Antiviral treatment of cytomegalovirus infection: an update.

Expert Opin Pharmacother. 2012 Feb 2;

Authors: Härter G, Michel D

Abstract
This editorial summarizes recent developments in the management of ganciclovir-resistant human cytomegalovirus (HCMV) infections. All current drugs available for systemic treatment, including ganciclovir (GCV), valganciclovir, foscarnet and cidofovir, target the viral polymerase. However, all such compounds are hampered by dose-related toxicities and the emergence of resistance. Different approaches (e.g., PCR-based direct sequencing, pyrosequencing, mass spectrometry-based comparative sequencing) allow the fast detection of resistant HCMV and are well suited to therapy monitoring. However, more studies are required on the dynamic of mixed HCMV populations under drug pressure. Alternate antiviral compounds with new mechanisms of action, such as artesunate, leflunomid, letermovir and maribavir, are now being investigated in clinical studies. An advantage of some of the new substances is lesser toxicity issues, which might lead to new prophylactic and treatment strategies.

PMID: 22299626 [PubMed - as supplied by publisher]

Tiotropium: what came after the UPLIFT study.

Expert Opin Pharmacother. 2012 Jan 28;

Authors: Santus P, Di Marco F, Radovanovic D, Centanni S

Abstract
Introduction: Chronic obstructive pulmonary disease (COPD) is characterized by a progressive bronchial obstruction, and bronchodilators represent the maintenance therapeutic choice. Tiotropium is an anticholinergic drug that is proved to be safe, efficient and simple to handle; Respimat® technology was recently introduced as a new device for tiotropium administration. Areas covered: This paper reviews clinical trials and meta-analyses, with tiotropium efficacy as a primary end point, found in MedLine, the Cochrane trials database and Embase. Only the literature published after the UPLIFT study has been considered. Expert opinion: Data published after the UPLIFT study confirms the efficacy of tiotropium as maintenance COPD therapy and its capacity to reduce airflow obstruction, as well as lung hyperinflation. Nevertheless, there is a certain inhomogeneity in the definition and evaluation of COPD exacerbations, in lung functional parameters and quality-of-life assessment, and there has not always been a proper comparison between tiotropium and other long-acting bronchodilators. Respimat is comparable in efficacy to the HandiHaler®, using bioequivalent doses of tiotropium.

PMID: 22283503 [PubMed - as supplied by publisher]

Tapentadol for pain: a treatment evaluation.

Expert Opin Pharmacother. 2011 Dec 23;

Authors: Hartrick CT, Rodríguez Hernandez JR

Abstract
Tapentadol is a newly approved novel analgesic drug with a dual mode of action: a mu-opioid agonist and an inhibitor of norepinephrine reuptake (MOR-NRI). Preclinical evidence supports a synergistic interaction between these two effects. It is the first opioid agonist to exhibit predominant norepinephrine reuptake inhibition with minimal serotonin effects. It is FDA approved for use in the US for moderate to severe pain in adults, available in the immediate release form for acute pain and as an extended-release formulation for chronic pain when continuous analgesia is required. Tapentadol has demonstrated reduced treatment-emergent opioid-related gastrointestinal adverse effects compared with pure opioid agonists. The synergistic mu-opioid and alpha(2)-adrenergic effects suggest the potential for particular utility in neuropathic pain states or other pain states associated with hyperalgesia.

PMID: 22192161 [PubMed - as supplied by publisher]

The use of insulin in elderly patients with type 2 diabetes mellitus.

