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RE:  NDA 216117
RELEXXII® (methylphenidate hydrochloride extended-release tablets) for oral use, CII MA 38

WARNING LETTER

Dear Harold A. Deas:

The U.S. Food and Drug Administration (FDA) has reviewed the promotional communications, Alora Pharmaceuticals, LLC’s (Alora) sponsored links¹² (3342-v2.1) for RELEXXII® (methylphenidate hydrochloride extended-release tablets) for oral use, CII (Relexxii), submitted by Osmotica Pharmaceutical US LLC (Osmotica) under cover of Form FDA 2253. FDA has determined that the sponsored links are false or misleading. Thus, the sponsored links misbrand Relexxii 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), (n); 321(n); 331(a). See 21 CFR 202.1 (e)(5). These violations are especially concerning from a public health perspective because the promotional communications create a misleading impression about the safety of Relexxii, 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 Relexxii.³ According to the INDICATIONS AND USAGE section of the FDA-approved Prescribing Information (PI):

RELEXXII is indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in adults (up to the age of 65 years) and pediatric patients 6 years of age and older.

The PI for Relexxii 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. Relexxii is contraindicated in patients with a known hypersensitivity to methylphenidate or other components of Relexxii 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 Relexxii 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; potential for gastrointestinal obstruction; 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 Relexxii in adults are decreased appetite, headache, dry mouth, nausea, insomnia, anxiety, dizziness, weight decreased, irritability, and hyperhidrosis. The most common adverse reaction in pediatric patients 6 to 17 years is abdominal pain upper.

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 Relexxii but fail to communicate any risk information. For example, the sponsored links appearing in searches include the statements, “Once-Daily ADHD Treatment” or “Tailored Treatment for ADHD” in the headline, in conjunction with “RELEXXII (methylphenidate ER).” In addition, the sitelink extension “Bring Life Into Focus” appears with these representations in some variations of the sponsored links.

We note the sponsored links include the statement, “See Boxed Warning, Full PI and Safety Information on relexxii.com”; however, this statement does not mitigate the misleading omission of risk information. By omitting risk information associated with Relexxii, 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.

Conclusion and Requested Action

For the reasons discussed above, the sponsored links misbrand Relexxii and make the distribution of the drug in violation of the FD&C Act. 21 U.S.C. 352(a), (n); 321(n); 331(a). See 21 CFR 202.1 (e)(5).

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 Relexxii that contain representations such as those described above, and explaining your plan for discontinuation of such communications, or for ceasing distribution of Relexxii.

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 Relexxii; 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 38 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. Additionally, the response submission should be coded as an Amendment to eCTD Sequence 0051 under NDA 216117. Questions related to the submission of your response letter should be emailed to CDER-OPDP-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/
CARTER M BEACH 09/09/2025 05:14:50 PM
On behalf of George Tidmarsh, M.D., Ph.D

1. 1The sponsored link materials submitted by Osmotica under Form FDA 2253 were titled “Alora Pharmaceuticals Relexxii Paid Search Campaign.” Alora is the parent company of Osmotica.
2. 2Available at https://www.google.com (Last accessed September 5, 2025). These communications are responsive to searches of consumers seeking information about Relexxii.
3. 3This 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.