Melphalan side effects: what 26,323 FDA adverse event reports show
Drug class
Not stated in label
Label matched
Melphalan Hydrochloride (Melphalan Hydrochloride)
Who reports
26,323 reports · 97% serious · 6,349 with death outcome · 43% female
Used for
Melphalan Hydrochloride for Injection is indicated for the palliative treatment of patients with multiple myeloma for whom oral therapy is not appropriate.
What it is
DESCRIPTION Melphalan, also known as L-phenylalanine mustard, phenylalanine mustard, L-PAM, or L-sarcolysin, is a phenylalanine derivative of nitrogen mustard. Melphalan is a bifunctional alkylating agent that is active against selected human neoplastic diseases.
Boxed warning
Melphalan should be administered under the supervision of a qualified physician experienced in the use of cancer chemotherapeutic agents. Severe bone marrow suppression with resulting infection or bleeding may occur. Controlled trials comparing intravenous (IV) to oral melphalan have shown more myelosuppression with the IV formulation.
Causality screen of the 40 strongest signals
What the badges mean
- Labeled (related wording) The label describes this effect under different wording (e.g. 'neutropenia' for 'neutrophil count decreased'). Treated as known.
- Not in label — unassessed Not found in the label text, not an artifact pattern. This is a genuine candidate for a formal causality assessment (Bradford Hill / WHO-UMC); it has NOT had one here.
Strongest disproportionality signals
Flagged terms (PRR ≥ 2, χ² ≥ 4, n ≥ 10), ranked by PRR; infinite PRRs (no comparator reports) excluded. The EBGM column is a second, shrinkage-based estimate (MGPS) with its 5th percentile EB05 and the BCPNN IC025; a pair flagged by PRR alone is marked PRR-only and should be read as fragile. The strata column recomputes the PRR on serious reports only and flags pairs whose reports are unusually skewed by sex or come mostly from consumers rather than clinicians. 1,078 further terms are in the interactive explorer. Reaction links open the term's cross-drug page.
| Reaction | Reports | PRR 95% CI · ROR · χ²/p | EBGM EB05 · IC025 | Label screen | Serious-only & strata | Trial cross-check |
|---|---|---|---|---|---|---|
| Meningomyelitis herpes | 15 | 806.5 402.8–1,614.7ROR 807.0 · χ² 5,990 / p <1e-300 | 277.4 EB05 178.4 · IC025 +4.0 3/3 methods agree | Not in label — unassessed | – | not reported in cached trials |
| Protothecosis | 37 | 603.9 398.8–914.6ROR 604.9 · χ² 13,050 / p <1e-300 | 306.4 EB05 232.1 · IC025 +5.4 3/3 methods agree | Not in label — unassessed | – | not reported in cached trials |
| Mucoepidermoid carcinoma of salivary gland | 15 | 326.4 181.1–588.6ROR 326.7 · χ² 3,350 / p <1e-300 | 184.6 EB05 118.7 · IC025 +3.9 3/3 methods agree | Not in label — unassessed | – | not reported in cached trials |
