Rx Report†

Abstract

Aliskiren, amlodipine, and hydrochlorothiazide tablets (Amturnide), a triple-combi-nation antihypertensive, has been approved by the U.S. Food and Drug Administration (FDA) for patients who have failed treatment with any of the following types of drugs: direct-renin inhibitors, dihydropyridine cal-cium channel antagonists, and thiazide diuretics.1 It is available in the follow-ing mg dosage combinations of aliski-ren, amlodipine, and hydrochlorothia-zide, 150/5/12.5, 300/5/12.5, 300/5/25, 300/10/12.5, and 300/10/25.

Clonidine extended-release tab-lets and extended-release oral suspen-sion (Nexiclon XR) have been FDA-approved for treating hypertension.2 The tablets are available in 0.17- and 0.26-mg dosage strengths, and the extended-release oral suspension is available as 0.09 mg/mL clonidine base. The recommended initial start-ing dose is 0.17 mg once daily at bedtime, with a lower dose in the elderly.3, 4 Further increases of 0.09 mg may be made at weekly intervals if needed until the desired blood pres-sure-lowering response is achieved. For patients with renal impairment, slow up-titration is recommended to prevent dose-related adverse events. For patients with end-stage renal dis-ease (ESRD) on maintenance dialysis, the starting dose should be 0.09 mg daily with slow up-titration. Equivalent doses of clonidine XR and clonidine IR (Catapres and generics) can be seen in Table I.5

Fidaxomicin, an oral macrolide, is cur-rently being evaluated by the FDA as a treatment for Clostridium dif-ficile infection (CDI), also known as Clostridium difficile-associated dis-ease (CDAD).6 In January, the FDA accepted the New Drug Application (NDA) and set a Prescription Drug User Fee Act (PDUFA) goal date of May 30, 2011. The drug was also sub-mitted for review in Europe in July 2010. Oral tablets and a suspen-sion are being developed for elderly patients and intensive care unit patients who cannot swallow tablets. Clinical cure, lower recurrence rate, and global cure rate were obtained in clinical trials.

Linagliptin, an investigational oral dipeptidyl peptidase 4 (DPP-4) inhibi-tor, does not appear to be primarily excreted by the kidneys. Compared with the DPP-4 inhibitors that are already FDA-approved (sitagliptin and saxa-gliptin), renal impairment did not reduce the renal elimination of linagliptin. This agent is currently in Phase 3 clinical trials as monotherapy and combination therapy to manage type 2 diabetes mel-litus.7, 8

A thrice-weekly insulin, known as ultra-long-acting insulin degludec, is in Phase 3 clinical trials and has been compared in clinical trials with insulin glargine, with similar HbA1c-lowering effects.9 Patients included those who were previously treated with oral anti-diabetic agents (OADs) or basal insulin or OADs plus basal insulin. In clinical trials, insulin degludec was given in a flexible regimen at 8 to 40-hour inter-vals and in the evening, while insulin glargine was administered as labeled. Patients who received insulin digludec had fewer nighttime hypoglycemic episodes compared with those receiv-ing insulin glargine. Patients who were able to go days without insulin (insulin degludec) had glucose control similar to those who received insulin once daily. Insulin DegludecPlus is a pre-mixed insulin including degludec and insulin aspart. This combination is also undergoing Phase 3 clinical trials.

On January 19, 2011, the FDA responded to the NDA for inhaled insulin (Afrezza, Mannkind) with a rejection, but requested additional data.10 Afrezza is an ultra-rapid-acting mealtime insulin being developed for treating adults with types 1 and 2 diabetes. Afrezza is a drug-device combination product of inhaled insulin powder pre-metered into single-use dose cartridges and a light, easy-to-use inhaler device. Peak insulin levels occur within 12 to 14 minutes of admin-istration. The main issue discussed by the FDA was related to in vitro performance data and clinical pharma-cology related to their next-generation inhaler. Mannkind reports that studies utilizing the next generation device are ongoing.

Ferumoxytol (Feraheme) is only indi-cated for the treatment of iron deficien-cy anemia in adults with chronic kidney disease.11, 12 Numerous reports of post-marketing adverse events have occurred, which led to an update to the product's Warnings and Precautions section. These adverse reactions included life-threatening hypersensitivity reactions including anaphylaxis and/or anaphy-lactoid reactions, including other reactions that may be associated with hypersensitivity such as rash, urticaria, pruritus, or wheezing. Following injec-tion, patients should be observed for at least 60 minutes for signs and symptoms of hypersensitivity reactions. In addition, ferumoxytol should only be administered when personnel and therapies are immediately available to treat hypersensitivity reactions or anaphylaxis. Clinically significant hypotension has also been observed following injection; therefore patients should be monitored for this adverse event as well. Patients should also be regularly monitored for a hematologic response to this agent, since iatrogenic hemosiderosis may occur. Additionally, this agent may transiently affect magnetic resonance diagnostic imaging studies for up to 3 months after receiving the last ferumoxytol dose.