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

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    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: Alipogene tiparvovec (Glybera®; AMT-011, AAV1-LPLS447X) is an adeno-associated virus serotype 1-based gene therapy for adult patients with familial lipoprotein lipase (LPL) deficiency (LPLD) and suffering from severe or multiple pancreatitis attacks despite dietary fat restrictions. It is administered as a one-time series of intramuscular injections in the legs. LPLD, a rare autosomal recessive disorder, results in hyperchylomicronaemia and severe hypertriglyceridaemia, which in turn, are associated with an increased risk of clinical complications, the most debilitating of which is recurrent severe and potentially life-threatening pancreatitis. In clinical studies (n = 27 patients), one-time administration of alipogene tiparvovec was associated with significant reductions in plasma triglyceride levels during the 12 or 14 week study period post administration. Although triglyceride levels returned to pre-treatment levels within 16–26 weeks after administration, patients had sustained improvements in postprandial chylomicron metabolism, with sustained expression of functional copies of the LPL S477X gene and of biologically active LPL in skeletal muscle. Moreover, after up to 6 years’ follow-up post administration, there were clinically relevant reductions in the incidence of documented pancreatitis and acute abdominal pain events consistent with pancreatitis. Alipogene tiparvovec was generally well tolerated, with most adverse events being localized, transient, mild to moderate injection-site reactions. This article reviews the pharmacology of alipogene tiparvovec and its efficacy and safety in adults with LPLD.
    Drugs 01/2015;
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    ABSTRACT: The norepinephrine prodrug droxidopa (NORTHERA™) is approved in the US for the treatment of orthostatic dizziness, lightheadedness, or the ‘feeling that you are about to black out’ in adults with symptomatic neurogenic orthostatic hypotension associated with primary autonomic failure (e.g. Parkinson’s disease, multiple system atrophy or pure autonomic failure), dopamine β-hydroxylase deficiency or nondiabetic autonomic neuropathy. This article reviews the clinical efficacy and tolerability of droxidopa in symptomatic neurogenic orthostatic hypotension, as well as summarizing its pharmacological properties. Oral droxidopa was effective in the shorter-term treatment of patients with symptomatic neurogenic orthostatic hypotension, with improvements seen in symptoms, the impact of symptoms on daily activities and standing systolic blood pressure. More data are needed to confirm the longer-term efficacy of droxidopa. Droxidopa was generally well tolerated, although patients should be monitored for supine hypertension.
    Drugs 01/2015;
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    ABSTRACT: Simeprevir (Olysio™; Galexos™; Sovriad®) is an orally-administered NS3/4A protease inhibitor for use in combined drug regimens against chronic hepatitis C virus (HCV) infection. This article reviews studies relevant to the EU simeprevir label. In proof-of-concept studies, simeprevir had potent antiviral activity against all HCV genotypes, except genotype 3. In trials in patients with chronic HCV genotype 1 infection, week-12 sustained virological response (SVR12) rates in treatment-naïve patients and prior relapsers were significantly higher with simeprevir plus peginterferon-α/ribavirin (PR) [79–89 %] than with placebo plus PR (36–62 %). In prior partial/null responders, the SVR12 rate with simeprevir plus PR (54 %) was noninferior to that with telaprevir plus PR (55 %). Simeprevir plus PR was also efficacious in patients with HCV genotype 1/HIV-1 co-infection. In prior null responders without severe liver fibrosis (cohort 1) and treatment-naïve patients with severe liver fibrosis (cohort 2) treated with simeprevir plus sofosbuvir, the SVR12 rate for the two cohorts combined was 92 %. In patients with chronic HCV genotype 4 infection, the SVR12 rates with simeprevir plus PR were 83, 87 and 40 % in treatment-naïve patients, prior relapsers and prior null responders, respectively. Grade 3–4 adverse event, serious adverse event and treatment withdrawal rates with simeprevir plus PR were similar to those with placebo plus PR. Skin rashes with simeprevir were mostly mild or moderate; serious photosensitivity reactions occur, but are rare. Simeprevir is efficacious and generally well tolerated in patients with chronic HCV genotypes 1 and 4 infection. Studies of simeprevir in interferon-free regimens and in other subpopulations with HCV infections will be of interest.
