Formulary Watch |

Vildagliptin: A dipeptidyl peptidase-IV inhibitor for the treatment of type 2 diabetes

Despite the variety of medications available to treat type 2 diabetes, the disease is inadequately controlled in many patients. In order to improve glycemic control, manufacturers are pursuing compounds that affect the incretin hormones that stimulate insulin release in response to increased glucose levels. Although stimulation of the incretin receptors by the glucagon-like peptide-1 (GLP-1) enhances the body's ability to produce insulin in response to elevated blood glucose concentrations, the clinical usefulness of GLP-1 is limited by its rapid degradation by dipeptidyl peptidase-IV (DPP-IV). Drug companies have developed compounds intended to act as inhibitors of DPP-IV. Vildagliptin (Galvus, Novartis) is the second DPP-IV inhibitor under investigation by FDA to offer this new mechanism to achieve glycemic control. An NDA for vildagliptin was submitted to FDA in March 2006, 1 month after the submission of the first DPP-IV inhibitor, sitagliptin.

Pipeline Preview (October 2006)

Dalteparin (Fragmin, Pfizer) for the extended treatment of symptomatic venous thromboembolism (proximal deep vein thrombosis and/or pulmonary embolus) to prevent recurrent venous thromboembolism in patients with cancer

First-time generic approvals (October 2006)

Trimipramine capsules, 25, 50, and 100 mg (equiv to Surmontil capsules)

Levetiracetam

Antiepileptic approved in an injectable formulation

Posaconazole

First antifungal approved for prevention of invasive fungal infections caused by Aspergillus species

Drug Watch: Agents in late-stage development for the treatment of acute coronary syndrome, angina, and myocardial infarction (October 2006) (PDF)

Review of agents in late-stage development for the treatment of acute coronary syndrome, angina, and myocardial infarction (October 2006).

A drug use evaluation of amphotericin B lipid complex injection following institution of new treatment guidelines at a tertiary teaching medical center

A drug use evaluation at Wake Forest University Baptist Medical Center (WFUBMC) was initiated following a change in institution-approved guidelines for the administration of amphotericin B lipid complex injection (ABLC) (Abelcet, Enzon). This study was conducted to determine compliance with the new guidelines among prescribers and to characterize the population of patients receiving ABLC. A total of 153 patients received ABLC from April 2001 through December 2002. One hundred thirty-three patients (87%) met 1 or more of the institutional criteria for ABLC administration and 20 (13%) receiving ABLC did not meet the guidelines. The mean baseline serum creatinine (SCr) value among patients meeting institutional guidelines (n=133) was 2.0 mg/dL (range, 0.5–5.0 mg/dL). Among patients who did not meet the guidelines (n=20), the mean baseline SCr level was 1.7 mg/dL (range, 0.6–2.9 mg/dL). The use of new guidelines, which were less stringent than previous guidelines, resulted in earlier administration..

Drug Watch: Agents in late-stage development for the treatment of hypertension and stroke (September 2006) (PDF)

Review of agents in late-stage development for the treatment of hypertension and stroke (September 2006).

Management of epoetin alpha use in the intensive care unit: a drug use evaluation

This study evaluates the appropriateness and cost implications of using epoetin alpha for transfusion reduction in Hartford Hospital's (Hartford, Conn) intensive care units (ICUs), with the goal of implementing a protocol for use in this setting. We conducted a literature review to determine the efficacy, safety, and clinical outcomes of epoetin alpha for transfusion reduction in the ICU. We also evaluated the safety and supply of red blood cell (RBC) transfusions and the cost considerations of epoetin alpha. The literature review demonstrated that epoetin alpha can reduce blood transfusions in the ICU setting but its use provided no difference in mortality or any other clinical outcome. Our epoetin alpha expenditure for transfusion reduction was $112,067 annually to theoretically save $14,349 in blood transfusion costs. The pharmacy and therapeutics (P&T) committee subsequently recommended that epoetin alpha not be used for transfusion reduction in the ICUs and requested that a drug use evaluation (DUE) be performed to monitor compliance, adverse effects, and cost avoidance. One year after implementation of the epoetin alpha DUE program, the compliance rate was >90%, there were no reported adverse events with blood transfusions or problems with blood supply, and a cost avoidance of $104,562 was realized. (Formulary. 2006;41:442?449.)

