Anakinra and Etanercept: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Jul 11, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Anakinra
Etanercept
No brand names on record
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
What happens
An increased risk of infections
Interaction Deep Dive
Concomitant use of anakinra and etanercept or etanercept biosimilar products results in an increased risk for serious infection and neutropenia without providing any additional benefit. The use of anakinra in combination with tumor necrosis factor (TNF) blocking agents, including etanercept or etanercept biosimilar products, is not recommended2341. In a 6-month, double-blind study in which 242 patients received both anakinra and etanercept (half-dose and full-dose etanercept plus anakinra) or etanercept only, the incidence of serious infection was 7.4% for the full-dose combination group compared with 0% for the etanercept alone group. Combination therapy did not offer additional clinical benefit compared with etanercept only therapy based on ACR50 response scores 5.
Why it happens (mechanism)
Unknown
Literature reports
1 report — tap to read
a) Concurrent use of anakinra and etanercept rendered no additional efficacy and increased safety risk compared with etanercept alone. In a double-blind study, 242 patients with active rheumatoid arthritis despite methotrexate therapy were treated with either subcutaneous injections of etanercept 25 mg twice/week (n=80), etanercept 25 mg twice/week (full dose) plus anakinra 100 mg once/day (n=81), or etanercept 25 mg once/week (half dose) plus anakinra 100 mg once/day (n=81) with a 6-month follow-up. The American College of Rheumatology 50% (ACR50) response did not differ significantly in the full-dose combination group compared with the etanercept only group (31% vs 41%, p=0.914). Serious infections, including pneumonia and cellulitis, herpes zoster, pneumonitis, and pyelonephritis, were reported with a frequency of 7.4% in the full-dose and 3.7% in the half-dose combination groups compared with 0% in the etanercept group. The mean time from exposure to serious infection was 2 months (range: 1 wk to 5 months). Changes in neutrophil count were similar for the three groups and not associated with serious infection. Neutropenia was reported in two patients in the full-dose group; however, both patients stayed in the study without any associated clinical events. The combination groups had a 50% greater incidence of injection site reactions (ie, transient, rarely severe) compared with the etanercept only group. Injection site reaction was the most common adverse event accounting for study withdrawal in the combination groups (5 of 13 withdrawals) 5.
Common questions
Can I take Anakinra and Etanercept together?
An increased risk of infections Always confirm with your pharmacist or prescriber before making any change.
How serious is the Anakinra and Etanercept interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "delayed". Effects tend to build up gradually over days to weeks.
How strong is the evidence for this interaction?
The evidence is graded "established". Well documented — supported by controlled studies or strong clinical data.
Questions for your pharmacist
- Does my dose of Anakinra or Etanercept need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (5)
- Product Information: KINERET(R) subcutaneous injection, anakinra subcutaneous injection. Amgen,Inc, Thousand Oaks, CA, 2006. DailyMed
- Product Information: Eticovo subcutaneous injection, etanercept-ykro subcutaneous injection. Samsung Bioepis Co Ltd (per FDA), Whitehouse Station, NJ, 2019.
- Product Information: ERELZI(TM) subcutaneous injection, etanercept-szzs subcutaneous injection. Sandoz Inc (per manufacturer), Princeton, NJ, 2016.
- Product Information: Enbrel(R) subcutaneous injection solution, etanercept subcutaneous injection solution. Amgen Inc. (per FDA), Thousand Oaks, CA, 2015. DailyMed
- Genovese MC, Cohen S, Moreland L, et al: Combination therapy with etanercept and anakinra in the treatment of patients with rheumatoid arthritis who have been treated unsuccessfully with methotrexate. Arthritis Rheum 2004; 50(5):1412-1419. PubMed
Keep reading about Anakinra
Keep reading about Etanercept
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