    Drugs 01/2015;
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    ABSTRACT: Inhibitors of sodium–glucose co-transporter type 2 (SGLT2) are proposed as a novel approach for the management of type 2 diabetes mellitus (T2DM). Several compounds are already available in many countries (dapagliflozin, canagliflozin, empagliflozin and ipragliflozin) and some others are in a late phase of development. The available SGLT2 inhibitors share similar pharmacokinetic characteristics, with a rapid oral absorption, a long elimination half-life allowing once-daily administration, an extensive hepatic metabolism mainly via glucuronidation to inactive metabolites, the absence of clinically relevant drug–drug interactions and a low renal elimination as parent drug. SGLT2 co-transporters are responsible for reabsorption of most (90 %) of the glucose filtered by the kidneys. The pharmacological inhibition of SGLT2 co-transporters reduces hyperglycaemia by decreasing renal glucose threshold and thereby increasing urinary glucose excretion. The amount of glucose excreted in the urine depends on both the level of hyperglycaemia and the glomerular filtration rate. Results of numerous placebo-controlled randomised clinical trials of 12–104 weeks duration have shown significant reductions in glycated haemoglobin (HbA1c), resulting in a significant increase in the proportion of patients reaching HbA1c targets, and a significant lowering of fasting plasma glucose when SGLT2 inhibitors were administered as monotherapy or in addition to other glucose-lowering therapies including insulin in patients with T2DM. In head-to-head trials of up to 2 years, SGLT2 inhibitors exerted similar glucose-lowering activity to metformin, sulphonylureas or sitagliptin. The durability of the glucose-lowering effect of SGLT2 inhibitors appears to be better; however, this remains to be more extensively investigated. The risk of hypoglycaemia was much lower with SGLT2 inhibitors than with sulphonylureas and was similarly low as that reported with metformin, pioglitazone or sitagliptin. Increased renal glucose elimination also assists weight loss and could help to reduce blood pressure. Both effects were very consistent across the trials and they represent some advantages for SGLT2 inhibitors when compared with other oral glucose-lowering agents. The pharmacodynamic response to SGLT2 inhibitors declines with increasing severity of renal impairment, and prescribing information for each SGLT2 inhibitor should be consulted regarding dosage adjustments or restrictions in moderate to severe renal dysfunction. Caution is also recommended in the elderly population because of a higher risk of renal impairment, orthostatic hypotension and dehydration, even if the absence of hypoglycaemia represents an obvious advantage in this population. The overall effect of SGLT2 inhibitors on the risk of cardiovascular disease is unknown and will be evaluated in several ongoing prospective placebo-controlled trials with cardiovascular outcomes. The impact of SGLT2 inhibitors on renal function and their potential to influence the course of diabetic nephropathy also deserve more attention. SGLT2 inhibitors are generally well-tolerated. The most frequently reported adverse events are female genital mycotic infections, while urinary tract infections are less commonly observed and generally benign. In conclusion, with their unique mechanism of action that is independent of insulin secretion and action, SGLT2 inhibitors are a useful addition to the therapeutic options available for the management of T2DM at any stage in the natural history of the disease. Although SGLT2 inhibitors have already been extensively investigated, further studies should even better delineate the best place of these new glucose-lowering agents in the already rich armamentarium for the management of T2DM.
    Drugs 12/2014;
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    ABSTRACT: Nintedanib (Ofev(®)) is an orally available, small, multiple receptor tyrosine kinase inhibitor developed by Boehringer Ingelheim for the treatment of idiopathic pulmonary fibrosis (IPF) and cancer. Nintedanib received its first global approval in the US in October 2014 for the treatment of IPF. Nintedanib has received a positive opinion from the European Medicines Agency's Committee for Medicinal Products for Human Use for the treatment of IPF, and for the second-line treatment in combination with docetaxel of locally advanced, metastatic or locally recurrent non-small cell lung cancer of adenocarcinoma tumour histology. Phase 3 development programmes are also underway for colorectal cancer and ovarian cancer. Phase 2 investigation is being conducted for a variety of other solid tumours, including hepatocellular carcinoma, mesothelioma, prostate cancer, glioblastoma, renal cell carcinoma and endometrial cancer. This article summarizes the milestones in the development of nintedanib leading to this first approval for IPF.
