Drugs (DRUGS )

Description

Drugs is the definitive journal of drugs and therapeutics. It provides essential information required by all healthcare practitioners, teachers and researchers through independent and objective evaluations of drugs and their place in patient management. A comprehensive program of single agent drug reviews, drug class reviews and comparative reviews makes Drugs an essential Library title and an invaluable teaching tool. Drugs provides you with all the important and most current information on drug use to achieve optimal patient outcomes.

  • Impact factor
    4.13
    Show impact factor history
     
    Impact factor
  • 5-year impact
    4.05
  • Cited half-life
    8.50
  • Immediacy index
    0.72
  • Eigenfactor
    0.02
  • Article influence
    1.19
  • Website
    Drugs website
  • Other titles
    Drugs (Basel, Switzerland), Drugs
  • ISSN
    0012-6667
  • OCLC
    1566990
  • Material type
    Periodical, Internet resource
  • Document type
    Journal / Magazine / Newspaper, Internet Resource

Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: Indacaterol is the first once-daily, long-acting β2-adrenergic agonist (LABA) approved for the treatment of chronic obstructive pulmonary disease (COPD). Indacaterol was developed using a combination of informed drug design and molecular chemistry to generate a β2-adrenergic agonist with a fast onset and long duration of action, enabling once-daily dosing with an acceptable safety profile. Early preclinical studies with indacaterol demonstrated these characteristics, and this promising molecule was taken into clinical development, originally for asthma treatment. Subsequent safety concerns over LABA monotherapy in patients with asthma redirected indacaterol's development to centre on COPD, where a good evidence base and guideline recommendations for bronchodilator monotherapy existed. Clinical development was initially complicated by different inhaler devices and differing doses of indacaterol. Using a phase III innovative adaptive-design clinical trial (INHANCE), indacaterol 150 and 300 μg once-daily doses were selected to be taken forward into the phase III INERGIZE programme. This programme delivered placebo-controlled and active-comparator data, including comparisons with formoterol, tiotropium and salmeterol/fluticasone, as well as the use of indacaterol in combination with tiotropium. Together, these studies provided a comprehensive assessment of the benefit-risk profile of indacaterol, allowing for regulatory submission. Indacaterol was first approved at once-daily doses of 150 and 300 μg in the European Union in 2009, followed by 150 µg in Japan (2011) and China (2012), and 75 μg in the United States (2011). To date, indacaterol is approved and marketed in more than 100 countries worldwide for once-daily maintenance treatment of COPD.
    Drugs 09/2014;
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    ABSTRACT: The prevalence of use of long-term systemic glucocorticoid therapy in the general adult population is 1 %. This figure increases to up to 3 % in elderly women. Metabolic (i.e. diabetes mellitus, dyslipidemia, weight gain, lipodystrophy) and cardiovascular (i.e. hypertension, cardiovascular events) adverse events are commonly observed in these patients and can be life threatening. Paradoxically, there is very few data on some of these adverse events and many of the available studies remain inconclusive. Incidence of and risk factors for dyslipidemia, weight gain and lipodystrophy are poorly defined. The optimal treatment plan for patients diagnosed with glucocorticoid-induced diabetes or hypertension is undetermined. Finally, there is no medical consensus on the best strategies for the prevention and detection of these complications. However, certain of these questions can be answered by looking at available data on patients with endogenous hypercortisolism (i.e. Cushing's syndrome). This article reviews the pathophysiology, incidence, risk factors, screening, and treatment of glucocorticoid-induced weight gain, lipodystrophy, diabetes, dyslipidemia, hypertension, and cardiovascular events. It also focuses on the possible prevention of these adverse events by targeting the glucocorticoid receptor using selective glucocorticoid receptor modulators.
    Drugs 09/2014;
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    Drugs 06/2014;
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    ABSTRACT: Airway mucus has a key role in protective innate immune responses, but excessive mucus production and secretion in proximal and in distal airways are associated with disabling symptoms (cough and sputum), lung function decline, exacerbations and mortality in patients with chronic obstructive pulmonary disease (COPD). Cellular and molecular mechanisms leading to mucin production and secretion have largely been identified using cultured epithelial cells and animal models. Cigarette smoke and microbial products are potent triggers of mucin production, which involves recognition of specific molecular patterns by cognate receptors and activation of metalloproteases at the epithelial cell surface, leading to epidermal growth factor receptor activation and mucin mRNA and protein synthesis. After mucin synthesis has occurred, mucins are tightly packed into intracytoplasmic granules. Many stimuli induce secretion of mucin granules from epithelial cells, but neutrophil serine proteases are the most potent inducers of mucin secretion. Neutrophils recruited to the airway epithelium also promote mucin production via neutrophil proteases and oxidative stress. Several drugs currently available for the treatment of COPD patients reduced mucus hypersecretion in preclinical models relevant to COPD, but their effects on mucus hypersecretion in humans have not been assessed. Testing the effects of these drugs and of novel molecules designed for reducing mucus production and/or secretion will require performing specifically designed clinical trials. These trials will be necessary to explore the hypothesis that reducing mucus hypersecretion is beneficial in COPD patients.
