Drugs

Bonovas, Stefanos

doi: 10.1007/s40265-014-0309-2pmid: 25288321

3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) are currently among the most commonly prescribed pharmaceutical agents worldwide. Apart from their well-established therapeutic value in cardiovascular disease, there is a long-standing debate on their potential association with cancer. To obtain and discuss the existing clinical evidence, an overview of meta-analysis articles addressing this issue was carried out. As of today, the accumulated evidence does not support the hypothesis that statins affect the risk of developing cancer, when they are taken at low doses for managing hypercholesterolaemia. However, current data cannot exclude an increased cancer risk in elderly patients associated with hydrophilic statin use, or decreases in the risks of certain cancers, such as gastric, oesophageal, liver, colorectal and advanced/aggressive prostate cancer. On the other hand, some recent observational studies have provided evidence that statins might be useful in modifying the prognosis of patients diagnosed with malignancy. Until a definitive benefit is demonstrated in randomized controlled trials, statins cannot be recommended either for cancer prevention or for modifying cancer-related outcomes. Further research is warranted to clarify the potential role(s) of statins in the prevention and treatment of cancer.

Barboza, Jose; Talley, Nicholas; Moshiree, Baharak

doi: 10.1007/s40265-014-0292-7pmid: 25260888

Treatment of irritable bowel syndrome (IBS) is challenging for both primary care physicians and gastroenterologists because of the heterogeneity of the patient population and the multifactorial pathophysiologies responsible for the symptoms in IBS. This review focuses on the current and emerging pharmacological treatments for IBS. Many of the current medications used to treat this disorder have distinct properties such as efficacy for different symptoms, safety profiles, contraindications, costs, dosing regimens, treatment duration and long-term data. All of these factors, in addition to patient preference and cognitive, food and environmental triggers, must be considered prior to any medication selection. This review will focus on randomized controlled trials with a general uniformity in study design, a rigorous patient selection and appropriate treatment durations. We will also discuss other exciting emerging treatments for IBS such as the µ-opioid receptor (agonists and antagonists), selective κ-opioid receptor agonists, anti-inflammatory drugs, serotonergic agents, bile acid modulators and intestinal bile acid transporters, which may prove promising in treating our patients.

Liu, Fang; Ranmal, Sejal; Batchelor, Hannah; Orlu-Gul, Mine; Ernest, Terry; Thomas, Iwan; Flanagan, Talia; Tuleu, Catherine

doi: 10.1007/s40265-014-0297-2pmid: 25274536

Patient acceptability of a medicinal product is a key aspect in the development and prescribing of medicines. Children and older adults differ in many aspects from the other age subsets of population and require particular considerations in medication acceptability. This review highlights the similarities and differences in these two age groups in relation to factors affecting acceptability of medicines. New and conventional formulations of medicines are considered regarding their appropriateness for use in children and older people. Aspects of a formulation that impact acceptability in these patient groups are discussed, including, for example, taste/smell/viscosity of a liquid and size/shape of a tablet. A better understanding of the acceptability of existing formulations highlights opportunities for the development of new and more acceptable medicines and facilitates safe and effective prescribing for the young and older populations.

Keating, Gillian

doi: 10.1007/s40265-014-0302-9pmid: 25315029

The humanized monoclonal antibody bevacizumab (Avastin®) has been available in the EU since 2005. Results of phase III trials demonstrate that adding intravenous bevacizumab to antineoplastic agents improves progression-free survival and/or overall survival in patients with advanced cancer, including when used as first- or second-line therapy in metastatic colorectal cancer, as first-line therapy in advanced nonsquamous non-small cell lung cancer, as first-line therapy in metastatic renal cell carcinoma, as first-line therapy in metastatic breast cancer, and as first-line therapy in epithelial ovarian, fallopian tube or primary peritoneal cancer or in recurrent, platinum-sensitive or platinum-resistant disease. Results of these studies are supported by the findings of routine oncology practice studies conducted in real-world settings. The tolerability profile of bevacizumab is well defined and adverse events associated with its use (e.g. hypertension, proteinuria, haemorrhage, wound healing complications, arterial thromboembolism, gastrointestinal perforation) are generally manageable. In conclusion, bevacizumab remains an important option for use in patients with advanced cancer.

