Formulary Watch |

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.

The role of pharmacoeconomics in formulary decision-making

The role of cost- and pharmacoeconomic-related criteria in formulary decision-making was assessed in a literature review of 31 studies of hospital (n=18) and managed care (n=13) pharmacy and therapeutics (P&T) committees. In both settings, cost was important, although the elements of cost considered varied. Acquisition cost was mentioned more frequently than pharmacoeconomic or cost-effectiveness information. Other factors, including drug characteristics, quality of life, supply-related issues, and physician demand, also influenced decisions.

COX-2 inhibitor demonstrates lower incidence of adverse cardiorenal events compared with nonselective NSAIDs

A meta-analysis of data from randomized, parallel-designed, placebo-controlled studies involving >44,000 patients demonstrated that those who had taken the cycloxygenase-2 (COX-2) inhibitor celecoxib (50–800 mg TDD) had a lower incidence of adverse cardiorenal events including hypertension, edema, or congestive heart failure than those taking nonselective non-steroidal anti-inflammatory drugs (NSAIDs), according to an oral and poster presentation at the 21st annual scientific meeting of the American Society of Hypertension (ASH) in New York, NY.

High-dose non-COX-2 NSAIDs associated with increased vascular risk

While the increased risk of vascular events associated with cyclooxygenase-2 (COX-2) inhibitors has been well established, new data are emerging that demonstrate similar risk increases associated with non-steroidal anti-inflammatory drugs (NSAIDs) that are not selective for COX-2. The data, published in the British Medical Journal (BMJ), were from a meta-analysis of published and unpublished randomized trials. The study comes more than a year after the withdrawals of the COX-2-selective NSAIDs rofecoxib and valdecoxib from the US market.

COX-2 inhibitors, nonselective NSAID use increases risk of death, reinfarction in acute MI patients

A meta-analysis of data from national hospital records in Denmark and from the country's national prescription registry showed that the use of selective cyclooxygenase-2 (COX-2) inhibitors in all doses and nonselective non-steroidal anti-inflammatory drugs (NSAIDs) in high doses raised the risk of death in patients who experienced first-time acute myocardial infarction (MI).

First-time generic approvals (August 2006)

Metronidazole topical gel, 0.75% (equiv to Metrogel topical gel)

Pipeline Preview (August 2006)

Hepatitis B immune globulin (human) (Nabi-HB, Nabi Bio-pharmaceuticals) for the treatment of hepatitis B infection

FDA actions in brief

FDA approved the etonogestrel 68-mg implant (Implanon, Organon), a single-rod implantable device that prevents pregnancy for up to 3 years.

Atripla

This fixed-dose combination tablet contains: efavirenz, a non-nucleoside reverse transcriptase inhibitor (NNRTI); emtricitabine, a synthetic nucleoside analog of cytidine; and tenofovir disoproxil, which is converted in vivo to tenofovir, an acyclic nucleoside phosphonate (nucleotide) analog of adenosine 5'-monophosphate.

Sprycel

Dasatinib is an inhibitor of multiple tyrosine kinases and is active in vitro against leukemic cell lines representing variants of imatinib-sensitive and -resistant disease.

Prezista

This inhibitor of human immunodeficiency virus type 1 (HIV-1) protease selectively inhibits the cleavage of HIV-encoded Gag-Pol polyproteins in infected cells, thereby preventing the formation of mature virus particles.

Lucentis

This recombinant humanized IgG1 monoclonal antibody fragment binds to the receptor-binding site of active forms of human vascular endothelial growth factor A (VEGF-A).

Drug Watch: Agents in late-stage development for the treatment of generalized anxiety disorder and sleep disorders (August 2006) (PDF)

A review of agents in late-stage development for the treatment of generalized anxiety disorder and sleep disorders (August 2006).

Salmeterol/fluticasone combination lowers asthma exacerbations

A salmeterol/fluticasone combination (SFC) surpassed a formoterol/budesonide combination (FBC) in reducing the rate of moderate-to-severe exacerbations in patients with persistent asthma, according to a study published by the journal Respiratory Medicine.

Antihypertensives demonstrate benefit in reducing Alzheimer's disease risk

Potassium-sparing diuretics reduced the risk of Alzheimer's disease (AD) by >70% in patients aged >64 years while other antihypertensive (AH) medications, including all diuretics, beta blockers, and dihydropyridine calcium channel blockers, were linked with somewhat smaller decreases in Alzheimer's risk.

Statins, beta blockers may reduce vulnerability of coronary disease patients to acute ischemic events

An observational case-control study of 1,384 adults presenting with coronary disease for the first time found that patients who presented with acute myocardial infarction (MI) received statins and beta blockers less often than patients who presented with stable exertional angina.

Use of ACE inhibitors in first trimester raises risk of fetal cardiovascular, CNS malformation

An observational cohort study found that the risk of major congenital malformations for infants who were exposed to angiotensin-converting enzyme (ACE) inhibitors during their first trimester increased by a factor of more than 2, while exposure to other antihypertensive medications did not demonstrate an increased risk.

NSAID use among elderly increases risk of first-time hospitalization for heart failure

A cohort study with a nested case-control analysis of first hospitalizations for heart failure (HF) associated the use of non-steroidal anti-inflammatory drugs (NSAIDs) with a 30% increase in the target end point among patients aged 60 to 84 years.