    Drugs 06/2014;
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    ABSTRACT: Invasive fungal disease (IFD) remains life threatening in premature infants and immunocompromised children despite the recent development of new antifungal agents. Optimal dosing of antifungals is one of the few factors clinicians can control to improve outcomes of IFD. However, dosing in children cannot be extrapolated from adult data because IFD pathophysiology, immune response, and drug disposition differ from adults. We critically examined the literature on pharmacokinetics (PK) and pharmacodynamics (PD) of antifungal agents and highlight recent developments in treating pediatric IFD. To match adult exposure in pediatric patients, dosing adjustment is necessary for almost all antifungals. In young infants, the maturation of renal and metabolic functions occurs rapidly and can significantly influence drug exposure. Fluconazole clearance doubles from birth to 28 days of life and, beyond the neonatal period, agents such as fluconazole, voriconazole, and micafungin require higher dosing than in adults because of faster clearance in children. As a result, dosing recommendations are specific to bracketed ranges of age. PD principles of antifungals mostly rely on in vitro and in vivo models but very few PD studies specifically address IFD in children. The exposure-response relationship may differ in younger children compared with adults, especially in infants with invasive candidiasis who are at higher risk of disseminated disease and meningoencephalitis, and by extension severe neurodevelopmental impairment. Micafungin is the only antifungal agent for which a specific target of exposure was proposed based on a neonatal hematogenous Candida meningoencephalitis animal model. In this review, we found that pediatric data on drug disposition of newer triazoles and echinocandins are lacking, dosing of older antifungals such as fluconazole and amphotericin B products still need optimization in young infants, and that target PK/PD indices need to be clinically validated for almost all antifungals in children. A better understanding of age-specific PK and PD of new antifungals in infants and children will help improve clinical outcomes of IFD by informing dosing and identifying future research areas.
    Drugs 05/2014;
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    ABSTRACT: Albiglutide (Eperzan® [EU]; Tanzeum™ [US]), a glucagon-like peptide 1 receptor agonist, has been developed by GlaxoSmithKline for the treatment of type 2 diabetes mellitus (T2DM). Albiglutide has received its first global approval in this indication in the EU, for use in combination with other antihyperglycaemic agents, including basal insulin, when these drugs and diet and exercise do not provide adequate glycaemic control, and as monotherapy in patients unable to take metformin due to contraindications or intolerance when diet and exercise alone do not provide adequate glycaemic control. Albiglutide has subsequently been approved for the second-line or later treatment of T2DM as an adjunct to diet and exercise in the US. This article summarizes the milestones in the development of albiglutide leading to this first approval for the treatment of T2DM.
    Drugs 05/2014;
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    ABSTRACT: Recent high-quality studies have confirmed the central role of lithium in the treatment of bipolar disorder and have established lithium as the drug of first choice for long-term prophylaxis in this condition. However, several indications for its use in unipolar major depression are also based on sound evidence. This includes lithium augmentation as a main strategy for depressed patients not responding to an antidepressant, lithium prophylaxis for recurrent unipolar depression as an alternative to prophylaxis with an antidepressant, and lithium's unique anti-suicidal properties. Lithium monotherapy, on the other hand, is not established for acute treatment of depression. Lithium therapy should be a core competency of every psychiatrist, enabling the safe use of lithium, to the benefit of our patients.
    Drugs 05/2014;
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    ABSTRACT: Atopic dermatitis is a very prevalent disease that affects children as well as adults. The disease has a severe impact on quality of life for the patients and their families. The skin in atopic dermatitis patients is a site of both a severe inflammatory reaction dominated by lymphocytes and decreased skin barrier function. The treatment of the disease is mainly aimed at reducing the inflammation in the skin and/or restoring the skin barrier function. However, most of the treatments used today singularly aim at reducing the inflammation in the skin. Depending on the severity of the disease, the anti-inflammatory treatment may be topical or systemic, but basic treatment, no matter the severity, should always be emollients. In addition, new studies have shown good effects of psychosocial interventions, such as eczema schools, for patients and their families. This review covers the latest trends in the treatment of atopic dermatitis.
