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Homeopathic company refuses to recall life-threatening nasal spray, FDA says

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Dangerous —

Consumers should stop using SnoreStop, FDA says.

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Homeopathic company refuses to recall life-threatening nasal spray, FDA says

The maker of a homeopathic nasal spray with a history of contamination is refusing to recall its product after the Food and Drug Administration once again found evidence of dangerous microbial contamination.

In a warning Thursday, the FDA advised consumers to immediately stop using SnoreStop nasal spray—made by Green Pharmaceuticals—because it may contain microbes that, when sprayed directly into nasal cavities, can cause life-threatening infections. The FDA highlighted the risk to people with compromised immune systems and also children, since SnoreStop is marketed to kids as young as age 5.

According to the regulator, an FDA inspection in April uncovered laboratory test results showing that a batch of SnoreStop contained “significant microbial contamination.” But, instead of discarding the batch, FDA inspectors found evidence that Green Pharmaceuticals had repackaged some of the contaminated lot and distributed it as single spray bottles or as part of a starter kit.

In response, Green Pharmaceuticals destroyed the remainder of the tainted lot and stopped selling the nasal spray on its website. (It is still selling its SnoreStop throat spray, chewable tablets, and pet products, which includes a nasal spray.) But, according to the FDA, it refused to recall products that may contain product from the tainted lot. The agency said it “reiterated its recall recommendation multiple times” in August and September. But, “To date, the company has not taken action to recall this potentially dangerous product from the market.”

Ars has reached out to Green Pharmaceuticals for comment but has not received a response.

Tainted history

SnoreStop.

Enlarge / SnoreStop.

This isn’t new territory for the company. In 2022, Green Pharmaceuticals got warnings from the FDA and issued a recall due to microbial contamination in its SnoreStop nasal spray. In June 2022, the FDA held a conference with the company over findings of bacteria and fungi in the spray. Some of the results suggested high levels of microbial contamination. “The individual sample results varied between 420 and up to 6,200 colony forming units (CFU)/mL for total aerobic microbial count… and between 30 and up to 3,800 CFU/mL for total yeast and mold counts,” the FDA reported in a December 2022 warning letter sent after the fact.

The FDA also noted finding the specific bacterial pathogen Providencia rettgeri, an opportunistic germ that can lurk in health care settings. It’s most often linked to urinary tract infections, but it can also cause pneumonia, brain and spinal cord infections, heart infections, and wound and bloodstream infections in vulnerable people, according to a 2018 review.

“The high bioburden in conjunction with the route of administration with this drug product poses a high risk of harm to vulnerable patients, including children,” the FDA wrote in its warning letter. Green Pharmaceuticals recalled SnoreStop in June 2022, after its meeting with the FDA.

Dangerous dilutions

Aside from the gross microbial contamination, the FDA also noted in its letter that SnoreStop appears to be an unapproved new drug, illegally claiming to treat a disease without FDA approval. SnoreStop is a homeopathic product, meaning it is based on pseudoscience. Homeopaths falsely believe that if substances, including poisons, cause the same symptoms as illnesses, the substance can cure those illnesses (“like cures like”). The reason the products don’t poison users is because homeopaths also believe that diluting substances into oblivion enhances their curative properties (“law of infinitesimals”). Some dilutions are so extreme that not a single molecule of the starting substance is present in homeopathic products. And some homeopaths have argued that water molecules can have a “memory” of the substance, which, they contend, explains how the products work.

SnoreStop is said to contain dilutions of: nux vomica (a natural source of strychnine), belladonna (deadly nightshade), Ephedra vulgaris (a source of the drug ephedrine), hydrastis canadensis (a toxic herb), Kali Bichromicum (potassium dichromate, which is considered toxic and carcinogenic), Teucrium marum (similar to catnip), and Histaminum hydrochloricum (Histamine dihydrochloride).

Consumer advocates have worked for years to try to get homeopathic products off of store shelves, where they’re sometimes sold alongside evidence-based, FDA-approved over-the-counter medicines. While homeopathic products are mostly harmless and ineffective—offering placebo effects at best—they can turn deadly when manufacturers mishandle the dilutions. For instance, in 2016, the FDA linked improperly diluted belladonna in homeopathic teething products to the deaths of 10 infants and the poisonings of more than 400 others.

Homeopathic company refuses to recall life-threatening nasal spray, FDA says Read More »

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ADHD med shortages push DEA to up drug allotment by 23.5%

adderall, ADHD, controlled substances, DEA, drug shortages, fda, health, Science, Vyvanse / /

drug boost —

The DEA’s quota increase is for Vyvanse and its generic forms.

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ADHD med shortages push DEA to up drug allotment by 23.5%

While supplies of Adderall and its generic versions are finally recovering after a yearslong shortage, the Drug Enforcement Administration is now working to curb the short supply of another drug for attention-deficit/hyperactivity disorder: Vyvanse (lisdexamfetamine) and its generic versions.

This week, the DEA said it will increase the allowed production amount of lisdexamfetamine by roughly 23.5 percent, increasing the current 26,500 kg quota by 6,236 kg, for a new total of 32,736 kg. The DEA also allowed for a corresponding increase in d-amphetamine, which is needed for production of lisdexamfetamine.

“These adjustments are necessary to ensure that the United States has an adequate and uninterrupted supply of lisdexamfetamine to meet legitimate patient needs both domestically and globally,” the DEA said.

Quotas

Just like Adderall (amphetamine/dextroamphetamine salts), Vyvanse (lisdexamfetamine) is an amphetamine-class stimulant classified by the DEA as a Schedule II drug. As such, the DEA controls its production levels to ensure demand is met while preventing excess supply that could find its way to the black market. The administration does this by setting an “aggregate production quota”—which is what the DEA adjusted for lisdexamfetamine this week—and doling out undisclosed allotments to drug manufacturers.

