FDA Makes Class-Wide Labeling Changes to Testosterone Products

On Feb. 28, 2025, FDA informed testosterone product sponsors of new changes to labeling, after the agency reviewed findings from a clinical trial and results from required postmarket ambulatory blood pressure (ABPM) studies (1).

The results of the clinical trial, Testosterone Replacement Therapy for Assessment of Long-term Vascular Events and Efficacy Response in Hypogonadal Men (TRAVERSE), will be added to language on all testosterone products, per FDA’s recommendation (1). “Limitation of Use” language is recommended to be retained with regard to hypogonadism—in other words, when the body’s sex glands produce an insufficient level of hormones—that is age-related, and language from the Boxed Warning pertaining to elevated risk of adverse cardiovascular outcomes is slated to be removed.

Meanwhile, data from the ABPM studies have prompted FDA to require other changes to current labeling, namely, adding product-specific information on increased blood pressure for those products that have had completed ABPM studies and a new warning about increased blood pressure for products on which such a warning does not currently appear (1).

FDA said that these labeling changes have roots as far back as 2014, when a Drug Safety Communication issued in January of that year warned of risks that had been reported of stroke, heart attack, and death, specifically, in men who had taken FDA-approved testosterone products (1). A joint meeting of the Bone, Reproductive and Urologic Drugs and the Drug Safety and Risk Management Advisory Committee later that year resulted in the launch of the TRAVERSE trial, for which results were reported in 2023. FDA further recommended APBM studies in premarket development of subcutaneous injection and oral testosterone products in 2016 and 2017, respectively, following that with the issuing of a postmarket requirement in March 2018 that individual ABPM studies be conducted for all such products.

FDA frequently provides updates on changes to drug labels, or when those labels have been deemed to be misleading. An example of the latter occurrence happened in December 2024, when the agency announced Endo USA, Inc.’s voluntary recall of all lots of a vasoconstrictor for topical application, Adrenalin Chloride Solution (EPINEPHrine nasal solution, USP) 30 mg/30 mL (1 mg/mL) 30 mL vials (2). In addition to that product never having been approved by FDA, it was found to be misbranded with a misleading label similar to another FDA-approved drug made by the same company, which, in FDA’s estimation made telling the difference between the non-sterile topical product and the approved sterile injectable difficult, leading to potential administration errors.

In February 2025, Astellas Pharma said that FDA updated the labeling for its avacincaptad pegol intravitreal solution (brand name IZERVAY) by approving the drug to treat geographic atrophy secondary to age-related macular degeneration without a limitation on duration of dosing (3). That approval followed a resubmission in December 2024 of a supplemental new drug application for the solution.

Furthermore, FDA issued a draft guidance in December 2024 explaining procedures and criteria for the agency’s accelerated drug approval for serious conditions (4). Contained in that document was a stipulation that one of the conditions or requirements for accelerated approval is that “a succinct description of limitations of usefulness and anticipated benefits must be included in the drug label’s Indications and Usage section with a reference to the Clinical Trials section” (4).

In its release regarding labeling changes based on the TRAVERSE trial, FDA reminded both patients and healthcare professionals to file anyadverse events or quality issues stemming from a medication’s use to its MedWatch Adverse Event reporting program, either by completing and submitting an online form, or downloading a PDF of the form and faxing it upon completion to 1-800-FDA-0178 (1).

References

1. FDA. FDA Issues Class-Wide Labeling Changes for Testosterone Products. Press Release. Feb. 28, 2025.
2. FDA. Endo USA, Inc. Issues Voluntary, Nationwide Recall of Adrenalin Chloride Solution (EPINEPHrine Nasal Solution, USP) Due to the Potential for Administration Errors. Press Release. Dec. 20, 2024.
3. Astellas Pharma. US FDA Approves Expanded Label for Astellas’ IZERVAY (avacincaptad pegol intravitreal solution) for Geographic Atrophy. Press Release. Feb. 13, 2025.
4. FDA. Expedited Program for Serious Conditions–Accelerated Approval of Drugs and Biologics, Guidance for Industry, Draft Guidance (CDER, CBER, December 2024).