    Drugs 05/2014;
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    ABSTRACT: Sevelamer carbonate (Renvela(®)), a buffered form of sevelamer hydrochloride (Renagel(®)), is an orally administered non-absorbed phosphate-binding anion exchange resin used in the treatment of hyperphosphataemia in chronic kidney disease (CKD). In the EU, sevelamer carbonate is approved in adult CKD patients who require dialysis and in those who do not require dialysis with serum phosphate levels ≥1.78 mmol/L, whereas in the USA sevelamer carbonate is approved in adult CKD patients who require dialysis. Sevelamer carbonate and sevelamer hydrochloride achieved similar reductions in serum phosphate levels in randomized comparative trials in patients with CKD receiving haemodialysis; sevelamer carbonate also reduced serum phosphate levels in noncomparative studies in CKD patients not requiring dialysis. The most common adverse events with sevelamer carbonate are gastrointestinal in nature. Sevelamer has pleiotropic effects, such as improving the serum lipid profile and attenuating endothelial and cardiovascular risk factors in CKD. All formulations of sevelamer have markedly higher acquisition costs than calcium-based phosphate binders. Cost-effectiveness analyses focusing specifically on sevelamer carbonate have not been conducted, and those based on clinical trial data with sevelamer hydrochloride have provided both favourable and unfavourable results compared with calcium-based phosphate binders, reflecting heterogeneity between modelled analyses in terms of data sources, assumptions, comparators, geographical regions, type of costs included and other factors. Although well-designed studies evaluating the impact of phosphate binders on hard clinical endpoints appear to be warranted, sevelamer carbonate may be particularly useful for the treatment of patients at risk of metabolic acidosis (offering advantages over sevelamer hydrochloride in this regard) and for individuals requiring treatment with a phosphate binding agent that does not contain aluminium or calcium.
    Drugs 05/2014;
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    ABSTRACT: Oral ponatinib (Iclusig(®)) is a novel kinase inhibitor structurally designed with a carbon-carbon triple bond to accommodate the T315I mutation in the ABL kinase domain. It has demonstrated inhibitory activity against native BCR-ABL tyrosine kinase and a variety of BCR-ABL mutants, including T315I. Ponatinib is approved for the treatment of adults with T315I-positive chronic-, accelerated- or blast-phase chronic myeloid leukaemia (CML), or Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukaemia (ALL) [in the EU and the USA], as well as those with chronic-, accelerated- or blast-phase CML, or Ph+ ALL who are resistant or intolerant to prior tyrosine kinase inhibitor therapy (EU) or for whom no other tyrosine kinase inhibitor therapy is indicated (USA). In a noncomparative, multinational, phase II study, therapy with ponatinib was associated with a major cytogenetic response within the first 12 months in over half of adults with chronic-phase CML and major haematological responses within the first 6 months in at least 50 % of adults with accelerated-phase CML and approximately 34 % of adults with blast-phase CML or Ph+ ALL after a median follow-up duration of 15, 16 and 6 months, respectively. Such benefits were observed regardless of whether the patients were resistant to dasatinib or nilotinib, or had the T315I mutation. Serious adverse reactions have been reported with ponatinib, with vascular occlusion, heart failure and hepatotoxicity prompting the US FDA to issue boxed warnings. Ponatinib is a valuable treatment option for adults with T315I-positive chronic-, accelerated- or blast-phase CML, or Ph+ ALL, as well as those with chronic-, accelerated- or blast-phase CML, or Ph+ ALL who are resistant or intolerant to prior tyrosine kinase inhibitor therapy, but before starting treatment, clinicians need to consider whether the potential benefits of therapy will outweigh the risks.
    Drugs 05/2014;
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    ABSTRACT: Alzheimer's disease (AD) is the most common cause of dementia in elderly people. Research focused on identifying compounds that restore cognition and memory in AD patients is a very active investigational pursuit. Cholinesterase inhibitors for the symptomatic treatment of cognitive decline in AD have been in use for more than a decade but provide only modest benefits in most patients. Preclinical research is constantly providing new information on AD. The involvement of the serotonergic system in higher cognitive processes such as memory and learning has been widely described and extensive serotonergic denervation has been reported in AD. This review aims to explain the rationale behind testing serotonergic therapies for AD in terms of current knowledge about the pathophysiology of the disease. Based on preclinical studies, certain serotonin (5-HT) receptor ligands have been suggested to have the ability to modify or improve memory/cognition, specifically 5-HT receptors acting at 5-HT1A, 5-HT4 and 5-HT6 receptors. This article summarizes the pharmacology, efficacy, safety and tolerability data for the various serotonergic agents currently in clinical development for AD.
