Are All Dopamine Agonists Essentially the Same?Torti, Margherita; Bravi, Daniele; Vacca, Laura; Stocchi, Fabrizio
doi: 10.1007/s40265-019-01103-2pmid: 30968290
Dopamine agonists (DAs) represent an excellent treatment option for patients with Parkinson’s disease, in both the early and advanced stages of the disease, improving motor symptoms, lowering the incidence of motor complications, and addressing several non-motor symptoms. Indeed, each of these compounds have different pharmacokinetic and pharmacodynamic properties, resulting in a unique efficacy and safety profile. Comorbidities, prominent non-motor symptoms and individual subjects’ clinical characteristics should guide the choice of a specific DA, allowing better management of the patient by optimizing the DA benefit/risk ratio. In this article we discuss brain distribution of dopamine receptors and their role in each of the dopaminergic pathways, the pharmacological profile of non-ergoline DAs and class-related adverse effects, as reported from post-marketing studies.
New Drugs for Multidrug-Resistant Gram-Negative Organisms: Time for StewardshipJean, Shio-Shin; Gould, Ian; Lee, Wen-Sen; Hsueh, Po-Ren
doi: 10.1007/s40265-019-01112-1pmid: 30972660
A gradual rise in drug-resistant trends among Gram-negative organisms, especially carbapenem-resistant (CR) Enterobacteriaceae (CRE), CR-Pseudomonas aeruginosa, and extensively-drug-resistant (XDR) Acinetobacter baumannii, poses an enormous threat to healthcare systems worldwide. In the last decade, many pharmaceutical companies have devoted enormous resources to the development of new potent antibiotics against XDR Gram-negative pathogens, particularly CRE. Some of these novel antibiotics against CRE strains are β-lactam/β-lactamase-inhibitor combination agents, while others belong to the non-β-lactam class. Most of these antibiotics display good in vitro activity against the producers of Ambler class A, C, and D β-lactamase, although avibactam and vaborbactam are not active in vitro against metallo-β-lactamase (MβL) enzymes. Nevertheless, in vitro efficacy against the producers of some or all class B enzymes (New Delhi MβL, Verona integron-encoded MβL, etc) has been shown with cefepime-zidebactam, aztreonam-avibactam, VNRX-5133, cefiderocol, plazomicin, and eravacycline. As of Feburary 2019, drugs approved for treatment of some CRE-related infections by the US Food and Drug Administration included ceftazidime-avibactam, meropenem-vaborbactam, plazomicin, and eravacycline. Although active against extended-spectrum and AmpC β-lactamase-producing Enterobacteriaceae, delafloxacin does not show in vitro activity against CRE. Murepavadin is shown to be specifically active against CR- and colistin-resistant P. aeruginosa strains. Despite successful development of novel antibiotics, strict implementation of an antibiotic stewardship policy in combination with the use of well-established phenotypic tests and novel multiplex PCR methods for detection of the most commonly encountered β-lactamases/carbapenemases in hospitals is important for prescribing effective antibiotics against CRE and decreasing the resistance burden due to CRE.
The Clinician’s Guide to Proton Pump Inhibitor Related Adverse EventsElias, Evan; Targownik, Laura
doi: 10.1007/s40265-019-01110-3pmid: 30972661
A substantial volume of literature exists linking proton pump inhibitor (PPI) use with a multitude of serious adverse events. There is uncertainty, however, over whether these associations are clinically important. Excessive concern about PPI-related adverse events may leave patients at risk of harm by leaving acid-related upper gastrointestinal disease untreated. Conversely, the risk of treatments may outweigh the benefits if any of the purported adverse events are directly caused by PPI use; this is of particular concern where indications for PPI use are not present. In this paper, we review the studies which have reported associations between adverse events and PPI use, discuss the proposed mechanisms of action, grade the confidence in whether these associations are truly causal, and provide advice regarding balancing the benefits of PPI use against their possible harms.
