2011 American Society of Consultant Pharmacists Annual Meeting and Exhibition

November 16-18, 2011; Phoenix, AZ

Product Theaters

Preventing Influenza With Fluzone High-Dose in Older Adults

With age, the risk of influenza increases because the immune system weakens, causing the body to produce fewer antibodies in response to vaccination. A decreased immunologic response may leave an individual more vulnerable to influenza infection and at an increased risk of severe complications. In a product theater for Fluzone, a high-dose (HD) injectable flu vaccine manufactured by Sanofi Pasteur, Inc, clinical pharmacist Frank Breve, president and CEO of Mid-Atlantic Pharma Tech in NJ, said older adults make up 15% of the US population, yet account for more than 60% of the estimated 226,000 annual hospitalizations and 90% of the 3000 to 49,000 annual deaths attributed to influenza and pneumonia. He said the presence of comorbidities—practically universal in nursing home residents—increases the risk of mortality from influenza and/or pneumonia dramatically. The disproportionate burden of these illnesses on older adults, which is an ever-growing segment of the population, highlights the need to improve influenza prevention.

The Fluzone HD vaccine contains four times the standard dose of antigen (60 mcg vs 15 mcg hemagglutinin), and its approval by the US Food and Drug Administration (FDA) was based on demonstrations of its ability to engender superior immune response in individuals aged 65 years and older. Although none of the data available to date demonstrate superior effectiveness of Fluzone at preventing influenza illnesses and complications, Breve said three clinical studies have shown that the mega-dose results in significantly higher antibody levels in older adults compared with the regular dose.

In 2009, Ann Falsey, MD, and colleagues, University of Rochester, Rochester, NY, published findings in The Journal of Infectious Diseases (JID) of a randomized, double-blind phase 3 trial that compared Fluzone HD (n=2575) with the standard dose (n=1262) in adults 65 years of age and older. The HD induced a statistically significant level of antibody response compared with the standard dose, meeting superiority criteria for influenza A strains H1N1 and H3N2 and noninferiority criteria for the influenza B strain.

The JID issue included a commentary by Gregory Poland, MD, a physician and researcher with the Mayo Clinic, Rochester, MN, and Mark Mulligan, MD, professor of medicine, Emory University, Atlanta, GA. In the commentary, they encouraged manufacturers to seek licensure from the FDA for HD vaccines. They said this step would be critical to reduce the annual epidemics of influenza and morbidity and mortality associated with influenza. Poland and Mulligan said it would be irresponsible for manufacturers not to make providing better options for influenza vaccination a priority.

According to Breve, data from multiple studies show that elevated levels of antibodies generally correlate with greater resistance to influenza, and it is important for patients to be aware of this fact and their option to receive Fluzone HD. He expects data demonstrating the vaccine’s ability to prevent influenza to come eventually, as regular vaccination has already been found to be successful at preventing the illness in older adults. Regular influenza vaccinations reduce the risk of hospitalization in adults aged 65 years and older by approximately 30% and nearly halve the risk of cause-specific mortality (including cardiovascular disease, stroke, renal disease, and diabetes).   

The most common adverse effects seen with Fluzone HD are mild pain at the injection site, erythema, fever, headache, malaise, and myalgia. Safety information warns against giving the HD vaccination to anyone with a severe allergic reaction to eggs or egg products or to a previous dose of any influenza vaccine. HD vaccination should be discussed with a clinician if the patient has ever experienced Guillain-Barré syndrome.—David Despain

This product theater was sponsored by Sanofi Pasteur, Inc.

Nuedexta is First Approved Therapy for Pseudobulbar Affect

In a product theater sponsored by Avanir Pharmaceuticals, a video is shown that features a dementia patient being interviewed by her physician. She begins crying uncontrollably for seemingly no reason. This is a hallmark of pseudobulbar affect (PBA), which involves episodes of laughing and/or crying that are frequent, stereotypical, inappropriate to the situation (incongruent or exaggerated), and last seconds to minutes. Mary Catherine Yaggy, MSN, GNP-BC, gerontological nurse practitioner, Extended Care Specialists, Fort Wayne, IN, discussed this patient and her treatment with Nuedexta (dextromethorphan hydrobromide 20 mg and low-dose quinidine sulfate 10 mg), the first approved therapy for PBA, at the recent ASCP annual meeting. Yaggy said after 10 days of taking Nuedexta, the patient saw a 50% reduction in the number of PBA episodes each day. Yaggy has been treating patients with Nuedexta since April, only a couple of months after it first became available, and said it has proven extremely effective in patients who previously received mood stabilizers. She expects it will serve a valuable role in the long-term care and behavior management arenas.

PBA is a disorder of disinhibition of emotional expression characterized by involuntary, sudden, and frequent crying and/or laughing. It occurs secondary to neurological conditions commonly affecting residents of long-term care, including multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), Parkinson’s disease, Alzheimer’s disease, and traumatic brain injury. The symptoms can severely disrupt the lives of patients and caregivers and may lead to social phobia, withdrawal, and isolation. Historically, various terms have been used to describe the disorder, including excessive emotionality, affective instability, emotional dyscontrol, post-stroke emotionality, pathological laughing and crying, and pathological affect.

Dana Saffel, PharmD, DPh, CGP, FASCP, president and CEO, PharmaCare Strategies, Inc, discussed the etiology of PBA and the prescribing information for Nuedexta at the meeting. She said recent research suggests PBA results from lesions in the frontal cortex that cause disruption along the corticopontocerebellar pathways, which control emotional motor expression. Saffel said the treatment should not be seen as a cure, but it does help normalize signaling, allowing the patient to control these inappropriate, unprompted displays of laughing or crying. The dextromethorphan ingredient is thought to have two mechanisms of action: presynaptic inhibition of glutamate release and postsynaptic glutamate response modulation. The low-dose quinidine in the compound inhibits the CYP2D6 enzyme from metabolizing dextromethorpan and allows it to enter the brain. 

The effectiveness of Nuedexta was established in studies involving patients with ALS and MS, patient populations with a high prevalence of PBA. The primary end point was the reduction in number of episodes. One randomized, double-blind, placebo-controlled, multicenter study randomized 326 patients to Nuedexta (n=107) or placebo (n=109) for 12 weeks. Patients in the Nuedexta group had significantly fewer episodes of laughing and crying compared with patients in the placebo group. Episodes in Nuedexta-treated patients were also significantly less severe compared with episodes in patients given placebo. Saffel said patients had an average 60% to 70% reduction in the number of episodes, a rate that was sustained over the 12-week duration of the study. Half the patients in the Nuedexta arm were episode-free during the final 14 days of the study. Adverse events that occurred in approximately 3% of patients treated with Nuedexta, and at a significantly greater rate than observed in the placebo arm, included diarrhea (13% vs 6%, respectively) and dizziness (10% vs 6%, respectively).

Saffel said the recommended starting dose of Nuedexta is one capsule daily, given by mouth. After 7 days of therapy, the dose is increased to two capsules daily (one every 12 hours). Nuedexta is contraindicated in patients who are taking quinidine and related drugs or monoamine oxidase inhibitors; in patients with a history of hypersensitivity to the drug or either of its ingredients; and in patients with hepatitis or QT abnormality.—David Despain

This product theater was sponsored by Avanir Pharmaceuticals.