Expert Opin Pharmacother. 2011 Nov 16;

Authors: Mannucci E, Cremasco F, Romoli E, Rossi A

Abstract
Introduction: Older patients with diabetes sometimes present comorbidities that increase the risk of other common geriatric syndromes. In such patients, treatment with insulin is usually started when full doses of oral hypoglycemic agents are no longer adequate to achieve acceptable glycemic control. Areas covered: This article reviews the available literature on the use of insulin in elderly patients with type 2 diabetes. The aims are to gain information on: the benefits and risks of initiating insulin treatment, the efficacy and safety of different types of insulin and the most appropriate initial dosing and titration regimens. Thirteen published trials have evaluated the effects of different insulin regimens in the management of elderly subjects with type 2 diabetes but, given that older people are generally excluded in clinical studies with insulin, only three published reports on subgroup analyses are limited to elderly patients. Expert opinion: The available literature shows that the addition of insulin to current oral treatments is generally safe and effective in improving metabolic control, with a low risk for hypoglycemia. Further research is needed to better understand the most appropriate insulin regimens necessary to achieve glycemic goals while appropriately addressing the risk of hypoglycemia.

PMID: 22087577 [PubMed - as supplied by publisher]

Medical management of neurocysticercosis.

Expert Opin Pharmacother. 2011 Nov 15;

Authors: Takayanagui OM, Odashima NS, Bonato PS, Lima JE, Lanchote VL

Abstract
Introduction: Neurocysticercosis (NCC) is considered to be the most common cause of acquired epilepsy worldwide. Formerly restricted to palliative measures, therapy for NCC has advanced with the advent of two drugs that are considered to be effective: praziquantel (PZQ) and albendazole (ALB). Areas covered: All available articles regarding research related to the treatment of NCC were searched. Relevant articles were then reviewed and used as sources of information for this review. Expert opinion: Anticysticercal therapy has been marked by intense controversy. Recent descriptions of spontaneous resolution of parenchymal cysticercosis with benign evolution, risks of complications and reports of no long-term benefits have reinforced the debate over the usefulness and safety of anticysticercal therapy. High interindividual variability and complex pharmacological interactions will require the close monitoring of plasma concentrations of ALB and PZQ metabolites in future trials. Given the relative scarcity of clinical trials, more comparative interventional studies ? especially randomized controlled trials in long-term clinical evolution ? are required to clarify the controversy over the validity of parasitic therapy in patients with NCC.

PMID: 22082143 [PubMed - as supplied by publisher]

Mineralocorticoid receptor antagonists for heart failure.

Expert Opin Pharmacother. 2011 Nov 14;

Authors: Richards AM

Abstract
Introduction: Although mineralocorticoid receptor (MR) antagonists are indicated in systolic heart failure, they are underprescribed in patients with appropriate indications for their prescription and often used in those in whom the evidence for probable benefit is scant. The rate of adverse events in practice has exceeded that foreshadowed by randomized controlled trials (RCTs). With the recent publication of the landmark therapeutic trial (EMPHASIS), it is timely to review the appropriate use of these agents in heart failure. Areas covered: This review addresses the pathophysiological importance of MR activation in heart failure and summarizes pivotal RCTs of MR antagonists in heart failure. Expert opinion: MR antagonism reduces mortality and morbidity in heart failure with reduced systolic function in severe chronic disease, in heart failure complicating myocardial infarction and also in those with impaired systolic function (but only mild symptoms). Evidence for benefits in a significant proportion of ?real-life? patients with heart failure, including those with preserved left ventricular ejection fraction, is lacking. MR antagonism is an important part of the pharmaceutical armamentarium in managing heart failure but must be prescribed with careful case selection, taking note of the evidence of where risks are acceptable and benefits are likely.

PMID: 22082128 [PubMed - as supplied by publisher]

Telavancin for the treatment of serious gram-positive infections, including hospital acquired pneumonia.

Expert Opin Pharmacother. 2011 Dec;12(17):2737-50

Authors: Rubinstein E, Corey GR, Stryjewski ME, Kanafani ZA

Abstract
Introduction: Hospital-acquired pneumonia is a common infection, associated with substantial mortality. Despite the increasing prevalence of nosocomial pneumonia caused by methicillin-resistant Staphylococcus aureus (MRSA), approved treatment options for this pathogen are limited. Areas covered: This article reviews the pharmacokinetics, dosing, preclinical studies and clinical efficacy, and safety of telavancin, with a particular focus on results from trials in nosocomial pneumonia. PubMed and Congress websites were searched for relevant articles published between 2003 and 2010. Expert opinion: Telavancin is a lipoglycopeptide antibiotic with rapid, bactericidal activity against MRSA, and may provide another option for the treatment of nosocomial pneumonia, owing to Gram-positive pathogens.