While various factors have contributed to the shortages of ADHD medications, some medical and industry groups have placed blame on the DEA’s quota system for underestimating demand and choking supply. For instance, the Adderall shortage began in 2022 following a labor shortage on the product’s production line at Teva, Adderall’s maker. But, while that production snag was resolved, prescription rates increased significantly, in part due to increased awareness of ADHD, broadening diagnosis criteria, and an increase in access with the rise of telehealth services, which boomed during the COVID-19 pandemic. In a report earlier this year, the American Society of Health-System Pharmacists pointed to the DEA’s quotas, saying they’re “exacerbating” shortages.

In an August 2023 joint letter, the DEA and the FDA responded to such criticism, suggesting that the quotas aren’t to blame. Rather, it’s that some manufacturers are not using up their allotment of controlled drugs.

“Based on DEA’s internal analysis of inventory, manufacturing, and sales data submitted by manufacturers of amphetamine products [which include the two ADHD drugs], manufacturers only sold approximately 70 percent of their allotted quota for the year, and there were approximately 1 billion more doses that they could have produced but did not make or ship. Data for 2023 so far show a similar trend,” the FDA and DEA wrote.

The FDA and DEA said they would work with manufacturers to ensure they would ramp up production of drugs in short supply or relinquish their remaining allotments.

Vyvanse shortage

A similarly complicated situation is seen with the current shortfall of Vyvanse and its generics. The DEA raised the quota after prodding from the Food and Drug Administration. In July, the FDA sent the DEA a letter requesting a quota increase. However, the shortage had actually begun in June 2023. At that time, Vyvanse’s maker, Takeda, said that a “manufacturing delay compounded by increased demand” had led to low inventory.

In August 2023, the FDA approved multiple generic versions of Vyvanse after Takeda’s patent exclusivity expired, raising hopes that the shortage would ease with the injection of new generics. But supply problems have persisted. In November, the Association for Accessible Medicines, which represents generic drugmakers, sent a letter to the DEA saying that generic manufacturers weren’t able to obtain enough raw material to “launch their products at full commercial scale,” because the quotas were standing in the way, according to reporting by Bloomberg.

FiercePharma reported another potential factor raised by lawmakers and industry watchers. Those onlookers took note of the timing of Takeda’s “manufacturing delays” just months before generics entered the market. With the significantly thinner profit margin of generic and off-patent drugs, there’s concern that manufacturers may de-prioritize production.

Last, the DEA flagged yet another factor in the supply chain: exports to foreign markets. While the FDA estimated a 6 percent increase in the domestic need for lisdexamfetamine between 2023 and 2024, the DEA’s export data showed a 34 percent increase in exports of lisdexamfetamine between 2022 and 2023, with expectations that exports would continue to increase this year and beyond. As such, the current 23.5 percent quota increase for lisdexamfetamine is only partly for domestic production. In fact, only a quarter of the 6,236 kg is intended for the US. Of the increased allotment, 1,558 kg is for domestic drug production, while the other 4,678 kg addresses increases in foreign demand, the DEA said.

ADHD med shortages push DEA to up drug allotment by 23.5% Read More »

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Tattoo ink sold on Amazon has high levels of weird and rare bacteria

bacteria, contamination, fda, health, microbiology, pathogens, recall, Science, Tattoo, tattoo ink / /

Infectious ink —

The recall announcement noted that the germs “present a health concern.”

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BARCELONA, SPAIN - 2021/10/02: Spanish tattoo artist Oscar Garcia works on a man, during the Expo. Fira de Barcelona hosts the XXIV edition of the Barcelona Tattoo Expo where tattoo artists from Spain and other countries exhibit tattoos and tattoo material such as ink, needles and special machinery for tattoo work. (Photo by Ramon Costa/SOPA Images/LightRocket via Getty Images)

Enlarge / BARCELONA, SPAIN – 2021/10/02: Spanish tattoo artist Oscar Garcia works on a man, during the Expo. Fira de Barcelona hosts the XXIV edition of the Barcelona Tattoo Expo where tattoo artists from Spain and other countries exhibit tattoos and tattoo material such as ink, needles and special machinery for tattoo work. (Photo by Ramon Costa/SOPA Images/LightRocket via Getty Images)

The Food and Drug Administration has been warning for years that some tattoo inks are brimming with bacteria—a large assortment that, when injected into your skin, can cause inflammatory reactions, allergic hypersensitivity, toxic responses, and, of course, straight-up infections. And, worse yet, the labels that say the inks are sterile are not reliable.

But, a recent recall of three tattoo pigments from the same manufacturer does a good job of illustrating the FDA’s concerns. The water-based inks, all from Sierra Stain, had a bizarre array of bacteria, which were found at high levels, according to FDA testing.

One ink product—described as “Carolina Blue”—offered a microbial menagerie, with six odd species identified. They included a bacterium that often dwells in the gastrointestinal system and can inflame the mucosal lining of the intestines (Citrobacter braakii), a water-borne bacterium (Cupriavidus pauculus), and several that cause opportunistic infections (Citrobacter farmer, Achromobacter xylosoxidans, Ochrobactrum anthropi, and Pseudomonas fluorescens). These are bacteria that don’t typically go about attacking humans but will if the conditions are right, including when they find themselves inside a human with a compromised immune system.

An ink called “UV China Pink” contained an unusual soil bacterium (Curtobacterium citreum/pusillum). And an “All Purpose Black” ink puzzlingly contained Acetobacter senegalensis, a bacterium first isolated from mangos in Senegal and used for industrial vinegar production in low-income countries.

The three inks were sold nationwide through Amazon. To date, there have been no reported infections or adverse reactions linked to these inks. But the FDA notes that reactions to contaminated inks can be difficult to accurately diagnose. The infections and skin responses can look like generic rashes and allergic responses, sometimes including lesions with red papules in areas where the ink was injected, the FDA notes. However, infections from tattoo ink can leave permanent scarring.

In a study published in July in Applied and Environmental Microbiology, FDA researchers tested 75 samples of tattoo and permanent makeup inks from 14 manufacturers. Of the 75 inks, 26 (35 percent) were contaminated with a total of 34 types of bacteria, many that were possibly disease-causing. Some of the bacteria were anaerobic, meaning they don’t need oxygen to grow, suggesting they could thrive in the low-oxygen environment of skin layers. Of the 40 tattoo inks specifically, nine (22 percent) were contaminated. Among all the ink samples, 49 were labeled “sterile” and, of those, 16 (33 percent) were contaminated.

