NAPROXEN

What is naproxen?

Naproxen is a non-steroidal anti-inflammatory (NSAID) medication commonly used to relieve pain and reduce fevers. Unlike acetaminophen, naproxen has anti-inflammatory properties and can be used for inflammatory diseases such as osteoarthritis and rheumatoid disorders. It is typically taken as 500 mg followed by 250-500 mg every 12 hours as needed for the immediate-release formulation or 1 g once daily for the extended-release formulation.

How can naproxen help alleviate certain long COVID symptoms? 

Naproxen works by reversibly inhibiting enzymes in our body called COX-1 and COX-2 that help reduce fever, pain, and inflammation. It is also believed to reduce pro-inflammatory substances called cytokines and inhibit the activation of other immune cells that can cause inflammation.

The prevalence of post-COVID pain is estimated to be up to 63.3%, and patients with chronic pain can have exacerbated symptoms after COVID.¹ There are multiple possible mechanisms behind post-COVID pain. Post-COVID pain may be caused by the virus entering and attacking musculoskeletal and nervous systems, including the brain. Persistent inflammation from overactivated inflammatory pathways and excessive activation of blood clotting can also contribute to pain. Various types of pain can also be caused by COVID, such as headaches, neuropathic pain, musculoskeletal pain, chest pain, arthralgia, and fibromyalgia.

While other prescription medications are typically used to treat headaches, neuropathic pain, chest pain, and fibromyalgia, naproxen can be used to relieve short-term headaches, musculoskeletal pain, arthralgia, and myalgias that persist or worsen after COVID; however, it should not be used to treat COVID or to reduce the duration of COVID symptoms. Post-COVID headache can also be treated with acetaminophen or NSAIDs like naproxen.² Compared to ibuprofen, naproxen acts longer and can be taken every 8-12 hours, while ibuprofen acts faster and can be taken every four to six hours.

What evidence supports naproxen’s use for long COVID?

Early on in the pandemic, anecdotal reports suggested that NSAIDs could increase susceptibility to COVID due to their ability to increase expression of ACE2 receptors that are targeted by the SARS-CoV-2 virus.³ However, several studies have since debunked this theory and have shown that the use of NSAIDs is not associated with increased COVID severity or risk of all-cause mortality.⁴ A study in which hospitalized COVID patients were randomized to either naproxen 500 mg twice a day or placebo for five days along with standard treatment demonstrated improvement in cough and shortness of breath.⁵ This result requires additional studies to confirm these findings, but naproxen has also been found to improve headache, malaise, myalgia, and cough in a study of patients with rhinovirus.⁶

A survey of 696 COVID patients in Italy reported that the use of standard analgesics such as naproxen in the post-acute phase of COVID had a temporary reduction in pain severity.⁵ NSAIDs can be effective in managing migraines and are commonly used for headaches as well.²

What are some things to watch out for with naproxen?

Naproxen is not recommended in people at risk for or with existing cardiovascular disease, GI disease, kidney impairment, chronic liver disease, or people at higher risk of bleeding. Use of NSAIDs is associated with an increased risk of serious cardiovascular events such as heart attacks and strokes. New-onset hypertension can also occur with NSAIDs and can exacerbate heart failure. There is also a higher risk of gastrointestinal adverse events such as GI bleeding or ulcers. Do not take naproxen for more than 10-15 days per month for headaches. Naproxen should be taken with food, and you should let your doctor know if you are taking it regularly for long COVID symptoms.

References:

1)      El-Tallawy SN, Perglozzi JV, Ahmed RS, Kaki AM, Nagiub MS, LeQuang JK, Hadarah MM. Pain Management in the Post-COVID Era-An Update: A Narrative Review. Pain Ther. 2023 Apr;12(2):423-448. doi: 10.1007/s40122-023-00486-1

2)     Arca KN, Smith JH, Chiang CC, Starling AJ, Robertson CE, Halker Singh RB, Schwedt TJ, Kissoon NR, Garza I, Rozen TD, Boes CJ, Whealy MA, VanderPluym JH. COVID-19 and Headache Medicine: A Narrative Review of Non-Steroidal Anti-Inflammatory Drug (NSAID) and Corticosteroid Use. Headache. 2020 Sep;60(8):1558-1568. doi: 10.1111/head.13903

3)     Kushner, P., McCarberg, B.H., Grange, L. et al. The use of non-steroidal anti-inflammatory drugs (NSAIDs) in COVID-19. npj Prim. Care Respir. Med. 32, 35 (2022). doi: 10.1038/s41533-022-00300-z

4)     Reese JT, Coleman B, Chan L, Blau H, Callahan TJ, Cappelletti L, Fontana T, Bradwell KR, Harris NL, Casiraghi E, Valentini G, Karlebach G, Deer R, McMurry JA, Haendel MA, Chute CG, Pfaff E, Moffitt R, Spratt H, Singh J, Mungall CJ, Williams AE, Robinson PN. NSAID use and clinical outcomes in COVID-19 patients: A 38-center retrospective cohort study. medRxiv [Preprint]. 2021 Dec 22:2021.04.13.21255438. doi: 10.1101/2021.04.13.21255438

5)     Galluzzo V, Zazzara MB, Ciciarello F, Tosato M, Bizzarro A, Paglionico A, Varriano V, Gremese E, Calvani R, Landi F on behalf of Gemelli against COVID-19 Post-Acute Care Team. Use of First-Line Oral Analgesics during and after COVID-19: Results from a Survey on a Sample of Italian 696 COVID-19 Survivors with Post-Acute Symptoms. J Clin Med. 2023; 12(8):2992. doi: 10.3390/jcm12082992

6)    Asadi M, Sayar S, Radmanesh E, et al. Efficacy of naproxen in the management of patients hospitalized with COVID-19 infection: A randomized, double-blind, placebo-controlled, clinical trial. Diabetes Metab Syndr. 2021 Nov-Dec;15(6):102319. doi: 10.1016/j.dsx.2021.102319.

7)     Sperber SJ, Hendley JO, Hayden FG, Riker DK, Sorrentino JV, Gwaltney JM Jr. Effects of naproxen on experimental rhinovirus colds. A randomized, double-blind, controlled trial. Ann Intern Med. 1992 Jul 1;117(1):37-41. doi: 10.7326/0003-4819-117-1-37