Clinical Highlights: January 2025 - Prime Therapeutics
Clinical Highlights: January 2025
Your monthly source for drug information highlights.
The Lancet Diabetes & Endocrinology Commission has published diagnostic criteria and definitions for clinical obesity. Obesity is distinguished by excess adiposity, with normal or abnormal distribution/function of adipose tissue. Causes of obesity are multifactorial and not completely understood. The Commission provides definitions for “clinical obesity” and “preclinical obesity” with the distinguishing factor being related to alterations in the function of tissues, organs, the person, etc. for clinical obesity and preserved function of tissues and organs for preclinical obesity. More specifically, clinical obesity is a chronic, systemic illness whereby patients exhibit changes in the function of tissues, organs, the entire body or a combination of these, due to excess adipose tissue. Furthermore, clinical obesity can result in severe end-organ damage as well as other complications (e.g., heart attack, stroke, renal failure). Patients with preclinical obesity are considered to have excess adipose tissue but maintain preserved function of tissues and organs. These patients still generally exhibit an increased likelihood for developing clinical obesity as well as other chronic diseases (e.g., type 2 diabetes mellitus [T2DM], cardiovascular disease [CVD], certain cancers, mental disorders). The Commission further details the diagnostic criteria for “clinical obesity” and “preclinical obesity” and the role of body-mass index (BMI).
The United States (U.S.) Food & Drug Administration (FDA) has issued a communication regarding concerns with unapproved glucagon-like peptide-1 (GLP-1) agents used for weight loss (e.g., semaglutide, tirzepatide). Dosing issues have arisen with use of compounded versions of these products, including some events that have led to hospitalization. Dosing errors have been caused by incorrect self-administration of the drugs by patients as well as miscalculation of the dose by health care professionals (HCPs). Furthermore, some patients have been prescribed higher doses than what is listed in the FDA-approved labeling. Inappropriate use of salt forms of semaglutide (e.g., semaglutide acetate, semaglutide sodium) has also been reported. These are different active ingredients than used in the approved drug, and the FDA does not have data showing if these salt forms have the same physiological properties as FDA-approved semaglutide. Illegal online sales of GLP-1s as well as counterfeit product (e.g., Ozempic) have also been described by the FDA.
In December 2024, the FDA concluded that the tirzepatide (Zepbound, Mounjaro) shortage had resolved. However, for both Zepbound and Mounjaro, it was noted that although a medication may be available, patients may not consistently be able to immediately fill a prescription at a certain pharmacy. The variation in availability can be due to ordering practices, retailer capacity constraints, and cold chain storage considerations. As a result, there may be variability at a given pharmacy location regardless of if the drug is in shortage. The FDA has issued a statement clarifying policies for compounders of GLP-1 medications as supply of these products stabilizes. The statement includes a description of when the agency does not intend to act against compounders for violations of the Federal Food, Drug & Cosmetic (FD&C) Act. State-licensed pharmacies under section 503A of the FD&C Act are permitted to compound, distribute or dispense tirzepatide injections until Feb. 18, 2025, and 503B outsourcing facilities are permitted to compound, distribute or dispense tirzepatide injections until March 19, 2025.
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The FDA’s Center for Drug Evaluation and Research (CDER) has published its annual report detailing new drug approvals in 2024. Fifty new drugs not previously approved or marketed in the U.S. received approval and 26 of these medications were approved for rare diseases affecting less than 200,000 individuals in the U.S. Nearly half of these 50 approvals were first-in-class agents. A total of 18 new biosimilars were approved, with eight of these biosimilars being approved for three reference products which did not previously have an FDA-approved biosimilar. The report also summarizes other notable actions including new/expanded indications, new formulations and new dosage forms that were approved in the past year. In 2024, the FDA’s Center for Biologics Evaluation and Research (CBER) approved 17 biologics license applications (BLAs) and 26 supplemental BLAs. A listing of 2024 BLA approvals is available on CBER’s website.