The recall announcement noted that Sierra Stain is no longer in business. While the company lists a remaining email address, it did not immediately respond to a comment request from Ars on the bacteria found in their inks.

The FDA recommends that consumers be vigilant about the quality and safety of tattoo supplies and techniques. It also encourages tattoo artists to work in professional environments that can reduce the risk of contamination.

Tattoo ink sold on Amazon has high levels of weird and rare bacteria Read More »

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COVID shot now or later? Just getting it at all is great, officials respond.

CDC, COVID-19, fda, flu, health, HHS, Infectious disease, respiratory virus, RSV, Science, vaccines / /

Viral defences —

As the summer wave peaks, officials are prepping for the coming winter wave.

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A 13-year-old celebrates getting the Pfizer-BioNTech COVID-19 vaccine in Hartford, Connecticut, on May 13, 2021.

Enlarge / A 13-year-old celebrates getting the Pfizer-BioNTech COVID-19 vaccine in Hartford, Connecticut, on May 13, 2021.

With the impending arrival of the 2024–2025 COVID-19 vaccines approved yesterday, some Americans are now gaming out when to get their dose—right away while the summer wave is peaking, a bit later in the fall to maximize protection for the coming winter wave, or maybe a few weeks before a big family event at the end of the year? Of course, the group pondering such a question is just a small portion of the US.

Only 22.5 percent of adults and 14 percent of children in the country are estimated to have gotten the 2023–2024 vaccine. In contrast, 48.5 percent of adults and 54 percent of children were estimated to have gotten a flu shot. The stark difference is despite the fact that COVID-19 is deadlier than the flu, and the SARS-CoV-2 virus is evolving faster than seasonal influenza viruses.

In a press briefing Friday, federal health officials were quick to redirect focus when reporters raised questions about the timing of COVID-19 vaccination in the coming months and the possibility of updating the vaccines twice a year, instead of just once, to keep up with an evolving virus that has been producing both summer and winter waves.

“The current problem is not that the virus is evolving so much, at least in terms of my estimation,” Peter Marks, the top vaccine regulator at the Food and Drug Administration, told journalists. “It’s that we don’t have the benefits of the vaccine, which is [to say] that it’s not vaccines that prevent disease, it’s vaccination. It’s getting vaccines in arms.” When exactly to get the vaccine is a matter of personal choice, Marks went on, but the most important choice is to get vaccinated.

Estimates for this winter

The press briefing, which featured several federal health officials, was intended to highlight the government’s preparations and hopes for the upcoming respiratory virus season. The FDA, the Centers for Disease Control and Prevention, and the Department of Health and Human Services (HHS) are urging all Americans to get their respiratory virus vaccines—flu, COVID-19, and RSV.

CDC Director Mandy Cohen introduced an updated data site that provides snapshots of local respiratory virus activity, national trends, data visualizations, and the latest guidance in one place. HHS, meanwhile, highlighted a new outreach campaign titled “Risk Less. Do More.” to raise awareness of COVID-19 and encourage vaccination, particularly among high-risk populations. For those not at high risk, health officials still emphasize the importance of vaccination to lower transmission and prevent serious outcomes, including long COVID. “There is no group without risk,” Cohen said, noting that the group with the highest rates of emergency department visits for COVID-19 were children under the age of 5, who are not typically considered high risk.

So far, CDC models are estimating that this year’s winter wave of COVID-19 will be similar, if not slightly weaker on some metrics, than last year’s winter wave, Cohen said. But she emphasized that many assumptions go into the modeling, including how the virus will evolve in the near future and the amount of vaccine uptake. The modeling assumes the current omicron variants stay on their evolutionary path and that US vaccination coverage is about the same as last year. Of course, beating last year’s vaccine coverage could blunt transmission.

COVID shot now or later? Just getting it at all is great, officials respond. Read More »

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Path to precision: Targeted cancer drugs go from table to trials to bedside

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Path to precision: Targeted cancer drugs go from table to trials to bedside

Aurich Lawson

In 1972, Janet Rowley sat at her dining room table and cut tiny chromosomes from photographs she had taken in her laboratory. One by one, she snipped out the small figures her children teasingly called paper dolls. She then carefully laid them out in 23 matching pairs—and warned her kids not to sneeze.

The physician-scientist had just mastered a new chromosome-staining technique in a year-long sabbatical at Oxford. But it was in the dining room of her Chicago home where she made the discovery that would dramatically alter the course of cancer research.

Rowley's 1973 partial karyotype showing the 9;22 translocation

Enlarge / Rowley’s 1973 partial karyotype showing the 9;22 translocation

Looking over the chromosomes of a patient with acute myeloid leukemia (AML), she realized that segments of chromosomes 8 and 21 had broken off and swapped places—a genetic trade called a translocation. She looked at the chromosomes of other AML patients and saw the same switch: the 8;21 translocation.

Later that same year, she saw another translocation, this time in patients with a different type of blood cancer, called chronic myelogenous leukemia (CML). Patients with CML were known to carry a puzzling abnormality in chromosome 22 that made it appear shorter than normal. The abnormality was called the Philadelphia chromosome after its discovery by two researchers in Philadelphia in 1959. But it wasn’t until Rowley pored over her meticulously set dining table that it became clear why chromosome 22 was shorter—a chunk of it had broken off and traded places with a small section of chromosome 9, a 9;22 translocation.

Rowley had the first evidence that genetic abnormalities were the cause of cancer. She published her findings in 1973, with the CML translocation published in a single-author study in Nature. In the years that followed, she strongly advocated for the idea that the abnormalities were significant for cancer. But she was initially met with skepticism. At the time, many researchers considered chromosomal abnormalities to be a result of cancer, not the other way around. Rowley’s findings were rejected from the prestigious New England Journal of Medicine. “I got sort of amused tolerance at the beginning,” she said before her death in 2013.