| Choroidal infarction | 28 | 281.2 184.2–429.5ROR 281.6 · χ² 5,767 / p <1e-300 | 187.9 EB05 136.4 · IC025 +4.9 3/3 methods agree | Not in label — unassessed | – | not reported in cached trials |
| Chorioretinal atrophy | 48 | 274.2 198.7–378.5ROR 274.8 · χ² 9,842 / p <1e-300 | 194.9 EB05 152.8 · IC025 +5.6 3/3 methods agree | Not in label — unassessed | – | not reported in cached trials |
| Juvenile melanoma benign | 14 | 250.9 138.9–453.2ROR 251.1 · χ² 2,541 / p <1e-300 | 155.7 EB05 98.6 · IC025 +3.8 3/3 methods agree | Not in label — unassessed | – | not reported in cached trials |
| Pre-engraftment immune reaction | 17 | 250.6 146.6–428.5ROR 250.8 · χ² 3,124 / p <1e-300 | 161.5 EB05 106.8 · IC025 +4.1 3/3 methods agree | Not in label — unassessed | – | not reported in cached trials |
| Engraftment syndrome | 122 | 243.5 199.5–297.2ROR 244.8 · χ² 23,073 / p <1e-300 | 186.9 EB05 160.7 · IC025 +6.5 3/3 methods agree | Not in label — unassessed | – | not reported in cached trials |
| Refractory cytopenia with multilineage dysplasia | 21 | 237.0 146.7–382.9ROR 237.2 · χ² 3,733 / p <1e-300 | 161.1 EB05 111.1 · IC025 +4.4 3/3 methods agree | Not in label — unassessed | – | not reported in cached trials |
| Clonal haematopoiesis | 15 | 236.4 134.0–417.0ROR 236.5 · χ² 2,609 / p <1e-300 | 152.0 EB05 97.8 · IC025 +3.9 3/3 methods agree | Not in label — unassessed | – | not reported in cached trials |
| Malignant transformation | 85 | 217.0 171.4–274.8ROR 217.8 · χ² 14,596 / p <1e-300 | 169.0 EB05 140.9 · IC025 +6.1 3/3 methods agree | Not in label — unassessed | – | not reported in cached trials |
| Iris atrophy | 39 | 214.7 151.5–304.3ROR 215.1 · χ² 6,547 / p <1e-300 | 160.5 EB05 122.5 · IC025 +5.2 3/3 methods agree | Not in label — unassessed | – | not reported in cached trials |
| Neuroblastoma recurrent | 34 | 188.3 130.2–272.4ROR 188.6 · χ² 5,099 / p <1e-300 | 143.9 EB05 107.7 · IC025 +5.0 3/3 methods agree | Not in label — unassessed | – | not reported in cached trials |
| Blood stem cell transplant failure | 35 | 179.7 125.1–258.2ROR 180.0 · χ² 5,050 / p <1e-300 | 139.1 EB05 104.6 · IC025 +5.0 3/3 methods agree | Not in label — unassessed | – | not reported in cached trials |
| Myelodysplastic syndrome with excess blasts | 19 | 179.0 109.5–292.7ROR 179.2 · χ² 2,666 / p <1e-300 | 130.5 EB05 88.3 · IC025 +4.2 3/3 methods agree | Not in label — unassessed | – | not reported in cached trials |
| Poems syndrome | 17 | 178.6 106.2–300.3ROR 178.7 · χ² 2,365 / p <1e-300 | 128.4 EB05 84.9 · IC025 +4.0 3/3 methods agree | Not in label — unassessed | – | not reported in cached trials |
| Adenovirus reactivation | 21 | 165.5 104.0–263.3ROR 165.6 · χ² 2,769 / p <1e-300 | 124.6 EB05 86.0 · IC025 +4.3 3/3 methods agree | Not in label — unassessed | – | not reported in cached trials |
| Idiopathic pneumonia syndrome | 45 | 165.2 120.3–226.9ROR 165.5 · χ² 6,081 / p <1e-300 | 132.3 EB05 102.9 · IC025 +5.3 3/3 methods agree | Not in label — unassessed | – | not reported in cached trials |
