and sustained reduction in disease activity, improved function and reduced structural damage. Given that most patients prefer SC to IV medication, TCZ-SC will likely become a mainstay, along with other biologic agents, for the treatment of RA patients who have failed traditional non-biologic DMARDs.
    Expert Opinion on Drug Safety 01/2015;
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    ABSTRACT: Introduction: Psychiatric disorders are among the leading causes of disability in Western societies. Selective serotonin reuptake inhibitors (SSRIs) are the most frequently prescribed antidepressant drugs during pregnancy and the postpartum period. Over the last decade, conflicting findings regarding the safety of SSRI drugs during pregnancy and lactation have questioned whether such treatments should be used during this period. Areas covered: We discuss the main criteria that should be considered in the risk/benefit assessment of SSRI treatment in pregnant and/or breastfeeding patients (i.e., risks associated with SSRI use and with untreated depression as well as therapeutic benefits of SSRI and some alternative treatment strategies). For each criterion, available evidence has been synthesized and stratified by methodological quality as well as discussed for clinical impact. Expert opinion: Currently, it is impossible for most of the evaluated outcomes to distinguish between the effects related to the mother's underlying disease and those inherent to SSRI treatment. In women suffering from major depression and responding to a pharmacological treatment, introduction or continuation of an SSRI should be encouraged in order to prevent maternal complications and to preserve maternal-infant bonding. The choice of the right drug depends above all on individual patient characteristics such as prior treatment response, diagnoses and comorbid conditions.
    Expert Opinion on Drug Safety 01/2015;
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    ABSTRACT: Introduction: Liver cancer is one of the most common cancers. Hepatocellular carcinoma (HCC) represents > 90% of primary liver cancers and is a major global health problem today. Chronic hepatitis B virus (HBV) infection is associated with more than half of HCCs. Areas covered: Long-term therapy with nucleos(t)ide analogues (NUCs) improves outcomes in HBV-infected patients by slowing the progression of liver disease. It is associated with improvements in histological and clinical outcomes, improved patient survival, reduced need for liver transplantation and improved liver function in patients with decompensated liver disease. This review highlights the results of previous studies conducted on HCC prevention with long-term NUC therapy. Studies include the use of all available drugs in different clinical scenarios, and the comparison between treated and untreated patients. Expert opinion: NUCs have been studied extensively in HCC prevention. A comprehensive review of the literature has shown that they can be safely and effectively used for this purpose. Despite some discrepancies between studies, most of the evidence favors using NUC therapy for HCC prevention.
    Expert Opinion on Drug Safety 12/2014;
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    ABSTRACT: Introduction: The emergence of multidrug-resistant (MDR) infections has been extensively observed worldwide and has become a priority issue over past decade. Tigecycline, a broad spectrum antibiotic covering against many MDR organisms, has been widely used. However, recent meta-analysis studies have raised a concern for its efficacy and safety. Reviewing tigecycline safety data would enhance the appropriate use of this medication.Areas covered: This article reviews the safety profile of tigecycline, including its side effects and drug interactions.Expert opinion: The increased mortality associated with tigecycline is not yet well understood. Based on current evidence, alternative options must be prioritized over tigecycline if available. When tigecycline use is warranted, vigilant observation to identify any breakthrough infections and careful monitoring of progression of the original infection are highly recommended. Considering a second agent (either for synergism or enhancing coverage) may be required.
    Expert Opinion on Drug Safety 12/2014;
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    ABSTRACT: Obesity is a common and morbid disease, but its treatment remains far from ideal. Many doctors, regulatory agencies, media outlets and patients consider lifestyle modification as the only possible intervention. Pharmacological agents, although with limitations, are useful weapons but are highly stigmatized. Some reasons for this stigma are discussed in this editorial and include: the failure of short-term medication use to achieve long-term results (due to the chronic and recurrent condition of obesity); common perception of obesity as a lifestyle choice; difficulty to treat obesity in the primary care setting; less than desired weight-loss results with medications; misuse of medications for cosmetic reasons; and unfavorable history of other anti-obesity drugs that were withdrawn in previous decades.