The Unique Pharmacological and Pharmacokinetic Profile of Teneligliptin: Implications for Clinical PracticeCeriello, Antonio; Nigris, Valeria; Iijima, Hiroaki; Matsui, Takahiro; Gouda, Maki
doi: 10.1007/s40265-019-01086-0pmid: 30982160
Teneligliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor that was approved for the treatment of type 2 diabetes mellitus (T2DM) in Japan and Korea and is being researched in several countries. Teneligliptin is a potent, selective, and long-lasting DPP-4 inhibitor with a t
½ of approximately 24 h and unique pharmacokinetic properties: it is metabolized by cytochrome P450 (CYP) 3A4 and flavin-containing monooxygenase 3 (FMO3), or excreted from the kidney in an unchanged form. Because of its multiple elimination pathways, dose adjustment is not needed in patients with hepatic or renal impairment, and it is considered to have a low potential for drug–drug interactions. Clinical studies and postmarketing surveillance show that teneligliptin, administered as monotherapy and/or in combination with antihyperglycemic agents, is effective and well tolerated in T2DM patients, including in elderly patients and those with renal impairment. Furthermore, teneligliptin has antioxidative properties, which induce the antioxidant cascade, as well as ·OH scavenging properties. In addition, it has shown endothelial protective effects in several non-clinical and clinical studies. From its unique profile and clinical data, teneligliptin represents a potential therapeutic option in a wide variety of patients, including elderly diabetic patients and those with renal impairment. The fixed-dose combination (FDC) tablet of teneligliptin and canagliflozin has been approved in Japan; this is the first FDC tablet of a DPP-4 inhibitor and sodium glucose co-transporter 2 inhibitor in Japan, and the third globally. The FDC tablet may also provide additional prescribing and adherence benefits.
Pegaspargase: A Review in Acute Lymphoblastic LeukaemiaHeo, Young-A.; Syed, Yahiya; Keam, Susan
doi: 10.1007/s40265-019-01120-1pmid: 31030380
Pegaspargase (Oncaspar®), a pegylated form of native Escherichia coli-derived l-asparaginase (hereafter referred as E. coli
l-asparaginase), is indicated in the USA and EU for the treatment of acute lymphoblastic leukaemia (ALL) as a component of multi-agent chemotherapy in paediatric and adult patients. Relative to E. coli
l-asparaginase, pegaspargase has a prolonged circulation time, thereby offering less frequent administration. Moreover, pegylation of E. coli
l-asparaginase may diminish the immunogenicity of the enzyme. Based on extensive evidence, intramuscular (IM) or intravenous (IV) administration of pegaspargase as a component of a multi-agent chemotherapy is an effective first-line treatment for paediatric and adult patients with ALL, as well as for the treatment of paediatric and adult patients with ALL and hypersensitivity to E. coli
l-asparaginase. Pegaspargase had a manageable tolerability profile in paediatric and adult patients with newly diagnosed ALL, with the most commonly occurring adverse events being generally consistent to that seen with E. coli
l-asparaginase. Pegaspargase treatment in patients with relapsed ALL and hypersensitivity to E. coli
l-asparaginase had a similar tolerability profile to that observed in patients with newly diagnosed ALL. Given the potentially reduced immunogenicity and more convenient dosage regimen over E. coli
l-asparaginase, pegaspargase remains an important and effective treatment option for paediatric and adult patients with ALL, including those with hypersensitivity to E. coli
l-asparaginase.
Brexanolone: First Global ApprovalScott, Lesley
doi: 10.1007/s40265-019-01121-0pmid: 31006078
Brexanolone (ZULRESSO™) is an intravenously administered, small molecule, neuroactive steroid GABAA receptor positive allosteric modulator that was developed by Sage Therapeutics under license to the University of California for the treatment of postpartum depression (PPD). The formulation is a mixture of allopregnanolone, an endogenous inhibitory pregnane neurosteroid, and sulfobutylether-beta-cyclodextrin (a solubilizing agent). In mid-March 2019 brexanolone received its first global approval in the USA for the treatment of PPD in adult women. This article summarizes the milestones in the development of brexanolone leading to its first approval for the treatment of adult women with PPD.
Solriamfetol: First Global ApprovalMarkham, Anthony
doi: 10.1007/s40265-019-01123-ypmid: 31062265
Solriamfetol (Sunosi™) is an orally active, selective dopamine and norepinephrine reuptake inhibitor that was recently approved in the USA as a treatment for excessive daytime sleepiness (hypersomnia) associated with narcolepsy and obstructive sleep apnoea (OSA). Norepinephrine and dopamine influence various physiologic functions, including sleep-wake regulation, and excessive sleepiness has been linked with dysregulation of dopaminergic and norepinephrine systems. This article summarizes the milestones in the development of solriamfetol leading to this first approval as a treatment for excessive daytime sleepiness associated with narcolepsy and OSA.