McKeage, Kate

doi: 10.1007/s40265-014-0308-3pmid: 25297911

Linagliptin (Trajenta®, Tradjenta®) is a dipeptidyl peptidase (DPP)-4 inhibitor approved for the treatment of adults with type 2 diabetes mellitus in several countries. A fixed-dose combination of linagliptin/metformin (Jentadueto®) is also available. This article reviews the pharmacology, therapeutic efficacy and tolerability of linagliptin in the management of type 2 diabetes, with the aim of updating its place in therapy based on recently published data. In randomized, controlled trials, oral linagliptin 5 mg once daily (or 2.5 mg twice daily when combined with metformin) improved glycaemic control when used alone or in combination with other antidiabetic agents, including metformin, a sulfonylurea, thiazolidinedione or insulin. Improvements in glycaemic control were also shown in patients with renal impairment, including severe impairment, and the elderly (aged ≥70 years). Linagliptin is the first DPP-4 inhibitor to be eliminated primarily via a nonrenal route, enabling its use without dosage adjustment in patients with any degree of renal impairment. Linagliptin is generally well tolerated and, as with other DPP-4 inhibitors, it is associated with a low risk of hypoglycaemia and has no effect on bodyweight. Some data indicate that linagliptin may have beneficial effects on cardiovascular and renal safety profiles in patients with type 2 diabetes, but more data are needed. Meanwhile, the low risk of hypoglycaemia and the nonrenal route of elimination may provide important advantages for some patient groups, including elderly or renally impaired patients.

Keating, Gillian

doi: 10.1007/s40265-014-0313-6pmid: 25312594

The ultrashort-acting dihydropyridine calcium channel antagonist clevidipine (Cleviprex®) has a rapid onset and offset of effect and reduces blood pressure (BP) by decreasing arteriolar resistance without affecting venous capacitance vessels. This article reviews the clinical efficacy and tolerability of intravenous clevidipine when used to manage BP in perioperative and intensive care settings, as well as summarizing its pharmacological properties. Intravenous clevidipine effectively treated preoperative and postoperative hypertension in patients undergoing cardiac surgery, according to the results of the randomized, multicentre, double-blind, phase III ESCAPE-1 and ESCAPE-2 trials. The randomized, open-label, multicentre, phase III ECLIPSE trials indicated that in terms of keeping systolic BP within the target range, clevidipine was more effective than nitroglycerin or sodium nitroprusside perioperatively and had similar efficacy to nicardipine postoperatively in cardiac surgery patients. In small, double-blind trials in patients undergoing coronary artery bypass graft surgery, perioperative clevidipine was noninferior to nitroglycerin, and postoperative clevidipine had similar efficacy to sodium nitroprusside. Noncomparative studies demonstrated that clevidipine provided rapid BP control in patients with acute neurological injuries (including intracerebral haemorrhage, subarachnoid haemorrhage and acute ischaemic stroke), and was not associated with ‘overshoot’ in the vast majority of patients. Intravenous clevidipine was generally well tolerated and was usually associated with no reflex tachycardia or only very modest increases in heart rate. In conclusion, intravenous clevidipine is a valuable agent for the management of BP in perioperative and intensive care settings.

Burness, Celeste

doi: 10.1007/s40265-014-0312-7pmid: 25331767

Eltrombopag (Revolade®; Promacta®) is an orally bioavailable, small-molecule, thrombopoietin receptor agonist that selectively binds to thrombopoietin receptors on megakaryocyte precursors and megakaryocytes leading to increased platelet production. It is approved in a number of countries for the treatment of thrombocytopenia, including adult patients with chronic hepatitis C virus (HCV) infection to allow for the initiation and maintenance of peginterferon-based therapy, which is the focus of this review. In two, well-designed, randomized controlled trials in adults with chronic HCV infection and thrombocytopenia (ENABLE-1 and ENABLE-2), eltrombopag increased platelet counts to sufficient levels to allow for the initiation of peginterferon-based antiviral therapy in 95 % of patients whose baseline platelet counts would have made them ineligible or marginal candidates for peginterferon therapy. Moreover, a significantly higher proportion of eltrombopag recipients than placebo recipients achieved a sustained virological response (primary endpoint) 24 weeks after the completion of antiviral therapy. Of note, the additional benefit over placebo was relatively small (<10 %). Compared with placebo, eltrombopag was associated with fewer patients discontinuing antiviral therapy early and a numerically greater proportion of patients not requiring antiviral dose reduction. Oral eltrombopag had an acceptable tolerability profile; however, there is an increased risk of adverse events, including potentially fatal hepatic decompensation and thromboembolic events. Eltrombopag provides a new treatment option for thrombocytopenia in patients with chronic HCV infection to allow for optimal antiviral therapy.

Poole, Raewyn

doi: 10.1007/s40265-014-0314-5pmid: 25331768

Pembrolizumab [Keytruda® (US)], a humanized monoclonal antibody against the programmed death receptor-1 (PD-1) protein, has been developed by Merck & Co for the treatment of cancer. Pembrolizumab has received its first global approval for the treatment of advanced, unresectable or metastatic malignant melanoma in the US, for use in patients with disease progression after prior treatment with ipilimumab and, for BRAF V600 mutation-positive patients, a BRAF inhibitor. It is the first anti-PD-1 therapy to receive regulatory approval in the US, and is currently under regulatory review in the EU. This article summarizes the milestones in the development of pembrolizumab leading to this first approval for the treatment of malignant melanoma.