Drug Pipeline

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 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 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..

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.)

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.

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.

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

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.

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.

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.

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.

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 (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.

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.

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.

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.

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).

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

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.

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.

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.

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).

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.

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.

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.

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.

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.

A meta-analysis of 19 randomized, controlled clinical studies that lasted at least 3 months indicates that long-acting beta-agonists (LABAs) more than double the rates at which asthma patients may become hospitalized.

Bupropion extended-release tablets

Ambrisentan, a propanoic acid type-A selective endothelin receptor antagonist, improved exercise capacity and delayed clinical worsening in patients with pulmonary arterial hypertension (PAH) in phase 3 clinical trial results presented at the annual international conference of the American Thoracic Society in San Diego, Calif.