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The agency has issued a Federal Register notice recommending labeling changes for buprenorphine-containing transmucosal products for the treatment of opioid dependence (BTODs). The recommended changes aim to provide clarity regarding the maximum dosage of these therapies (e.g., Suboxone, Zubsolv, generics). The FDA states that neither 16 mg/day nor 24 mg/day should be considered the maximum dosage for these medications but rather that the maintenance dosages can be increased incrementally based on therapeutic need. Furthermore, doses higher than 24 mg per day may be appropriate for some individuals. As such, the phrase “target dose” is recommended to be removed from the labeling of these products, and the new labeling is recommended to read, “Dosages higher than 24 mg buprenorphine daily have not been investigated in randomized clinical trials but may be appropriate for some patients.”
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The FDA has issued a final rule with the intent of broadening the types of nonprescription drugs available to consumers. The rule establishes requirements for nonprescription drug products with an additional condition for nonprescription use (ACNU) that ensures appropriate self-selection and/or or appropriate actual use (e.g., questionnaire). The intent of the rule, effective Jan. 27, 2025, is to enhance consumer options for appropriate, safe and effective drug products. Currently, there are no FDA-approved nonprescription medications with ACNUs. Additional resources on this topic are available from the FDA.
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The agency announced an amendment to the color additive regulations to no longer allow FD&C Red No. 3 in ingested drugs. Manufacturers have until Jan. 18, 2028, to reformulate their products. The revocation is based on the Delaney Clause of the Federal FD&C Act that prohibits food additives or color additives if the additive has been shown to induce cancer in humans or animals. Due to a hormonal mechanism in male rats, elevated levels of FD&C Red No. 3 have been shown to cause cancer in male rat studies. Other animal and human studies did not demonstrate this same concern, and there is no evidence demonstrating FD&C Red No. 3 causes cancer in humans.
Shortage updates
Shortages of stimulants for the treatment of attention-deficit/hyperactivity disorder (ADHD) continue to be reported. Availability of generic methylphenidate hydrochloride (HCl) extended-release (ER) tablets is variable depending on the manufacturer. Brand-name Relexxii from Vertical, as well as brand-name Concerta from Janssen, are currently available. Generic amphetamine aspartate monohydrate, amphetamine sulfate, dextroamphetamine saccharate, and dextroamphetamine sulfate immediate release (IR) tablet shortages are also being reported; all strengths of brand-name Adderall IR tablets from Teva are available. Shortages of the generic version of Vyvanse, lisdexamfetamine dimesylate capsules and chewable tablets persist. Brand-name Vyvanse capsules and chewable tablets remain available from Takeda.
Drug information highlights
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The FDA has released a Drug Safety Communication on the addition of a Boxed Warning for anaphylaxis for multiple sclerosis (MS) medication glatiramer acetate (Copaxone, Glatopa). The FDA is aware of 82 cases of anaphylaxis associated with glatiramer acetate from December 1996 to May 2024 with 19 of these cases occurring more than a year after therapy initiation; six fatalities occurred related to these 82 cases. Symptoms of anaphylaxis have generally started within an hour of the injection; anaphylaxis can occur after the first dose or after months or years of therapy. It can be distinguished from common post-injection reactions based on symptom severity and worsening over time (severe rash, shock).
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The agency has updated the September 2024 Drug Safety Communication on fezolinetant (Veozah) to include the addition of a Boxed Warning to the product labeling. The Boxed Warning covers the potential for rare but serious liver injury associated with use of Veozah. In September 2024, the FDA added a warning to the product label regarding the risk for hepatic injury; this was added to the existing warning on increased liver function test values.
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The FDA has issued a Safety Communication on the risk of Guillain-Barré syndrome (GBS) with respiratory syncytial virus (RSV) vaccines Abrysvo and Arexvy. Findings from a post-marketing observational study conducted among Medicare beneficiaries ≥ 65 years of age suggest an increased risk of GBS with these vaccines in the 42 days following vaccination. As a result, product labeling for each vaccine has been updated to include these safety findings in the Warnings/Precautions sections.
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The U.S. Centers for Disease Control and Prevention (CDC) is reporting influenza-like illness (ILI) for the week ending Jan. 18, 2025 (week three). Seasonal influenza activity continues to increase across most of the U.S. with 24 jurisdictions reporting high activity and 15 reporting very high activity. The remainder of jurisdictions are reporting moderate, low or minimal activity. Influenza A(H1N1)pdm09 and A(H3N2) viruses continue to co-circulate this week. As of Jan. 10, 2024, the FDA is reporting available product from most manufacturers of antiviral influenza medications.
