Drug Safety Label Updates: February 2024
A report on notable recent FDA safety label changes: contrast agents used in MRIs, eczema drug Dupixent, cancer drug Keytruda, diabetes drug Rybelsus, and bipolar drug Lybalvi.
New Boxed Warning for MRI Gadolinium Contrast Agents
Boxed warnings were added to the labels of six gadolinium-based contrast agents (GBCAs). These drugs are used as part of magnetic resonance imaging (MRI) procedures to provide enhanced image quality for diagnosis of conditions such as multiple sclerosis or cancer. The new notice warns users not to inject the drug into the spinal canal (intrathecally) because of the risk of serious adverse reactions including death, coma, encephalopathy, and seizures.
“Macrocyclic” GBCAs Safety Labeling Change:
“Linear” GBCAs Safety Labeling Change:
More on Emerging GBCA Health Warnings:
The U.S. Food & Drug Administration issued a safety communication in May 2018 regarding gadolinium retention in the body and the brain and the risk of Nephrogenic Systemic Fibrosis (NSF) that may affect those with impaired kidney function who use the drug. However, the FDA maintains that “Gadolinium retention has not been directly linked to adverse health effects in patients with normal kidney function, and we have concluded that the benefit of all approved GBCAs continues to outweigh any potential risks.”
There are two types of GBCAs based on chemical structure: the older linear GBCAs, which result in more retention of gadolinium in the body and retention for a longer time, and the more recent macrocyclic GBCAs, which are associated with far less retention in the body. Because of this, macrocyclic agents are often the first-choice type of contrast agents for both brain and full-body MRIs.
The National Center for Health Research, a patient advocacy group, conducted its own investigation of GBCAs: “NCHR Report: The Health Risks of MRIs with Gadolinium-Based Contrast Agents.” They state that gadolinium-associated conditions that are not associated with poor kidney function have not been recognized by the FDA, WHO, or major medical societies, but should be. They also advocate for research on treatments for gadolinium retention and related symptoms.
https://www.center4research.org/health-risks-of-gbcas/
“Gadolinium Toxicity” website is devoted to increasing awareness of the effects of gadolinium. One of the authors wrote an editorial suggesting a reason why some patients may have side effects even from macrocyclic GBCAs.
https://gadoliniumtoxicity.com/2021/03/06/are-macrocyclic-gbcas-safer-than-linear-agents/
“An estimated 13 million contrast-enhanced MRI procedures are performed annually in the United States to help inform doctors’ decisions,” said Konstanze Diefenbach, MD, global head of radiology research & development at Bayer. Nevertheless, since no one wants any trace of a heavy metal like gadolinium in their body days or years after an MRI, Bayer is developing a potentially safer contrast agent called Gadoquatrane, currently in Phase 3 clinical trials. It has a 60% lower dose of gadolinium than currently available GBCAs. The trial is scheduled to conclude in November 2024.
https://multiplesclerosisnewstoday.com/news-posts/2023/07/03/gadoquatrane-mri-contrasting-agent-safety-phase-3-trials/
Dupixent
Regeneron’s eczema drug Dupixent (dupilumab) had a safety label change to report additional results of pediatric studies and to approve Dupixent for use in children age 1 to 11 with allergic inflammation of the esophagus. The drug was approved for the same condition (eosinophilic esophagitis) in children 12 and up in 2022. Children with the condition often find it difficult to swallow food. One study involved 72 pediatric patients age 12 to 17 and the other included 61 patients age 1 to 11. Researchers determined the safety profile of Dupixent for children was similar to that for adults. Last month, the label was updated to report dry eye as a common side effect.
https://www.reuters.com/business/healthcare-pharmaceuticals/us-fda-approves-dupixent-treat-younger-kids-with-esophageal-condition-2024-01-25/
Keytruda
Keytruda (pembrolizumab injection) had a safety label change to report clinical trials results (KEYNOTE-394) relating to Hepatocellular Carcinoma (HCC), which is a liver cancer. Merck’s Keytruda is approved for HCC for people who have previously been treated sorafenib.
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Rybelsus
Novo Nordisk’s Rybelsus (semaglutide), the only non-injectable (pill) form of GLP-1 diabetes drug, had a safety label update to warn of newly discovered post marketing experiences of dizziness and distorted sense of taste (dysgeusia).
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Lybalvi
The drug label for Alkermes’ bipolar drug Lybalvi (olanzapine; samidorphan) was updated to warn that the drug may cause false positive test results for opioid detection tests. This is because LYBALVI contains samidorphan, an opioid antagonist, that may be cross-reactive with urinary immunoassay methods. The label advises to tell your healthcare provider that you are taking Lybalvi if you take a urine drug screening test because LYBALVI may affect your test results.