Drug Pipeline

Disease-free survival in postmenopausal women with primary breast cancer significantly improved when tamoxifen monotherapy treatment was switched to exemestane therapy after 2-3 years, according to a study published in the New England Journal of Medicine. The existing treatment paradigm calls for tamoxifen, an estrogen-receptor modulator, to be taken alone for all 5 years, but some patients have experienced relapse.

First therapy approved for “off” episodes in advanced Parkinson’s disease

First therapy approved for “off” episodes in advanced Parkinson’s disease

Biologic approved for plaque psoriasis

Two published studies from the 1970s describe a higher inappropriate use of antimicrobials among surgeons compared to internal medicine physicians. If this assertation is indeed true, institutions with limited resources should focus interventions on surgical services to improve antimicrobial use. The appropriateness of antimicrobial use in internal medicine and general surgical patients over a 10-month period was evaluated at the University of Louisville Hospital (Louisville, Ky) based upon established institutional antimicrobial guidelines. Antimicrobial selection and dose were evaluated for 1,300 antimicrobial courses. Compliance to institutional guidelines for antimicrobial selection and dose were found in 448 (93%) of 480 courses prescribed by internal medicine services and 728 (88%) of 820 courses prescribed by surgical services (P=.009). Although we were able to identify a 5% difference among specialties, we did not consider this to be a clinically significant difference. We concluded that focused interventions to improve antimicrobial use at the University of Louisville should be applied equally to medical and surgical specialties.

Darifenacin (Enablex, Novartis) is a muscarinic antagonist in phase 3 clinical trials for the treatment of overactive bladder (OAB). Darifenacin demonstrates relative selectivity for the M3 muscarinic receptor subtype over the M1 and M2 subtypes. In clinical trials, darifenacin has been compared to placebo for the treatment of symptoms of OAB in adult men and women. Patients treated with darifenacin experienced significantly greater reductions in the number of incontinence episodes per week, nocturnal awakenings, and warning time before micturitions. It appears to have similar efficacy to available anticholinergic agents for the treatment of OAB. Commonly reported adverse events include dry mouth and constipation, and preliminary data suggest that darifenacin may be associated with decreased impairment of salivary flow versus oxybutynin. Darifenacin has not been found to have an effect on the cardiovascular system or cognition in clinical trials. Further research is needed to determine the efficacy of darifenacin compared to other available anticholinergic agents such as oxybutynin and tolterodine, as well as emerging therapies. In addition, further investigation of the adverse effect profile in elderly patients is warranted.

In phase 3 trials, the first agent in a novel class known as the selective cannabinoid type 1 receptor blockers doubled the odds of quitting smoking while reducing post-cessation weight gain compared with placebo. The agent, rimonabant, also improved several features of the metabolic syndrome in patients with abdominal obesity, reported researchers at the 53rd Annual Scientific Session of the American College of Cardiology (ACC).

>Enoxaparin is an effective and safe alternative to unfractionated heparin (UFH) in the early and invasive management of high-risk patients with non-ST-elevation acute coronary syndromes (ACS), said Robert Califf, MD, at the 53rd Annual Scientific Session of the American College of Cardiology (ACC).

Mark McClellan, MD, PhD, now administrator of the Centers for Medicare and Medicaid Services (CMS), is seeking more evidence-based information about how medical treatments affect patients in the real world. Dr McClellan says his first priority is to use the new Medicare pharmacy program, starting with the drug discount card, to lower drug costs. One prime strategy for doing so is to evaluate which therapies are most efficacious as well as cost-effective for specific patient subgroups in order to curb unnecessary spending on prescription drugs.

Ezetimibe added to a stable dose of statin therapy reduces low-densitylipoprotein (LDL) cholesterol by an additional 23% and results in significantlymore patients achieving their LDL cholesterol goals, said Thomas Pearson,MD, MPH, at the 53rd Annual Scientific Session of the American College ofCardiology (ACC) in New Orleans.

Erectile dysfunction (ED) is now recognized as a common problem in men. Several medical problems, including diabetes mellitus, coronary artery disease, hypertension, and hyperlipidemia are known to increase the likelihood of developing ED. Diagnosis depends on an adequate history and physical examination. Several therapies are now available for the treatment of ED. With the advent of the phosphodiesterase type 5 (PDE5) inhibitors, therapy for ED has become more acceptable for many men. Oral therapy is usually the first-line treatment due to the ease of use and the effectiveness of this therapy. For men who do not respond to or have a contraindication to PDE5 therapy, intrapenile injection therapy, intraurethral therapy, and vacuum devices are effective alternatives.

