Hyperphosphataemia: Treatment Options.

Drugs. 2013 Apr 27;

Authors: Malberti F

Abstract
Hyperphosphataemia can be induced by three main conditions: a massive acute phosphate load, a primary increase in renal phosphate reabsorption, and an impaired renal phosphate excretion due to acute or chronic renal insufficiency. Renal excretion is so efficient in normal subjects that balance can be maintained with only a minimal rise in serum phosphorus concentration even for a large phosphorus load. Therefore, acute hyperphosphataemia usually resolves within few hours if renal function is intact. The most frequent cause of chronic hyperphosphataemia is chronic renal failure. Hyperphosphataemia in chronic kidney disease (CKD) is associated with increased cardiovascular morbidity and mortality. Lowering the phosphate load and maintaining serum phosphorus levels within the normal range are considered important therapeutic goals to improve clinical outcomes in CKD patients. Treatment consists of diminishing intestinal phosphate absorption by a low phosphate diet and phosphate binders. In CKD patients on dialysis an efficient dialysis removal of phosphate should be ensured. Dietary restriction of phosphorus while maintaining adequate protein intake is not sufficient to control serum phosphate levels in most CKD patients; therefore, the prescription of a phosphate binder is required. Aluminium-containing agents are efficient but no longer widely used because of their toxicity. Calcium-based salts are inexpensive, effective and most widely used, but there is now concern about their association with hypercalcaemia, parathyroid gland suppression, adynamic bone disease, and vascular and extraosseous calcification. The average daily dose of calcium acetate or carbonate prescribed in the randomised controlled trials to control hyperphosphataemia in dialysis patients ranges between 1.2 and 2.3 g of elemental calcium. Such doses are greater than the recommended dietary calcium intake and can lead to a positive calcium balance. Although large amounts of calcium salts should probably be avoided, modest doses (<1 g of elemental calcium) may represent a reasonable initial approach to reduced serum phosphorus levels. A non-calcium-based binder can then be added when large doses of binder are required. At present, there are three types of non-calcium-based phosphate binders available: sevelamer, lanthanum carbonate and magnesium salts. Each of these compounds is as effective as calcium salts in lowering serum phosphorus levels depending on an adequate prescribed dose and adherence of the patient to treatment. Sevelamer is the only non-calcium-containing phosphate binder that does not have potential for systemic accumulation and presents pleiotropic effects that may impact on cardiovascular disease. In contrast, lanthanum carbonate and magnesium salts are absorbed in the gut and their route of excretion is biliary for lanthanum and urinary for magnesium. There are insufficient data to establish the comparative superiority of non-calcium binding agents over calcium salts for such important patient-level outcomes as all-cause mortality and cardiovascular end points. Moreover, full adoption of sevelamer and lanthanum by government drug reimbursement agencies in place of calcium salts would lead to a large increase in health-care expenditure. Therefore, the choice of phosphate binder should be individualised, considering the clinical context, the costs, and the individual tolerability the concomitant effects on other parameters of mineral metabolism, such as serum calcium and parathyroid hormone, besides those on serum phosphorus.

PMID: 23625273 [PubMed - as supplied by publisher]

Ranolazine : A Review of Its Use as Add-On Therapy in Patients with Chronic Stable Angina Pectoris.

Drugs. 2013 Jan 11;

Authors: Keating GM

Abstract

Extended-release ranolazine (ranolazine ER) [Ranexa(®)] is an antianginal agent that achieves its effects via a novel mechanism of action (inhibition of the late phase of the inward sodium current), without affecting heart rate or blood pressure (BP). This article reviews the efficacy, safety and tolerability of ranolazine ER as add-on therapy in patients with chronic stable angina pectoris, as well as summarizing its pharmacological properties and its use in non-ST-elevation acute coronary syndromes. In the CARISA and ERICA trials, add-on therapy with ranolazine ER improved exercise tolerance and/or reduced angina frequency and nitroglycerin use in patients with chronic stable angina; benefits were seen across a variety of patient subgroups. Although results of the MERLIN-TIMI 36 trial do not support the use of ranolazine ER in the acute management of non-ST-elevation acute coronary syndromes, they do support its use as an antianginal therapy. Ranolazine ER was generally well tolerated, with the most commonly reported adverse events including dizziness, nausea, asthenia and constipation. Despite being associated with modest increases in the corrected QT interval, ranolazine ER demonstrated antiarrhythmic effects in the MERLIN-TIMI 36 trial. In conclusion, ranolazine ER provides an important option for use as add-on therapy to reduce symptoms in patients with chronic stable angina.

PMID: 23329466 [PubMed - as supplied by publisher]

Dapagliflozin: a review of its use in type 2 diabetes mellitus.

Drugs. 2012 Dec 3;72(17):2289-312

Authors: Plosker GL

Abstract

Dapagliflozin (Forxiga®) is the first in a novel class of glucose-lowering agents known as sodium-glucose co-transporter-2 (SGLT2) inhibitors and is used in the treatment of patients with type 2 diabetes. By inhibiting the transporter protein SGLT2 in the kidneys, dapagliflozin reduces renal glucose reabsorption, leading to urinary glucose excretion and a reduction in blood glucose levels. Unlike oral antidiabetic drugs from several other classes, the efficacy of dapagliflozin is independent of insulin secretion and action. Therefore, when used in combination with other antidiabetic drugs, dapagliflozin provides complementary therapy via its unique mechanism of action. A consistent finding across phase III, randomized, double-blind trials in patients with inadequately controlled type 2 diabetes was that dapagliflozin 5 or 10?mg/day for 24 weeks as monotherapy in previously untreated patients, or as add-on combination therapy with metformin, glimepiride, pioglitazone or insulin-based therapy, significantly reduced both glycosylated haemoglobin values (primary endpoint) and fasting plasma glucose levels compared with placebo. Various randomized trials have also shown improvements in postprandial blood glucose with dapagliflozin monotherapy and combination therapy compared with placebo. In addition, dapagliflozin was noninferior to glipizide, in terms of glycaemic control after 52 weeks, when used as add-on therapy in patients with type 2 diabetes that was inadequately controlled with metformin. In most clinical trials, dapagliflozin was associated with reductions in body weight that were statistically superior to placebo or active comparators. Longer-term extension studies indicate that the efficacy of dapagliflozin is maintained for up to ?2 years. Dapagliflozin was generally well tolerated in clinical trials of 24 or 52 weeks duration and in extension studies of up to ?2 years. Events suggestive of genital infections and urinary tract infections occurred more frequently among dapagliflozin than placebo recipients. These adverse events are of special interest because they appear to be related to the mechanism of action of dapagliflozin. Dapagliflozin has a low propensity to cause hypoglycaemia, especially when used alone or in combination with metformin, although the incidence of hypoglycaemic events reported with dapagliflozin in clinical trials varied depending on the background therapy. Longer-term tolerability/safety data with dapagliflozin are awaited with interest. In conclusion, dapagliflozin, with its unique and complementary mechanism of action, appears to be an important addition to the therapeutic options for the management of type 2 diabetes, particularly when used as add-on therapy.

PMID: 23170914 [PubMed - in process]