Sep 232014
 
Related Articles

Oritavancin: First Global Approval.

Drugs. 2014 Sep 20;

Authors: Markham A

Abstract
Oritavancin (Orbactiv(®)) is a lipoglycopeptide antibacterial drug with activity against Gram-positive bacteria developed by The Medicines Company as a single-dose treatment for acute bacterial skin and skin structure infections (ABSSSI). The drug received its first global approval for this indication in the US in August 2014, and is under regulatory review in the EU. This article summarises the milestones in the development of oritavancin leading to this first approval for the treatment of ABSSSIs caused by Gram-positive bacteria.

PMID: 25239268 [PubMed - as supplied by publisher]

Link to Article at PubMed

Share


Sep 112014
 
Related Articles

Systemic Glucocorticoid Therapy: a Review of its Metabolic and Cardiovascular Adverse Events.

Drugs. 2014 Sep 10;

Authors: Fardet L, Fève B

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.

PMID: 25204470 [PubMed - as supplied by publisher]

Link to Article at PubMed

Share


Sep 032014
 
Related Articles

Clinical Use of Rivaroxaban: Pharmacokinetic and Pharmacodynamic Rationale for Dosing Regimens in Different Indications.

Drugs. 2014 Sep 2;

Authors: Trujillo T, Dobesh PP

Abstract
Target-specific oral anticoagulants have become increasingly available as alternatives to traditional agents for the management of a number of thromboembolic disorders. To date, the direct Factor Xa inhibitor rivaroxaban is the most widely approved of the new agents. The dosing of rivaroxaban varies and adheres to specific schedules in each of the clinical settings in which it has been investigated. These regimens were devised based on the results of phase II dose-finding studies and/or pharmacokinetic modeling, and were demonstrated to be successful in randomized, phase III studies. In most cases, the pharmacodynamic profile of rivaroxaban permits once-daily dosing. A once-daily dose is indicated for the prevention of venous thromboembolism (VTE) in patients undergoing hip or knee replacement surgery, the long-term prevention of stroke in patients with non-valvular atrial fibrillation, and the long-term secondary prevention of recurrent VTE. Twice-daily dosing is required in the acute phase of treatment in patients with VTE and in the combination of rivaroxaban with standard single or dual antiplatelet therapy for secondary prevention after acute coronary syndrome events. This article reviews the empirical and clinical rationale supporting the dose regimens of rivaroxaban in each clinical setting.

PMID: 25178252 [PubMed - as supplied by publisher]

Link to Article at PubMed

Share


Aug 152014
 
Related Articles

Ceftobiprole Medocaril: A Review of Its Use in Patients with Hospital- or Community-Acquired Pneumonia.

Drugs. 2014 Aug 13;

Authors: Syed YY

Abstract
Ceftobiprole, the active metabolite of the prodrug ceftobiprole medocaril (Zevtera(®)), is a new generation broad-spectrum intravenous cephalosporin with activity against methicillin-resistant Staphylococcus aureus. Ceftobiprole exhibits potent in vitro activity against a number of Gram-positive and Gram-negative pathogens associated with hospital-acquired pneumonia (HAP) and community-acquired pneumonia (CAP). It is the first cephalosporin monotherapy approved in the EU for the treatment of both HAP (excluding ventilator associated-pneumonia [VAP]) and CAP. In phase III trials, ceftobiprole medocaril was noninferior, in terms of clinical cure rates at the test-of-cure visit, to ceftazidime plus linezolid in patients with HAP and to ceftriaxone ± linezolid in patients with CAP severe enough to require hospitalization. In patients with HAP, noninferiority of ceftobiprole medocaril to ceftazidime plus linezolid was not demonstrated in a subset of patients with VAP. In patients with CAP, ceftobiprole medocaril was effective in those at risk for poor outcomes (pneumonia severity index ≥91, Pneumonia Patient Outcomes Research Team score IV-V or bacteraemic pneumonia). In the phase III trials, ceftobiprole medocaril was generally well tolerated, with ≈10 % of patients discontinuing the treatment because of adverse events. The most common treatment-related adverse events occurring in ceftobiprole recipients in the trials in patients with HAP or CAP included nausea, diarrhoea, infusion site reactions, vomiting, hepatic enzyme elevations and hyponatraemia. Therefore, ceftobiprole medocaril monotherapy offers a simplified option for the initial empirical treatment of patients with HAP (excluding VAP) and in those with CAP requiring hospitalization.

PMID: 25117196 [PubMed - as supplied by publisher]

Link to Article at PubMed

Share


Aug 012014
 

Nemonoxacin: First Global Approval.

Drugs. 2014 Jul 31;

Authors: Poole RM

Abstract
Nemonoxacin (Taigexyn(®)), a non-fluorinated quinolone antibacterial agent, is under development with TaiGen Biotechnology for the oral and intravenous treatment of community-acquired pneumonia (CAP) and the oral treatment of diabetic foot ulcer infections and skin and soft tissue infections. Oral nemonoxacin has been approved in Taiwan for the treatment of CAP in adults. This article summarizes the milestones in the development of nemonoxacin leading to this first approval for the treatment of CAP.

PMID: 25079302 [PubMed - as supplied by publisher]

Link to Article at PubMed

Share


Jul 192014
 

Edoxaban: An Update on the New Oral Direct Factor Xa Inhibitor.

Drugs. 2014 Jul 18;

Authors: Bounameaux H, Camm AJ

Abstract
Edoxaban is a once-daily oral anticoagulant that rapidly and selectively inhibits factor Xa in a concentration-dependent manner. This review describes the extensive clinical development program of edoxaban, including phase III studies in patients with non-valvular atrial fibrillation (NVAF) and symptomatic venous thromboembolism (VTE). The ENGAGE AF-TIMI 48 study (N = 21,105; mean CHADS2 score 2.8) compared edoxaban 60 mg once daily (high-dose regimen) and edoxaban 30 mg once daily (low-dose regimen) with dose-adjusted warfarin [international normalized ratio (INR) 2.0-3.0] and found that both regimens were non-inferior to warfarin in the prevention of stroke and systemic embolism in patients with NVAF. Both edoxaban regimens also provided significant reductions in the risk of hemorrhagic stroke, cardiovascular mortality, major bleeding and intracranial bleeding. The Hokusai-VTE study (N = 8,292) in patients with symptomatic VTE had a flexible treatment duration of 3-12 months and found that following initial heparin, edoxaban 60 mg once daily was non-inferior to dose-adjusted warfarin (INR 2.0-3.0) for the prevention of recurrent VTE, and also had a significantly lower risk of bleeding events. Both studies randomized patients at moderate-to-high risk of thromboembolic events and were further designed to simulate routine clinical practice as much as possible, with edoxaban dose reduction (halving dose) at randomisation or during the study if required, a frequently monitored and well-controlled warfarin group, a well-monitored transition period at study end and a flexible treatment duration in Hokusai-VTE. Given the phase III results obtained, once-daily edoxaban may soon be a key addition to the range of antithrombotic treatment options.

PMID: 25034361 [PubMed - as supplied by publisher]

Link to Article at PubMed

Share