    Drugs 11/2014;
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    ABSTRACT: Alectinib (Alecensa(®)) is a second-generation, orally active, potent and highly selective inhibitor of anaplastic lymphoma kinase (ALK). Alectinib is approved for the treatment of ALK fusion-gene positive, unresectable, advanced or recurrent non-small cell lung cancer (NSCLC) in Japan, where it has been given orphan drug designation. Approval was based on a phase 1-2 study in ALK inhibitor-naive patients with ALK-rearranged advanced NSCLC who received twice-daily alectinib 300 mg. In the phase 2 portion, 93.5 % of patients achieved an objective response. Treatment response was rapid, with a partial response achieved in two-thirds of patients within 3 weeks (cycle 1). Patient follow-up is ongoing, and after approximately 2 years, 19.6 % of patients had achieved a complete response, and the 2-year progression-free survival rate is 76 %. During treatment with alectinib (median follow-up approximately 8 months), there was no progression of CNS lesions among patients with known CNS metastases at baseline (although prior radiation therapy may have confounded results). In preclinical models, alectinib was active against most ALK fusion-gene mutations related to crizotinib resistance, and preliminary results from clinical trials indicate efficacy in crizotinib-refractory NSCLC. Alectinib was generally well tolerated in clinical trials, and there were no treatment-related grade 4 adverse events or deaths. The most common grade 3 treatment-related adverse events were decreased neutrophil counts and increased creatinine phosphokinase. While more data are needed to confirm the efficacy of alectinib and to evaluate its activity in crizotinib-resistant disease, the drug provides a very promising option for the treatment of ALK-rearranged advanced NSCLC.
    Drugs 11/2014;
  • Drugs 11/2014;
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    ABSTRACT: In the USA, binge eating disorder (BED) is the most common eating disorder, with a lifetime prevalence of ~3.5 % in adult women, 2.0 % in adult men, and 1.6 % in adolescents. BED is characterized by frequent episodes of binge eating that are accompanied by a sense of loss of control over eating and result in marked psychological distress. BED is highly co-morbid with obesity and with depression and other psychiatric conditions, and it is associated with substantial role impairment. Currently, there are no US FDA-approved pharmacological treatments for BED. Animal and human studies implicate underlying dysregulation in dopamine, opioid, acetylcholine, and serotonin neurocircuitry within brain reward regions in the pathogenesis and maintenance of BED. To date, the efficacy of various agents that target these and other neurotransmitter systems involved in motivated feeding behavior, mood regulation, and impulse control have been investigated in the treatment of BED. Several antidepressant and anticonvulsant agents have demonstrated efficacy in reducing binge eating frequency, but only in limited cases have these effects resulted in patients achieving abstinence, which is the primary goal of treatment; they also range from less (fluvoxamine) to more (topiramate) effective in achieving weight loss that is both clinically meaningful and significantly greater than placebo. Collectively, the literature on pharmacological treatment approaches to BED is limited in that very few agents have been studied in multiple, confirmatory trials with adequate follow up, and almost none have been evaluated in large patient samples that are diverse with respect to age, sex, and ethnicity. In addition, prior trials have not adequately addressed, through study design, the high placebo response commonly observed in this patient population. Several novel agents are in various phases of testing, and recent animal studies focusing on glutamate-signaling circuits linking the amygdala to the lateral hypothalamus offer new avenues for exploration and potential therapeutic development. Studies of newly FDA-approved medications for long-term obesity treatment and further explorations of dietary supplements and neutraceuticals with appetite- and mood-altering properties may also be worthwhile.
    Drugs 11/2014;
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    ABSTRACT: Fixed-dose dextromethorphan/quinidine capsules (Nuedexta(®)) utilize quinidine to inhibit the metabolism of dextromethorphan, enabling high plasma dextromethorphan concentrations to be reached without using a larger dose of the drug. The drug combination is the first treatment to be approved for pseudobulbar affect (PBA), a condition of contextually inappropriate/exaggerated emotional expression that often occurs in adults with neurological damage conditions, such as amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), stroke, traumatic brain injury, Alzheimer's disease or Parkinson's disease. Dextromethorphan/quinidine at the recommended dosages of 20/10 or 30/10 mg twice daily reduced the rate of PBA episodes and improved PBA severity in a 12-week, double-blind, placebo-controlled trial in adults with ALS or MS (STAR), with further improvements in the severity of the condition observed in a 12-week open-label extension phase. Dextromethorphan/quinidine 20/10 mg twice daily also improved PBA secondary to dementia in a cohort of a 12-week noncomparative trial (PRISM II). The drug combination was generally well tolerated in these studies, with no particular safety or tolerability concerns. Although longer-term efficacy and tolerability data for dextromethorphan/quinidine 20/10 or 30/10 mg twice daily would be beneficial, current evidence indicates that it is a useful option in the treatment of adults with PBA.