PMID: 22077833 [PubMed - in process]

Mometasone furoate dry powder inhaler for the treatment of asthma.

Expert Opin Pharmacother. 2011 Nov 4;

Authors: Fausnight TB, Craig TJ

Abstract
Introduction: Asthma is a chronic inflammatory disease that causes significant morbidity and mortality. Inhaled corticosteroids are the preferred initial treatment for this disorder. Mometasone furoate dry powder is an inhaled corticosteroid that is approved for once-daily treatment of asthma in both adults and children as young as 4 years. Areas covered: The goal of this paper is to review the clinical efficacy and safety of mometasone furoate dry powder inhaler for the treatment of asthma. A literature search using PubMed was done using the terms 'mometasone furoate', 'inhaled corticosteroid' and 'asthma', focusing on articles that highlighted clinical trials and addressed efficacy of the medication. Expert opinion: Mometasone furoate dry powder inhaler has an excellent safety and efficacy profile. For patients with persistent asthma who require treatment with an inhaled corticosteroid, mometasone furoate is an excellent therapeutic choice.

PMID: 22049912 [PubMed - as supplied by publisher]

Current review of antimicrobial treatment of nosocomial pneumonia caused by multidrug-resistant pathogens.

Expert Opin Pharmacother. 2011 Oct;12(14):2145-8

Authors: Jean SS, Hsueh PR

Abstract
Nosocomial pneumonia (including ventilator-associated pneumonia; VAP), a consistently difficult-to-treat entity, is frequently caused by multidrug-resistant (MDR) or pandrug-resistant (PDR) bacteria. Given the high mortality rates caused by drug-resistant bacteria and the difficulty of developing new potent antibiotics to target the problematic pathogens, combination regimens are under ardent evaluation as new strategies to overcome increasing drug resistance. Adjustment of the administration method of certain ?-lactams (meropenem, or imipenem/cilastatin), or combination of tigecycline with some agents, may show promise with regard to successful management of MDR or PDR Acinetobacter baumannii pneumonia. Additionally, vancomycin plus rifampicin is an effective regimen against nosocomial pneumonia caused by methicillin-resistant Staphylococcus aureus (MRSA) responding poorly to vancomycin monotherapy. The clinical appropriateness of parenteral colistin against pneumonia caused by MDR A. baumannii has been established in a clinical trial. Facing the decline of clinical vancomycin efficacy after initial use, linezolid might be the drug of choice with regard to the treatment of MRSA-VAP. The role of tigecycline monotherapy for the management of nosocomial pneumonia caused by MRSA and extended-spectrum ?-lactamase-producing Enterobacteriaceae needs to be cautiously evaluated.

PMID: 21895553 [PubMed - in process]

Montelukast for the treatment of asthma in the adult population.

Expert Opin Pharmacother. 2011 Jul 22;

Authors: Amlani S, Nadarajah T, McIvor RA

Introduction: Asthma is a complex process that results from airway inflammation and manifests as bronchoconstriction. Infiltration of the airway mucosa and lumen by activated inflammatory cells, along with release of mediators, can occur extensively. Chemical mediators known as leukotrienes are believed to play a major role in this process. At present, inhaled corticosteroids (ICS) are the pharmacologic cornerstone of asthma management. However, asthma control may remain suboptimal when relying on ICS because of problems with compliance, poor inhaler technique and concerns about the side effects of steroids; additional agents are often required to control symptoms. Leukotriene receptor antagonists (LTRA), namely montelukast, provide a safe and effective additional anti-inflammatory treatment option. There is particular benefit for patients with asthma and concomitant allergic rhinitis. Areas covered: Montelukast has been well studied through rigorous clinical trials. A thorough review of the literature has been undertaken to assess the evidence supporting the use of LTRAs. This review focuses on the role of montelukast not only as monotherapy but also as add-on therapy to ICS in the adult asthma population, as well as adult asthmatics with concomitant allergic rhinitis. In addition, there is often some discrepancy between the evidence generated in the idealized asthma patients recruited into randomized clinical trials and results obtained in the real-life setting. This review assesses recent clinical trials evaluating the real-life evaluation of montelukast, achieved mainly through open-label observational studies. Expert opinion: Oral LTRA bring remarkable ease of anti-inflammatory treatment administration and symptom improvement with minimal side effects to the management of adult asthma. Basic asthma mechanisms and much-valued scientific groundwork has been identified by exploring target asthma treatment with anti-leukotriene therapy. This will have a significant impact in the future development of targeted asthma therapies as well as the current management of asthma and other inflammatory medical conditions.

