Meloxicam and Rizatriptan (SYMBRAVO): A Bad Choice for Migraine

In January 2025 the Food and Drug Administration (FDA) approved a new fixed-dose oral combination drug (SYMBRAVO) for adults with acute migraine headaches with or without aura.[1] The drug combines meloxicam (generic only), a COX-2 selective nonsteroidal anti-inflammatory drug (NSAID), with a triptan called rizatriptan (MAXALT and generics).

Migraines are recurrent throbbing or pulsating headaches that are often debilitating and are frequently accompanied by bothersome symptoms such as nausea and sensitivity to light or sound.[2] Mild to moderate migraine attacks should first be treated with over-the-counter drugs such as acetaminophen (TYLENOL and generics) and non-selective, non-aspirin NSAIDs such as ibuprofen (ADVIL, MIDOL, MOTRIN and generics). Only if those medications fail to provide relief can triptans (such as sumatriptan [IMITREX and generics]) be tried.

There also is some evidence that combining a NSAID with a triptan can be more effective than using either class of drugs alone.[3] In 2008 the FDA approved such a fixed-dose combination drug (TREXIMET and generics) that combines sumatriptan and naproxen (ALEVE, NAPRELAN, NAPROSYN and generics) for the treatment of migraines.[4],[5]

Both meloxicam and rizatriptan are associated with important adverse effects, described in detail below. Moreover, meloxicam is not approved for the management of acute pain; the drug is approved for relief of osteoarthritis and rheumatoid arthritis symptoms.[6]

Public Citizen’s Health Research Group has designated meloxicam as a Do Not Use drug because of inadequate evidence that it is safer or more effective than some of the older NSAIDs, such as naproxen or ibuprofen.[7] We have designated triptans, including rizatriptan, as Limited Use drugs. We recommend triptans only be considered for migraine headaches if acetaminophen and NSAIDs have failed to provide relief.[8]

We are designating the new meloxicam-rizatriptan combination drug as Do Not Use because of the lack of adequate data about its efficacy and safety. Based on the limited data available, it appears that the combination drug is not more effective than rizatriptan alone.

At $128 per dose,[9] meloxicam-rizatriptan is much more expensive than the two component drugs that are available as generics: rizatriptan, which was approved in 1998,[10] and meloxicam, which was approved in 2004.[11]

Although the new drug includes a fast-acting form of meloxicam that is enabled by a proprietary technology called “Molecular Solubility Enhanced Inclusion Complex,” no publicly available data on this technology are available.[12] The prescribing information states that the new drug combination is “not substitutable with other formulations of oral meloxicam or oral rizatriptan products,” but no evidence to support this claim, such as a direct comparison of the fast-acting form of meloxicam with the generic drug, is included.

Evidence about effectiveness

The FDA approved the new meloxicam-rizatriptan combination based on the results of two clinical trials in adults with a history of migraine with or without aura.[13] One was a double-blind trial including 1,594 adults with a history of inadequate response to prior migraine treatments.[14] The participants

were randomized to receive either a single dose of the meloxicam-rizatriptan combination drug, meloxicam or rizatriptan alone (each in same doses as in the combination drug) or placebo after the onset of a migraine attack of moderate to severe pain intensity.

After two hours significantly more participants who received the combination drug were pain free (20% versus 7%) and free of their most bothersome migraine symptoms, such as nausea and sensitivity to sound or light (37% versus 24%), than those who had received placebo.[15] The median time to pain relief also was significantly faster for the combination drug (1.5 hours) than for rizatriptan or meloxicam alone (both 4 hours) or placebo (12 hours).[16]

However, the benefits were modest to nonexistent when the combination drug was compared with its component ingredients alone, especially compared with rizatriptan.[17] For example, almost as many participants in the rizatriptan (36%) and meloxicam (33%) groups were free of their most bothersome symptoms after two hours as those who received the combination drug (37%). Moreover, 32% of those who received the combination drug and 30% of those who received rizatriptan were able to perform normal daily activities after two hours, compared with 21% of those in the placebo group.

The second double-blind trial randomized 302 adults with a history of migraine to receive either the combination drug or placebo at the earliest onset of a migraine, when the pain was mild.[18],[19] As in the first trial, after two hours significantly more participants who received the drug treatment were free of pain (33% versus 16%) or free of their most bothersome symptoms (44% versus 27%) than those in the placebo group.

