Methotrexate vs Tocilizumab: side effects in FDA adverse event reports
At a glance
| Methotrexate | Tocilizumab | |
|---|---|---|
| Drug class | – | Interleukin-6 Receptor Antagonist |
| Brand names | – | Actemra, Actemra Actpen |
| FAERS reports | 483,097 | 113,340 |
| Serious | 73% | 77% |
| Death outcome | 37,640 | 12,342 |
| Boxed warning | Yes WARNING: EMBRYO-FETAL TOXICITY, HYPERSENSITIVITY REACTIONS, BENZYL ALCOHOL TOXICITY, and OTHER SERIOUS ADVERSE REACTIONS • Methotrexate Injection can cause embr | Yes RISK OF SERIOUS INFECTIONS Patients treated with ACTEMRA are at increased risk for developing serious infections that may lead to hospitalization or death [see |
Signals both drugs share
| Reaction | Methotrexate | Tocilizumab | Label screen (A / B) |
|---|---|---|---|
| Duodenal ulcer perforation | 5,067 · PRR 97.3 | 5,011 · PRR 406.8 | Labeled (related wording) / Labeled — boxed warning |
| Sleep disorder due to general medical condition, insomnia type | 3,191 · PRR 42.2 | 3,133 · PRR 176.4 | Not in label — unassessed / Labeled (related wording) |
| Bone erosion | 2,084 · PRR 61.7 | 1,573 · PRR 148.3 | Labeled (related wording) / Not in label — unassessed |
| Synovitis | 13,569 · PRR 133.8 | 10,546 · PRR 263.3 | Not in label — unassessed / Not in label — unassessed |
| Pemphigus | 9,382 · PRR 135.9 | 9,201 · PRR 543.9 | Not in label — unassessed / Not in label — unassessed |
| Hand deformity | 8,885 · PRR 92.3 | 7,961 · PRR 291.7 | Not in label — unassessed / Not in label — unassessed |
| Helicobacter infection | 5,277 · PRR 46.1 | 5,103 · PRR 186.7 | Not in label — unassessed / Not in label — unassessed |
| Folliculitis | 5,035 · PRR 40.8 | 4,662 · PRR 152.9 | Not in label — unassessed / Not in label — unassessed |
| Muscle injury | 4,306 · PRR 47.5 | 4,172 · PRR 192.6 | Not in label — unassessed / Not in label — unassessed |
| Rheumatic fever | 3,282 · PRR 133.3 | 3,320 · PRR 607.2 | Likely indication confounding / Likely indication confounding |
| Facet joint syndrome | 1,964 · PRR 71.6 | 1,954 · PRR 306.1 | Not in label — unassessed / Not in label — unassessed |
| Deep vein thrombosis postoperative | 1,372 · PRR 101.8 | 1,381 · PRR 451.4 | Not in label — unassessed / Not in label — unassessed |
| Dislocation of vertebra | 1,211 · PRR 51.4 | 1,043 · PRR 164.1 | Not in label — unassessed / Not in label — unassessed |
| Adjustment disorder with depressed mood | 1,109 · PRR 52.7 | 1,018 · PRR 190.0 | Not in label — unassessed / Not in label — unassessed |
| Lupus vulgaris | 867 · PRR 117.7 | 807 · PRR 397.8 | Not in label — unassessed / Not in label — unassessed |
| Retinitis | 790 · PRR 38.5 | 672 · PRR 124.9 | Not in label — unassessed / Not in label — unassessed |
| Granuloma skin | 539 · PRR 80.8 | 525 · PRR 325.1 | Not in label — unassessed / Not in label — unassessed |
Labeled signals distinctive to Methotrexate
- Pericarditis — n=6,863, PRR 30.0 Labeled adverse reaction
- Lymphoproliferative disorder — n=1,503, PRR 44.9 Labeled (related wording)
- Rheumatoid lung — n=451, PRR 37.7 Labeled (related wording)
Labeled signals distinctive to Tocilizumab
- Hepatic enzyme — n=85, PRR 291.0 Labeled (related wording)
Common questions
Which has more reported side effects, Methotrexate or Tocilizumab?
Methotrexate has 483,097 FAERS reports and Tocilizumab 113,340. More reports does not mean more dangerous: volume follows how widely and how long a drug has been used, prescription vs over-the-counter status, and publicity. The seriousness share (73% vs 77%) is a better like-for-like signal of the kind of problems reported.
Which side effects do Methotrexate and Tocilizumab share?
Both drugs carry disproportionality signals for duodenal ulcer perforation, sleep disorder due to general medical condition, insomnia type, bone erosion, synovitis, pemphigus. Shared signals often reflect a shared drug class or the condition both are used for.
Is Methotrexate or Tocilizumab safer?
FAERS cannot answer that: it has no denominator and no comparator. Use this page to see which risks are already on each label and which signals are unlabeled, then check the prescribing information and your clinician for your situation.
Sources: openFDA FAERS pair statistics (OpenPV build 2026-09-14), FDA labels via openFDA, openFDA count queries for seriousness and deaths. Pair chosen because it is a commonly searched comparison. Generated 2026-10-08.