The birth of targeted treatments

But the evidence mounted quickly. In 1977, Rowley and two of her colleagues at the University of Chicago identified another chromosomal translocation—15;17—that causes a rare blood cancer called acute promyelocytic leukemia. By 1990, over 70 translocations had been identified in cancers.

The significance mounted quickly as well. Following Rowley’s discovery of the 9;22 translocation in CML, researchers figured out that the genetic swap creates a fusion of two genes. Part of the ABL gene normally found on chromosome 9 becomes attached to the BCR gene on chromosome 22, creating the cancer-driving BCR::ABL fusion gene on chromosome 22. This genetic merger codes for a signaling protein—a tyrosine kinase—that is permanently stuck in “active” mode. As such, it perpetually triggers signaling pathways that lead white blood cells to grow uncontrollably.

Schematic of the 9;22 translocation and the creation of the BCR::ABL fusion gene.

Enlarge / Schematic of the 9;22 translocation and the creation of the BCR::ABL fusion gene.

By the mid-1990s, researchers had developed a drug that blocks the BCR-ABL protein, a tyrosine kinase inhibitor (TKI) called imatinib. For patients in the chronic phase of CML—about 90 percent of CML patients—imatinib raised the 10-year survival rate from less than 50 percent to a little over 80 percent. Imatinib (sold as Gleevec or Glivec) earned approval from the Food and Drug Administration in 2001, marking the first approval for a cancer therapy targeting a known genetic alteration.

With imatinib’s success, targeted cancer therapies—aka precision medicine—took off. By the early 2000s, there was widespread interest among researchers to precisely identify the genetic underpinnings of cancer. At the same time, the revolutionary development of next-generation genetic sequencing acted like jet fuel for the soaring field. The technology eased the identification of mutations and genetic abnormalities driving cancers. Sequencing is now considered standard care in the diagnosis, treatment, and management of many cancers.

The development of gene-targeting cancer therapies skyrocketed. Classes of TKIs, like imatinib, expanded particularly fast. There are now over 50 FDA-approved TKIs targeting a wide variety of cancers. For instance, the TKIs lapatinib, neratinib, tucatinib, and pyrotinib target human epidermal growth factor receptor 2 (HER2), which runs amok in some breast and gastric cancers. The TKI ruxolitinib targets Janus kinase 2, which is often mutated in the rare blood cancer myelofibrosis and the slow-growing blood cancer polycythemia vera. CML patients, meanwhile, now have five TKI therapies to choose from.

Path to precision: Targeted cancer drugs go from table to trials to bedside Read More »

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Buying shady weight loss drugs online is a bad idea, in case you were wondering

counterfeit drugs, diabetes, fda, JAMA, obesity, Ozempic, Science, wegovy, weight loss / /

buyer beware —

Risk assessment study of illegal online pharmacies offers some unsurprising data.

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Buying shady weight loss drugs online is a bad idea, in case you were wondering

Buying counterfeit weight loss drugs from illegal online pharmacies that don’t require prescriptions is, in fact, a very bad idea, according to a study published Friday in JAMA Network Open.

The counterfeit drugs are sold as equivalents to the blockbuster semaglutide drugs, Ozempic and Wegovy, which are prescription only. When researchers got their hands on three illegal versions, they found that the counterfeit drugs had low-purity semaglutide, had dosages that exceeded the labeled amount, and one had signs of bacterial contamination.

The three substandard drugs tested came from three different illegal online pharmacies, which sold them as generic semaglutide drugs for weight loss, appetite suppression, diabetes, and cardiovascular health. However, the researchers, led by scientists at the University of California, San Diego, and the University of Pécs in Hungary, had initially tried purchasing counterfeit drugs from six such sellers.

Three of the illegal pharmacies, which specifically sold Ozempic knockoffs, never delivered the drugs after researchers paid for them. Instead, the researchers were hit with “nondelivery” scams, in which the sellers requested additional, hefty payments, supposedly needed to get through customs. These extra fees ranged from $650 to $1,200—much more than what the researchers paid for small dosages of the counterfeit drugs, which ranged from $113 to $360 across the six sellers.

Rogue pharmacies

The Ozempic scams were run out of the rogue online pharmacies: weightcrunchshop.com, puremedsonline.com, and genius-pharmacy.com. The three pharmacies that delivered dubious drugs included semaspace.com, uschemlabs.com, and biotechpeptides.com.

Two of the sellers—semaspace.com and uschemlabs.com—have already received warning letters from the Food and Drug Administration for selling unapproved, misbranded drugs. At the time of publication, the Semaspace website was no longer reachable. The US Chem Labs site was still available, but their semaglutide vials were all listed as out of stock.

The study’s findings, while unsurprising, highlight the risk people may take in efforts to get hold of the popular drugs. Steep prices, lack of insurance coverage, and drug shortages have kept the drugs out of reach for many who could benefit from them. Compounding pharmacies have stepped in to make copycat versions. While these are legal and can come from legitimate pharmacies—ones that are properly registered and require prescriptions—they also carry risks. Compounded drugs are not approved by the FDA and may pose safety and efficacy risks. Last week, the FDA warned of increasing reports of people overdosing on semaglutide products made in compounding pharmacies, leading some patients to be hospitalized.

Buying shady weight loss drugs online is a bad idea, in case you were wondering Read More »

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People are overdosing on off-brand weight-loss drugs, FDA warns

diabetes, fda, GLP-1, health, Science, semaglutide, weight loss / /

Dosage disarray —

Bad math and unclear directions are behind overdoses of up to 20 times the normal amount.

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Wegovy is an injectable prescription weight-loss medicine that has helped people with obesity.

Enlarge / Wegovy is an injectable prescription weight-loss medicine that has helped people with obesity.

The US Food and Drug Administration has approved two injectable versions of the blockbuster weight-loss and diabetes drug, semaglutide (Wegovy and Ozempic). Both come in pre-filled pens with pre-set doses, clear instructions, and information about overdoses. But, given the drugs’ daunting prices and supply shortages, many patients are turning to imitations—and those don’t always come with the same safety guardrails.