    Drugs 11/2014;
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    ABSTRACT: The mitogen-activated protein kinase kinases (MAPKK) MEK1 and MEK2 are integral members of the MAPK/ERK signaling pathway and are of interest in the development of anti-cancer therapeutics. The MAPK/ERK pathway is dysregulated in more than 30 % of cancers, predominately by mutations in RAS and BRAF proteins, and MEK serves as a potential downstream target for both of these. The biology of MEK inhibition is complex, as the molecule is differentially regulated by upstream RAS or RAF. This has impacted on the past development of MEK inhibitors as treatments for cancer and may be exploited in more rational, molecularly selected drug development plans in the future. The role of MEK in cancer and the mechanism of action of MEK inhibitors is reviewed. Furthermore, MEK inhibitors that are available in standard practice, as well as those most advanced in clinical development, are discussed. Finally, next steps in the development of MEK inhibitors are considered.
    Drugs 11/2014;
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    ABSTRACT: Lung tissue remodelling in chronic inflammatory lung diseases has long been regarded as a follow-up event to inflammation. Recent studies have indicated that, although airway and lung tissue remodelling is often independent of inflammation, it precedes or causes inflammation. None of the available therapies has a significant effect on airway and lung tissue remodelling in asthma, bronchiectasis, fibrosis and chronic obstructive pulmonary disease (COPD). The goal of stopping or reversing lung tissue remodelling is difficult, as the term summarizes the net effect of independent events, including (1) cell proliferation, (2) cell volume increase, (3) cell migration, (4) modified deposition and metabolism of specific extracellular matrix components, and (5) local action of infiltrated inflammatory cells. The extracellular matrix of the lung has a very high turnover, and thus small changes may accumulate to significant structural pathologies, which seem to be irreversible. The most important question is 'why are pathological changes of the lung structure irreversible and resistant to drugs?' Many drugs have the potential to reduce remodelling mechanisms in vitro but fail in clinical trials. New evidence suggests that muscarinic receptor inhibitors have the potential to improve lung function through modifying tissue remodelling. However, the role of muscarinic receptors in lung remodelling, especially their supportive role for other remodelling driving factors, needs to be further investigated. The focus of this review is the role of muscarinic receptors in lung tissue remodelling as it has been reported in the human lung.
    Drugs 11/2014;
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    ABSTRACT: Ripasudil hydrochloride hydrate (Glanatec® ophthalmic solution 0.4 %; hereafter referred to as ripasudil) is a small-molecule, Rho-associated kinase inhibitor developed by Kowa Company, Ltd. for the treatment of glaucoma and ocular hypertension. This compound, which was originally discovered by D. Western Therapeutics Institute, Inc., reduces intraocular pressure (IOP) by directly acting on the trabecular meshwork, thereby increasing conventional outflow through the Schlemm's canal. As a result of this mechanism of action, ripasudil may offer additive effects in the treatment of glaucoma and ocular hypertension when used in combination with agents such as prostaglandin analogues (which increase uveoscleral outflow) and β blockers (which reduce aqueous production). The eye drop product has been approved in Japan for the twice-daily treatment of glaucoma and ocular hypertension, when other therapeutic agents are not effective or cannot be administered. Phase II study is underway for the treatment of diabetic retinopathy. This article summarises the milestones in the development of ripasudil leading to the first approval for glaucoma and ocular hypertension.
    Drugs 11/2014;
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    ABSTRACT: Most patients with diabetes mellitus require multiple medications to achieve glycemic goals. Considering this and the increasing incidence of type 2 diabetes worldwide, the need for effective combination therapy is pressing. Basal insulin and glucagon-like peptide 1 (GLP-1) receptor agonists are frequently used to treat type 2 diabetes. Though both classes of medication are exclusively injectable, which may cause initial hesitation from providers, evidence for their combined use is substantial. This review summarizes the theoretical benefit, supporting evidence, and implementation of a combined basal insulin-GLP-1 receptor agonist regimen. Basal insulin added to a GLP-1 receptor agonist reduces hemoglobin A1c (HbA1c) without weight gain or significantly increased hypoglycemia. A GLP-1 receptor agonist added to basal insulin reduces HbA1c and body weight. Compared with the addition of meal-time insulin to basal insulin, a GLP-1 receptor agonist produces similar or greater reduction in HbA1c, weight loss instead of weight gain, and less hypoglycemia. Gastrointestinal adverse events are common with GLP-1 receptor agonists, especially during initiation and titration. However, combination with basal insulin is not expected to augment expected adverse events that come with using a GLP-1 receptor agonist. Basal insulin can be added to a GLP-1 receptor agonist with a slow titration to target goal fasting plasma glucose. In patients starting a GLP-1 receptor agonist, the dose of basal insulin should be decreased by 20 % in patients with an HbA1c ≤8 %. The evidence from 15 randomized prospective studies supports the combined use of a GLP-1 receptor agonist with basal insulin in a broad range of patients with uncontrolled type 2 diabetes.