    Expert Opinion on Drug Safety 12/2014;
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    ABSTRACT: Introduction: The development of biologic therapies has been an enormous leap in the management of patients with rheumatoid and psoriatic arthritis. Since the first anti-TNF-α therapies, numerous molecules have been identified as targets of immunomodulatory therapies, such as IL-1 (anakinra, canakinumab), IL-6 (tocilizumab), CD20(+) B cells (rituximab), CTLA4 (abatacept) and two additional anti-TNF-α therapies (certolizumab pegol, golimumab). Areas covered: In the present review, we will describe the safety issues related to the immunosuppressive action of these biologic drugs that are mainly represented by infection and malignancy. The risk of infection should be identified before initiating a biologic treatment and markers checked over time, in particular for tuberculosis and hepatitis B and C viruses. Other infections (bacterial, viral, parasitic; opportunistic; surgery-related) and safety issues may require temporary interruption of the treatment until complete resolution. No significantly increased risk of malignancy, both hematological and solid, has been associated with the use of biologic agents. In all cases, it is difficult to dissect the risks related to biologics from those related to baseline treatments. Expert opinion: Detailed medical history and laboratory screening should be performed before starting biologic therapies. Clinicians should be aware of the different safety profiles associated with different molecules and they should follow up data coming out of the existing registries for biologics in regard to new or old side effects.
    Expert Opinion on Drug Safety 12/2014;
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    ABSTRACT: Introduction: Glucagon-like peptide 1 receptor (GLP-1Rx) agonists might elicit unwelcome side effects and concerns have recently been raised about their safety.Areas covered: Available evidence about safety, tolerability and potential adverse events relative to GLP-1Rx agonists presently used. We searched the MEDLINE database using the terms: ‘GLP-1 receptor agonists’, ‘Incretin therapy side effects’, ‘exenatide’, ‘ liraglutide’, ‘exenatide long-acting release’, ‘lixisenatide’. Articles were selected on the basis of the study design and importance, in the light of authors’ clinical experience and personal judgment. The main safety concern about GLP-1Rx agonists use is the possible association with increased risk of pancreatitis and/or tumors. This concern stems mainly from limited observations in animal models not confirmed in similar studies. Furthermore, clinical studies reporting association between GLP-1Rx agonist use and pancreatitis/cancer are marred by several biases and both clinical trials and post-marketing analyses failed to demonstrate a significant association.Expert opinion: As stated by both FDA and EMA, the safety concerns emerged so far about GLP-1RX agonists should not affect present prescribing habits. Thus, although a strict data monitoring must be encouraged, they should not prevent access to the benefits of an innovative treatment, such as GLP-1Rx agonists use, to a large diabetic population still confronted with unmet needs.
    Expert Opinion on Drug Safety 12/2014;
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    ABSTRACT: Introduction: Azithromycin and levofloxacin have been shown to be efficacious in treating infections. The adverse drug events associated with azithromycin and levofloxacin were considered rare. However, the US FDA released warnings regarding the possible risk of QT prolongation with azithromycin and levofloxacin. Areas covered: Case reports/case series, observational studies and clinical trials assessing cardiovascular risks associated with azithromycin and levofloxacin were critically reviewed, including 15 case reports/series, 5 observational studies and 5 clinical trials that investigated the cardiac risks associated azithromycin and levofloxacin. Expert opinion: Results are discordant. Two retrospective studies utilizing large databases demonstrated an increased risk of cardiovascular death with azithromycin, when azithromycin was compared with amoxicillin. Two other retrospective studies found no difference in cardiovascular death associated with azithromycin and other antibiotics. For levofloxacin, the increased risk of cardiovascular death was only found in one retrospective study. Therefore, the risks and benefits of antibacterial therapies should be considered when making prescription decisions. This study should not preclude clinicians from avoiding azithromycin and levofloxacin. If a patient has an indication to receive an antibiotic and if azithromycin or levofloxacin is needed, it may be used, but the potential risks must be understood.
