Recent FDA Safety Warnings About Drugs for Insomnia, Dietary Supplements

The Food and Drug Administration (FDA) recently issued two important safety alerts for doctors and patients. The first alert described risks of serious, often fatal injuries linked to use of the three so-called “Z-drugs” for insomnia. The second warned women of childbearing age not to use vinpocetine, an ingredient found in many widely available dietary supplements.

Z-drugs alert

On April 30, the FDA issued a safety alert advising doctors and patients that some patients using the commonly prescribed insomnia drugs eszopiclone (LUNESTA), zaleplon (SONATA) and zolpidem (AMBIEN, EDLUAR, ZOLPIMIST) have suffered serious injuries, some resulting in death, because of dangerous complex sleep behaviors caused by the drugs.[1] These sleep behaviors include sleepwalking, sleep driving and engaging in other activities without being fully awake. As a result, the agency is requiring that the manufacturers of these drugs add black-box warnings, the most stringent warnings that the agency can require, about these risks to the labeling and patient Medication Guides for these products.

The FDA’s action was prompted by a review of adverse events reported to the agency and of additional cases published in medical journals. From December 1992 — when zolpidem, the first Z-drug, was approved — to February 2018, the FDA received reports of 62 cases of complex sleep behaviors that resulted in serious injury or death after use of eszopiclone, zaleplon or zolpidem. Four additional cases were described in medical journal articles.

Of the 66 cases, 20 resulted in death. For the 46 cases involving nonfatal injuries, the patients typically had no recollection of these complex sleep behaviors. The reported adverse events included falls with serious injury, such as head trauma with bleeding in or around the brain, spine fractures and hip fractures, or death; accidental overdoses; hypothermia (dangerously low body temperature from exposure to the cold); suicides; fatal motor vehicle accidents; gunshot wounds; carbon monoxide poisoning; and drowning or near drowning.

These adverse events were reported in patients with and without a history of complex sleep behaviors prior to taking a Z-drug. They also occurred in some patients at the lowest recommended dose and even after just a single dose. Additionally, these complex sleep behaviors can occur after taking Z-drugs with or without alcohol or other central nervous system depressant medications, such as tranquilizers, opioids and anti-anxiety drugs.

The FDA noted that how the Z-drugs cause complex sleep behaviors is not completely understood. The FDA advised patients to stop taking their insomnia medicine and contact their health care professional immediately if they experience complex sleep behaviors where they engaged in activities while not fully awake or if they do not remember activities that they have done while taking the medicine.

The new FDA warning reinforces our long-standing designation of Z-drugs and other drugs for insomnia as Do Not Use because their risks far outweigh their benefits. See the article “New Study Finds Frequent Unsafe Use of the Sleep Aid Zolpidem” in our February 2019 issue for steps you can take to sleep better and longer without resorting to drugs.

Vinpocetine alert

On June 3, the FDA issued a statement warning women of childbearing age about safety concerns regarding vinpocetine, an ingredient found in many widely available dietary supplements.[2] The agency’s warning was prompted by data from animal research conducted by the National Institutes of Health’s (NIH’s) National Toxicology Program, which showed that vinpocetine may cause miscarriage and harm fetal development. The FDA advised “pregnant women and women who could become pregnant not to take vinpocetine.” The agency also asked companies that manufacture dietary supplements containing vinpocetine to ensure that labeling of these products provides similar safety warnings.

Vinpocetine is a synthetic compound derived from certain naturally occurring substances found in a type of plant called Vinca minor L. and in Voacanga seeds.[3] Importantly, vinpocetine is not a naturally occurring component of these plants or any other plants. As a result, the FDA in 2016 announced its tentative conclusion that vinpocetine does not meet the legal definition of a dietary ingredient and is excluded from the definition of a dietary supplement. However, the FDA has since failed to take appropriate regulatory action to ban the use of vinpocetine in dietary supplements.