    Drugs 11/2014;
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    ABSTRACT: Delamanid (Deltyba(®)), a nitroimidazo-oxazole derivative, is a new anti-tuberculosis (TB) drug which exhibits potent in vitro and in vivo antitubercular activity against drug-susceptible and -resistant strains of Mycobacterium tuberculosis. It is approved in several countries, including Japan and those of the EU, for use as part of an appropriate combination regimen in adults with multidrug-resistant tuberculosis (MDR-TB) when an effective treatment regimen cannot otherwise be composed due to resistance or tolerability. In a robust phase II trial in adult patients with MDR-TB, oral delamanid 100 mg twice daily for 2 months plus an optimized background regimen improved sputum culture conversion rates to a significantly greater extent than placebo. In a 6-month extension study, long-term (≤8 months) treatment with delamanid was associated with a higher incidence of favourable outcomes (i.e. cured or completed all treatment) than short-term (≤2 months) treatment, with an accompanying reduction inunfavourable outcomes as defined by the WHO (i.e. pre-specified proportion of TB-positive sputum cultures, death or treatment discontinuation for ≥2 months without medical approval). Delamanid was not associated with clinically relevant drug-drug interactions, including with antiretroviral drugs and those commonly used in treating TB. Delamanid was generally well tolerated in patients with MDR-TB, with gastrointestinal adverse events and insomnia reported most commonly. Although the incidence of QT interval prolongation was higher with delamanid-based therapy, it was not associated with clinical symptoms such as syncope and arrhythmia. In conclusion, delamanid is a useful addition to the treatment options currently available for patients with MDR-TB.
    Drugs 11/2014;
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    ABSTRACT: Umeclidinium/vilanterol (Anoro(®) Ellipta™; Laventair™) is an inhaled fixed-dose combination of a long-acting muscarinic receptor antagonist and a long-acting β2-adrenoceptor agonist. It is available in several countries, including Japan, the USA, Canada and those of the EU, where it is indicated for oral inhalation in adults with chronic obstructive pulmonary disease (COPD). Umeclidinium/vilanterol is administered once daily using the Ellipta™ multi-dose dry powder inhaler, which is regarded as easy to use. Umeclidinium/vilanterol (62.5/25 µg once daily, equivalent to a delivered dose of 55/22 µg once daily) was effective and well tolerated in adult patients with COPD participating in large, multicentre trials of up to 24 weeks' duration. Umeclidinium/vilanterol improved pulmonary function to a significantly greater extent than placebo and each of the individual components. Moreover, umeclidinium/vilanterol was significantly more effective than once-daily tiotropium bromide monotherapy and a twice-daily fixed combination of salmeterol/fluticasone propionate at improving pulmonary function. Umeclidinium/vilanterol also had beneficial effects on dyspnoea, use of rescue medication, exacerbations, health-related quality of life and, in one study, exercise endurance. Umeclidinium/vilanterol is generally well tolerated in patients with COPD, with the most common adverse events in clinical trials being headache and nasopharyngitis. Umeclidinium/vilanterol was not associated with a clinically relevant increased risk of cardiovascular adverse events in patients with COPD, when data from several clinical trials were pooled. Thus, inhaled umeclidinium/vilanterol extends the treatment options currently available for the maintenance treatment of adults with COPD and has the convenience of once-daily administration.
    Drugs 11/2014;
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    ABSTRACT: Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by inflammation and joint destruction that causes significant morbidity and mortality. However, the combined use of methotrexate (MTX), a synthetic disease-modifying anti-rheumatic drug (sDMARD) and biological DMARDs (bDMARDs) has revolutionized treatment of RA and clinical remission or low disease activity (LDA) are now realistic targets, achieved by a large proportion of RA patients. We are now in a position to evaluate if it is possible to maintain remission or LDA while at the same time reducing the burden of treatment on the patient and healthcare system. Data are emerging from large, well-conducted studies designed to answer this question, shedding light on which patient populations and treatment algorithms can survive treatment discontinuation or tapering with low risk of disease flare. For early RA, approximately half of early RA patients could discontinue TNF-targeted bDMARDs without clinical flare and functional impairment after obtaining clinical remission by bDMARDs with MTX. In contrast, for established RA, fewer patients sustained remission or LDA after the discontinuation of bDMARDs and "deep remission" at the discontinuation was a key factor to maintain the treatment holiday of bDMARDs. Thus, this article provides a brief outline on withdrawing or tapering bDMARDs once patients have achieved remission or LDA in RA.