| Autologous haematopoietic stem cell transplant | 13 | 160.6 89.1–289.5ROR 160.7 · χ² 1,620 / p <1e-300 | 114.2 EB05 71.0 · IC025 +3.6 3/3 methods agree | Not in label — unassessed | – | not reported in cached trials |
| Adenoviral hepatitis | 34 | 159.4 110.7–229.4ROR 159.6 · χ² 4,422 / p <1e-300 | 126.4 EB05 94.6 · IC025 +5.0 3/3 methods agree | Not in label — unassessed | – | not reported in cached trials |
| Delayed engraftment | 19 | 159.3 97.9–259.3ROR 159.5 · χ² 2,412 / p <1e-300 | 119.8 EB05 81.0 · IC025 +4.2 3/3 methods agree | Not in label — unassessed | – | not reported in cached trials |
| Pneumonia adenoviral | 27 | 152.3 101.4–228.9ROR 152.5 · χ² 3,351 / p <1e-300 | 119.8 EB05 86.5 · IC025 +4.6 3/3 methods agree | Not in label — unassessed | – | not reported in cached trials |
| Engraft failure | 40 | 151.1 108.2–211.1ROR 151.3 · χ² 4,990 / p <1e-300 | 122.3 EB05 93.7 · IC025 +5.1 3/3 methods agree | Not in label — unassessed | – | not reported in cached trials |
| Chronic graft versus host disease in intestine | 26 | 150.4 99.4–227.7ROR 150.6 · χ² 3,186 / p <1e-300 | 118.3 EB05 84.8 · IC025 +4.6 3/3 methods agree | Not in label — unassessed | – | not reported in cached trials |
| Mucoepidermoid carcinoma | 13 | 144.9 80.7–260.1ROR 145.0 · χ² 1,482 / p <1e-300 | 106.1 EB05 66.0 · IC025 +3.5 3/3 methods agree | Not in label — unassessed | – | not reported in cached trials |
| Light chain disease | 18 | 129.5 79.1–212.2ROR 129.7 · χ² 1,900 / p <1e-300 | 101.6 EB05 68.0 · IC025 +4.0 3/3 methods agree | Not in label — unassessed | – | not reported in cached trials |
| Acute graft versus host disease in intestine | 165 | 123.6 105.1–145.4ROR 124.5 · χ² 17,571 / p <1e-300 | 107.7 EB05 94.6 · IC025 +6.1 3/3 methods agree | Not in label — unassessed | – | not reported in cached trials |
| Human herpesvirus 6 encephalitis | 33 | 121.6 84.6–174.8ROR 121.8 · χ² 3,379 / p <1e-300 | 101.3 EB05 75.5 · IC025 +4.8 3/3 methods agree | Not in label — unassessed | – | not reported in cached trials |
| Gastroenteritis adenovirus | 18 | 120.1 73.5–196.3ROR 120.2 · χ² 1,775 / p <1e-300 | 95.8 EB05 64.1 · IC025 +4.0 3/3 methods agree | Not in label — unassessed | – | not reported in cached trials |
| Adenovirus infection | 325 | 118.5 105.7–133.0ROR 120.3 · χ² 33,430 / p <1e-300 | 104.4 EB05 95.2 · IC025 +6.3 3/3 methods agree | Not in label — unassessed | – | not reported in cached trials |
| Retinal depigmentation | 33 | 112.1 78.1–160.9ROR 112.3 · χ² 3,139 / p <1e-300 | 94.7 EB05 70.5 · IC025 +4.8 3/3 methods agree | Not in label — unassessed | – | not reported in cached trials |
| Hepatic infection fungal | 13 | 112.1 63.0–199.4ROR 112.2 · χ² 1,178 / p 2e-258 | 87.5 EB05 54.4 · IC025 +3.5 3/3 methods agree | Labeled (related wording) related wording | – | not reported in cached trials |
