Nuedexta Manufacturer Avanir Pharmaceuticals Targets the Elderly

Danny Glover talking about PBA
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About two years ago, advertisements for the drug Nuedexta began appearing on televisions across the United States. They showed actor Danny Glover alternately laughing and crying uncontrollably, mimicking the behaviors seen in people with a condition known as pseudobulbar affect, or PBA. Most common in people suffering from multiple sclerosis and ALS, the illness is characterized by sudden outbursts of emotion that are inconsistent with the person’s self-described mood. As a rule, these outbursts are unrelated to any specific stimulus or are inappropriately severe in relation to a stimulus that occurred.

Pseudobulbar affect is a rare condition. According to the drug manufacturer’s own data, it affects about 1 percent of American adults, reports CNN. Yet sales of Nuedexta rose over 400 percent between 2012 and 2016. According to experts interviewed by CNN, inappropriate prescribing is the primary reason behind these burgeoning sales.

Approved for Limited Use

The Food and Drug Administration approved Nuedexta (a combination of dextromethorphan hydrobromide and quinidine sulfate) as a treatment for pseudobulbar affect in 2010. Initially, the manufacturer, Avanir Pharmaceuticals, focused marketing efforts on raising awareness of PBA. But sales were lackluster until 2012, when the company shifted its marketing message and began pushing the benefits of Nuedexta for patients with dementia, specifically those who reside in nursing homes. Since that time, more than half of all Nuedexta prescriptions went to long-term care facilities, earning the company nearly $300 million in just four years.

To be clear, PBA can occur in patients with dementia and Alzheimer’s disease. However, Avanir’s own data shows that only about 100,000 of the 1.8 million Americans who suffer from PBA live in long-term care facilities. Yet, according to CNN, company documents indicate that nursing homes were key to Avanir’s growth. In fact, in a 2013 earnings call, former Avanir CEO Rohan Palekar, said Avanir had “just scratched the surface of its full potential” in nursing homes.

Aggressive Sales Tactics Skirt the Law

But Avanir faced a dilemma: Few patients with Alzheimer’s disease or dementia are actually diagnosed with PBA. People with dementia may exhibit inappropriate behaviors, including agitation, restlessness and aggression. But these behaviors are inconsistent with established criteria for PBA. And Medicare typically will not pay for a medication that’s prescribed for “off-label” use.

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To solve the problem and drive up sales, Avanir representatives began to identify and actively court physicians, pharmacists and nurse practitioners who would be willing to serve as “advocates” for the drug. They then worked with these providers to locate patients who might meet the criteria for PBA. According to CNN, in one case an Avanir representative and a doctor’s office manager actually reviewed patient records to identify those who might have PBA and inserted Nuedexta brochures in their charts. They also coached office staff on how to contest Medicare denials of the drug.

But Avanir’s efforts didn’t end there. Using controversial but mostly legal tactics, they induced health care providers to diagnose dementia patients with PBA through a series of financial incentives, including meals, travel expenses, and other “perks.” According to an analysis by CNN, Avanir and its parent company, the Japanese pharmaceutical company Otsuka, paid doctors over $14 million in Nuedexta “consulting fees” between 2013 and 2016. It also spent over $4.5 million on travel expenses and other costs for professional speakers and doctors who attended Nuedexta promotional events.

Several physicians have since come under investigation for fraudulently diagnosing patients with PBA and/or taking kickbacks for prescribing the drug. (Kickbacks are illegal under federal law.)

Potentially Dangerous and Unwarranted

Since Nuedexta has become a staple in long-term care facilities across the United States, the FDA has received over 1,000 reports of adverse events involving the drug. Of these, 52 were serious enough to warrant hospitalization, and eight resulted in the patient’s death. In one case from 2015, an 86-year old woman with Alzheimer’s disease who was already receiving three psychotropic drugs was prescribed Nuedexta for “weeping.” Shortly thereafter, she became nearly unresponsive; yet for reasons that are unclear the dose of Nuedexta was increased. She subsequently lost the ability to eat or drink, went into kidney failure, and died. According to the patient’s nurse, she was doing well until she started taking the drug.

Drugs are rarely the answer for agitated patients with dementia
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Nor are these effects entirely unexpected. According to its own prescribing information, Avanir has not studied Nuedexta extensively in the elderly. And the one small study it did conduct showed that patients with Alzheimer’s who were given the drug fell at nearly twice the rate of those who received a placebo. (Falls are a significant cause of death and disability in people over the age of 65.) And two physicians who participated in the FDA approval process voiced strong objections to allowing the drug to be used in patients other than those with MS or ALS. They argued that evidence of its efficacy in patients with dementia was weak; its safety profile in the elderly was unclear; and there was little evidence that PBA even existed in people with Alzheimer’s disease.  

Nonetheless, the FDA eventually approved the drug for patients with PBA who had variety of “neurologic conditions,” including Alzheimer’s disease and dementia.

Regulators in several states are now investigating Avanir’s marketing tactics, which appear remarkably similar to those of opiate manufacturer Insys Pharmaceuticals, whose former CEO was arrested last October for fraud. Yet, no arrests have been made, and the company’s marketing tactics remain unchanged. In fact, Avanir doubled-down on its strategy in a statement countering CNN’s analysis posted on its website on Dec. 12, 2017.

More Staff, Fewer Drugs

Long term care facilities undoubtedly face challenges in caring for patients with dementia. There are currently no FDA-approved drugs available to treat dementia-related agitation, and regulators have come down hard on companies that promote sedating drugs for off-label use. What’s more, anti-psychotic drugs are often contraindicated in the elderly, and most carry a black-box warning against excessive use.

But according to Helen Kales, a geriatric psychiatrist and University of Michigan professor, increased staffing, not more medication, may well be the answer to calming agitated patients down. What’s more research supports her assertion. Trained staff using words and planned de-escalation techniques are often extremely successful in bringing even the most confrontational situation to a successful end. 

But hiring more staff is an expensive proposition, and one that few long-term care facilities seem convinced will help. So they instead opt for a pharmaceutical solution, which is all too often a heavily promoted yet potentially unsafe drug.