Q&A: Common medicines may weaken immune response to vaccinations, infections

Common drugs like paracetamol and ibuprofen may reduce a patient’s immune response if taken before or immediately following a vaccination, according to findings published in the British Journal of Clinical Pharmacology.

The study also found that common medications may hinder an immune response to infection while others may improve it.

“Our review shows some of the common pain and fever medications may work with the immune system to fight infection, whereas others work against it and increase the risk of contracting or responding badly to infectious diseases,” Christina Abdel Shaheed, PhD, an academic fellow at the University of Sydney’s Faculty of Medicine and Health, said in a press release.

“In 14 years of studying pain, this is the most important research I have been involved in,” she added.

Using electronic databases, Abdel Shaheed and colleagues conducted the largest clinical review on immune responses to paracetamol, NSAIDs and opioid analgesics, according to the press release.

The researchers said their findings have “wide-reaching implications.” For example, Abdel Shaheed said that ibuprofen is not recommended for patients with chickenpox since it might increase the risk for secondary bacterial skin infections. Also, morphine can increase the risk for infection after surgery, particularly cancer surgery, the researchers reported.

Healio spoke with Abdel Shaheed to learn more about the findings and how physicians should advise patients on this matter.

Healio: What is the take-home message for physicians?

Abdel Shaheed: Common medicines used to treat pain and fever such as acetaminophen (paracetamol) and ibuprofen can have unintended impacts on the immune system, sometimes in a positive way and sometimes adversely. There needs to be consideration of the potential immune system effects of these medicines.

Our key findings included:

• For pain, morphine suppresses key cells of the immune system and may increase the risk of infection.
• For fever, antipyretics (eg, paracetamol, ibuprofen and aspirin) should not be used prior to vaccination as they can reduce the desirable immune response when taken at this time.
• The anti-inflammatory indomethacin may reduce viral replication in COVID-19 but large-scale human trials are needed to understand how it can be used in people with COVID-19.
• Aspirin could be an affordable and accessible therapeutic option for tuberculosis, which mainly afflicts poor countries.

Healio: How can common medicines impact immune responses to vaccines?

Abdel Shaheed: Taking paracetamol and ibuprofen before vaccination is not currently recommended as there is some suggestion that these medicines might reduce the body’s desirable immune response to the vaccine. For example, some studies have demonstrated a reduction in antibody response of 30% or more in children. Whilst the clinical implications of these findings remain unclear, the theoretical risks include increased risk for infection or reduced vaccine efficacy.

In children, prophylactic medicines are started at the time of vaccination (or immediately prior) and repeated around 6 to 8 hours afterwards. Whilst this approach has been shown to reduce fever, it can also have unintended impacts on the immune response to vaccines. Paracetamol has been shown to reduce antibody response to pneumococcal vaccine but the clinical implications remain unclear.

Paracetamol and ibuprofen would appear to affect different vaccine types in different ways. In some cases, ibuprofen has demonstrated no effect on pneumococcal response, but reduced antibody response to pertussis (whooping cough) and tetanus toxoid, for example.

The general recommendation is to avoid use of these medicines immediately prior to receiving a vaccination to try to ward off a fever or headache. Therapeutic use can be considered but should be reserved for severe symptoms after vaccination.

Healio: What medicines should physicians be recommending to patients leading up to a vaccination? What should they recommend against?

Abdel Shaheed: None prior to or at the time of vaccination. Paracetamol or ibuprofen can still be considered to treat symptoms of pain, headache or fever after the vaccination has been administered, but our review findings would suggest this should be reserved for severe symptoms. If symptoms are mild and can be managed, it is best to allow the body to mount an immune response without interference.

Healio: What about after a vaccination?

Abdel Shaheed: There are no hard and fast rules but there is some evidence to suggest that the possible blunting effect of these medicines on immune response to vaccination is reduced, or disappears, if given after 8 hours following a vaccine.

Healio: What medicines have an effect on SARS-CoV-2 infection?

Abdel Shaheed: Indomethacin has shown some promise in vitro and in human clinical trials but further studies are needed to determine its benefits for COVID-19, particularly in moderate to severe COVID-19 disease where the patient is not responding well to current best treatments. It has been shown to reduce pain and fever, but also reduce viral replication of COVID-19 based on in vitro studies. In a small human clinical trial, it was shown to reduce the requirements for oxygenation and progression to severe lung complications.

Healio: What scenarios or patient populations are more at risk for weakened immunity due to fever and pain medicines?

Abdel Shaheed: People with cancer may unfortunately already have a compromised immune system. People who are critically ill (for any reason) and people who have just had surgery are also at higher risk of infection. In this review, we found research that suggests morphine, one of the most commonly used opioid analgesics in post-surgical and critical care, suppresses key innate immune cells which could result in increased risk of infection. Other opioids like oxycodone and fentanyl were also associated with increased risk of infection.

Use of ibuprofen is not advised in people with chickenpox due to increased risk of secondary bacterial skin infections. There is also uncertainty around the use of ibuprofen for bacterial pneumonia, but large trials are needed to resolve this uncertainty.

Healio: If a patient requires one or more of the medicines you looked at, is there anything physicians can recommend to avoid a diminished immune response?

Abdel Shaheed: Avoid prophylactic use of paracetamol or ibuprofen before a vaccination. They should only be used to treat symptoms like fever or headache following vaccination if symptoms warrant use, but ideally not if symptoms are mild and manageable.

References:

Abdel Shaheed C, et al. Br J Clin Pharmacol. 2022;doi:10.1111/bcp.15281.

Are medicines affecting our response to infections like COVID-19? https://www.sydney.edu.au/news-opinion/news/2022/03/02/are-medicines-affecting-our-response-to-infections-like-covid19.html. Published March 2, 2022. Accessed March 2, 2022.