FDA warns Alkermes about OD risk on Vivitrol ads

The Food and Drug Administration (FDA) has warned Alkermes for omitting warnings about serious risks of Vivitrol in a print ad for the medication. The warning was posted Dec. 11 on the FDA's website.     

Antidepressants & suicide: putting the risk in perspective

Suicidal thoughts are a symptom of depression, and completed suicide is a tragic complication of depressive illness. Although pharmacotherapy is effective for the treatment of depression, the U.S. Food and Drug Administration has ordered that all antidepressant medications carry a warning indicating that they are associated with an increased risk of suicidal thinking, feeling, and behavior in children, adolescents, and young adults. These warnings have received much attention in the general media and have caused much controversy and debate about the relative safety of these commonly used drugs and the appropriateness of their use, especially in younger patients. In this article, I will discuss this issue with the goal of putting the risk in perspective.     

FDA cracks down on CBD claims

Last week, the Food and Drug Administration (FDA) issued a warning letter to Curaleaf Inc. of Wakefield, Massachusetts, for illegally selling cannabidiol (CBD) with claims that their products treat cancer, Alzheimer's disease, opioid withdrawal, pain and “pet anxiety,” among other conditions and diseases.     

Briefly Noted

Last month, the federal Food and Drug Administration (FDA) warned that combining gabapentin or pregabalin with central nervous system (CNS) depressants such as opioids could result in serious breathing problems for patients with underlying respiratory problems, or in the elderly. New labeling will be required on gabapentin and pregabalin, the FDA said. There is less evidence supporting such a risk in otherwise healthy people, the FDA said in the Dec. 19, 2019, warning. Gabapentin, first approved in 1993, is not a controlled substance. It is approved to treat various conditions, including seizures, nerve pain, fibromyalgia and restless legs syndrome. Pregabalin, first approved in 2004, is Schedule V on the Controlled Substances Act, the lowest‐risk category of controlled substance. “With the evolution of the opioid crisis, getting ahead of new concerns or addressing those that are already evident requires examining signs of misuse and abuse as soon as any signal emerges,” said Douglas Throckmorton, M.D., deputy director for regulatory programs in the FDA's Center for Drug Evaluation and Research, in announcing the warning. “Reports of gabapentinoid abuse alone, and with opioids, have emerged and there are serious consequences of this co‐use, including respiratory depression and increased risk of opioid overdose death. In response to these concerns, we are requiring updates to labeling of gabapentinoids to include new warnings of potential respiratory depressant effects.” Drug manufacturers are also being required to conduct clinical trials to evaluate the abuse potential of all gabapentinoids, particularly when combined with opioids, said Throckmorton. The downside is that prescribers could inadvertently increase opioid use by not using these medications, Throckmorton acknowledged, saying “we do not want to unintentionally increase opioid use by turning prescribers away from this class of pain medications.” For more information, go to https://www.fda.gov/drugs/drug‐safety‐and‐availability/fda‐warns‐about‐serious‐breathing‐problems‐seizure‐and‐nerve‐pain‐medicines‐gabapentin‐neurontin .     

Spin your science into gold: direct to consumer marketing within social media platforms

We describe the emerging issues related to warnings with respect to pharmaceutical company use of the internet as a vehicle for direct-to-consumer marketing (DTC) and market research. We describe the various techniques pharmaceutical companies have used to exploit this new communications medium which permits two way exchange of information. The Food and Drug Administration (FDA) has not issued any specific regulations to control internet based misbranding. We describe some examples of the FDA's application of historic regulations to pharmaceutical company use of this new medium and suggest.     

Medical cannabis needs tweaks to get full AMA support

Physicians who want help from the American Medical Association (AMA) in what to tell their patients about medical marijuana aren't going to get it — at least not yet. The AMA wants to see research, is opposed to legalization via a non–Food and Drug Administration (FDA) approach, wants a warning label, wants immunity for physicians and wants no criminal sanctions when patients and physicians discuss treatment options.     