Vinpocetine is sold in dietary supplements by itself and in combination with other ingredients.[4] It may be referred to on product labeling by other names, including Vinca minor extract, lesser periwinkle extract and common periwinkle extract. In some foreign countries, vinpocetine is regulated as a prescription medication.

According to the NIH’s National Toxicology Program, vinpocetine is marketed in the U.S. as a dietary supplement primarily to enhance cognitive function in patients with Alzheimer’s disease, dementia and ischemic stroke.[5] The agency noted that it also is promoted as a brain supplement for students to improve cognitive performance. Additionally, healthy athletes within the bodybuilding community use vinpocetine to reduce body fat and to enhance visual acuity, memory and focus. Other reported uses include treatment of urinary incontinence, tinnitus (ringing sensation in the ears), visual impairment, menopause symptoms, chronic fatigue syndrome and seizures, and prevention of motion sickness. As with all dietary supplements, the FDA has not assessed the safety and effectiveness of vinpocetine for any of these uses.

In studies sponsored by the NIH’s National Toxicology Program, scientists exposed pregnant rats to vinpocetine. These studies showed that the substance caused miscarriages and fetal abnormalities involving the heart and skeleton in the rats.[6] In its assessment of the data, the FDA noted that the blood levels of vinpocetine measured in the pregnant rats “were similar to those reported in people after taking a single dose of vinpocetine, indicating that pregnant women may experience [similar] adverse effects.”[7]

In its June 3 statement, the FDA indicated that it now plans to “expedite completion of the administrative proceeding” regarding the agency’s tentative conclusion in 2016 that vinpocetine, since it does not occur naturally, fails to meet the legal definition of a dietary ingredient and is excluded from the definition of a dietary supplement.[8]

You should not use dietary supplements containing vinpocetine (or Vinca minor extract, lesser periwinkle extract or common periwinkle extract), particularly if you are a woman who is pregnant or could become pregnant.
 

References

[1] Food and Drug Administration. FDA drug safety communication: FDA adds boxed warning for risk of serious injuries caused by sleepwalking with certain prescription insomnia medicines. April 30, 2019. https://www.fda.gov/drugs/drug-safety-and-availability/fda-adds-boxed-warning-risk-serious-injuries-caused-sleepwalking-certain-prescription-insomnia. Accessed July 18, 2019.

[2] Food and Drug Administration. Statement on warning for women of childbearing age about possible safety risks of dietary supplements containing vinpocetine. June 3, 2019. https://www.fda.gov/news-events/press-announcements/statement-warning-women-childbearing-age-about-possible-safety-risks-dietary-supplements-containing. Accessed June 11, 2019.

[3] Food and Drug Administration. Vinpocetine in dietary supplements. June 3, 2019. https://www.fda.gov/food/dietary-supplement-products-ingredients/vinpocetine-dietary-supplements. Accessed June 11, 2019.

[4] Food and Drug Administration. Statement on warning for women of childbearing age about possible safety risks of dietary supplements containing vinpocetine. June 3, 2019. https://www.fda.gov/news-events/press-announcements/statement-warning-women-childbearing-age-about-possible-safety-risks-dietary-supplements-containing. Accessed June 11, 2019.

[5] National Institutes of Health, National Toxicology Program. Peer Review Draft NTP Technical Report on the Prenatal Developmental Toxicity Study of Vinpocetine (CAS No. 42971-09-5) in Sprague Dawley (Hsd:Sprague Dawley SD) Rats and New Zealand White (Hra:NZW SPF) Rabbits (Gavage Studies). Scheduled peer review date: 2019. https://ntp.niehs.nih.gov/ntp/about_ntp/trpanel/2019/july/dart03_508.pdf. Accessed June 11, 2019.

[6] Ibid.

[7] Food and Drug Administration. Statement on warning for women of childbearing age about possible safety risks of dietary supplements containing vinpocetine. June 3, 2019. https://www.fda.gov/news-events/press-announcements/statement-warning-women-childbearing-age-about-possible-safety-risks-dietary-supplements-containing. Accessed June 11, 2019.

[8] Ibid.