| Human herpesvirus 6 infection reactivation | 37 | 110.5 78.6–155.4ROR 110.7 · χ² 3,485 / p <1e-300 | 94.0 EB05 71.3 · IC025 +4.9 3/3 methods agree | Not in label — unassessed | – | not reported in cached trials |
| Venoocclusive liver disease | 515 | 108.5 99.1–118.8ROR 111.0 · χ² 48,942 / p <1e-300 | 96.7 EB05 89.9 · IC025 +6.3 3/3 methods agree | Not in label — unassessed | – | not reported in cached trials |
| Acute graft versus host disease in skin | 289 | 108.5 96.1–122.5ROR 109.9 · χ² 27,419 / p <1e-300 | 96.5 EB05 87.5 · IC025 +6.2 3/3 methods agree | Not in label — unassessed | – | not reported in cached trials |
| Adenoviral haemorrhagic cystitis | 22 | 108.1 69.5–168.2ROR 108.2 · χ² 1,993 / p <1e-300 | 89.5 EB05 62.3 · IC025 +4.2 3/3 methods agree | Not in label — unassessed | – | not reported in cached trials |
| Acute graft versus host disease | 473 | 105.8 96.3–116.3ROR 108.1 · χ² 43,937 / p <1e-300 | 94.6 EB05 87.7 · IC025 +6.3 3/3 methods agree | Not in label — unassessed | – | not reported in cached trials |
| Atrophy of globe | 13 | 105.2 59.2–186.7ROR 105.2 · χ² 1,111 / p 6e-244 | 83.2 EB05 51.8 · IC025 +3.5 3/3 methods agree | Not in label — unassessed | – | not reported in cached trials |
| Epstein-barr virus infection reactivation | 128 | 104.4 87.0–125.3ROR 105.0 · χ² 11,669 / p <1e-300 | 92.5 EB05 79.8 · IC025 +5.8 3/3 methods agree | Not in label — unassessed | – | not reported in cached trials |
| Chronic graft versus host disease in skin | 91 | 102.9 82.9–127.8ROR 103.4 · χ² 8,166 / p <1e-300 | 90.9 EB05 76.3 · IC025 +5.6 3/3 methods agree | Not in label — unassessed | – | not reported in cached trials |
Trial evidence (ClinicalTrials.gov)
✓ Trial adverse-event data found on ClinicalTrials.gov
Largest completed trials with posted results that list Melphalan as a study intervention. The right-hand column of the signal table shows whether each FAERS term was also recorded in these trials, with a real denominator (0 of 40 signal terms matched).
- NCT00689936 — Study to Determine Efficacy and Safety of Lenalidomide Plus Low-dose Dexamethasone Versus Melphalan, Prednison (N=1623, PHASE3; 705 AE terms posted; arms: Lenalidomide and Low-Dose Dexamethasone ; Lenalidomide and Dexamethasone (Rd18); Melphalan + Prednisone + Thalidomide (MP)
- NCT01818752 — Phase 3 Study of Carfilzomib, Melphalan, Prednisone vs Bortezomib, Melphalan, Prednisone in Newly Diagnosed Mu (N=955, PHASE3; 345 AE terms posted; arms: Bortezomib, Melphalan, Prednisone; Carfilzomib, Melphalan, Prednisone)
Caveats: trial populations, doses and follow-up differ from the reporting population; AE terms are sponsor-coded and matched here by wording; absence from a trial list means the term was not reported above the sponsor's frequency threshold, not that it cannot occur.
Most frequently reported reactions
By raw co-report count, regardless of disproportionality. Common terms here are often the illness itself or generic outcomes.
