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WARNING LETTER

September 9, 2025

Dear Josh Disbrow:

As part of its monitoring and surveillance program, the U.S. Food and Drug Administration (FDA) has reviewed the promotional communications, Aytu Biopharma’s (Aytu) sponsored links¹ for COTEMPLA XR-ODT (methylphenidate extended-release orally disintegrating tablets), CII (Cotempla XR-ODT). FDA has determined that the sponsored links are false or misleading. Thus, the sponsored links misbrand Cotempla XR-ODT and make the distribution of the drug in violation of the Federal Food, Drug, and Cosmetic Act (FD&C Act). 21 U.S.C. 352(a), (e)(1)(B), (n); 321(n); 331(a). See 21 CFR 201.10(g)(1); 202.1(b)(1); 202.1 (e)(5); 314.81(b)(3)(i). These violations are especially concerning from a public health perspective because the promotional communications create a misleading impression about the safety and efficacy of Cotempla XR-ODT, a Schedule II controlled substance that bears a boxed warning due to the high potential for abuse and misuse, which can lead to overdose, death, and the development of a substance use disorder, including addiction.

Background

Below are the indication and summary of the most serious and most common risks associated with the use of Cotempla XR-ODT.² According to the INDICATIONS AND USAGE section of the PI:

COTEMPLA XR-ODT is indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in pediatric patients 6 to 17 years of age.

The PI for Cotempla XR-ODT contains a boxed warning regarding a high potential for abuse and misuse, which can lead to the development of a substance use disorder, including addiction. Cotempla XR-ODT is contraindicated in patients with a known hypersensitivity to methylphenidate or other components of Cotempla XR-ODT and in patients receiving concomitant treatment with monoamine oxidase inhibitors (MAOIs) or within 14 days following discontinuation of treatment with an MAOI. In addition, the PI for Cotempla XR-ODT includes warnings and precautions regarding risks to patients with serious cardiac disease; increased blood pressure and heart rate; psychiatric adverse reactions; priapism; peripheral vasculopathy, including Raynaud’s phenomenon; long-term suppression of growth in pediatric patients; acute angle closure glaucoma; increased intraocular pressure and glaucoma; and motor and verbal tics, and worsening of Tourette’s syndrome. The most common adverse reactions associated with methylphenidate products like Cotempla XR-ODT are appetite decreased, weight decreased, nausea, abdominal pain, dyspepsia, dry mouth, vomiting, insomnia, anxiety, nervousness, restlessness, affect lability, agitation, irritability, dizziness, vertigo, tremor, blurred vision, blood pressure increased, heart rate increased, tachycardia, palpitations, hyperhidrosis, and pyrexia.

False or Misleading Risk Presentation

Prescription drug advertisements and labeling (promotional communications) misbrand a drug if they are false or misleading with respect to risk. The determination of whether a promotional communication is misleading includes, among other things, not only representations made or suggested in the promotional communication, but also the extent to which the promotional communication fails to reveal facts material in light of the representations made or with respect to consequences that may result from the use of the drug as recommended or suggested in the promotional communication.

The sponsored links are misleading because they include representations about the efficacy of Cotempla XR-ODT but fail to communicate any risk information. For example, the sponsored links for Cotempla XR-ODT appearing in searches include statements such as “Cotempla XR-ODT for ADHD” or “Cotempla XR-ODT Works Fast - Once-Daily ADHD Medication” in the headline.

We acknowledge that some variations of the sponsored links include the statements “Medication Guide”, “Important Safety Info”, and/or “Side Effects”; however, these statements, alone or in combination, do not mitigate the misleading omission of risk information. By omitting risk information associated with Cotempla XR-ODT, the sponsored links fail to provide material information about the consequences that may result from the use of the drug and create a misleading impression about the drug’s safety.

False or Misleading Claims about Efficacy

Promotional communications misbrand a drug if they are false or misleading with respect to efficacy. The determination of whether a promotional communication is misleading includes, among other things, not only representations made or suggested in the promotional communication, but also the extent to which the promotional communication fails to reveal facts material in light of the representations made or with respect to consequences that may result from the use of the drug as recommended or suggested in the promotional communication.

The sponsored links for Cotempla XR-ODT include misleading representations about its efficacy, such as:

Cotempla XR-ODT for ADHD – Concerta Substitute Learn how Cotempla XR-ODT may help your child. Talk to your child’s doctor today. Having a hard time finding Concerta? Equivalent option to Concerta is available. Medication Guide. Important Safety Info. Patient Savings Offer.

The representation that Cotempla XR-ODT is a “substitute” for or is “equivalent” to Concerta® is misleading because it suggests that Cotempla XR-ODT is therapeutically equivalent to, and therefore substitutable for, Concerta, when that has not been demonstrated. Cotempla XR-ODT and Concerta are variations of methylphenidate;³ however, they have not been shown to be therapeutically equivalent to one another.⁴ An approved drug may be determined to be therapeutically equivalent to another if it is a pharmaceutical equivalent for which bioequivalence has been demonstrated, and it can be expected to have the same clinical effect and safety profile when administered to patients under the conditions specified in the labeling.⁵ In this case, the Cotempla XR-ODT PI states a dosage form, dosage strength, and maximum daily dosage that are different from those of Concerta. For example, the PI for Cotempla XR-ODT states that the drug is an extended-release orally disintegrating tablet, with dosage strengths of 8.6 mg, 17.3 mg, and 25.9 mg, and a maximum daily dosage not to exceed 51.8 mg. On the other hand, the Concerta PI states the drug is a tablet to be swallowed whole, with dosage strengths of 18 mg, 27 mg, 36 mg, and 54 mg, and a maximum daily dosage of 54 mg in children and 72 mg in adolescents and adults. Given Cotempla XR-ODT’s differences from Concerta in dosage form, dosage strengths, and maximum daily dosage, the drugs are not substitutable and representations suggesting the drugs are “equivalent” are misleading.