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Astellas has voluntarily recalled one lot of tacrolimus (Prograf) 0.5 mg capsules and one lot of tacrolimus ER (Astagraf XL) 0.5 mg capsules to the consumer level. Bottles from the recalled lots may contain empty capsules. Patients who take empty capsules may experience transplant rejection initiated by lack of immunosuppressive medication.
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Alcon has issued a voluntary recall for one lot of Systane Lubricant Eye Drops Ultra PF, Single Vials On-the-Go, 25-count to the consumer level. Following a customer complaint of foreign material inside a sealed single use vial, the manufacturer determined the foreign material to be fungal contamination. The product is used for the temporary relief of burning and irritation in individuals with dry eye symptoms.
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Endo has recalled all lots within expiry of Adrenalin Chloride Solution (epinephrine nasal solution) 30 mg/30 mL in 30 mL vials to the consumer level. As the product pre-dates the 1938 Federal FD&C Act, it was not submitted for FDA approval and is therefore an unapproved drug subject to recall. Furthermore, the FDA has found the product is misbranded with a misleading label similar in appearance to the FDA-approved drug Adrenalin (epinephrine injection) (1 mg/mL) 30 mL vial which is also manufactured by Endo.
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The FDA has issued a statement warning HCPs not to use unapproved epinephrine nasal solutions from BPI Labs and Endo as these products have been confused with FDA-approved injectable epinephrine (for intravenous [IV] use). Both the Endo and BPI Labs products are nasal solutions and should not be injected IV. The nasal solution and injectable formulation have similar packaging/containers and share the same manufacturers. Both products are used in hospitals and health care settings.
Drug information happenings
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The American Thoracic Society, CDC, European Respiratory Society and Infectious Diseases Society of America (IDSA) have published updated clinical practice guidelines for tuberculosis (TB) treatment in children and adults. Drug-susceptible TB recommendations include a four-month regimen for patients with pulmonary TB as well as a shortened four-month regimen for children with non-severe TB. Novel regimens including bedaquiline, pretomanid and linezolid +/- moxifloxacin are listed as updated drug-resistant TB recommendations.
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The Institute for Clinical and Economic Review (ICER) has released a final evidence report on the effectiveness of tabelecleucel (tab-cel) for treatment of Epstein-Barr virus positive post-transplant lymphoproliferative disease (EBV+ PTLD). The panel unanimously concluded that current evidence is adequate for a net health benefit for tab-cel compared to usual care for patients with relapsed/refractory EBV+ PTLD who have received at least one prior therapy.
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A Morbidity and Mortality Weekly Report (MMWR) details the expanded recommendations for use of pneumococcal conjugate vaccines (PVCs) among adults ≥ 50 years of age based on the Advisory Committee on Immunization Practices (ACIP) recommending a single dose of PCV for all adults ≥ 50 years of age who are PCV-naïve or who have unknown vaccination history. Previously, a single PCV dose was recommended for all adults ≥ 65 years of age. No changes were made to the existing recommendation of a single PCV dose for adults 19 to 64 years of age with risk conditions for pneumococcal disease.
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The U.S. Preventive Services Task Force (USPSTF) published final recommendations on screening for osteoporosis to prevent fractures. The Task Force recommends screening for osteoporosis to prevent osteoporotic fractures in (1) women ≥ 65 years of age and (2) postmenopausal women < 65 years of age who are at increased risk for an osteoporotic fracture as estimated by clinical risk assessment (Grade B for both populations). The Task Force concluded current evidence is inadequate to determine the balance of benefits and harms of screening for osteoporosis to prevent osteoporotic fractures in men (Grade I).
Disclaimer: The content in this publication is not a substitute for professional medical advice. For questions regarding any medical condition or if you need medical advice, please contact your health care provider.
All brand names are property of their respective owners.
Executive Editor: Anna Schreck Bird, PharmD
Deputy Editors: Erik Hamel, PharmD; Olivia Pane, PharmD, CDCES