Drug Pipeline

First biologic approved for the treatment of allergic asthma

Treatment and prevention of osteoporosis

Panic disorder is the most common anxiety disorder in the primary-care setting. It is characterized by episodes of acute, unexpected, and unprovoked anxiety and is often associated with depression and/or agoraphobia. Symptoms may become so pervasive that many life situations may be avoided. Management of panic disorder includes cognitive behavioral therapy, patient education, and pharmacotherapy. This article focuses on the rationale of drug therapy, methods of management, and other clinical considerations such as side effects. In addition, newer formulations are available that may subsequently change how patients are managed. Selective serotonin reuptake inhibitors (SSRIs) are considered first-line therapy, with tricyclic antidepressants (TCAs) as a possible alternative if the patient fails to respond. These agents are also useful in the management of comorbid depression. Benzodiazepines offer more rapid anxiolysis and may be used in combination with an SSRI for bridging. Although monoamine oxidase inhibitors (MAOIs) have been studied, they do not have a significant role in the pharmacological management of panic disorder. (Formulary 2003;38:431?38.)

Nausea and vomiting are among the serious complications of chemotherapy and can be associated with medical and psychological complications. Palonosetron (Aloxi, MGI Pharma/Helsinn) is a new agent in the class of serotonin type 3 (5-HT3) receptor antagonists that have become a standard of care for the prevention of chemotherapy-induced nausea and vomiting. Palonosetron has a much longer half-life (~40 h) than typical 5-HT3 receptor antagonists and potentially improved efficacy in the prevention of delayed nausea and vomiting associated with moderately and highly emetogenic chemotherapy. Clinical trials of palonosetron in patients with cancer demonstrate its efficacy in the control of acute nausea and vomiting and its superiority to 2 agents in this class, dolasetron and ondansetron, in the control of delayed nausea and vomiting. Palonosetron is well-tolerated, with an adverse effect profile similar to other 5-HT3 antagonists. Its efficacy in the prevention of both acute and delayed nausea and vomiting makes palonosetron an attractive option for patients receiving chemotherapy. Further studies need to be conducted to determine the role of palonosetron among its competitors. (Formulary 2003;38:414?430.)

Formulary committees, pharmacy benefit managers (PBMs), pharmacists, and physicians face increased scrutiny of their relationships with pharmaceutical manufacturers under a final fraud policy statement from the Office of the Inspector General (OIG) of the Department of Health and Human Services (HHS).

Controlling the rate of growth in prescription drug expenses continues to be a challenge. The cost of offering healthcare insurance benefits, including prescription drug benefit programs, has increased to a rate of nearly 20% in 2003. Costs are expected to rise by double digits over the next 5 years. This daunting trend has influenced HMOs and other benefit providers to consider moving pharmacy benefit management in-house to cut costs.

Seasonal allergic rhinitis is a disease characterized by sneezing, nasal congestion, rhinorrhea, and itching, conventionally treated with intranasal corticosteroids and antihistamines. The leukotriene receptor antagonist montelukast (Singulair, Merck) recently gained FDA approval for the treatment of seasonal allergic rhinitis. While studies have shown the efficacy of montelukast in the treatment of seasonal allergic rhinitis, there are no published clinical efficacy trials to date to support the use of montelukast alone or in combination with antihistamines as a superior therapy to intranasal corticosteroids in the management of seasonal allergic rhinitis. When combined with current economic considerations, the primary role of montelukast appears to be as an adjunct agent in patients whose seasonal allergic rhinitis symptoms cannot be controlled with intranasal corticosteroids or nonsedating antihistamines alone.

Fluoroquinolone approved for bacterial conjunctivitis

Broad-spectrum antibiotic available as ophthalmic solution

Multiple myeloma treatment represents new class: proteasome inhibitors

Treatment for lung cancer patients unresponsive to chemotherapy

A new echinocandin, micafungin (Mycamine, Fujisawa), is currently under review for the treatment of systemic mycoses. If approved, micafungin would be the second agent in the echinocandin class available for use in the United States. It is believed to exhibit fungicidal or fungistatic activity against a variety of commonly encountered fungal pathogens including Candida and Aspergillus species. In addition to its broad spectrum of activity, initial clinical studies with micafungin have identified relatively few side effects and drug interactions. Micafungin exerts its antifungal activity at the level of the fungal cell wall via inhibition of 1,3 b?d-glucan synthase. Plasma concentrations follow a 2-compartment model with a half-life of 10 to 15 hours and a volume of distribution of 0.2 to 0.27 L/kg. Dose adjustments of micafungin due to hepatic or renal dysfunction appear to be unnecessary. Adverse events associated with micafungin are infrequently encountered and are generally mild in severity. Micafungin has been available in Japan since late 2002 and is also currently under review in Canada and Europe. Micafungin may offer advantages over other recently approved antifungal agents because of its excellent tolerability and minimal drug interactions.

Antibiotic therapy has undergone enormous changes since the discovery of penicillin by Sir Alexander Fleming in 1928. 1. Today, clinicians face increasing reports of antibiotic resistance. Optimizing antibiotic regimens can maximize effectiveness and minimize adverse effects while decreasing the likelihood of the development of resistance. The task of designing optimal antibiotic dosing regimens incorporates pharmacodynamics (PDs), pharmacokinetics (PKs), and microbiological principles. PKs consist of absorption, distribution, metabolism, and excretion, with these parameters reflecting drug exposure over time. The relationship between drug exposure and the physiologic effect of the drug encompasses the principles of PDs. With antibiotic therapy, PDs incorporate exposure to the antibiotic and antimicrobial effect. The intricate relationship between these principles enhances the understanding of the efficacy of antibiotic therapy.