Failure to Use Required Established Name

The established name of a prescription drug must be presented prominently, in direct conjunction with the proprietary name. The sponsored links fail to present the established name for Cotempla XR-ODT, thereby misbranding the product.

Failure to Submit Under Form FDA-2253

FDA regulations require any labeling or advertising devised for promotion of the drug product to be submitted at the time of initial dissemination of the labeling and at the time of initial publication of the advertisement for a prescription drug product. Each submission is required to be accompanied by a completed transmittal Form FDA-2253 (Transmittal of Advertisements and Promotional Labeling for Drugs for Human Use) and is required to include a copy of the product’s current professional labeling. A copy of the sponsored links was not submitted to FDA under cover of Form FDA-2253 at the time of initial publication as required by 21 CFR 314.81(b)(3)(i).

Conclusion and Requested Action

For the reasons discussed above, the sponsored links misbrand Cotempla XR-ODT and make the distribution of the drug in violation of the FD&C Act. 21 U.S.C. 352(a), (e)(1)(B), (n); 321(n); 331(a). See 21 CFR 201.10(g)(1); 202.1(b)(1); 202.1 (e)(5). Furthermore, Aytu did not comply with 21 CFR 314.81(b)(3)(i).

This letter notifies you of our concerns and provides you with an opportunity to address them. You should take immediate action to address any violations (including, for example, ceasing and desisting promotional communications that are misleading as described above). Failure to adequately address any violations may result in legal action without further notice, including, without limitation, seizure and injunction. Please submit a written response to this letter within 15 working days from the date of receipt, addressing the concerns described in this letter, listing all other promotional communications (with the 2253 submission date) for Cotempla XR-ODT that contain representations such as those described above, and explaining your plan for discontinuation of such communications, or for ceasing distribution of Cotempla XR-ODT.

If you believe that your products are not in violation of the FD&C Act, please include in your submission to us your reasoning and any supporting information for our consideration within 15 working days from the date of receipt of this letter.

Additionally, we request that your submission include a comprehensive plan of action to disseminate truthful, non-misleading, and complete corrective communication(s) about the concern(s) discussed in this letter. The corrective communication(s) should be disseminated to the audience(s) that received the promotional communication(s) identified in the opening paragraph of this letter. We recommend that corrective communication(s) include a description of the promotional communication(s) identified in this letter, which misbrand Cotempla XR-ODT; include a summary of the concern(s) described in this letter; and provide information to correct each of these concern(s). Corrective communication(s) should be free of promotional claims and presentations. To the extent possible, corrective communication(s) should be distributed using the same media, and generally for the same duration of time and with the same frequency as the promotional communication(s) identified in the opening paragraph of this letter.

The concerns discussed in this letter do not necessarily constitute an exhaustive list of potential violations. It is your responsibility to ensure compliance with each applicable requirement of the FD&C Act and FDA implementing regulations.

Please direct your response to the Food and Drug Administration, Center for Drug Evaluation and Research, Office of Prescription Drug Promotion, 5901-B Ammendale Road, Beltsville, Maryland 20705-1266. A courtesy copy can be sent by facsimile to (301) 847-8444. Please refer to MA 143 in addition to the NDA number in all future correspondence relating to this particular matter. All correspondence should include a subject line that clearly identifies the submission as a Response to Warning Letter. You are encouraged, but not required, to submit your response in eCTD format. All correspondence submitted in response to this letter should be placed under eCTD Heading 1.15.1.6. Questions related to the submission of your response letter should be emailed to CDEROPDP- RPM@fda.hhs.gov.

Sincerely,
{See appended electronic signature page}
George Tidmarsh, M.D., Ph.D.
Director
Center for Drug Evaluation and Research

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This is a representation of an electronic record that was signed electronically. Following this are manifestations of any and all electronic signatures for this electronic record.
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/s/
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CARTER M BEACH
09/09/2025 05:08:26 PM
On behalf of George Tidmarsh, M.D., Ph.D

Promotional Material

1. 1Available at https://www.google.com (last accessed September 8, 2025).
2. 2This information is for background purposes only and does not necessarily represent the risk information that should be included in the promotional communication(s) cited in this letter.
3. 3Cotempla XR-ODT was approved as a 505(b)(2) application, referencing Metadate CD (methylphenidate hydrochloride).
4. 4Electronic Orange Book, Approved Drug Products with Therapeutic Equivalence Evaluations, current through March 2025. Available at https://www.accessdata.fda.gov/scripts/cder/ob/index.cfm (last accessed September 8, 2025)
5. 521 CFR 314.3(b)