Methotrexate vs Azathioprine: side effects in FDA adverse event reports
At a glance
| Methotrexate | Azathioprine | |
|---|---|---|
| Drug class | – | Purine Antimetabolite |
| Brand names | – | – |
| FAERS reports | 483,097 | 87,582 |
| Serious | 73% | 87% |
| Death outcome | 37,640 | 8,696 |
| Boxed warning | Yes WARNING: EMBRYO-FETAL TOXICITY, HYPERSENSITIVITY REACTIONS, BENZYL ALCOHOL TOXICITY, and OTHER SERIOUS ADVERSE REACTIONS • Methotrexate Injection can cause embr | Yes - MALIGNANCY Chronic immunosuppression with azathioprine, a purine antimetabolite increases risk of malignancy in humans. Reports of malignancy include post-tra |
Signals both drugs share
| Reaction | Methotrexate | Azathioprine | Label screen (A / B) |
|---|---|---|---|
| Bone erosion | 2,084 · PRR 61.7 | 814 · PRR 71.4 | Labeled (related wording) / Not in label — unassessed |
| Rheumatic fever | 3,282 · PRR 133.3 | 871 · PRR 59.5 | Likely indication confounding / Likely indication confounding |
| Facet joint syndrome | 1,964 · PRR 71.6 | 644 · PRR 61.4 | Not in label — unassessed / Not in label — unassessed |
| Deep vein thrombosis postoperative | 1,372 · PRR 101.8 | 413 · PRR 63.8 | Not in label — unassessed / Not in label — unassessed |
| Dislocation of vertebra | 1,211 · PRR 51.4 | 421 · PRR 55.8 | Not in label — unassessed / Not in label — unassessed |
| Adjustment disorder with depressed mood | 1,109 · PRR 52.7 | 404 · PRR 59.9 | Not in label — unassessed / Not in label — unassessed |
| Lupus vulgaris | 867 · PRR 117.7 | 437 · PRR 139.3 | Not in label — unassessed / Not in label — unassessed |
| Retinitis | 790 · PRR 38.5 | 491 · PRR 99.8 | Not in label — unassessed / Not in label — unassessed |
| Seronegative arthritis | 555 · PRR 42.0 | 247 · PRR 67.5 | Likely indication confounding / Likely indication confounding |
| Granuloma skin | 539 · PRR 80.8 | 181 · PRR 66.8 | Not in label — unassessed / Not in label — unassessed |
Labeled signals distinctive to Methotrexate
- Pericarditis — n=6,863, PRR 30.0 Labeled adverse reaction
- Duodenal ulcer perforation — n=5,067, PRR 97.3 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 Azathioprine
- Hepatosplenic t-cell lymphoma — n=155, PRR 171.2 Labeled — boxed warning
- Cholestasis of pregnancy — n=100, PRR 67.0 Labeled adverse reaction
- Lung transplant rejection — n=93, PRR 38.8 Labeled (related wording)
Common questions
Which has more reported side effects, Methotrexate or Azathioprine?
Methotrexate has 483,097 FAERS reports and Azathioprine 87,582. 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 87%) is a better like-for-like signal of the kind of problems reported.
Which side effects do Methotrexate and Azathioprine share?
Both drugs carry disproportionality signals for bone erosion, rheumatic fever, facet joint syndrome, deep vein thrombosis postoperative, dislocation of vertebra. Shared signals often reflect a shared drug class or the condition both are used for.
Is Methotrexate or Azathioprine 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.