PMID: 21777174 [PubMed - as supplied by publisher]

Valsartan plus hydrochlorothiazide: a review of its use since its introduction.

Expert Opin Pharmacother. 2011 Jul 6;

Authors: Bains J, Smith WB

Introduction: This review focuses on the role of the fixed-dose combination (FDC) drug valsartan/hydrochlorothiazide (HCTZ) in the treatment of hypertension. Effective blood pressure control often is not achieved with monotherapy and, instead, requires combinations of drugs with different mechanisms of action to produce additive or synergistic effects. Areas covered: FDC valsartan/HCTZ enhances not only efficacy for blood pressure control but also provides beneficial effects on target organs beyond that expected from arterial pressure reduction alone. Data describe key clinical trial experiences with the FDC, with particular attention to efficacy and tolerability. Literature searches of these various topics were conducted in January 2011. There is evidence of potential benefits with this combination associated with left ventricular hypertrophy, left ventricular dysfunction and renal disease. The FDC is an effective treatment for patients with hypertension and is superior to monotherapy than either drug alone. Expert opinion: In addition to the benefits of each drug, valsartan/HCTZ's metabolic interactions reduce some of the negative effects of both compounds. With its increased simplicity, minimal side-effect profile and efficacy without a significant cost penalty, valsartan/HCTZ represents an excellent choice for antihypertensive therapy.

PMID: 21728903 [PubMed - as supplied by publisher]

Pioglitazone: a valuable component of combination therapy for type 2 diabetes mellitus.

Expert Opin Pharmacother. 2011 Jul;12(10):1457-61

Authors: Papanas N, Katsiki N, Hatzitolios AI, Maltezos E

Several classes of drugs have been developed to treat type 2 diabetes mellitus (T2DM). Pioglitazone is now the only thiazolidinedione approved for the treatment of T2DM and can be administered in combination with metformin, sulfonylureas, exenatide, dipeptidyl peptidase 4 (DPP-4) inhibitors or insulin. It improves glycemic control with an extremely low incidence of hypoglycemia. In addition to reducing insulin resistance, it may also improve pancreatic beta-cell secretory function. Moreover, it exhibits a variety of favorable pleiotropic effects. The latter include anti-inflammatory, antioxidant, vasoprotective, antihypertensive and hypolipidemic actions. Finally, this agent has been shown to improve experimental diabetic neuropathy and alleviate neuropathic pain, as well as decreasing urinary albumin excretion in patients with diabetes. Thus, pioglitazone emerges as a valuable hypoglycemic agent for combination therapy in T2DM. Importantly, however, patients should be appropriately selected, especially to avoid those with heart failure, in order to minimize adverse events attributable to water retention.

PMID: 21651446 [PubMed - in process]

Sitagliptin: a review.