FDA proposes bar codes and new error reporting standards as part of an initiative to reduce medication errors

Pharmacodynamics, the relationship between drug exposure and physiologic effect, helps to differentiate the killing activity of antibiotic classes through various markers of outcome. Antibiotics are characterized by time-dependent or concentration-dependent bacterial killing activity. With antibiotic therapy, pharmacodynamics consists of an intricate relationship between drug exposure, bacterial susceptibility, and the antimicrobial effect of the drug. Due to increasing reports of resistance, many investigators and healthcare institutions are focused on the optimal use of antibiotic therapy. Studies on antimicrobial pharmacodynamics have been increasing in the hope of defining and establishing break points that are associated with various outcome markers to optimize therapy, but the application of these studies in clinical practice is still limited. Incorporating pharmacodynamics into the study of antibiotic therapy can enhance the design of rational and optimal dosing regimens and improve the understanding of the emergence of resistance.

Adalimumab is the newest addition to a class of medications called tumor necrosis factor-alpha (TNF-a) inhibitors. Adalimumab (Humira, Abbott) is the first fully human monoclonal antibody approved to treat rheumatoid arthritis, distinguishing it from the other TNF inhibitors. FDA approval was received in December 2002, which was earlier than expected, based on clinical trial results that demonstrated a slowed progression of joint damage in addition to an improved quality of life in adalimumab-treated RA patients. Adalimumab has been found to be effective when used alone or in combination with methotrexate and/or other disease-modifying antirheumatic drugs. Existing TNF inhibitors for RA are associated with inconvenient or complicated dosing schedules. Adalimumab offers patients the convenience of an infrequent dosing schedule. In the absence of clinical trials directly comparing adalimumab with other biologic therapies, choice will largely depend on patient factors. Pricing information places adalimumab in line with its competitors.

b-blocker indicated for reducingcardiovascular mortality

Fluoroquinolone approved for community-acquired pneumonia

Growth hormone receptor antagonist to treat acromegaly

First in a new class of anti-emetics

Antibiotic therapy has undergone enormous changes since the discovery of penicillin by Sir Alexander Fleming in 1928. 1. Today, clinicians face increasing reports of antibiotic resistance. Optimizing antibiotic regimens can maximize effectiveness and minimize adverse effects while decreasing the likelihood of the development of resistance. The task of designing optimal antibiotic dosing regimens incorporates pharmacodynamics (PDs), pharmacokinetics (PKs), and microbiological principles. PKs consist of absorption, distribution, metabolism, and excretion, with these parameters reflecting drug exposure over time. The relationship between drug exposure and the physiologic effect of the drug encompasses the principles of PDs. With antibiotic therapy, PDs incorporate exposure to the antibiotic and antimicrobial effect. The intricate relationship between these principles enhances the understanding of the efficacy of antibiotic therapy.

Osteoporosis affects more than 10 million Americans and accounts for 1.5 million fractures annually. Several treatment options have been shown to prevent fractures and improve outcomes in patients with osteoporosis. Alendronate and risedronate clearly reduce fractures and are good initial choices in many patients. Raloxifene and calcitonin reduce the risk of vertebral fractures and may be appropriate in certain patients. Teriparatide was recently approved by FDA for the treatment of osteoporosis and may offer another treatment option. Combination therapy has been shown to increase bone mineral density; however, a reduction in the risk of fractures remains to be established. Zoledronic acid may offer an advantage of reduced frequency of administration.

Omalizumab appears effective in patients with poorly controlled allergic asthma.

New agent reduces PTH levels in hemodialysis patients with secondary hyperparathyroidism.

Congress to weigh Medicare reform plan and patient safety; FDA addresses product risk and quality

Alprazolam, which was previously approved for the treatment of anxiety and panic disorder, has now received FDA approval as extended-release tablets for the treatment of panic disorder.

This drug from the thiazolidinedione class is now approved for use incombination therapy with insulin, expanding on the existing indicationsas monotherapy and as combination therapy with metformin or sulfonylureas.Rosiglitazone improves sensitivity to insulin in muscle and adipose tissueand inhibits hepatic gluconeogenesis.

FDA approval of this prescription eye drop makes it the first and only prostaglandin with a first-line indication for the treatment of elevated intraocular pressure (IOP) associated with open-angle glaucoma or ocular hypertension. Initially, latanoprost was only approved for second-line use.

Enfuvirtide is the first drug to be approved in a new class of anti-HIV drugs known as fusion inhibitors (see "Focus On... Enfuvirtide"). The drug interferes with the entry of HIV-1 into immune cells by inhibiting the fusion of viral and cellular membranes. This occurs when enfuvirtide prevents conformational changes required for the fusion of viral and cellular membranes by binding to the first heptad-repeat (HR1) in the gp41 subunit of the viral envelope glycoprotein. Enfuvirtide, in combination with other antiretroviral agents, is intended for the treatment of HIV-1 infection in treatment-experienced patients with evidence of HIV-1 replication despite ongoing antiretroviral therapy.

Two options are available for patients requiring treatment for arthritis who are at risk for ulcer disease: nonsteroidal anti-inflammatory drugs (NSAIDs) that are selective for cyclooxygenase-2 (COX-2) or the combination of a non-selective NSAID with a proton-pump inhibitor. A recent study of representative members from these therapeutic classes has offered findings that the two alternatives are statistically similar in their efficacy with respect to the prevention of recurrent ulcer bleeding.Celecoxib, a COX-2-selective NSAID, was given to 144 patients through random assignment. Another group of patients (N=143) were randomly assigned to receive a combination of diclofenac (a nonselective NSAID) plus omeprazole (a proton-pump inhibitor) during the 6-month trial.