FDA takes steps to automate drug registration; Plan B OTC availability still an area of contention

FDA issued a proposed rule late last month that would allow pharmaceutical manufacturers to register and list products electronically in an effort to minimize the paper-based element of the process, allowing the agency to host a comprehensive national database of medications and to be more flexible in its role of monitoring the safety of medications for sale, according to officials.

Moxifloxacin QD similar to piperacillin-tazobactam and amoxicillin-clavulanate dosed multiple times a day in treatment of complicated intra-abdominal infections

Intravenous (IV) moxifloxacin followed by oral (PO) moxifloxacin, both dosed once-daily, is at least as effective in the treatment of complicated intra-abdominal infections (cIAIs) as piperacillin-tazobactam and amoxicillin-clavulanate comparator regimens dosed multiple times per day, researchers reported in the Annals of Surgery.

New data emerge on the relationship between diabetic, pre-diabetic conditions and Alzheimer's disease

Three studies presented at the 10th International Conference on Alzheimer's Disease and Related Disorders in Madrid, Spain, yielded new data regarding the relationship between diabetic and pre-diabetic conditions and the subsequent development and treatment of Alzheimer's disease (AD).

Raloxifene benefits in breast cancer, increases risk of fatal stroke

The selective estrogen-receptor modulator (SERM) raloxifene reduces the risks of invasive breast cancer and vertebral fracture in postmenopausal women but also increases the risks of venous thromboembolism and fatal stroke, a study in the New England Journal of Medicine (NEJM) concluded.

Raloxifene fares as well as tamoxifen in 2 related comparison studies

Raloxifene, a second-generation selective estrogen receptor modulator (SERM) approved to treat osteoporosis, fared as effectively against breast cancer as tamoxifen in 2 related comparison studies published in the Journal of the American Medical Association (JAMA).

Elevated atorvastatin dosage reduces rate of cardiovascular events in CHD patients

Intensive therapy with atorvastatin 80 mg/d, in comparison with the same medication at 10 mg/d, significantly reduced the rate of major cardiovascular events by 25% in patients with clinically evident stable coronary heart disease (CHD) and diabetes, according to a study published in Diabetes Care.

Atorvastatin fails to demonstrate significant benefit in treatment of CV disease in patients with diabetes

Atorvastatin showed no statistically significant difference in the reduction of a composite cardiovascular disease (CVD) end point in type 2 diabetes patients, according to a randomized, double-blind, parallel-group study.

A drug use evaluation of amphotericin B lipid complex injection following institution of new treatment guidelines at a tertiary teaching medical center

A drug use evaluation at Wake Forest University Baptist Medical Center (WFUBMC) was initiated following a change in institution-approved guidelines for the administration of amphotericin B lipid complex injection (ABLC) (Abelcet, Enzon). This study was conducted to determine compliance with the new guidelines among prescribers and to characterize the population of patients receiving ABLC. A total of 153 patients received ABLC from April 2001 through December 2002. One hundred thirty-three patients (87%) met 1 or more of the institutional criteria for ABLC administration and 20 (13%) receiving ABLC did not meet the guidelines. The mean baseline serum creatinine (SCr) value among patients meeting institutional guidelines (n=133) was 2.0 mg/dL (range, 0.5–5.0 mg/dL). Among patients who did not meet the guidelines (n=20), the mean baseline SCr level was 1.7 mg/dL (range, 0.6–2.9 mg/dL). The use of new guidelines, which were less stringent than previous guidelines, resulted in earlier administration..

Sitagliptin: The first dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes

A variety of clinical approaches are utilized in the management of poor glycemic control in patients with type 2 diabetes. Sitagliptin (Januvia, Merck), a novel drug in a new medication class known as dipeptidyl peptidase-IV (DPP-IV) inhibitors, offers a new mechanism by which to achieve glycemic control. Although stimulation of receptors by the glucagon-like peptide-1 (GLP-1) enhances the body's ability to produce insulin in response to elevated blood glucose concentrations, rapid degradation of GLP-1 by DPP-IV limits its clinical effectiveness. The development of medications to reduce this degradation is being pursued by numerous manufacturers. An NDA for the first of these medications, sitagliptin, was submitted to FDA in February 2006. Currently available clinical studies have demonstrated improved glycemic control with sitagliptin therapy in patients who have not achieved target glucose levels with diet and oral medications. (Formulary. 2006;41:434–441.)