Rasagiline (Teva/Eisai), a second-generation irreversible MAO inhibitor highly selective for type B of the enzyme, is expected to gain FDA approval in late 2004/early 2005 for the treatment of Parkinson’s disease in monotherapy or as adjunct therapy to levodopa. Rasagiline is more potent than selegiline, the only FDA-approved drug within the same class, and may be devoid of the undesirable effects (blood pressure increases, euphoria, and sleep disturbances) often reported with selegiline. Rasagiline has been studied and proven effective versus placebo in patients with moderate and advanced Parkinson’s disease in both phase 2 and 3 clinical trials. The drug is administered orally once daily and does not require titration. Furthermore, rasagiline has demonstrated neuroprotective activity in various in vitro models and may show promise in the treatment of other neurologic diseases; however, these properties have yet to be studied in humans.

Aggressive lipid-lowering with high-dose atorvastatin initiated immediatelyafter hospitalization for an acute coronary syndrome (ACS) significantlyreduces the risk of long-term adverse cardiovascular outcomes compared withlipid-lowering with standard-dose pravastatin. As such, target levels oflow-density lipoprotein cholesterol (LDL-C) may need to be lower than theones currently recommended in patients at risk of cardiovascular events,said Christopher Cannon, MD, at the 53rd annual scientific session of theAmerican College of Cardiology in New Orleans.

Chronic obstructive pulmonary disease (COPD) is a major public health problem, with inhaled anticholinergic agents being the treatment of choice. The disadvantage of currently approved therapies for the treatment of COPD is that agents such as ipratropium (Atrovent, Boehringer Ingelheim) must be administered numerous times daily. Tiotropium (Spiriva, Pfizer/Boehringer Ingelheim) is a new, recently FDA-approved, long-acting anticholinergic drug that requires only once-daily dosing. Tiotropium displays selective receptor kinetics by dissociating more slowly from M1 and M3 receptors than M2 receptors. In patients with COPD, tiotropium 18 mcg inhaled once daily results in significant improvement in lung function. Furthermore, improvements appear sustained for up to 3 weeks after discontinuing tiotropium. Tiotropium is well tolerated with minimal systemic absorption resulting in a favorable adverse effect profile. The most common adverse effect associated with tiotropium is dry mouth. Given the longer duration of action, once-daily dosing, minimal adverse effects, and documented improvements in lung function, tiotropium is poised to replace ipratropium as the inhaled anticholinergic of choice.

One of the most common ophthalmic conditions that directs a patient to a primary-care physician or eye-care practitioner is the red, itchy eye. The highest percentage of conjunctivitis is noninfectious or inflammatory, and frequently these cases are allergic in nature. The ophthalmic armamentarium is now filled with a number of pharmaceutical compounds that act specifically at different points along the inflammatory cascade. Formulary decision-making should be based on sound knowledge of the ocular inflammatory cascade and the pathways through which the various ophthalmic antiallergic preparations exert their anti-inflammatory effects.

FDA rolls out new policies on DTC advertising,counterfeit drugs, and bar codes before McClellan departs

Calcium channel blocker/statin combination receives approval

First angiogenesis-inhibiting cancer therapy approved

Anticholinergic approved for COPD

Chimeric monoclonal antibody targets EGFR for the treatment of colon cancer

Fosamprenavir (Lexiva, GlaxoSmithKline/Vertex) is the latest protease inhibitor (PI) approved by FDA for the treatment HIV-1 infection. A prodrug of amprenavir (APV), fosamprenavir has improved solubility and bioavailability over the parent PI, allowing for once- or twice-daily dosing and a decreased pill size and burden. In clinical trials, fosamprenavir was studied alone or boosted with ritonavir (RTV) in both HIV treatment-naïve and -experienced patients. In both patient populations, fosamprenavir decreased HIV RNA, increased CD4 cell counts from baseline, and increased the proportion of patients reaching undetectable viral loads (<400 and <50 copies/mL). Patients who received treatment with fosamprenavir demonstrated protease gene mutations different than those commonly seen with other PIs (except APV). Fosamprenavir appears to have an adverse effect profile similar to that of other PIs.