| Reaction | Reports | PRR 95% CI · ROR · χ²/p | EBGM EB05 · IC025 | Label screen | Serious-only & strata | Trial cross-check |
|---|---|---|---|---|---|---|
| Off label use (used outside approved label) | 2,448 | 2.6 2.5–2.7ROR 2.8 · χ² 2,550 / p <1e-300 | 2.6 EB05 2.5 · IC025 +1.3 3/3 methods agree | Reporting / coding artifact | – | not reported in cached trials |
| Drug ineffective (drug did not work) | 1,378 | 1.0 0.9–1.0ROR 1.0 · χ² 1 / p 0.128 | 1.0 EB05 0.9 · IC025 -0.1 PRR-only: not supported by EBGM or IC | Reporting / coding artifact | – | not reported in cached trials |
| Plasma cell myeloma | 1,274 | 31.2 29.6–33.0ROR 33.0 · χ² 36,066 / p <1e-300 | 30.2 EB05 28.8 · IC025 +4.8 3/3 methods agree | Likely indication confounding shares a disease stem with the indications wording | – | NCT01818752: 2/470 (0.4%) on Melphalan (serious AE) |
| Febrile neutropenia | 1,217 | 17.3 16.4–18.3ROR 18.3 · χ² 18,437 / p <1e-300 | 17.0 EB05 16.2 · IC025 +4.0 3/3 methods agree | Not in label — unassessed | – | NCT00689936: 13/541 (2.4%) on Melphalan (serious AE) |
| Neutropenia (low neutrophils (infection-fighting cells)) | 1,114 | 7.7 7.3–8.1ROR 8.0 · χ² 6,453 / p <1e-300 | 7.6 EB05 7.2 · IC025 +2.8 3/3 methods agree | Not in label — unassessed | – | NCT00689936: 13/541 (2.4%) on Melphalan (serious AE) |
| Mucosal inflammation | 1,097 | 40.7 38.4–43.2ROR 42.7 · χ² 40,705 / p <1e-300 | 39.0 EB05 37.1 · IC025 +5.2 3/3 methods agree | Not in label — unassessed | – | NCT00689936: 1/532 (0.2%) on Melphalan (serious AE) |
| Pyrexia (fever) | 1,060 | 2.8 2.7–3.0ROR 2.9 · χ² 1,283 / p 2e-281 | 2.8 EB05 2.7 · IC025 +1.4 3/3 methods agree | Not in label — unassessed | – | NCT00689936: 1/540 (0.2%) on Melphalan (serious AE) |
| Pneumonia (lung infection) | 1,055 | 3.0 2.9–3.2ROR 3.1 · χ² 1,453 / p <1e-300 | 3.0 EB05 2.9 · IC025 +1.5 3/3 methods agree | Labeled — boxed warning synonym match | – | NCT00689936: 1/540 (0.2%) on Melphalan (serious AE) |
| Thrombocytopenia (low platelets) | 1,043 | 8.7 8.2–9.3ROR 9.1 · χ² 7,118 / p <1e-300 | 8.7 EB05 8.2 · IC025 +3.0 3/3 methods agree | Labeled — boxed warning exact term | – | NCT00689936: 10/541 (1.8%) on Melphalan (serious AE) |
| Diarrhoea (diarrhea) | 979 | 1.4 1.3–1.5ROR 1.4 · χ² 121 / p 2e-28 | 1.4 EB05 1.3 · IC025 +0.4 | Labeled adverse reaction exact term | – | NCT00689936: 4/541 (0.7%) on Melphalan (serious AE) |
| Product use in unapproved indication | 921 | 3.5 3.3–3.7ROR 3.6 · χ² 1,660 / p <1e-300 | 3.5 EB05 3.3 · IC025 +1.7 3/3 methods agree | Reporting / coding artifact | – | not reported in cached trials |
| Sepsis (blood infection) | 800 | 6.7 6.2–7.2ROR 6.9 · χ² 3,857 / p <1e-300 | 6.6 EB05 6.2 · IC025 +2.6 3/3 methods agree | Not in label — unassessed | – | NCT00689936: 1/532 (0.2%) on Melphalan (serious AE) |
| Disease progression | 777 | 6.1 5.7–6.6ROR 6.3 · χ² 3,338 / p <1e-300 | 6.1 EB05 5.7 · IC025 +2.5 3/3 methods agree | Reporting / coding artifact | – | NCT01818752: 1/474 (0.2%) on Melphalan (serious AE) |
| Infection | 708 | 4.6 4.3–4.9ROR 4.7 · χ² 1,975 / p <1e-300 | 4.5 EB05 4.3 · IC025 +2.1 3/3 methods agree | Labeled — boxed warning exact term | – | NCT00689936: 1/540 (0.2%) on Melphalan (serious AE) |
| Neuropathy peripheral (nerve damage in hands/feet) | 694 | 6.9 6.4–7.4ROR 7.0 · χ² 3,452 / p <1e-300 | 6.8 EB05 6.4 · IC025 +2.6 3/3 methods agree | Not in label — unassessed | – | NCT00689936: 1/541 (0.2%) on Melphalan (serious AE) |
Unlabeled candidate signals
These flagged terms were not found in the FDA label text and do not match an artifact pattern. They are the pairs that would merit a structured assessment (temporality, dose-response, biological plausibility, consistency across databases, trial or cohort evidence). The screen has not done that; string-matching misses label wording, and a strong PRR can still be stimulated reporting, co-medication, or the disease itself.