FDA orders addition to boxed warning for benzodiazepines

Last week, the Food and Drug Administration (FDA) announced it is requiring an update to the boxed warning on benzodiazepines to include the risks of abuse, misuse, addiction, physical dependence and withdrawal reactions.     

FDA warns against high doses of Benadryl

In a Drug Safety Communication issued Sept. 24, the U.S. Food and Drug Administration (FDA) is warning that taking higher‐than‐recommended doses of the common over‐the‐counter (OTC) allergy medicine diphenhydramine (Benadryl) can lead to serious heart problems, seizures, coma or even death.     

FDA relents on Brixadi,competitor to Sublocade

Last week, Braeburn won its fight against Indivior to bring its injectable form of buprenorphine, Brixadi, to the U.S. market. The Food and Drug Administration (FDA) granted Braeburn's request to the FDA to revoke the orphan drug designation for Indivior's Sublocade. However, the FDA has reaffirmed exclusivity for Sublocade until next November.     

Pharmacotherapy for psychotropic drug-related weight gain

Weight gain is a significant problem for many patients taking various psychotropic medications. The U.S. Food and Drug Administration (FDA) has approved certain medications for the treatment of obesity. Other medications known to be associated with weight loss could be used for treating obesity, although they are not FDA approved for this indication. This article briefly describes the sympathomimetic, antidepressant, anticonvulsant, histamine-modulating, antidiabetic, and gastrointestinal drugs that have been found to cause weight loss and might be considered for adjunctive use in the overall management of psychotropic drug-related weight gain. However, even if such drugs are effective, all patients should receive ongoing dietary and physical activity counseling.     

AMA: Ban flavored vapes (House of Delegates: Ban all vapes)

It's time to ban all vaping products that are not approved by the Food and Drug Administration (FDA), according to a policy adopted by the American Medical Association (AMA) House of Delegates at the association's interim meeting in San Diego in November.     

Braeburn asks FDA to revoke Sublocade's orphan designation

Braeburn, which makes Brixadi, a buprenorphine injection, has filed a Citizen Petition calling on the Food and Drug Administration (FDA) to revoke “orphan designation” — exclusivity — for Sublocade, Indivior's injectable buprenorphine. Saying that unless the FDA does this, no competitive buprenorphine opioid use disorder (OUD) treatment will enter the market until 2024, Braeburn said the Orphan Drug Act was enacted to treat rare conditions with small patient populations. In some cases, the act is utilized even if a large population could benefit, if there is “no reasonable expectation” of recovering developing and marketing costs. Indeed, orphan drug designation (ODD) was granted to Subutex (buprenorphine) in 1994, when Indivior's predecessor was the sponsor. Now the FDA has “grandfathered” the Subutex designation to Sublocade “simply because the developer of Subutex and Sublocade is the same,” according to a press statement from Braeburn released earlier this month.     

A Note on CBD: It's All in a Name

I recently saw an article with the following title: “Medical cannabis relieves symptoms in children with autism.” On reading it, I realized that the Drug Target Review was talking about cannabidiol, otherwise known as CBD, not THC (tetrahydrocannabinol, the psychoactive ingredient in cannabis). I also realized the words cannabis and marijuana are no longer useful in talking about marijuana now that CBD has been moved to Schedule V of the Controlled Substances Act when manufactured by GW Pharmaceuticals. Still, it is common to see CBD lumped with the hundreds of other cannabinoids, especially if not produced by a Food and Drug Administration (FDA)–approved pharmaceutical company where it is still classified as Schedule I by the Drug Enforcement Administration (DEA). I think this has implications for popular understanding and clinical utility.     

Sublocade: Why a placebo arm?

In a time when people are dying from illicit fentanyl overdoses, why would a trial for a new medication to treat opioid use disorder — a formulation of buprenorphine, already proven to be safe and effective in oral form — include a placebo arm? This was the question asked by many when the results of Indivior's trial for Sublocade, a buprenorphine injection that lasts a month, were published last month in The Lancet (see ADAW, Feb. 25). The trial results were what led to Sublocade's approval by the Food and Drug Administration (FDA) for the treatment of opioid use disorder more than a year ago (see ADAW, Dec. 11, 2017).     

