Expert opinion on pharmacotherapy
-
Hepatitis C virus (HCV) infection has been associated with a large spectrum of glomerular lesions in both native and transplanted kidneys. The most common HCV-associated renal disease is type I membranoproliferative glomerulonephritis usually, but not invariably, in the context of type II mixed cryoglobulinemia (MC). HCV infection is also the major cause of MC, a systemic vasculitis characterized by involvement of small and, less frequently, medium-sized vessels. Conflicting data exist on the treatment of HCV-associated glomerular disease. ⋯ Various approaches have been recommended for the treatment of HCV-related glomerular disease, including immunosuppressive therapy (corticosteroids, cytotoxic agents and mAbs) and antiviral therapy. These regimens should be considered according to the level or proteinuria and kidney failure. Immunosuppressive agents are recommended in patients with nephrotic syndrome and/or rapidly progressive kidney failure. Antiviral treatment based on IFN and/or ribavirin or triple antiviral therapy (PEGylated-IFN/ribavirin/telaprevir or boceprevir) has been adopted in patients with moderate proteinuria and slow loss of kidney failure; however, the number of patients enrolled was small. Some patients with HCV-related cryoglobulinemic glomerulonephritis have been treated with rituximab but some issues about its role remain to be clarified. The antiviral treatment of HCV-related glomerular disease is expected to improve in the near future with new agents provided with greater efficacy and safety. However, the affordability of these drugs remains a pivotal issue, particularly in low-income countries.
-
Expert Opin Pharmacother · Jan 2015
ReviewDalbavancin for the treatment of acute bacterial skin and skin structure infections.
Acute bacterial skin and skin structure infections (ABSSSI) have increased in incidence and severity. The involvement of resistant organisms, particularly methicillin-resistant Staphylococcus aureus, presents additional challenges. The lipoglycopeptide dalbavancin has a prolonged half-life, high protein binding, and excellent tissue levels which led to its development as a once-weekly treatment for ABSSSI. In the pivotal DISCOVER 1 and DISCOVER 2 trials, dalbavancin proved non-inferior to vancomycin followed by linezolid when used sequentially for ABSSSI, forming the basis for its recent approval in the US and Europe for ABSSSI. ⋯ DISCOVER 1 and DISCOVER 2 demonstrated dalbavancin's non-inferiority to vancomycin followed by linezolid for ABSSSI and confirmed its safety and tolerability. They were among the first trials to use new, early primary efficacy endpoints, and dalbavancin was among the first agents designated a Qualified Infectious Disease Product for expedited review. Dalbavancin may prove to be a valuable option for ABSSSI patients in whom conventional therapy is limited.
-
Expert Opin Pharmacother · Jan 2015
ReviewAdvances in PARP inhibitors for the treatment of breast cancer.
Poly(ADP-Ribose) polymerases (PARPs) are one of the important components of base excision repair pathway for single strand DNA breaks. Currently accepted hypothesis for the mechanism of action for PARP inhibitors in tumors with homologous recombination deficiency is synthetic lethality, as the simultaneous blockage of both pathways prevents the tumor cells from repairing DNA damage. Other proposed mechanisms include PARP trapping, defective BRCA1 and POLQ recruitment to sites of DNA repair. Breast cancer subgroups with germline BRCA mutations or non-mutational functional defects in BRCA proteins exemplify potential targets for PARP inhibitors. ⋯ PARP inhibitors show promise in cancers with BRCA mutation and in the treatment of sporadic cancers with defective homologous recombination. Predictors of response, strategies to overcome resistance, combination with other chemotherapies and targeted agents, optimum dose and schedule of administration should be investigated in future trials.
-
Expert Opin Pharmacother · Jan 2015
Editorial ReviewAntidotes to non-vitamin K oral anticoagulants: necessary or not?
In the last few years, a new category of anticoagulants have been developed, the non-vitamin K oral anticoagulants (NOACs). The NOACs are of two classes: the direct thrombin inhibitor, namely dabigatran etexilate; and the oral factor Xa inhibitors rivaroxaban, apixaban and edoxaban, which have been proven to be as effective and safe (and sometimes, superior) compared to warfarin in the treatment of both atrial fibrillation (AF) and venous thromboembolism (VTE). ⋯ The objective of this editorial is to provide an overview of the characteristics of NOAC antidotes that are in development. Moreover, we review their likely place in the management of NOAC-related bleeding episodes.
-
Most lymphomas and lymphoid leukemias are of B cell origin. Indolent B cell lymphomas, most commonly follicular lymphoma but including Waldenstrom's macroglobulinemia and mantle cell lymphoma, as well as chronic lymphocytic leukemia, are incurable with standard therapy. New treatments are needed. Survival of normal and many abnormal B cells depends on signals through the B-cell receptor, and a key element of this pathway is Bruton's tyrosine kinase (BTK). The oral BTK inhibitor ibrutinib is already US FDA approved in four different indications based on marked treatment benefit in indolent B cell lymphoma/leukemia. ⋯ Ibrutinib is a well-tolerated once-daily oral BTK inhibitor with impressive activity in treating indolent B cell lymphoproliferative disorders. As a single agent, it is already altering treatment paradigms in its approved indications. Ongoing studies will determine its movement to the front-line setting in these and other B cell disorders, as well as combination approaches.