- Protothecosis — n=37, PRR 603.9
- Choroidal infarction — n=28, PRR 281.2
- Chorioretinal atrophy — n=48, PRR 274.2
- Engraftment syndrome — n=122, PRR 243.5
- Refractory cytopenia with multilineage dysplasia — n=21, PRR 237.0
- Malignant transformation — n=85, PRR 217.0
- Iris atrophy — n=39, PRR 214.7
- Neuroblastoma recurrent — n=34, PRR 188.3
- Blood stem cell transplant failure — n=35, PRR 179.7
- Adenovirus reactivation — n=21, PRR 165.5
Want to assess one of these properly? The runbook describes the Bradford Hill / trial-evidence workflow used on the assessment page, and handoff_top1000_signals.csv lists the strongest unassessed pairs across all drugs.
Common questions
What are the most reported side effects of Melphalan?
In FDA FAERS, the most frequently co-reported reaction terms for Melphalan are plasma cell myeloma, febrile neutropenia, neutropenia, mucosal inflammation, pyrexia, pneumonia. These are report counts, not rates: FAERS has no denominator, reporting is voluntary and uneven, and a term can be reported because of the illness being treated rather than the drug.
Does Melphalan have an FDA boxed warning?
Yes. The current FDA label carries a boxed warning: Melphalan should be administered under the supervision of a qualified physician experienced in the use of cancer chemotherapeutic agents. Severe bone marrow suppression with resulting infection or bleeding may occur. Controlled trials comparing intravenous (IV) to oral melphalan have shown more myelosuppression with the IV formulation.
Do FAERS signals prove that Melphalan causes these side effects?
No. A disproportionality signal (PRR, ROR) means a reaction is reported more often with this drug than with others in the database. That can reflect a real effect, but also the disease being treated, stimulated reporting after news or litigation, co-medications, or how reports are coded. Causality needs temporality, dose-response, biological plausibility, consistency across data sources and, ideally, trial or cohort evidence. This page screens each term against the FDA label and ClinicalTrials.gov results; it does not establish causation.
Sources & methods
- FDA label via openFDA (set ID 2254450e-4803-b947-e063-6394a90a4624, effective 20260108; matched on
openfda.generic_name:"MELPHALAN") - Bayesian shrinkage measures computed offline over all 1,317,300 cached pairs: BCPNN information component (IC, with Norén closed-form IC025) and MGPS empirical-Bayes geometric mean (EBGM, EB05) with a two-component gamma prior fitted by maximum marginal likelihood (α₁=0.57, β₁=0.02, α₂=1.42, β₂=0.70, w=0.17); unstratified
- FAERS pair statistics from the OpenPV build of 2026-09-14 (openFDA
count=aggregation, fieldpatient.drug.openfda.generic_name.exact, 1,118 reaction terms, min 3 co-reports); PRR/ROR with 95% CI, chi-square with Yates correction - Serious-only and stratified counts (serious:1, patient.patientsex, primarysource.qualification) from openFDA count queries; serious-only PRR uses the drug serious report total and the term global serious total (N_serious=11,882,979); strata shown only when n ≥ 20
- Seriousness and sex counts from openFDA
count=serious,patient.patientsex,seriousnessdeath - ClinicalTrials.gov API v2 (query
MELPHALAN, results-bearing studies sorted by enrollment)
Page generated 2026-10-08. Label and PubChem text are retrieved automatically and may lag the current label; always check the current prescribing information. OpenPV is a beta research tool of the Open Source Medicine Foundation.