Methotrexate vs Rituximab: side effects in FDA adverse event reports
At a glance
| Methotrexate | Rituximab | |
|---|---|---|
| Drug class | – | CD20-directed Cytolytic Antibody |
| Brand names | – | Rituxan |
| FAERS reports | 483,097 | 210,132 |
| Serious | 73% | 89% |
| Death outcome | 37,640 | 37,069 |
| Boxed warning | Yes WARNING: EMBRYO-FETAL TOXICITY, HYPERSENSITIVITY REACTIONS, BENZYL ALCOHOL TOXICITY, and OTHER SERIOUS ADVERSE REACTIONS • Methotrexate Injection can cause embr | Yes FATAL INFUSION-RELATED REACTIONS, SEVERE MUCOCUTANEOUS REACTIONS, HEPATITIS B VIRUS REACTIVATION and PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY WARNING: FATAL I |
Signals both drugs share
| Reaction | Methotrexate | Rituximab | Label screen (A / B) |
|---|---|---|---|
| Duodenal ulcer perforation | 5,067 · PRR 97.3 | 4,935 · PRR 208.1 | Labeled (related wording) / Labeled — boxed warning |
| Rheumatic fever | 3,282 · PRR 133.3 | 3,199 · PRR 280.1 | Likely indication confounding / Labeled (related wording) |
| Sleep disorder due to general medical condition, insomnia type | 3,191 · PRR 42.2 | 2,715 · PRR 72.7 | Not in label — unassessed / Labeled (related wording) |
| Peripheral venous disease | 1,635 · PRR 29.6 | 1,611 · PRR 67.4 | Not in label — unassessed / Labeled (related wording) |
| Lupus vulgaris | 867 · PRR 117.7 | 827 · PRR 231.6 | Not in label — unassessed / Labeled (related wording) |
| Granuloma skin | 539 · PRR 80.8 | 507 · PRR 158.9 | Not in label — unassessed / Labeled (related wording) |
| Synovitis | 13,569 · PRR 133.8 | 8,767 · PRR 94.5 | Not in label — unassessed / Not in label — unassessed |
| Pemphigus | 9,382 · PRR 135.9 | 9,375 · PRR 315.6 | Not in label — unassessed / Likely indication confounding |
| Hand deformity | 8,885 · PRR 92.3 | 7,685 · PRR 143.3 | Not in label — unassessed / Not in label — unassessed |
| Helicobacter infection | 5,277 · PRR 46.1 | 5,074 · PRR 99.1 | Not in label — unassessed / Not in label — unassessed |
| Folliculitis | 5,035 · PRR 40.8 | 4,291 · PRR 70.8 | Not in label — unassessed / Likely indication confounding |
| Muscle injury | 4,306 · PRR 47.5 | 3,701 · PRR 82.0 | Not in label — unassessed / Not in label — unassessed |
| Facet joint syndrome | 1,964 · PRR 71.6 | 2,003 · PRR 176.0 | Not in label — unassessed / Not in label — unassessed |
| Deep vein thrombosis postoperative | 1,372 · PRR 101.8 | 1,318 · PRR 207.9 | Not in label — unassessed / Not in label — unassessed |
| Dislocation of vertebra | 1,211 · PRR 51.4 | 1,091 · PRR 96.2 | Not in label — unassessed / Not in label — unassessed |
| Adjustment disorder with depressed mood | 1,109 · PRR 52.7 | 1,074 · PRR 114.3 | Not in label — unassessed / Not in label — unassessed |
| Retinitis | 790 · PRR 38.5 | 721 · PRR 75.8 | Not in label — unassessed / Not in label — unassessed |
Labeled signals distinctive to Methotrexate
- Pericarditis — n=6,863, PRR 30.0 Labeled adverse reaction
- Bone erosion — n=2,084, PRR 61.7 Labeled (related wording)
- 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 Rituximab
- Diffuse large b-cell lymphoma recurrent — n=1,437, PRR 205.1 Labeled (related wording)
- Follicular lymphoma — n=383, PRR 81.3 Labeled adverse reaction
Common questions
Which has more reported side effects, Methotrexate or Rituximab?
Methotrexate has 483,097 FAERS reports and Rituximab 210,132. 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 89%) is a better like-for-like signal of the kind of problems reported.
Which side effects do Methotrexate and Rituximab share?
Both drugs carry disproportionality signals for duodenal ulcer perforation, rheumatic fever, sleep disorder due to general medical condition, insomnia type, peripheral venous disease, lupus vulgaris. Shared signals often reflect a shared drug class or the condition both are used for.
Is Methotrexate or Rituximab 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.