Expert Opin Pharmacother. 2011 Jul;12(10):1613-22

Authors: Subbarayan S, Kipnes M

Introduction: The ever-increasing burden of type 2 diabetes mellitus (T2DM) and inadequate control in the majority of patients has led to a quest for newer therapeutic options. There have been recent exciting advances in the treatment of T2DM, targeting the enteroinsular axis with incretin-based therapies that include the dipeptidyl peptidase IV (DPP-IV) inhibitors. Areas covered: The background, pharmacodynamic and pharmacokinetic profile of sitagliptin and important clinical trials with this drug are discussed in this paper. This review is intended to provide a comprehensive overview of the DPP-IV inhibitor sitagliptin, its clinical use and an expert opinion about its place in the treatment algorithm of diabetes management. Expert opinion: Sitagliptin is a well-tolerated, moderately efficacious, weight-neutral oral antidiabetic agent, with a low incidence of hypoglycemia. It may have a particular role in the management of diabetic patients with kidney or liver dysfunction. Animal studies indicate a protective effect on the pancreatic beta cell, thus limiting the progression of the disease, but this remains to be proven in humans.

PMID: 21651449 [PubMed - in process]

Combination perindopril/indapamide for the treatment of hypertension: A review.

Expert Opin Pharmacother. 2011 Jun 9;

Authors: de Leeuw PW

Introduction: Hypertension is an important risk factor for cardiovascular complications and the need to treat this condition has been well established. Despite the availability of many antihypertensive drugs, it is often necessary to combine several of these drugs. The compound perindopril/indapamide offers the opportunity to start with a fixed combination of two effective agents as first-line treatment. Large outcome trials so far show that the perindopril/indapamide compound has favourable prognostic effects in elderly hypertensives as well as in patients with high cardiovascular riks, regardless of their level of blood pressure. Areas covered: This review examines the prevalence of hypertension, the major risk factors, its pharmacodynamics, pharmacokinetics and clinical efficacy, and also looks at the results of large outcome trials. This review will allow the reader to put the role of the perindopril/indapamide combination in perspective, at least from a clinical point of view. Expert opinion: Despite the positive trial results, there are still issues that deserve attention, for example safety with respect to drug levels in special patient groups. Also, in the large outcome trials placebo treatment (whether or not in addition to other medication) was taken as the comparator, and it is uncertain whether the combination of perindopril and indapamide performs better than established modes of treatment. More studies are needed to establish whether the combination drug has similar positive effects in the long run in 'ordinary' patients and those with comorbid conditions or those who are treated with other drugs as well. Nevertheless, it is fair to state that the low-dose perindopril/indapamide combination adds to our pharmaceutical arsenal and can be applied as first-line treatment by physicians who care for patients with elevated blood pressure or, more broadly, those with cardiovascular disease.

PMID: 21651456 [PubMed - as supplied by publisher]

Anticoagulation prescription in atrial fibrillation.

Expert Opin Pharmacother. 2011 Jun 2;

Authors: Bertomeu-González V, Cordero A, Mazón P, Moreno-Arribas J, Fácila L, Nuñez J, Rodríguez-Mañero M, Cosín-Sales J, González-Juanatey JR, Quiles J, Bertomeu-Martínez V,

Aims: We seek to assess the factors associated with the anticoagulation prescription in a cohort of patients with atrial fibrillation (AF) collected from out-patient clinics. Methods: A total of 1524 patients with a history of AF were collected from out-patients clinics. CHADS(2), CHA(2)DS(2)-VASc and HAS-BLED scores were calculated in every patient. Variables associated with anticoagulant treatment prescription were analyzed in univariant and multivariant models. Results: Most patients received either anticoagulant (62%) or antiplatelet treatment (37%). Anticoagulation rates increased among higher CHADS(2) and CHA(2)DS(2)-VASc score values. A logistic regression model was performed to assess the variables associated with the prescription of anticoagulant treatment; the variables with stronger association were the presence of arrhythmia at the current visit (odds ratio (OR) 33, 95% CI 27 - 40, p < 0.001) and lack of concomitant antiplatelet treatment (OR 0.17, 95% CI 0.14 - 0.21, p < 0.001). Conclusions: Although prognosis of patients with AF is mainly determined by the long-term thrombotic risk, the prescription of antithrombotic therapy depends more on the bleeding risk and the immediate thrombotic risk perception.

PMID: 21635195 [PubMed - as supplied by publisher]