Safety concerns

The most common adverse events of the combination drug are nausea, somnolence and dizziness. These adverse events were observed in the double-blind trials, as well as in an additional open-label safety extension trial that enrolled 706 participants who completed either of the two clinical trials.[20],[21]

Both components of the combination drug are associated with serious adverse events.[22] The prescribing information for the new drug has a boxed warning — the FDA’s strongest warning — about an increased risk of serious and life-threatening cardiovascular thrombotic events, including stroke and myocardial infarction (heart attack), as well as an increased risk of serious and potentially life-threatening gastrointestinal adverse events, including bleeding and perforation of the stomach or intestines associated with the use of NSAIDs. The agency also warns that this drug should not be taken before or after coronary artery bypass graft surgery.

Serious adverse events include arrhythmias; medication overuse headaches; pain or pressure in the chest, throat, neck or jaw; serotonin syndrome (which can include hallucinations, irregular or fast heartbeat, and walking problems); heart failure; liver or kidney problems; and life-threatening skin reactions.[23],[24] The combination drug also should not be taken during pregnancy, especially after week 20 of gestation, because it can harm the developing fetus.

Additional concerns

As of September 2025, reports on the clinical trials had not been published and the results were only available in the form of short abstracts.[25] The investigators in both trials declared numerous ties to industry, and the manufacturer sponsored all three trials.[26],[27] There is also no evidence that the new drug combination performs better than the previously approved sumatriptan-naproxen combination, as the two drug combinations have not been directly compared in a clinical trial.

Although the meloxicam-rizatriptan combination drug is broadly approved for the treatment of acute migraine, the participants in clinical trials had a history of inadequate treatment responses and characteristics that are associated with poor treatment outcomes, such as obesity.[28],[29] The clinical trials also did not include participants aged 65 years or older, a group that is known to be at higher risk of some NSAID-associated adverse events.

What You Can Do

If you have migraine headaches, Public Citizen’s Health Research Group recommends that you do not use the new meloxicam-rizatriptan combination drug. To relieve acute migraine symptoms, try acetaminophen or NSAIDs first. If these drugs do not adequately relieve pain, discuss triptans and other treatment options with your clinician.
 

References

[1] Axsome Therapeutics. Label: meloxicam and rizatriptan (SYMBRAVO). January 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/215431s000lbl.pdf. Accessed August 27, 2025.

[2] Gepants, an expensive new class of migraine drugs: Do not use for seven years. Worst Pills, Best Pills News. April 2025. https://www.worstpills.org/newsletters/view/1652. Accessed August 27, 2025.

[3] Schwedt TJ, Garza, I. Acute treatment of migraine in adults. UpToDate. Updated May 2, 2025.

[4] A fixed-dose combination of meloxicam and rizatriptan (Symbravo) for migraine. Med Lett Drugs Ther. 2025;67(1727):68-70.

[5] Currax Pharmaceuticals. Label: sumatriptan and naproxen (TREXIMET). November 2024. https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/021926s019lbl.pdf. Accessed August 27, 2025.

[6] Avondal Pharmaceuticals. Label: Meloxicam. November 2024. https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/021530s020lbl.pdf. Accessed August 27, 2025.

[7] Drug profile. COX-2 inhibitors. Worst Pills, Best Pills. Last reviewed February 28, 2025. https://www.worstpills.org/monographs/view/121. Accessed August 27, 2025.

[8] Drug profile. Triptans. Worst Pills, Best Pills. Last reviewed February 28, 2025. https://www.worstpills.org/monographs/view/50. Accessed August 27, 2025.

[9] A fixed-dose combination of meloxicam and rizatriptan (Symbravo) for migraine. Med Lett Drugs Ther. 2025;67(1727):68-70.

[10] Exelan Pharmaceuticals. Label: rizatriptan. May 2020. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=9e82135a-3371-4012-92af-0cc7d7d4d0e3&type=display. Accessed August 27, 2025.

[11] Avondal Pharmaceuticals. Label: Meloxicam. November 2024. https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/021530s020lbl.pdf. Accessed August 27, 2025.