In an alert Friday, the FDA warned that people are overdosing on off-brand injections of semaglutide, which are dispensed from compounding pharmacies in a variety of concentrations, labeled with various units of measurement, administered with improperly sized syringes, and prescribed with bad dosage math. The errors are leading some patients to take up to 20 times the amount of intended semaglutide, the FDA reports.

Though the agency doesn’t offer a tally of overdose cases that have been reported, it suggests it has received multiple reports of people sickened by dosing errors, with some requiring hospitalizations. Semaglutide overdoses cause nausea, vomiting, abdominal pain, fainting, headache, migraine, dehydration, acute pancreatitis, and gallstones, the agency reports.

Bad math

In typical situations, compounding pharmacies provide personalized formulations of FDA-approved drugs, for instance, if a patient is allergic to a specific ingredient, requires a special dosage, or needs a liquid version of a drug instead of a pill form. But, when commercially available drugs are in short supply—as semaglutide drugs currently are—then compound pharmacies can legally step in to make their own versions if certain conditions are met. However, these imitations are not FDA-approved and, as such, don’t come with the same safety, quality, and effectiveness assurances as approved drugs.

In the warning Friday, the FDA said that some patients received confusing instructions from compounding pharmacies, which indicated they inject themselves with a certain number of “units” of semaglutide—the volume of which may vary depending on the concentration—rather than milligrams or milliliters. In other instances, patients received U-100 (1-milliliter) syringes to administer 0.05-milliliter doses of the drug, or five units. The relatively large syringe size compared with the dose led some patients to administer 50 units instead of five.

The figure demonstrates how syringe size could lead some to an incorrect dosage.

Enlarge / The figure demonstrates how syringe size could lead some to an incorrect dosage.

FDA-approved semaglutide drugs, meanwhile, are dosed in milligrams and come in standardized concentrations. The agency received several reports of health care providers incorrectly converting from milligrams to units or milliliters, leading them to calculate the wrong dosages. With these math errors, some patients administered five to 10 times more semaglutide than intended.

“FDA recognizes the substantial consumer interest in using compounded semaglutide products for weight loss,” the agency wrote. “However, compounded drugs pose a higher risk to patients than FDA-approved drugs.” The agency urged patients and prescribers to only use compounded versions when absolutely necessary.

People are overdosing on off-brand weight-loss drugs, FDA warns Read More »

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Soda additive “no longer considered safe,” gets long-awaited FDA ban

brominated vegetable oil, BVO, fda, food additives, health, Mountain Dew, Science, Sun drop / /

Decades coming —

Brominated vegetable oil (BVO) is used in citrus sodas but has largely been phased out.

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Tops of citrus sodas at a manufacturing plant.

Enlarge / Tops of citrus sodas at a manufacturing plant.

After more than five decades of limbo, the Food and Drug Administration on Wednesday revoked the authorization of brominated vegetable oil (BVO) in food, banning an additive long known to have toxic effects that is already banned in Europe, Japan, Australia, New Zealand, and California.

BVO—simply vegetable oil that is modified with bromine—has been used in foods since the 1920s. It has often been used as a stabilizer for fruit flavorings, particularly in citrusy beverages, including sodas, to keep the citrus flavoring from separating and floating to the top. The FDA authorized the use of BVO just after gaining the authority to regulate food additives in 1958. By the early 1960s, the FDA had put BVO on its first inventory of food additives it deemed generally safe—designated “generally recognized as safe” or GRAS. But safety concerns quickly surfaced, and by the late 1960s, the FDA had already limited its use to a flavoring stabilizer and capped the amount that could be used to 15 parts per million.

That 15-ppm limit was authorized on an “interim basis,” pending more safety studies. In 1970, the FDA revoked the GRAS designation for BVO, but continued to allow the 15-ppm limit—on an interim basis—given that safety studies “did not indicate an immediate health threat from the limited use.”

“Disgraceful”

The interim safety limit stayed in place until now, as the FDA was waiting for more safety data. In the mid-2010s, following bans in Europe and Japan, the agency began to review BVO and commissioned its own studies. A resulting rat study, which the agency published in 2022, found that when rats were fed BVO at levels that mimicked humans’ exposure at the 15-ppm limit, the animals developed abnormalities in their thyroids, alterations in their hormone signaling, and accumulation of brominated fatty acids in their hearts, livers, and fat.

The FDA proposed its ban in November 2023. At the time, the FDA’s Deputy Commissioner for Human Foods, James Jones, hinted at the agency’s inactions by noting that the proposed restructuring at the agency was intended to “develop a faster and more nimble process for evaluating chemicals in the food supply.”

By then, most major soda makers had already phased BVO out of their citrusy sodas and other drinks amid public pressure. Coca-Cola pledged to remove BVO from its drinks in 2014, and PepsiCo confirmed in 2020 that it had removed it from its drinks, including Mountain Dew and Gatorade. The FDA reports that only a few beverages in the US still use the additive. Among the lingering users is Sun Drop, according to its product page.

Manufacturers have one year to reformulate their products, the FDA notes.

Consumer advocates chided the FDA while celebrating the ban. “The FDA’s decision to ban brominated vegetable oil in food is a victory for public health,” Scott Faber, senior vice president of government affairs at the Environmental Working Group, said in a statement. “But it’s disgraceful that it took decades of regulatory inaction to protect consumers from this dangerous chemical.”

Soda additive “no longer considered safe,” gets long-awaited FDA ban Read More »

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Microdosing candies finally recalled after psychoactive muscimol found

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Finally —

Muscimol, found in the candy, is from hallucinogenic Amanita muscaria mushrooms.

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Microdosing candies finally recalled after psychoactive muscimol found

After weeks of reports of severe illnesses across the country, the maker of Diamond Shruumz microdosing chocolates, gummies, and candy cones has finally issued a recall. It covers all lots and all flavors of all the brand’s products.

