Should Patients Avoid Pain Relievers Before the COVID-19 Vaccine?

Great strides have been made in understanding, preventing, and treating severe COVID-19 infections.

The emergency use authorization by the FDA for the available COVID-19 vaccines and the recent full FDA approval of the Pfizer COVID-19 vaccine were monumental moments in the fight against this relentless virus. As the COVID-19 pandemic persists, pharmacists continue to be instrumental in providing patients with reliable information about the prevention, detection, treatment, and management of COVID-19. Pharmacists can be influential in dispelling common misinformation and myths about the COVID-19 virus, its variants, and the available vaccines. In the beginning of the pandemic, there were initial concerns about the safety of individuals with COVID-19 taking ibuprofen, but these claims originated from anecdotal and low-quality evidence.¹ Major public health organizations around the globe do not advise against using ibuprofen to ease COVID-19 symptoms or the adverse effects (AEs) associated with the vaccine.¹ As accessible health care providers, pharmacists are likely to encounter patients seeking counsel on the use of nonprescription analgesic/antipyretics, such as acetaminophen, and the non-steroidal anti-inflammatory agents (NSAIDS), such as ibuprofen and naproxen sodium, for the symptomatic relief of some of the common mild to moderate symptoms associated with COVID-19 that may be amenable to self-treatment and to manage AEs, such as fever and pain, associated with the COVID-19 vaccines.

In a recent publication on the Medical News Today website, the author indicates that the CDC recommends consulting a health care professional about taking analgesics/antipyretic to manage the AEs of the COVID-19 vaccine.¹

The CDC stated, “It is not recommended you take over-the-counter medicine, such as ibuprofen, aspirin, or acetaminophen, before vaccination for the purpose of trying to prevent vaccine-related side effects. It is not known how these medications might affect how well the vaccine works. However, if you take these medications regularly for other reasons, you should keep taking them before you get vaccinated. It is also not recommended to take antihistamines before getting a COVID-19 vaccine to try to prevent allergic reactions.”²

In response to the early concerns about the use of NSAIDs and the evolving information about these issues, GlaxoSmithKline (GSK), a leading manufacturer for OTC analgesics issued a statement about the use of ibuprofen and COVID-19 vaccines, saying, “The appropriate use of antipyretics/analgesics, like Advil (ibuprofen), is recommended by public health authorities to help relieve symptoms that may be experienced following vaccination.^3-5 This is consistent with the fact that in the COVID-19 vaccine studies, participants were allowed to use antipyretics/analgesics to treat symptoms.”⁵

Additionally, GSK posted information on its Advil product website about a patient education initiative referred to as #AfterMyShot, which provides patients with valuable information about COVID-19 and the vaccines.⁶

On August 12, 2021, the manufacturer, Janssen also issued a statement about the use of antipyretics and analgesics and the COVID-19 vaccine. In its response, the manufacturer indicated the following:⁷

• Pre-vaccination: There are no robust clinical data on how pre-treatment use of antipyretics affects COVID-19 vaccine-induced antibody responses.⁷
• Post-vaccination: There is no clinical evidence that the use of antipyretics post-vaccination has a negative effect on COVID-19 vaccine efficacy.⁷
• During the Janssen COVID-19 Vaccine clinical trial program, antipyretics were recommended post-vaccination for symptom relief as necessary. Prophylactic antipyretic use was not encouraged. However, in some instances, it could have been considered for participants with special circumstances and/ or comorbidities.^7,8

Bayer Consumer Health, the manufacturer of the OTC NSAID marketed as Aleve also has information on its website about the COVID-19 virus and the use of the product, stating: “To date, public health authorities, including the Centers for Disease Control and Prevention, the U.S. Food and Drug Administration, the European Medicines Agency and the World Health Organization, are not aware of any scientific evidence supporting a link between the use of non-steroidal anti-inflammatory medicines (NSAIDs), such as Aleve, and worsened outcomes from COVID-19.”9

CLINICAL STUDIES

Available clinical evidence regarding other vaccines indicate that analgesics/antipyretics are commonly used around the time of vaccination to ameliorate fever and pain, and the use is primarily post vaccination.^10-12 Although the results of several studies show that prophylactic analgesic/antipyretic administration decreases post-vaccination adverse reactions, there are also study results showing that their use may decrease the antibody responses to several vaccine antigens.¹³

In a recent 2021 publication, Etminan et al, indicated that several regulatory bodies have made statements regarding the use of antipyretics around the time of vaccination. In 2015, the World Health Organization stated that use of antipyretics is not recommended before or at the time of vaccination but approved in the days after vaccination, and the CDC concurs with these recommendations.^14,15 Etminan et al, noted that to date, there are no clinical data on this issue with regard to the COVID-19 vaccines, and the data provided in clinical trials for the mRNA vaccines only mentioned that the use of antipyretics was increased with increasing dose concentrations and dose number, but data on immunogenicity were not given.^14,16,17 Finally, Etminan et al, indicated that moving forward, clinical trials need to urgently investigate and answer 4 questions: ¹⁴