[12] Axsome. News release. Axsome Therapeutics announces FDA acceptance of NDA resubmission for AXS-07 for the acute treatment of migraine. September 4, 2024. https://axsometherapeuticsinc.gcs-web.com/news-releases/news-release-details/axsome-therapeutics-announces-fda-acceptance-nda-resubmission. Accessed August 27, 2025.

[13] Axsome Therapeutics. Label: meloxicam and rizatriptan (SYMBRAVO). January 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/215431s000lbl.pdf. Accessed August 27, 2025.

[14] Jones A, Tepper S, Lipton R, et al. Efficacy and safety of AXS-07 (MoSEIC meloxicam-rizatriptan) for the acute treatment of migraine: Results from the MOMENTUM phase 3, randomized, double-blind, active-and placebo-controlled trial (P13-2.005). Neurology. 2022;98(18_supplement).

[15] Axsome Therapeutics. Label: meloxicam and rizatriptan (SYMBRAVO). January 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/215431s000lbl.pdf. Accessed August 27, 2025.

[16] Jones A, Tepper S, Lipton R, et al. Efficacy and safety of AXS-07 (MoSEIC meloxicam-rizatriptan) for the acute treatment of migraine: Results from the MOMENTUM phase 3, randomized, double-blind, active-and placebo-controlled trial (P13-2.005). Neurology. 2022;98(18_supplement).

[17] Axsome Therapeutics. Label: meloxicam and rizatriptan (SYMBRAVO). January 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/215431s000lbl.pdf. Accessed August 27, 2025.

[18] Ibid.

[19] Jones A, Tepper S, Lipton R, et al. Efficacy and safety of AXS-07 (MoSEIC meloxicam-rizatriptan) for the acute treatment of migraine: Results from the INTERCEPT phase 3, randomized, double-blind, placebo-controlled trial (P14-2.004). Neurology. 2022;98(18_supplement).

[20] Axsome Therapeutics. Label: meloxicam and rizatriptan (SYMBRAVO). January 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/215431s000lbl.pdf. Accessed August 27, 2025.

[21] Tepper S, Lipton R, Chhabra A, et al. Combined efficacy and safety of AXS-07 (MOSEICTM meloxicam and rizatriptan) in two phase 3 clinical trials (P7-12.002). Neurology. 2024;102(7_supplement_1).

[22] Axsome Therapeutics. Label: meloxicam and rizatriptan (SYMBRAVO). January 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/215431s000lbl.pdf. Accessed August 27, 2025.

[23] Ibid.

[24] Drug profile. Triptans. Worst Pills, Best Pills. Last reviewed February 28, 2025. https://www.worstpills.org/monographs/view/50. Accessed August 27, 2025.

[25] A fixed-dose combination of meloxicam and rizatriptan (Symbravo) for migraine. Med Lett Drugs Ther. 2025;67(1727):68-70.

[26] Jones A, Tepper S, Lipton R, et al. Efficacy and safety of AXS-07 (MoSEIC meloxicam-rizatriptan) for the acute treatment of migraine: Results from the MOMENTUM phase 3, randomized, double-blind, active-and placebo-controlled trial (P13-2.005). Neurology. 2022;98(18_supplement).

[27] Jones A, Tepper S, Lipton R, et al. Efficacy and safety of AXS-07 (MoSEIC meloxicam-rizatriptan) for the acute treatment of migraine: Results from the INTERCEPT phase 3, randomized, double-blind, placebo-controlled trial (P14-2.004). Neurology. 2022;98(18_supplement).

[28] Tepper S, Lipton R, Chhabra A, et al. Combined efficacy and safety of AXS-07 (MOSEICTM meloxicam and rizatriptan) in two phase 3 clinical trials (P7-12.002). Neurology. 2024;102(7_supplement_1).

[29] BioSpace. Axsome Therapeutics announces AXS-07 achieves co-primary and key secondary endpoints in MOMENTUM phase 3 migraine trial in patients with history of inadequate response. December 30, 2019. https://www.biospace.com/axsome-therapeutics-announces-axs-07-achieves-co-primary-and-key-secondary-endpoints-in-momentum-phase-3-migraine-trial-in-patients-with-history-of-inadequate-response. Accessed August 27, 2025.