More from Louis Baxter on doctors taking MAT

The question of whether or not doctors and other health care professionals on medication‐assisted treatment (MAT) are safe to practice medicine has been debated for the last few years since the advent of Food and Drug Administration (FDA)–approved MAT for opioid use disorder (OUD). The newly approved medications have been primarily buprenorphine formulations for OUD, naltrexone formulations for OUD and alcohol use disorder (AUD), and, most recently, an alpha 2‐adrenergic medication that specifically targets amelioration of opioid‐withdrawal symptoms from OUD (lofexidine). Quite frankly, the question of safety about medications to treat substance use disorder (SUD) has been asked since the development of methadone for OUD treatment more than 30 years ago.     

Sublocade trial data published: Better than placebo

Sublocade, a buprenorphine injection that lasts a month, was approved by the Food and Drug Administration (FDA) for the treatment of opioid use disorder more than a year ago (see ADAW, Dec. 11, 2017), but the data that led to the approval was not public. It was made public in an article by Sublocade manufacturer Indivior published Feb. 18 in The Lancet.     

Briefly Noted

Clayton Stafford died after using Vivitrol, and his family is suing Alkermes, the manufacturer, saying that the medication doesn't adequately treat addiction, compared to buprenorphine and methadone, and that the manufacturer knew this. In the lawsuit, California‐based law firm Lieff Cabraser alleges that Stafford, his parents and his treatment providers were misled into thinking Vivitrol was an appropriate treatment for his opioid use disorder. “Clayton Stafford's tragic death could have been avoided,” notes Lieff Cabraser partner Fabrice N. Vincent, who filed the lawsuit on behalf of the Stafford family. “The well‐reported defects in Vivitrol made Clayton's overdose a near‐foregone conclusion, and had the Staffords received accurate information about Vivitrol's risks and effective deficiencies from Alkermes, they would never have consented to its use by Clayton.” Naltrexone doesn't work to treat addiction and cravings, but just to block the effects of opioids, according to the lawsuit (and many others agree with this). “Because the patient's addiction is not adequately treated, the patient requires indefinite Vivitrol use to merely block the euphoric effects and keep the patient from seeking opiates,” Vincent said. “Patients therefore remain highly likely to relapse despite indefinite use of Vivitrol.” The lawsuit also makes note of Alkermes' direct‐to‐consumer marketing campaign, which extended into influencing the criminal justice system to use Vivitrol. Stafford had been mandated to use Vivitrol. Last year, the Food and Drug Administration issued a warning letter to Alkermes stating that its advertising did not state that stopping Vivitrol can lead to relapse and overdose, as is clearly stated by the label and package insert (see “FDA warns Alkermes about OD risk on Vivitrol ads,” ADAW, Dec. 16, 2019, https://onlinelibrary.wiley.com/doi/10.1002/adaw.32566 ).     

A critical evaluation of the cardiac toxicity of citalopram: part 1

In August 2011, the U.S. Food and Drug Administration issued a safety announcement that the antidepressant drug citalopram (Celexa(?)) should not be used at dosages greater than 40 mg per day (or greater than 20 mg per day for patients 60 and older) because it can cause abnormal changes in the electrical activity of the heart. This warning was based on the results of a "thorough QT/QTc study" of citalopram and on post-marketing reports of QT prolongation and torsade de pointes in some patients taking the drug. The statistically significant results from the "thorough QT/QTc study" were small in magnitude, and their clinical significance is questionable. Additional electrocardiogram analyses from other studies do not confirm these findings. Nearly 600 cases of citalopram overdoses have been described. Although citalopram overdose is not entirely "cardiac safe," only a proportion of patients develop QTc prolongation without serious cardiac sequelae and no deaths. Three studies comparing citalopram overdoses to other antidepressant overdoses do not demonstrate clinically meaningful differences in cardiotoxic effects.