Can the respiratory syncytial virus (RSV) vaccine be administered to a patient taking hydroxychloroquine (Olaquenil) and methotrexate?

Medical Advisory BoardAll articles are reviewed for accuracy by our Medical Advisory Board
Educational purpose only • Exercise caution as content is pending human review
Article Review Status
Submitted
Under Review
Approved

Last updated: February 20, 2026View editorial policy

Personalize

Help us tailor your experience

Which best describes you? Your choice helps us use language that's most understandable for you.

RSV Vaccination in Patients on Hydroxychloroquine and Methotrexate

Yes, the RSV vaccine can and should be administered to patients taking hydroxychloroquine (Plaquenil) and methotrexate, as all currently approved RSV vaccines are non-live recombinant subunit vaccines that are safe for immunocompromised patients. 1, 2

Vaccine Safety Profile for Immunosuppressed Patients

The approved RSV vaccines (Arexvy/RSVPreF3 and Abrysvo/RSVpreF) are completely inactivated recombinant protein subunit vaccines containing no live viral particles and cannot replicate in the human body. 2 This makes them fundamentally safe for patients on immunosuppressive therapy, including those taking methotrexate and hydroxychloroquine. 1, 2

Key distinction: Unlike live-attenuated vaccines (such as the old Zostavax for shingles), these RSV vaccines carry no risk of vaccine-strain infection or disseminated disease in immunocompromised individuals. 3

Vaccination Recommendations Based on Age and Risk Factors

For Patients Aged ≥60 Years

  • All adults aged ≥60 years should receive RSV vaccination, with immunocompromise (including those on DMARDs like methotrexate) being a recognized risk factor for severe RSV disease. 1, 2
  • Adults aged ≥75 years should receive vaccination regardless of other comorbidities due to significantly elevated hospitalization and mortality rates. 1

For Patients Aged 50-59 Years

  • Adults in this age range with risk factors (including immunocompromise from methotrexate therapy) should receive RSVPreF3 (Arexvy), which is the only vaccine currently approved for this younger age group. 1, 2

Medication Management Around Vaccination

Critical consideration: While the RSV vaccine itself is safe to administer, you should consider whether to hold methotrexate around the time of vaccination to optimize immunogenicity.

Methotrexate-Specific Guidance

  • Current ACR guidelines conditionally recommend continuing methotrexate around the time of non-influenza vaccinations (which includes RSV vaccines). 4
  • The evidence for holding methotrexate applies primarily to influenza vaccination, where holding for 2 weeks post-vaccination improves immunogenicity. 4
  • For RSV vaccination specifically, there are no published studies addressing whether holding methotrexate improves vaccine response. 4

Hydroxychloroquine

  • Hydroxychloroquine does not require any dose adjustment or holding around vaccination time. 4
  • This medication is considered a mild immunosuppressant that does not significantly impair vaccine responses. 4

Practical Administration Algorithm

  1. Verify age and indication: Confirm patient is ≥60 years (or ≥50 years with risk factors including immunosuppression). 1, 2

  2. Select appropriate vaccine: Either RSVPreF3 (Arexvy) or RSVpreF (Abrysvo) for patients ≥60 years; only RSVPreF3 for ages 50-59 years. 1, 2

  3. Timing: Preferably administer between September and November before RSV season peaks. 1, 2

  4. Methotrexate decision: Continue methotrexate per current guidelines, though shared decision-making with the patient's rheumatologist may be considered if disease activity is stable and optimizing vaccine response is a priority. 4

  5. Co-administration: RSV vaccine can be given simultaneously with influenza vaccine at different injection sites. 4, 1, 2

  6. Dosing: Single 0.5 mL intramuscular injection; currently recommended as a one-time dose with no booster indicated. 1, 2

Important Clinical Caveats

Patient attestation is sufficient: Do not require extensive medical documentation of immunosuppressive therapy or risk factors, as this creates unnecessary barriers to vaccination. 1, 2

Previous RSV infection: Does not confer long-lasting immunity and does not contraindicate vaccination. 1, 2

Safety monitoring: Postlicensure surveillance has identified a potential increased risk of Guillain-Barré syndrome after protein subunit RSV vaccination, though this remains rare. 1

Expected side effects: Most common adverse events include injection site pain, fatigue, myalgia, and headache, which are typically mild to moderate and transient. 4, 5, 6

References

Guideline

RSV Vaccine Guidelines

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

RSV Vaccination Recommendations

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

Guideline

Shingles Vaccination in Immunocompromised Patients

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

Have a follow-up question?

Our Medical A.I. is used by practicing medical doctors at top research institutions around the world. Ask any follow up question and get world-class guideline-backed answers instantly.