The illnesses have been marked by several severe symptoms, which notably include seizures, loss of consciousness, and the need for intubation and intensive care. To date, there have been 39 people sickened, including 23 hospitalizations across 20 states, according to the Food and Drug Administration and the Centers for Disease Control and Prevention. The FDA first issued a warning on the brand’s chocolate bars on June 7, when there were reports of eight cases, including six hospitalizations, in four states.

Diamond Shruumz’s parent company, Prophet Premium Blends, said in the recall notice that it had received only two complaints about the products to date and, upon receiving those complaints, reviewed recent laboratory analyses (Certificates of Analysis) of its products. According to the company, those CoAs noted “higher than normal amounts of muscimol,” which is one of two key compounds found in hallucinogenic Amanita mushrooms. Muscimol “could be a potential cause of symptoms consistent with those observed in persons who became ill after eating Diamond Shruumz products,” the company said in the recall notice.

In a statement posted on Diamond Shruumz’s website, Prophet Premium Blends announced the recall and added that it has also ceased production and distribution of all of the brand’s products.

“Due to consumers becoming ill after consuming the entire chocolate bar and some products containing higher levels of Muscimol than normal, it is crucial that all of our consumers refrain from ingesting this product while we, alongside the FDA, continue our investigation as to what is the cause of the serious adverse effects,” Prophet Premium Blends wrote on its website.

Diamond Shruumz has not responded to multiple requests for comment from Ars. Prophet Premium Blends did not respond to a request for comment and a list of questions.

What’s normal?

It’s unclear what amounts of muscimol were found in the company’s products and which products were affected. While the company reported only “higher than normal” amounts, it’s also unclear what the “normal” amount is. Diamond Shruumz posts third-party lab reports on its website, most of which indicate that the products are tested for muscimol. For instance, the reports show muscimol testing for all flavors of Cones and Extreme Gummies. For the brand’s chocolate bars, which the FDA first linked to the illnesses, all the bars except for the dark chocolate flavor showed muscimol results. For the gummies, only the report for the Hawaiian Punch flavor shows muscimol results. Of all the reports that include results for muscimol, all indicate that the amounts are lower than the limit of quantitation, which suggests that they are not supposed to contain any amount of muscimol. All of the reports reviewed by Ars were dated at various times throughout 2023.

Muscimol, along with related ibotenic acid, are both key psychoactive components of some Amanita mushrooms. That includes the hallucinogenic toadstool mushroom A. muscaria var. muscaria, which is notable for its unique bright red-orange caps with white warts. Both muscimol and ibotenic acid resemble neurotransmitters, namely GABA and glutamate, respectively. Muscimol is associated with depression of the central nervous system, while Ibotenic acid is associated with excitation of the central nervous system.

Fuzzy findings

According to the recall notice, it’s possible that the muscimol could cause some of the symptoms in people sickened, which included seizures, agitation, involuntary muscle contractions, loss of consciousness, confusion, sleepiness, nausea and vomiting, abnormal heart rates, and hyper/hypotension. The FDA said in its own update that it was “evaluating this information.”

The agency had previously identified the undisclosed synthetic psychedelic compound 4-AcO-DMT in the company’s chocolates, as well as undisclosed compounds found in a potentially toxic Kava plant (Piper methysticum). It remains unclear if any of those compounds explain the illnesses.

The totality of the ingredients in Diamond Shruumz’s products remains unclear. The company does not list the ingredients on its website, selling the products only with terms indicating they contain psychedelic compounds and the vague, buzzword-loaded description of having a “primo proprietary blend of nootropic and functional mushrooms.”

The CDC warns that such “edibles” are often sold as candies and snack food and might contain undisclosed ingredients, including illicit substances, adulterants, or potentially harmful contaminants. Common marketing terms to look out for include “microdosing,” “adaptogens,” “nootropics,” and “functional mushrooms,” the CDC warns.

Consumers should not eat, sell, or serve any Diamond Shruumz product. For those who have already purchased the products, they can be returned for a full refund to 1019 Arlington St., Orlando, Florida, 32805, according to Diamond Shruumz’s website.

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Synthetic psychedelic found in candies linked to seizures, intubation

4-AcO-DMT, candies, CDC, chocolate, diamond shruumz, fda, kava, piper methysticum, psilocybin, psychedelic, Science / /

Toxic trip —

Cases grow to 39, including 23 hospitalizations, across 20 states.

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A Diamond Shruumz chocolate bar, which comes in a variety of flavors.

Enlarge / A Diamond Shruumz chocolate bar, which comes in a variety of flavors.

The US Food and Drug Administration has identified a synthetic psychedelic compound as well as compounds from a potentially toxic plant in the Diamond Shruumz-brand microdosing candies linked to a growing number of severe illnesses nationwide that have included seizures, intubation, and admissions to intensive care units.

As of June 25, the case total has grown to 39, including 23 hospitalizations, across 20 states, the FDA and the Centers for Disease Control and Prevention reported.

It remains unclear what is in the candies and what may be causing the severe illnesses. Diamond Shruumz does not provide a full list of ingredients. The term “microdosing” and other marketing used by Diamond Shruumz suggests the candies contain a psychedelic compound, but the company does not name any. To figure it out, the FDA has been analyzing multiple samples of Diamond Shruumz-brand candies, including chocolates, gummies, and candy cones. On Tuesday, the FDA reported finding the synthetic psychedelic compound 4-AcO-DMT in the company’s Dark Chocolate Bar and its Birthday Cake Chocolate Bar.

As Ars reported previously, 4-AcO-DMT (aka 4- acetoxy-N,N-dimethyltryptamine, O-acetylpsilocin, or psilacetin) is a common synthetic tryptamine used in psychedelics and was previously suspected to be in the Diamond Shruumz candies. The psychoactive drug has a chemical structure similar to the most notable mushroom-derived psychedelic, psilocybin, as well as LSD. Though safety data on the compound is scant, it is not known to be linked to some of the severe symptoms seen in the current string of illnesses. People who use 4-Aco-DMT describe it as producing effects similar to psilocybin, but without some of the unpleasant side effects noted with natural mushrooms, such as nausea. Still, according to the CDC, some people who use it could experience nausea, vomiting, fast heart rate, anxiety, agitation, lightheadedness, or tremor.