One of the primary etiologies of acute renal failure (ARF) is nephropathy secondary to the administration of radiocontrast dye. In the United States alone, the cost of ARF-related expenses is estimated at more than $8 billion per year. Since ARF contributes such a substantial burden to the cost of healthcare and may be associated with significant morbidity and mortality, initiatives to educate pharmacists, physicians, and other health-care providers about how to decrease the incidence of radiocontrast-induced ARF are warranted. It is important to identify patients at risk for developing this pathology and to play an active role in disease state prevention. This review covers the pathogenesis, signs and symptoms, and current treatment options for reducing the risk of radiocontrast-induced nephropathy. Current pharmacotherapy focuses on the use of aggressive hydration before and after the administration of a contrast agent. Clinical trials evaluating the application of periprocedural drugs are also reviewed.

First combination approved specifically for bipolar depression

SSRI approved for generalized anxiety disorder

Authors Derek Van Amerongen, MD, MS Chief Medical Officer Humana Health Plan of Ohio Cincinnati, Ohio DonnaChiefari, RPH Director, Clinical Services NMHC Rx Latham, NY The views and opinions expressed in this supplement are those of the faculty and do not necessarily reflect the views of Advanstar Communications, Inc., publishers of Formulary, or Barr Laboratories Copyright 2004 Advanstar Communications, Inc., All rights reserved.

Extended use of combination monophasic oral contraceptives (OCs) used to treat women with menstrual disorders, such as endometriosis and dysmenorrhea, has been proven to be safe, effective, and acceptable to women. Even women without a medical indication for menstrual suppression may find that extending OC therapy may yield an improvement in their quality of life by diminishing menstrual symptoms associated with hormone withdrawal during the placebo interval. Most physicians and many women are aware of how to extend OC therapy, and commonly manipulate their cycles to avoid unwanted menstruation at inopportune times, such as during a honeymoon, vacation, or exams.

The oral contraceptive marketplace has undergone evolutionary changes over the years. Early oral contraceptive formulations contained higher doses of estrogen and progestin, which were associated with several safety concerns. Consequently, scientists returned to the laboratories to develop lower-dose formulations that would minimize risk without compromising efficacy. To date, numerous formulations have entered the marketplace that allow for tailored dosing to meet a woman?s clinical and individual needs. In order to provide additional treatment options and create more convenient oral contraceptive regimens, monophasic, multiphasic, extended-cycle, progestin-only, and chewable regimens have emerged. This article will review the main health risks and benefits of oral contraceptives, the concept of extended-cycle regimens, and the financial implications associated with oral contraceptive use.

Extended use of combination monophasic oral contraceptives (OCs) used to treat women with menstrual disorders, such as endometriosis and dysmenorrhea, has been proven to be safe, effective, and acceptable to women. Even women without a medical indication for menstrual suppression may find that extending OC therapy may yield an improvement in their quality of life by diminishing menstrual symptoms associated with hormone withdrawal during the placebo interval. Most physicians and many women are aware of how to extend OC therapy, and commonly manipulate their cycles to avoid unwanted menstruation at inopportune times, such as during a honeymoon, vacation, or exams.

Memantine (Namenda, Forest) is the newest medication to receive FDA approval for the treatment of Alzheimer?s disease and the first to be approved with a moderate-to-severe indication. All previously approved Alzheimer?s disease treatments belong to the cholinesterase inhibitor class and are approved with a mild-to-moderate indication. Memantine has been used for more than 10 years in Germany and features a novel mechanism of action: N-methyl-d-aspartate (NMDA) antagonism. It has been shown to be effective in double-blind, placebo-controlled trials as monotherapy and in combination therapy with the cholinesterase inhibitor donepezil in patients with moderate-to-severe Alzheimer?s disease.

Efalizumab (Raptiva, Genentech/Xoma) is a humanized monoclonal antibody of CD11a that exerts its effect through the blockade of the interaction between leukocyte function-associated antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1). FDA recently granted approval for efalizumab in the treatment of chronic moderate-to-severe plaque psoriasis in adults aged 18 years and older. Efalizumab does not achieve clinical response rates equal to cyclosporine or methotrexate, but it lacks the systemic organ toxicities of these agents and is associated with a more rapid onset of action (significant improvements in Psoriasis Area and Severity Index [PASI] response after 2 doses). In addition, efalizumab will likely compete with another approved biologic, alefacept, and off-label use of 2 other biologics currently on the market, etanercept and infliximab. At this time, until further studies comparing efalizumab to other drugs indicated for the treatment of psoriasis are completed and post-marketing surveillance is conducted, the agent?s place on the formulary remains unclear.