FDA Grants Approval to Generic Extended-Release Memantine/Donepezil and Everolimus

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Updated Thursday, January 23 at 12:06PM.

The FDA approved memantine/donepezil (Amneal Pharmaceuticals) oral extended-release capsules, a generic of Namzaric (AbbVie), for the treatment of moderate to severe dementia of the Alzheimer type. In addition, the FDA granted approval to everolimus (Amneal Pharmaceuticals), a generic for Afinitor Disperz (Novartis), extended-release capsules for the treatment of tuberous sclerosis complex (TSC)-associated subependymal giant cell astrocytoma in adult and pediatric patients who are 1 year and older.¹

Newly approved generic memantine/donepezil is available in 14-mg/10-mg and 28-mg/10-mg extended-release capsules, and generic everolimus is available in 2-mg, 3-mg and 5-mg extended-release tablets.¹

Memantine/donepezil extended-release capsules are a made up of memantine hydrochloride (HCl), an NMDA receptor antagonist, and donepezil HCl, an acetylcholinesterase inhibitor indicated for the treatment of moderate to severe dementia of the Alzheimer type in patients who are stabilized on 10 mg of once-daily donepezil HCl.² For patients on donepezil hydrochloride 10 mg only, the recommended starting dose of memantine/donepezil extended-release capsules is 7 mg/10 mg, taken once daily in the evening. The dose should be increased in 7-mg increments at a 1-week minimum interval between increases to the recommended maintenance dose of 28 mg/10 mg.²

In a 24-week double-blind, placebo-controlled trial which enrolled 676 patients with moderate to severe dementia of the Alzheimer type, patients were randomly assigned to receive either memantine HCl at 28 mg per day (n = 341) or placebo plus a stable dose of donepezil for 3 months prior to screening (n = 335). The most common adverse events (AEs)—which occurred at a frequency of at least 5% and greater than placebo—were headache, diarrhea, and dizziness. In the memantine HCl and placebo groups, the rate of AEs that led to treatment discontinuation were about 10% and 6%, respectively. The most common was dizziness, which affected about 1.5% of patients.²

Additionally, donepezil HCl also demonstrated safety in controlled clinical trials evaluating patients with severe Alzheimer disease. For patients on donepezil HCl, the rate of discontinuation because of AEs was approximately 12%, compared with 7% for those on placebo. The most common were anorexia (2%), nausea (2%), diarrhea (2%), and urinary tract infection (2%). Other common AEs reported were diarrhea, anorexia, vomiting, nausea, and ecchymosis, and in mild to moderate Alzheimer disease, they were insomnia, muscle cramp, and fatigue.²

Further, everolimus oral extended-release tablets are indicated for both adult and pediatric patients who are aged 1 year and older with TSC-SEGA that requires therapeutic intervention but cannot be curatively resected. Doses are available in 2-, 3-, and 5-mg tablets, and for patients with TSC-SEGA, 4.5 mg/m² can be taken once per day and doses can be adjusted to attain trough concentrations of 5 ng/mL to 15 ng/mL.³

In a randomized, double-blind, placebo-controlled phase 3 clinical trial, EXIST-1 (NCT00789828), 117 patients with TSC-SEGA were enrolled and randomly assigned to receive either oral everolimus at a starting dose of 4.5 mg/m² (which was subsequently titrated to attain a whole blood trough concentration of 5 to 15 ng/mL) or placebo.^3,4 The median treatment was 52 weeks (24-89 weeks) for patients receiving everolimus.³

During the trial, the most common AEs reported were stomatitis and respiratory tract infection, and grade 3 or 4 AEs included stomatitis, pyrexia, pneumonia, gastroenteritis, aggression, agitation, and amenorrhea. Additionally, the most common laboratory abnormalities were hypercholesterolemia and elevated partial thromboplastin time. Neutropenia was grade 3 or 4 in severity. Further, there were no AEs which led to permanent discontinuation of treatment.³

REFERENCES

1. Businesswire. 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. News release. January 23, 2025. Accessed January 23, 2025. https://www.businesswire.com/news/home/20250123740756/en/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

2. National Institutes of Health. Memantine and donepezil hydrochlorides extended-release- memantine and donepezil capsule, extended release—Amneal Pharmaceuticals NY LLC. Accessed January 23, 2025. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=2335950c-be3b-4248-ad04-e9763aee47d2&type=display

3. National Institutes of Health. Everolimus- everolimus tablet, for suspension. Accessed January 23, 2025. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=6f1ae129-c21e-4c25-84c1-a6757d9a7eb2&type=display

4. Efficacy and Safety of Everolimus (RAD001) in Patients of All Ages With Subependymal Giant Cell Astrocytoma Associated With Tuberous Sclerosis Complex (TSC)(EXIST-1) (EXIST-1). ClinicalTrials.gov identifier: NCT00789828. Updated February 3, 2016. Accessed January 23, 2025. https://clinicaltrials.gov/study/NCT00789828