FDA Grants Tentative Approval to Generic Version of Rifaximin for IBS-D

Andy Boyer

Credit: Amneal Pharmaceuticals

The US Food and Drug Administration (FDA) has granted tentative approval to Amneal Pharmaceuticals’ rifaximin 550 mg oral tablets, which references Bausch Health’s Xifaxan, for the treatment of adults with irritable bowel syndrome with diarrhea (IBS-D).¹

According to a January 23, 2025, press release, the tentative approval is due to the product’s involvement in litigation. The decision comes alongside approvals for memantine/donepezil 14-10 mg and 28-10 mg extended-release capsules referencing Abbvie’s Namzaric for moderate to severe dementia of the Alzheimer’s type and Everolimus 2 mg, 3 mg, and 5 mg extended-release capsules referencing Novartis’ Afinitor Disperz for Tuberous Sclerosis Complex-Associated Subependymal Giant Cell Astrocytoma in adult and pediatric patients ≥ 1 year of age.¹

“Amneal’s competitive advantage in the Affordable Medicines business remains our core capabilities to drive innovation at scale across complex categories to expand the breadth and depth of our portfolio,” Andy Boyer, executive vice president and chief commercial officer of Affordable Medicines for Amneal Pharmaceuticals, said in a press release.¹ “With our 180-day exclusivity on memantine/donepezil, increasing supply for everolimus, and the tentative approval of rifaximin, we are continuing to expand our differentiated portfolio and providing new key therapies for our customers, providers and patients.”

Estimated to affect 10-15% of people in the US, IBS treatment has historically focused on changes in lifestyle, diet, and stress management. In the absence of a cure, medical treatment seeks for IBS to alleviate symptoms associated with the condition, although very few therapies are efficacious for all symptoms, which can include diarrhea and/or constipation, increased gas, and bloating.²

A synthetic antimicrobial derived from the parent compound, rifamycin, rifaximin has broad-spectrum bactericidal activity against both gram-positive and gram-negative aerobic and anaerobic bacteria. It acts on and inhibits the bacteria's ability to synthesize proteins by irreversibly binding to rpoB. Of note, because rifaximin is non-absorbable, it reaches high concentrations within the gastrointestinal lumen and can work effectively on various gastrointestinal diseases without systemic effects.³

Approved for the treatment of traveler's diarrhea in 2005 and hepatic encephalopathy risk reduction in 2010, the FDA approved Salix Pharmaceuticals’ Xifaxan (rifaximin) 550 mg for the treatment of IBS-D in adults in 2015. The decision was based on data from 3 phase 3 studies of more than 3000 patients, TARGET 1, TARGET 2, and TARGET 3, demonstrating its impact on stool consistency and abdominal pain as well as response to retreatment for recurrent symptoms versus placebo.⁴

In 2024, Bausch Health and Salix Pharmaceuticals filed a lawsuit against Amneal Pharmaceuticals after Amneal submitted an Abbreviated New Drug Application (ANDA) to the FDA seeking approval to market a generic version of rifaximin 550 mg tablets. The action formally initiated the litigation process and triggered a 30-month stay of any potential FDA approval for Amneal’s ANDA.⁵

References

1. ^{Amneal. Amneal Receives U.S. FDA Approval for Memantine/Donepezil Extended-Release Capsules and Everolimus Tablets for Oral Suspension, and Tentative U.S. FDA Approval for Rifaximin. January 23, 2025. Accessed January 23, 2025. https://investors.amneal.com/news/press-releases/press-release-details/2025/Amneal-Receives-U.S.-FDA-Approval-for-MemantineDonepezil-Extended-Release-Capsules-and-Everolimus-Tablets-for-Oral-Suspension-and-Tentative-U.S.-FDA-Approval-for-Rifaximin/default.aspx}
2. ^{ACG. Irritable Bowel Syndrome. Accessed January 23, 2025. https://gi.org/topics/irritable-bowel-syndrome/#tabs2}
3. ^{Robertson KD, Nagalli S. Rifaximin. StatPearls. May 22, 2023. Accessed January 23, 2025. https://www.ncbi.nlm.nih.gov/books/NBK562329/}
4. ^{Fierce Pharma. Salix Announces FDA Approval of Xifaxan® 550 mg for the Treatment of IBS-D (Irritable Bowel Syndrome with Diarrhea). December 14, 2015. Accessed January 23, 2025. https://www.fiercepharma.com/marketing/salix-announces-fda-approval-of-xifaxan%C2%AE-550-mg-for-treatment-of-ibs-d-irritable-bowel}
5. ^{Bausch Health. Bausch Health Announces Patent Lawsuit Against Amneal Pharmaceuticals. April 5, 2024. Accessed January 23, 2025. https://ir.bauschhealth.com/news-releases/2024/04-05-2024}