Medication safety in brief

The labeling for dextroamphetamine (Dexedrine, GlaxoSmithKline) was revised to include new warnings. The warnings describe reports of sudden death in association with CNS stimulant treatment at usual doses in children and adolescents with structural cardiac abnormalities or other serious heart problems.

Alterations in mitochondrial function are likely cause of imatinib-induced cardiotoxicity

The tyrosine kinase inhibitor imatinib is cardiotoxic and can lead to severe left ventricular dysfunction and heart failure in humans, according to research involving humans, mice and cultured cardiomyocytes.

First-time generic approvals (September 2006)

Azithromycin for oral suspension, 100 mg/5 mL and 200 mg/5 mL (equiv to Zithromax for oral suspension)

Pipeline Preview (September 2006)

Approvable designations; Priority review; Fast-track designations; Orphan drug designations; Nonapprovable designations

FDA actions in brief

Budesonide/formoterol (Symbicort, AstraZeneca) was approved as maintenance therapy for asthma in patients aged 12 years and older.

Duetact

The combination of pioglitazone and glimepiride was approved on July 28, 2006, as an adjunct to diet and exercise as a once-daily combination therapy to improve glycemic control in patients with type 2 diabetes who are already treated with a combination of pioglitazone and a sulfonylurea or whose diabetes is not adequately controlled with a sulfonylurea alone, or for those patients who have initially responded to pioglitazone alone and require additional glycemic control.

Famvir

A prodrug of penciclovir, famciclovir is ultimately phosphorylated by the viral thymidine kinase and subsequently cellular kinases to a penciclovir triphosphate, which inhibits herpes simplex 2 (HSV-2) DNA polymerase in a competitive manner.

Plavix

This antiplatelet agent exerts its effect through direct inhibition of adenosine diphosphate (ADP) binding to its receptor and of the subsequent ADP-mediated activation of the lipoprotein GPIIb/IIIa complex.

DPP-IV inhibitors effectively reduce levels of HbA1c as monotherapy or in combination with other agents

New incretin-based therapies will soon enter the therapeutic armamentarium for type 2 diabetes. Two dipeptidyl peptidase (DPP)-IV inhibitors in phase 3 clinical trials, vildagliptin and sitagliptin, are oral agents that can be used once daily as monotherapy or in combination with other oral antidiabetic agents to reduce levels of hemoglobin A1c (HbA1c) with few side effects, little risk of hypoglycemia, and no promotion of weight gain, researchers reported at the 66th scientific sessions of the American Diabetes Association (ADA) in Washington, DC.

FDA announces advisory committee reform, supports adaptive trial designs; HHS report criticizes FDA postmarketing study policies

In response to criticism about the composition of its independent advisory committees, FDA announced it would modify its procedures dealing with committee appointments and clarify the circumstances under which waivers for conflicts of interest occur.

Anidulafungin: An echinocandin antifungal for the treatment of Candida infection

Anidulafungin (Eraxis, Pfizer) is a new echinocandin approved for the treatment of Candida infection in adults. Like other echinocandins, anidulafungin acts on the fungal cell wall by inhibiting 1,3 beta-D glucan synthesis. Studies suggest that among the echinocandins, anidulafungin may have more potent in vitro activity against Candida spp and Aspergillus spp. Further, phase 2 and 3 clinical studies with anidulafungin have supported a high end of therapy success rates for invasive candidiasis, including esophageal candidiasis. Anidulafungin appears to be well tolerated, with headache, nausea, vomiting, phlebitis, neutropenia, and hypokalemia being the most commonly reported adverse effects. Importantly, as anidulafungin is chemically degraded, it has no clinically significant drug interactions and does not require any dose adjustment for renal or hepatic impairment.

Labeling updates & new warnings

FDA notified healthcare professionals and consumers of new safety information regarding taking 5-hydroxy-tryptamine receptor agonists (triptans) and selective serotonin reuptake inhibitors (SSRIs) or selective serotonin/norepinephrine reuptake inhibitors (SNRIs) concomitantly.