    Expert Opinion on Drug Safety 12/2014;
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    ABSTRACT: Introduction: VEGF is a mediator of angiogenesis. Thus, concerns have been expressed following the use of VEGF inhibitors for the treatment of neovascular age-related macular degeneration (nAMD). Ranibizumab, and more recently aflibercept, are VEGF inhibitors licensed for the treatment of nAMD. Bevacizumab is also used but unlicensed for this application.Areas covered: A non-systematic review of nAMD trials was undertaken to investigate four outcomes: all-cause mortality, all systemic serious adverse events (SSAEs), arteriothrombotic events (ATEs) and gastrointestinal (GI) complications. Differences in event rates with injections of ranibizumab compared to bevacizumab, aflibercept, photodynamic therapy (PDT) and sham were explored and quantified using fixed-effect meta-analyses.Expert opinion: Anti-VEGF agents can influence vascular health; however, the data suggest no difference in the risk of an ATE or death between anti-VEGF agents. Clinical trials are limited in their size and eligibility criteria and databases of patients treated in routine practice should also be scrutinized.
    Expert Opinion on Drug Safety 12/2014;
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    ABSTRACT: Introduction: Dipeptidyl peptidase inhibitors (DPP-4-i) are highly selective inhibitors of the enzyme DPP-4. They act by increasing levels of incretin hormones, which have potent effects on insulin and glucagon release, gastric emptying, and satiety. Our goal is to review the safety issues related to DPP-4-i. Areas covered: This review is based upon a PubMed search of the literature using keywords alogliptin, linagliptin, saxagliptin, sitagliptin and vildagliptin, DPP-4-i, glucagon-like polypeptide-1 agonists, as well as extensive personal clinical trial experience with each of these agents. The current DPP-4-i have very different chemical structures. Saxagliptin has significant cytochrome P450 metabolism and carries a risk of drug interactions. Linagliptin has primarily entero-hepatic excretion, a benefit in renally impaired patients. A concern arose related to congestive heart failure in the SAVOR TIMI trial of saxagliptin. Several major cardiac studies are underway, with two concluded. Despite lingering uncertainty related to pancreatitis and pancreatic cancer, large randomized trials have not shown an increased risk with DPP-4-i treatment. Cutaneous adverse effects occur with a low frequency with some of these agents. Expert opinion: DPP-4-i are an additional choice in the group of anti-hyperglycemics. Their principal advantage is a low incidence of hypoglycemia, making these agents desirable in patients such as the elderly and those with cardiac disease. Several large trials have hinted at less cardiac risk with DPP-4-i than with sulfonylureas. The CAROLINA Trial comparing linagliptin and glimepiride may provide a conclusive answer to this question.
    Expert Opinion on Drug Safety 12/2014;
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    ABSTRACT: Introduction: The approval of belimumab and other advances in the field have narrowed the window for off-label use of biologicals in systemic lupus erythematosus (SLE). For consideration in severe and refractory disease, safety will play a major role. Areas covered: We reviewed the literature on safety aspects of off-label biological use in SLE. Significant evidence is available for rituximab, whereas data on the off-label SLE therapy with other biologicals are much more limited. Published trials and open-label experience in SLE allow for some conclusions on abatacept, and on approaches targeting TNF, IL-1 and IL-6 receptors. Expert opinion: Anti-TNF antibodies apparently are the only ones inducing SLE-specific autoantibodies, but even these were not associated with flares. Risks for severe infections certainly remain a major serious concern, particularly in combinations with glucocorticoids and/or immunosuppressants. These findings reiterate that experience with both the disease and the drugs will be essential for keeping patients safe. The available data suggest a manageable adverse event profile for rituximab and do not prove unacceptable risks for other biologicals. Reports frequently only include very few patients, with the inherent danger of bias due to lacking reports on failed treatment attempts.
    Expert Opinion on Drug Safety 12/2014;