• Do either acetaminophen or ibuprofen affect antibody response by COVID-19 vaccines, and if so, is there a difference in antibody titers between the 2 agents?
• Does a potential interaction with antipyretics vary with different vaccine types (mRNA vs non-mRNA vaccines)?
• Does the timing of antipyretic administration (before vaccination or immediately after) affect antibody titers?
• Does a possible negative interaction only affect antibody titers for the first dose, second dose, or both? ¹⁴

Conclusion

As clinicians and patient educators, pharmacists can educate patients about the benefits of vaccines and provide patients with facts and dispel common myths and misconceptions about vaccines particularly the COVID-19 vaccine. Until more clinical data become available, patients should be directed to adhere to CDC recommendations, and when in doubt they should consult their primary health care providers before taking any medications, including OTC drugs.

Yvette C Terrie, BSPharm, RPh, is a consulting pharmacist and a medical writer in Haymarket, Virginia.

REFERENCES

1. Kandola A. Ibuprofen and COVID-19: is it safe? Medical News Today. August 17, 2021. Accessed August 26, 2021. https://www.medicalnewstoday.com/articles/ibuprofen-and-covid
2. Preparing for your COVID-19 vaccination. CDC. Updated August 19, 2021. Accessed August 26, 2021. https://www.cdc.gov/coronavirus/2019-ncov/vaccines/prepare-for-vaccination.html
3. Possible side effects after getting a COVID-19 vaccine. CDC. Updated August 6, 2021. Accessed August 26, 2021. https://www.cdc.gov/coronavirus/2019-ncov/vaccines/expect/after.html.
4. Coronavirus (COVID-19) vaccines. United Kingdom National Health Service. Reviewed August 19, 2021. Accessed August 26, 2021. https://www.nhs.uk/conditions/coronavirus-covid-19/coronavirus-vaccination/coronavirus-vaccine/
5. The facts about ibuprofen and COVID-19. GSK. Accessed August 26, 2021. https://www.gskhealthpartner.com/en-us/pain-relief/brands/advil/covid19/
6. #AfterMyShot: what Will You do? Advil. Accessed August 26, 2021. https://www.advil.com/coronavirus/vaccination/
7. Janssen COVID-19 vaccine. Janssen MD. Updated August 27, 2021. Accessed August 31, 2021. https://www.janssenmd.com/janssen-covid19-vaccine/clinical-use/concomitant-use/antipyretics/janssen-covid19-vaccine-use-of-janssen-covid19-vaccine-with-antipyretics-and-analgesics
8. Janssen vaccines & Prevention B.V.. Janssen. December 14, 2020. Accessed August 26, 2021. https://www.jnj.com/coronavirus/covid-19-phase-3-study-clinical-protocol
9. Aleve and COVID-19. Aleve. Accessed August 26, 2021. https://www.aleve.com/aleve-and-covid-19
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11. Taddio A, Manley J, Potash L, Ipp M, Sgro M, Shah V. Routine immunization practices: use of topical anesthetics and oral analgesics. Pediatrics. 2007;120(3):e637-643. doi:10.1542/peds.2006-3351
12. Manley J, Taddio A. Acetaminophen and ibuprofen for prevention of adverse reactions associated with childhood immunization. Ann Pharmacother. 2007;41:1227-1232; doi:10.1345/aph.1H647
13. Das RR, Panigrahi I, Naik SS. The effect of prophylactic antipyretic administration on post-vaccination adverse reactions and antibody response in children: a systematic review. PLoS One. 2014;9(9):e106629. doi:10.1371/journal.pone.0106629
14. Etminan M, Sodhi M, Ganjizadeh-Zavareh S. Should Antipyretics Be Used to Relieve Acute Adverse Events Related to COVID-19 Vaccines? Chest. 2021;159(6):2171-2172. doi:10.1016/j.chest.2021.01.080
15. Vaccine recommendations and guidelines of the ACIP. CDC. Updated May 4, 2021. Accessed August 26, 2021. https://www.cdc.gov/vaccines/hcp/acip-recs/general-recs/administration.html
16. Polack FP, Thomas SJ, Kitchin N, et al. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N Engl J Med. 2020;383(27):2603-2615. doi:10.1056/NEJMoa2034577
17. Baden LR, El Sahly MH, Essink B, et al. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N Engl J Med. 2021;384(5):403-416. doi:10.1056/NEJMoa203538