RISPERDAL BLACK BOX WARNING

Risperdal drug is approved to treat patients with schizophrenia, Bipolar I Disorder and irritable or aggressive behavior associated with autism spectrum disorders.

Risperdal Black Box Warning

Risperdal is an atypical, also known as second generation, antipsychotic medication that was approved by the U.S. Food and Drug Administration (FDA) in 1993. The drug is approved to treat patients with schizophrenia, Bipolar I Disorder and irritable or aggressive behavior associated with autism spectrum disorders. Risperdal is prescribed for these indications, but it is also used “off-label”, or in ways not approved by the FDA. While physicians can prescribe drugs off-label as they deem appropriate, it is illegal for pharmaceutical companies to promote drugs for off-label purposes. This is because using a drug off-label may be dangerous to patients. With Risperdal, a common off-label use is in elderly patients who suffer from dementia. The FDA has placed a black box warning on the medication indicating that using Risperdal for this purpose is associated with an increased risk of death.

Increased Risk of Death in Patients with Dementia

The use of Risperdal off-label in patients with dementia was so concerning that the FDA placed a “black box warning” on the prescribing information in 2005. A black box warning, also known as a boxed warning, is the strongest warning required by the FDA. When a drug carries a boxed warning, it means that studies show that it has a risk of serious or life-threatening side effects.

Patients with dementia sometimes experience behavioral problems, aggression, agitation and psychosis. Risperdal is sometimes used to mitigate these psychotic symptoms, but it turns out that the risks may far outweigh any benefits. In 2005, the FDA warned that patients who were treated with Risperdal for dementia-related psychosis had a high rate of death compared to those taking a placebo. The agency stated at the time “Based on currently available data, FDA has requested that the package insert for Risperdal be revised to include a black box warning describing this risk and noting that this drug is not approved for this indication.” In September 2006, the FDA announced the product labeling has been revised to address this issue.

The black box warning was placed after the FDA analyzed seventeen placebo controlled trials consisting of 5,106 elderly patients. These individuals had behavioral disorders related to dementia. The clinical trials, which lasted about 10 weeks on average, evaluated Zyprexa (olanzapine), Abilify (apripiprazole), Risperdal (risperdone) and Seroquel (quetiapine). Overall, the trials showed that the risk of death in patients treated with drugs was 1.6 to 1.7 times higher than those who took a placebo. The rate of death in placebo group was about 2.6 percent, compared to 4.5 percent in patients treated with antipsychotics. FDA noted that most deaths were caused by cardiovascular issues (such as heart failure or sudden death) and infection or diseases (such as pneumonia), although the causes varied.

There was also a higher incidence of mortality in patients treated with furosemide plus Risperdal compared to Risperdal alone or with placebo plus furosemide, findings from two of four placebo-controlled trials indicated.

The black box warning reads: “WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS

Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Risperdal® (risperidone) is not approved for the treatment of patients with dementia-related psychosis.”

Risperdal is a highly profitable drug for its manufacturer, Janssen, a division of Johnson & Johnson. Sales of the drug reached $4.5 billion per year in 2007. Even after generic versions became available, sales exceed $1.5 billion each year.

Janssen Pleads Guilty to Marketing Risperdal Off-label for Dementia Patients, Pays Criminal Fine and Settles Civil Allegations

In November 2013, the Department of Justice charged that Janssen marketed Risperdal for unapproved uses between March 3, 2002 through December 31, 2003. The government alleged that the product was misbranded; evidence indicated that Janssen sales representatives marketed Risperdal to physicians as a means to treat anxiety, agitation, depression, hostility and confusion in patients with dementia, even though the drug was only approved for schizophrenia at the time. The government also alleged that Janssen focused on symptoms without mentioning FDA-approved indications and offered incentives for off-label promotions.

Janssen pled guilty to charges that it marketed Risperdal off-label in dementia patients with psychotic and behavioral symptoms. The company paid a criminal fine of $334 million and forfeiture of $66 million.

Janssen also settled civil allegations that it targeted vulnerable patients, including the elderly nursing home residents, children and individuals with mental disabilities. The government accused the company of causing false claims to be submitted to federal health programs by marketing the drug for unapproved uses not covered by these programs. The complaint also alleged that Janssen paid illegal kickbacks to physicians as an incentive to prescribe Risperdal and made misleading statements about its safety.

“J&J’s promotion of Risperdal for unapproved uses threatened the most vulnerable populations of our society – children, the elderly and those with developmental disabilities,” said U.S. Attorney for the Eastern District of Pennsylvania Zane Memeger, according to the DOJ press release. “This historic settlement sends the message that drug manufacturers who place profits over patient care will face severe criminal and civil penalties.”

Janssen was repeatedly warned by the FDA that it was “misleading” to market Risperdal as safe and effective for the elderly, but it continued to do so nonetheless, according to the complaint. The government also alleged that Janssen knew Risperdal could increase the risk of strokes and other serious health problems in the elderly but hid this information. The complaint alleges that Janssen’s ElderCare sales force was used to aggressively market Risperdal for behavioral symptoms related to dementia from 1999 to 2005, despite being aware of the risks.