Diphenhydramine vs Hydrocortisone: side effects in FDA adverse event reports
At a glance
| Diphenhydramine | Hydrocortisone | |
|---|---|---|
| Drug class | – | Corticosteroid |
| Brand names | Nightime Sleep Aid | – |
| FAERS reports | 164,753 | 88,710 |
| Serious | 71% | 82% |
| Death outcome | 22,785 | 11,614 |
| Boxed warning | No | No |
Signals both drugs share
| Reaction | Diphenhydramine | Hydrocortisone | Label screen (A / B) |
|---|---|---|---|
| Deep vein thrombosis postoperative | 318 · PRR 24.5 | 947 · PRR 222.3 | No label text to screen / Not in label — unassessed |
| Adjustment disorder with depressed mood | 335 · PRR 25.2 | 757 · PRR 142.6 | No label text to screen / Not in label — unassessed |
| Dislocation of vertebra | 352 · PRR 23.8 | 728 · PRR 115.1 | No label text to screen / Not in label — unassessed |
| Lupus vulgaris | 359 · PRR 54.8 | 553 · PRR 206.4 | No label text to screen / Not in label — unassessed |
| Retinitis | 384 · PRR 37.8 | 427 · PRR 81.2 | No label text to screen / Likely indication confounding |
| Vaginal flatulence | 200 · PRR 244.2 | 191 · PRR 399.5 | No label text to screen / Not in label — unassessed |
| Seronegative arthritis | 163 · PRR 21.5 | 194 · PRR 49.3 | No label text to screen / Likely indication confounding |
Labeled signals distinctive to Diphenhydramine
- None stood out among the strongest labeled signals.
Labeled signals distinctive to Hydrocortisone
- Duodenal ulcer perforation — n=2,466, PRR 119.8 Labeled (related wording)
- Steroid withdrawal syndrome — n=250, PRR 76.9 Labeled (related wording)
- Secondary immunodeficiency — n=223, PRR 54.2 Labeled (related wording)
- Adrenal suppression — n=148, PRR 50.2 Labeled (related wording)
- Topical steroid withdrawal reaction — n=146, PRR 145.5 Labeled (related wording)
Common questions
Which has more reported side effects, Diphenhydramine or Hydrocortisone?
Diphenhydramine has 164,753 FAERS reports and Hydrocortisone 88,710. 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 (71% vs 82%) is a better like-for-like signal of the kind of problems reported.
Which side effects do Diphenhydramine and Hydrocortisone share?
Both drugs carry disproportionality signals for deep vein thrombosis postoperative, adjustment disorder with depressed mood, dislocation of vertebra, lupus vulgaris, retinitis. Shared signals often reflect a shared drug class or the condition both are used for.
Is Diphenhydramine or Hydrocortisone 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.