Additionally, the FDA found three compounds from the Kava plant (Piper methysticum) in the company’s dark chocolate bar, though not the birthday-cake flavored bar. The compounds are kavalactones—desmethoxyyangonin, dihydrokavain, and kavain.

Concerning kava

Kava is a plant found on some Pacific Islands and is used in traditional herbal remedies for the treatment of anxiety, insomnia, stress, and other ailments. But, over the years, it has also occasionally been linked to severe liver toxicity. In the early 2000s, this led to warnings, withdrawals, and even bans in several countries, including Germany, Switzerland, France, Canada, and the UK. In 2002, the FDA issued an advisory of its own over the associated liver injuries, which include hepatitis, cirrhosis, and liver failure. Later that same year, researchers published case reports of 11 people (two in the US and nine in Europe) who developed liver failure after using kava products and needed subsequent liver transplants.

In an update on the illnesses linked to Diamond Shruumz candies, the CDC noted that kava can cause numbness of the mouth and skin, loss of coordination, dizziness, sedation, and gastrointestinal effects, such as nausea and vomiting. Consuming kava products alongside alcohol or drugs like benzodiazepines (e.g. Valium and Xanax) can heighten the sedative effects. But, the CDC seemed to downplay the risk of liver toxicity here, noting that it has only occasionally been associated with chronic or heavy ingestion of kava.

In all, it’s still unclear if the compounds the FDA identified in the Diamond Shruumz chocolate bars so far can explain the illnesses seen in the linked cases. The CDC lists the severe and common symptoms from those cases as including seizures, decreased level of consciousness, respiratory failure, nausea, vomiting, abdominal pain, hallucinations, uncontrolled movements, abnormal heart rate (e.g., too fast or too slow), high or low blood pressure, excessive sweating or secretions, and flushed skin.

The FDA said testing of other Diamond Shruumz products is still in progress. The agency noted that there can be differences across products and batches. In the meantime, the agency advises consumers not to eat, sell, or serve any of the company’s products and, instead, discard them.

There is still no recall of the candies. Diamond Shruumz has not responded to multiple inquiries from Ars. The FDA said Tuesday that the agency has “been in contact with the firm about a possible voluntary recall,” but to date, Diamond Shruumz has not initiated one.

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Top FDA official overrules staff to approve gene therapy that failed trial

clinical data, clinical trials, duchenne muscular dystrophy, elevidys, fda, fda approval, gene therapy, Peter Marks, sarepta, Science / /

Internal conflict —

Peter Marks overruled three teams and two top directors.

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Dr. Peter Marks, Director of the Center for Biologics Evaluation and Research within the Food and Drug Administration on March 18, 2021 in Washington, DC.

Enlarge / Dr. Peter Marks, Director of the Center for Biologics Evaluation and Research within the Food and Drug Administration on March 18, 2021 in Washington, DC.

The Food and Drug Administration (FDA) on Thursday announced expanded approval for a gene therapy to treat Duchenne muscular dystrophy (DMD)—despite the fact that it failed a Phase III clinical trial last year and that the approval came over the objections of three of FDA’s own expert review teams and two of its directors.

In fact, the decision to expand the approval of the therapy—called Elevidys (delandistrogene moxeparvovec-rokl)—appears to have been decided almost entirely by Peter Marks, Director of the FDA’s Center for Biologics Evaluation and Research.

Elevidys initially gained an FDA approval last year, also over objections from staff. The therapy intravenously delivers a transgene that codes for select portions of a protein called dystrophin in healthy muscle cells; the protein is mutated in patients with DMD. Last year’s initial approval occurred under an accelerated approval process and was only for use in DMD patients ages 4 and 5 who are able to walk. In the actions Thursday, the FDA granted a traditional approval for the therapy and opened access to DMD patients of all ages, regardless of ambulatory status.

“Today’s approval broadens the spectrum of patients with Duchenne muscular dystrophy eligible for this therapy, helping to address the ongoing, urgent treatment need for patients with this devastating and life-threatening disease,” Marks said in the announcement Thursday. “We remain steadfast in our commitment to help advance safe and effective treatments for patients who desperately need them.”

Criticism

The move, which follows a string of controversies in recent years of the FDA issuing questionable approvals over the assessments of advisors and its own staff, has quickly drawn criticism from agency watchers.

In a blog post Friday, a notable pharmaceutical industry expert and commentator, Derek Lowe, admonished the approval. Lowe expressed concern that the agency seems to be tilting toward emotional rhetoric and the will of patient advocates over scientific and medical evidence.

“It appears that all you need is a friend high up in the agency and your clinical failures just aren’t an issue any more,” he wrote. “Review committees aren’t convinced? Statisticians don’t buy your arguments? Who cares! Peter Marks is here to deliver hot, steaming takeout containers full of Hope. … And while I realize that this may make me sound like a heartless SOB, I think this is a huge mistake that we will be paying for for a long time.”

In a comment to Stat News, former FDA chief scientist Luciana Borio echoed concerns about how decisions like this will affect the agency in the longer term.

“I don’t know what to say. Peter Marks makes a mockery of scientific reasoning and approval standards that have served patients well over decades,” said Borio, who has also opposed earlier controversial approvals. “This type of action also promotes the growing mistrust in scientific institutions like the FDA.”

Internal dissent

In a series of review documents and memos released by the FDA, the divide between Marks and agency staff is abundantly clear. A review by FDA statisticians concluded that the collective clinical trial results “do not suggest there is substantial evidence to support the effectiveness of [Elevidys] for the expanded indication to all DMD patients and do not support the conversion of accelerated to traditional approval.”

A joint review from the agency’s Clinical and Clinical Pharmacology teams likewise concluded that the “totality of the data does not provide substantial evidence of effectiveness of Elevidys for treatment of ambulatory DMD patients of any age” and that the results “argue against” expanding access.