    Drugs 05/2014;
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    ABSTRACT: Asthma is a common disease with a complex pathophysiology. It can present in various clinical forms and with different levels of severity. Unbiased cluster analytic methods have unravelled several phenotypes in cohorts representative of the whole spectrum of severity. Clusters of severe asthma include those on high-dose corticosteroid treatment, often with both inhaled and oral treatment, usually associated with severe airflow obstruction. Phenotypes with concordance between symptoms and sputum eosinophilia have been reported, including an eosinophilic inflammation-predominant group with few symptoms and late-onset disease who have a high prevalence of rhinosinusitis, aspirin sensitivity, and exacerbations. Sputum eosinophilia is also a biomarker that can predict therapeutic responses to antibody-based treatments to block the effects of the T-helper (Th)-2 cytokine, interleukin (IL)-5. Low Th2-expression has been predictive of poor therapeutic response to inhaled corticosteroid therapy. Current asthma schedules emphasise a step-up approach to treating asthma in relation to increasing severity, but, in more severe disease, phenotyping or endotyping of asthma will be necessary to determine new treatment strategies as severe asthma is recognized as being a particularly heterogeneous disease. Much less is known about 'non-eosinophilic' asthma. Phenotypic characterisation of corticosteroid insensitivity and chronic airflow obstruction of severe asthma is also needed. Phenotype-driven treatment of asthma will be further boosted by the advent of transcriptomic and proteomic technologies, with the application of systems biology or medicine approaches to defining phenotypes and biomarkers of disease and therapeutic response. This will pave the way towards personalized medicine and healthcare for asthma.
    Drugs 05/2014;
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    ABSTRACT: Apremilast (Otezla(®)), an oral small molecule inhibitor of type-4 cyclic nucleotide phosphodiesterase (PDE-4), is under development with Celgene Corporation for the treatment of psoriatic arthritis, psoriasis, ankylosing spondylitis, Behçet's syndrome, atopic dermatitis, and rheumatoid arthritis. Apremilast is indicated for the treatment of active psoriatic arthritis in adults. Apremilast has received its first global approval for this indication in the USA. Regulatory submissions for approval in this indication are under review in Canada and Europe. Regulatory filings have also been submitted for apremilast in the treatment of plaque psoriasis in the USA and Europe. This article summarizes the milestones in the development of apremilast leading to its first approval for the treatment of psoriatic arthritis.
    Drugs 05/2014;
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    ABSTRACT: Degarelix (Firmagon(®); Gonax(®)) is a gonadotropin-releasing hormone receptor antagonist that is approved for the treatment of advanced (hormone-dependent) prostate cancer in the US and EU and the treatment of prostate cancer in Japan. In a pivotal randomized, controlled, 12-month phase III study, degarelix (initial subcutaneous dose of 240 mg followed by monthly dosages of 80 mg) was noninferior to leuprolide (monthly intramuscular dosages of 7.5 mg) in patients with prostate cancer of any stage for which endocrine treatment was indicated (except neoadjuvant hormonal therapy) with regard to suppression of testosterone to castration levels (i.e. ≤0.5 ng/mL). Suppression of testosterone and prostate-specific antigen (PSA) levels was faster with degarelix than with leuprolide, and no testosterone surges or microsurges were seen in degarelix recipients. Suppression of testosterone and PSA levels was maintained for the 12-month study duration and continued for up to 5 years in an extension to the main trial (including in patients switching from leuprolide to degarelix in the extension). The drug was generally well tolerated, with most adverse events being mild to moderate in severity. Injection-site reactions and events reflecting the expected effects of testosterone suppression (e.g. hot flushes, weight increase) were the most common treatment-emergent adverse events. Thus, degarelix is a useful option for the treatment of prostate cancer in patients for whom endocrine treatment is indicated.