    Drugs 11/2014;
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    ABSTRACT: Dapagliflozin (Forxiga(®), Farxiga(®)) is an orally administered sodium-glucose co-transporter-2 (SGLT2) inhibitor used in the management of patients with type 2 diabetes. Dapagliflozin reduces renal glucose reabsorption by inhibiting the transporter protein SGLT2 in the renal proximal tubule, thereby increasing urinary glucose excretion and reducing blood glucose levels. Its mechanism of action is independent of insulin secretion or action; therefore, dapagliflozin provides complementary therapy when used in combination with other antihyperglycaemic drugs. This article updates an earlier review of dapagliflozin and focuses on longer-term efficacy and tolerability data (e.g. from extensions of earlier clinical trials), as well as data from studies in special patient populations (e.g. history of cardiovascular disease). Numerous well-designed clinical trials with dapagliflozin, primarily as add-on therapy for 24 weeks (but also as monotherapy or initial combination therapy), have consistently demonstrated reductions in glycosylated haemoglobin, fasting plasma glucose levels and bodyweight. Extensions of these trials show the effects are maintained over longer-term follow-up periods of ≈1-4 years and dapagliflozin is generally well tolerated. Dapagliflozin has a low risk of hypoglycaemia, although the incidence varies depending on background therapy, and genital mycotic infections (particularly in women) are the most common adverse events. Dapagliflozin is not recommended in patients with moderate or severe renal impairment. In view of its unique mechanism of action and now well-established efficacy and tolerability profile, dapagliflozin is a useful treatment option in the management of type 2 diabetes, although its effects on diabetic complications remain to be evaluated.
    Drugs 11/2014;
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    ABSTRACT: Pramipexole, a non-ergolinic, D3-preferring dopamine agonist (DA), is well established as a treatment option for motor symptoms at all stages of Parkinson's disease (PD). It is administered orally and is available as both a three-times daily immediate-release (IR) formulation and a once-daily extended-release (ER) formulation (Mirapex(®) ER, Mirapexin(®) ER; Pexola(®) ER, Sifrol(®) ER). The two formulations are bioequivalent; the majority (>80 %) of patients can be switched overnight from pramipexole IR to ER without the need for dosage adjustment. In terms of improving activities of daily living and motor function in short-term (≤33-week), double-blind studies, pramipexole ER was noninferior to pramipexole IR and significantly more effective than placebo as monotherapy in patients with early PD, and similar to pramipexole IR and significantly more effective than placebo as adjunctive therapy to levodopa in patients with advanced PD. In long-term (80-week) extensions of these trials, open-label treatment with pramipexole ER was associated with sustained symptomatic benefit. Moreover, the majority of extension participants who responded to a simple convenience questionnaire expressed a preference for once-daily over three-times daily dosing. Pramipexole ER was generally well tolerated in clinical trials; no new or unexpected safety signals were identified compared with the IR formulation. Head-to-head trials are needed in order to fully define the role of pramipexole ER relative to other once-daily formulations of DAs (oral ropinirole and transdermal rotigotine). Nonetheless, by reducing the pill burden, the ER formulation of pramipexole provides a more convenient alternative to the IR formulation; studies specifically testing whether this translates into improved patient compliance and symptom control are worthwhile.
    Drugs 11/2014;
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    ABSTRACT: Dulaglutide (Trulicity™) is a long-acting, glucagon-like peptide-1 (GLP-1) receptor agonist that has been developed by Eli Lilly and Company for the treatment of type 2 diabetes mellitus. It consists of a dipeptidyl peptidase-IV-protected GLP-1 analogue covalently linked to a human IgG4-Fc heavy chain by a small peptide linker. The subcutaneous formulation is approved for use in type 2 diabetes in the US, has been recommended for approval in the EU in this indication, and is under regulatory review in other countries. This article summarizes the milestones in the development of subcutaneous dulaglutide leading to this first approval for type 2 diabetes.
    Drugs 11/2014;