The FDA has approved Dr. Reddy’s Laboratories’ celecoxib oral solution (Elyxyb) for the treatment of acute migraine in adults with or without aura. Notably, the non-steroidal anti-inflammatory drug (NSAID) was given the go-ahead with a boxed warning related to a risk of serious cardiovascular and gastrointestinal (GI) adverse events (AEs).1
The agency approval was granted based on the findings of 2 randomized, double-blind, placebo-controlled clinical trials: Study 1 (NCT03009019) and Study 2 (NCT03006276). Study 1 randomized patients to either 120-mg celecoxib (n = 316) or placebo (n = 315), while Study 2 randomized patients to 120-mg celecoxib (n = 311) or placebo (n = 311). Both studies reported a significant percentage of patients with freedom from the most bothersome symptom at 2 hours compared with placebo, and in Study 1, a markedly greater percentage achieved pain freedom at 2 hours post-dose.2
Current evidence-based guidelines for migraine care recommend nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin, diclofenac, ibuprofen, and naproxen, though literature suggests that these medications might increase the risk of GI AEs.
This oral solution’s boxed warning notes that NSAIDs can increase the risk of serious cardiovascular thrombotic events, such as myocardial infarction and stroke, thus Elyxyb is contraindicated in the setting of coronary artery bypass graft (CABG) surgery. Additionally, the label warns of possible spontaneous bleeding, ulceration, and perforation of the stomach or intestines, and that the elderly and those with prior history of peptic ulcer disease and/or GI bleeding are at higher risk.2
The selective cyclooxygenase (COX)-2 inhibitor was originally approved in capsule form as Celebrex (Pfizer) in 1998 and was indicated for the treatment of acute pain in patients with ankylosing spondylitis, osteoarthritis, primary dysmenorrhea, and rheumatoid arthritis. Of note, data suggest that compared with naproxen and ibuprofen, among those with patients with osteoarthritis and rheumatoid arthritis, celecoxib is associated with a significantly lower risk of gastrointestinal events and significantly lower risk of renal events.
In October 2019, the data from Study 1, which was conducted by Richard B. Lipton, MD, director, Montefiore Headache Center and professor of neurology, Albert Einstein College of Medicine and colleagues, were published in Headache. The assessment included 622 participants.3
At 2 hours post-dose, celecoxib treatment resulted in pain freedom for 35.6% (n = 98) of patients, compared with 21.7% (n = 57) of those on placebo (odds ratio [OR], 2.00; 95% CI, 1.36–2.94; P < .001) and most bothersome symptom freedom for 57.8% (n = 134) compared with 44.8% (n = 104) of those with placebo (OR, 1.68; 95% CI, 1.17–2.43; P = .007).
In total, 13.3% (n = 38) of those on celecoxib-treated subjects and 8.9% (n = 25) of placebo‐treated subjects reported a treatment‐emergent AE, with celecoxib‐related AEs reported by 9.1% (n = 26) of treated patients and 6.0% (n = 17) of those in the placebo group. The most common AEs were dysgeusia (celecoxib: 4.2%, n = 12; placebo: 1.4%, n = 4) and nausea (celecoxib: 3.2%, n = 9; placebo: 1.8%, n = 5). There were no deaths nor serious AEs reported, and no patients treated with celecoxib discontinued due to treatment AEs.
1. BRIEF-FDA Approves Dr. Reddy's Laboratories' Elyxyb Oral Solution For Acute Treatment Of Migraine With Or Without Aura In Adults. Reuters. Published online May 5, 2020. Accessed May 5, 2020. reuters.com/article/brief-fda-approves-dr-reddys-laboratorie/brief-fda-approves-dr-reddys-laboratories-elyxyb-oral-solution-for-acute-treatment-of-migraine-with-or-without-aura-in-adults-idUSFWN2CN10I
2. Elyxyb. FDA Label. FDA website. Updated May 2020. Accessed May 5, 2020. accessdata.fda.gov/drugsatfda_docs/label/2020/212157s000lbl.pdf
3. Lipton RB, Munjal S, Brand-Schieber E, Tepper SJ, Dodick DW. Efficacy, Tolerability, and Safety of DFN‐15 (Celecoxib Oral Solution, 25 mg/mL) in the Acute Treatment of Episodic Migraine: A Randomized, Double‐Blind, Placebo‐Controlled Study. Headache. Published online October 24, 2019. doi: 10.1111/head.13663