In a memo, Lola Fashoyin-Aje, Director of the Office of Clinical Evaluation in the Office of Therapeutic Products (OTP), and Dr. Nicole Verdun, Super Office Director of the OTP, concluded that the clinical results “cast significant uncertainty regarding the benefits of treatment of DMD with Elevidys.” The two directors found the primary clinical trial endpoint results were “not statistically significant” and smaller analyses looking at secondary endpoints of specific patient measures—such as the time it takes patients to rise from the floor or walk 10 meters—were “inconclusive,” in some cases “conflicting,” and overall illustrated the “unreliability of exploratory analyses to support regulatory decision-making.”

In a memo of his own, Marks agreed that primary endpoint result of the trial—based on scores on a standardized assessment of motor function in patients—did not show a statistically significant benefit. But he argued that the secondary endpoints were convincing enough for him. Marks wrote:

Specifically, although acknowledging that the Applicant’s randomized study of Elevidys failed to meet its statistical primary endpoint … I find that the observations regarding the secondary endpoints and exploratory endpoints are compelling and, combined with other data provided in the efficacy supplement and the original [Biologics License Application], meet the substantial evidence of effectiveness standard …

If Marks had not overruled the agency’s reviewers and directors, Fashoyin-Aje wrote that she would have recommended the therapy’s maker, Sarepta, conduct “an additional adequate and well-controlled study of Elevidys in the subgroup(s) of patients for which [Sarepta] believes the effects of Elevidys to be most promising.” However, Marks’ decision to approve renders the possibility of such a trial “highly infeasible to explore in a post-approval setting,” she wrote.

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Microdosing candy-linked illnesses double; possible recall in “discussions”

CDC, chocolate, cones, diamond shruumz, fda, gummies, intubation, microdosing, outbreak, psychedelic, recall, Science, seizures / /

No recall —

Of the 26 cases identified so far, 25 sought medical care and 16 were hospitalized.

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Microdosing candy-linked illnesses double; possible recall in “discussions”

Cases of illnesses linked to microdosing candies have more than doubled, with reports of seizures and the need for intubation, mechanical ventilation, and intensive care stays. But, there remains no recall of the products—microdosing chocolates, gummies, and candy cones by Diamond Shruumz—linked to the severe and life-threatening illnesses. In the latest update from the Food and Drug Administration late Tuesday, the agency said that it “has been in contact with the firm about a possible voluntary recall, but these discussions are still ongoing.”

In the update, the FDA reported 26 cases across 16 states, up from 12 cases in eight states last week. Of the 26 reported cases, 25 sought medical care and 16 were hospitalized. No deaths have been reported.

Last week, the Centers for Disease Control and Prevention released a health alert about the candies. The agency noted that as of June 11, the people sickened after eating Diamond Shruumz candies presented to health care providers with a host of severe symptoms. Those include: central nervous system depression with sedation, seizures, muscle rigidity, clonus (abnormal reflex responses), tremor, abnormal heart rate (bradycardia or tachycardia), abnormal blood pressure (hypotension or hypertension), gastrointestinal effects (nausea, vomiting, or abdominal pain), skin flushing, diaphoresis (excessive sweating), and metabolic acidosis with increased anion gap (an acid-based disorder linked to poisonings).

At the time of the CDC alert, 10 patients had been hospitalized, and “several required intubation, mechanical ventilation, and admission to an intensive care unit,” the agency reported.

It remains unclear what ingredient in the candies could be causing the poisonings. The FDA reports that it has worked with state partners to collect multiple samples of Diamond Shruumz products so they can be analyzed for potential toxic components. That analysis is still ongoing, the agency said.

Diamond Shruumz has not responded to multiple requests for comment from Ars.

Untold toxic ingredients

Diamond Shruumz does not list the ingredients of its products on its website. They are sold as “microdosing” candies, a term that typically suggests a small amount of a psychedelic compound is present. The company describes its chocolates, gummies, and cones as “trippy,” “psychedelic,” and “hallucinogenic,” and also claims they contain a “primo proprietary blend of nootropic and functional mushrooms.” But, it’s unclear what, if any, psychoactive compound is present in the candies.

The CDC notes that products like these “might contain undisclosed ingredients, including illicit substances, other adulterants, or potentially harmful contaminants that are not approved for use in food.”

Diamond Shruumz posted documents on its website from third-party laboratories claiming to indicate that the candies do not contain the most notable mushroom-derived psychedelic compound, psilocybin. The reports also indicate that some of the products do not contain cannabinoids or compounds from the hallucinogenic Amanita muscaria mushroom. Additionally, the company said in a blog post that its products contain a blend of Lion’s mane, Reishi, and Chaga mushrooms, but these are all non-hallucinogenic mushrooms used in herbal and traditional medicines and supplements.

In recent decades, hundreds of new synthetic psychoactive substances have hit the market in such products, including many new phenethylamines and tryptamines, which are chemically related to LSD and psilocybin. Some experts and members of the psychedelic community have speculated that Diamond Shruumz products could potentially contain one of the more popular tryptamines, 4-AcO-DMT, often pronounced  “4-akko-DMT,” and also known as 4- acetoxy-N,N-dimethyltryptamine, O-acetylpsilocin, or psilacetin. According to a qualitative 2020 study, users describe 4-AcO-DMT as producing effects similar to psilocybin, but without some of the unpleasant side effects noted with natural mushrooms, such as nausea. Animal experiments have confirmed that 4-AcO-DMT appears to produce psilocybin-like effects.

Still, it’s unclear if such ingredients could explain the symptoms seen in the current outbreak. Though clinical data on 4-AcO-DMT is scant, it has not been linked to such severe symptoms. On the other hand, some novel synthetic compounds, such as Dox and NBOMe, often misrepresented as LSD, are considered dangerous. For instance, NBOMe compounds (N-methoxybenzyl, also called N-bombs or 251), first discovered in 2003, have been linked to overdoses and deaths. In the scientific literature, they’ve been linked to “unpleasant hallucinations, panic, agitation, hypertension, seizures, acute psychosis, and/or excited delirium that can result in cardiac arrest,” according to the 2020 study.

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