    Drugs 04/2014;
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    ABSTRACT: Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease and pathologically is characterised by a progressive loss of dopaminergic cells of the nigrostriatal pathway. Clinically, PD is mainly defined by the presence of the motor symptoms of bradykinesia, rigidity, rest tremor and postural instability, but non-motor symptoms such as depression, dementia and autonomic disturbances are recognised as integral parts of the disease. Although pharmacotherapy for PD was introduced almost 50 years ago, and has improved significantly over the intervening period, the timing of initiation of treatment in newly diagnosed PD remains controversial. While some physicians favour an early start of pharmacotherapy at or soon after diagnosis, others prefer to delay pharmacological treatment until a certain degree of disability has developed. This article aims to discuss the advantages and disadvantages of both strategies by exploring their effects on symptoms, disease progression and quality of life. Although the data on putative disease-modifying effects of early pharmacological intervention in PD are still inconclusive, we believe that the most important indication for an early initiation of anti-parkinsonian treatment should be to maintain the quality of life of PD patients and to secure their socioeconomic status as long as possible.
    Drugs 04/2014;
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    ABSTRACT: Treatment of multiple sclerosis (MS) is challenging: disease-modifying treatments (DMTs) must both limit unwanted immune responses associated with disease initiation and propagation (as T and B lymphocytes are critical cellular mediators in the pathophysiology of relapsing MS), and also have minimal adverse impact on normal protective immune responses. In this review, we summarize key preclinical and clinical data relating to the proposed mechanism of action of the recently approved DMT teriflunomide in MS. Teriflunomide selectively and reversibly inhibits dihydro-orotate dehydrogenase, a key mitochondrial enzyme in the de novo pyrimidine synthesis pathway, leading to a reduction in proliferation of activated T and B lymphocytes without causing cell death. Results from animal experiments modelling the immune activation implicated in MS demonstrate reductions in disease symptoms with teriflunomide treatment, accompanied by reduced central nervous system lymphocyte infiltration, reduced axonal loss, and preserved neurological functioning. In agreement with the results obtained in these model systems, phase 3 clinical trials of teriflunomide in patients with MS have consistently shown that teriflunomide provides a therapeutic benefit, and importantly, does not cause clinical immune suppression. Taken together, these data demonstrate how teriflunomide acts as a selective immune therapy for patients with MS.
    Drugs 04/2014;
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    ABSTRACT: Chronic myeloid leukemia (CML) is a disease of the hematopoietic stem cell characterized by a median age at diagnosis of 60-65 years according to most epidemiologic registries. Prior to the tyrosine kinase inhibitor (TKI) era, older age was considered an adverse prognostic factor and was included in two of the most used scoring systems for CML, the Sokal score and the Euro score. Moreover, older age was generally considered a limitation for the use of allogeneic stem-cell transplantation, given the higher toxicity observed. After the introduction of TKIs, age lost much of its prognostic impact in patients in chronic phase (CP), and the EUTOS score, developed in patients treated with imatinib, did not identify age as a risk variable. However, most CML patients require life-long treatment; therefore, as patients age while taking a TKI, the complexity of the management of elderly patients may increase over time. To date, imatinib, the first TKI introduced, and two second-generation TKIs, nilotinib and dasatinib, have been approved in most Western countries for the first-line treatment of CML. These drugs differ in terms of efficacy, safety, and costs; therefore, knowledge of their characteristics is extremely relevant for optimal management of elderly CML patients. We reviewed the impact of age on the first-line treatment of CP CML patients in the TKI era, considering the epidemiology of the disease, the role of comorbidities, and analyzing data from population-based studies and clinical trials.
    Drugs 04/2014;
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    ABSTRACT: Elosulfase alfa (Vimizim™) is a recombinant form of N-acetylgalactosamine-6-sulfatase (GALNS) that was developed by BioMarin Pharmaceutical Inc. as an enzyme replacement therapy for patients with mucopolysaccharidosis type IVA (MPS IVA), also known as Morquio A syndrome. Patients with MPS IVA have a GALNS deficiency, which results in serious musculoskeletal, cardiorespiratory and other system disturbances. Elosulfase alfa was approved by the US FDA on 14 February 2014 for the treatment of MPS IVA. The European Medicines Agency Committee for Medicinal Products for Human Use (CHMP) has recently recommended that elosulfase alfa be approved for use in the EU in the same indication. Within the last year, the manufacturer has also filed applications for approval for the use of elosulfase alfa in MPS IVA in Brazil, Australia, Canada and Mexico. This article summarizes the milestones in the development of elosulfase alfa leading to its first global approval in MPS IVA.
    Drugs 04/2014;