Treosulfan side effects: what 2,640 FDA adverse event reports show
Drug class
Alkylating drug
Brand names
Grafapex
Who reports
2,640 reports · 98% serious · 579 with death outcome · 44% female
Used for
GRAFAPEX is an alkylating drug indicated for: Use in combination with fludarabine as a preparative regimen for allogeneic hematopoietic stem cell transplantation (alloHSCT) in adult and pediatric patients 1 year of age and older with acute myeloid leukemia (AML). ( 1.1 ).
What it is
GRAFAPEX for injection contains treosulfan, an alkylating drug. Treosulfan is known chemically as L-‑threitol ‑1,4-‑dimethanesulfonate. Treosulfan is soluble in water (7% m/v) at 25ᴼC. Treosulfan is not hygroscopic.Treosulfan has the molecular formula C 6 H 14 O 8 S 2 and a molecular weight of 278.3 g/mole.
Boxed warning
MYELOSUPPRESSION GRAFAPEX causes severe and prolonged myelosuppression at the recommended dosage. Hematopoietic stem cell transplantation is required to prevent potentially fatal complications of the prolonged myelosuppression. Monitor hematologic laboratory parameters [see Warnings and Precautions ( 5.1 )] .
Causality screen of the 40 strongest signals
What the badges mean
- Labeled — boxed warning The term (or its clinical synonym) appears in the FDA boxed warning: causality is regulator-recognised and considered serious.
- Labeled adverse reaction The exact term appears in the label's warnings or adverse-reactions sections: a known, expected effect. The FAERS signal confirms the label rather than discovering anything.
- Labeled (related wording) The label describes this effect under different wording (e.g. 'neutropenia' for 'neutrophil count decreased'). Treated as known.
- Likely indication confounding The term appears in the label's indications: reports probably describe the disease being treated (or its progression), not a drug effect. Classic confounding by indication.
- Reporting / coding artifact An administrative, monitoring or exposure term (product issue, off-label use, 'test normal', overdose...). Not a biological reaction; a high PRR here reflects how reports are coded.
- 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. 53 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 |
|---|---|---|---|---|---|---|
| Cytomegalovirus infection | 262 | 127.1 113.2–142.7ROR 141.0 · χ² 32,159 / p <1e-300 | 124.0 EB05 111.9 · IC025 +6.5 3/3 methods agree | Not in label — unassessed | serious PRR 74.4 · 98% clinician | no trial data cached |
| Mucosal inflammation | 234 | 72.0 63.6–81.4ROR 78.9 · χ² 16,174 / p <1e-300 | 70.9 EB05 63.6 · IC025 +5.7 3/3 methods agree | Labeled (related wording) related wording | serious PRR 44.6 · 100% clinician | no trial data cached |
| Posterior reversible encephalopathy syndrome | 66 | 55.5 43.7–70.4ROR 56.8 · χ² 3,452 / p <1e-300 | 54.3 EB05 44.1 · IC025 +4.9 3/3 methods agree | Not in label — unassessed | serious PRR 32.4 · 100% clinician | no trial data cached |
| Thrombotic microangiopathy | 57 | 47.0 36.3–60.8ROR 48.0 · χ² 2,507 / p <1e-300 | 46.1 EB05 36.9 · IC025 +4.6 3/3 methods agree | Not in label — unassessed | serious PRR 27.5 · 100% clinician | no trial data cached |
| Multiple organ dysfunction syndrome | 127 | 36.3 30.6–43.0ROR 38.1 · χ² 4,311 / p <1e-300 | 36.0 EB05 31.0 · IC025 +4.7 3/3 methods agree | Not in label — unassessed | serious PRR 21.2 · 95% clinician | no trial data cached |
| Acute respiratory distress syndrome | 44 | 19.8 14.8–26.6ROR 20.1 · χ² 765 / p 9e-169 | 19.6 EB05 15.2 · IC025 +3.5 3/3 methods agree | Not in label — unassessed | serious PRR 11.6 · 100% clinician | no trial data cached |
| Lymphopenia | 31 | 17.5 12.4–24.9ROR 17.7 · χ² 466 / p 1e-103 | 17.3 EB05 12.6 · IC025 +3.2 3/3 methods agree | Not in label — unassessed | serious PRR 11.1 · 100% clinician | no trial data cached |
| Pneumonitis | 58 | 17.1 13.2–22.0ROR 17.4 · χ² 861 / p 2e-189 | 16.9 EB05 13.5 · IC025 +3.5 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 10.4 · 100% clinician | no trial data cached |
| Bacteraemia | 25 | 16.9 11.4–25.0ROR 17.1 · χ² 358 / p 4e-80 | 16.5 EB05 11.6 · IC025 +3.0 3/3 methods agree | Not in label — unassessed | serious PRR 10.0 · 100% clinician | no trial data cached |
| Staphylococcal infection | 66 | 15.9 12.5–20.1ROR 16.2 · χ² 904 / p 7e-199 | 15.7 EB05 12.8 · IC025 +3.4 3/3 methods agree | Not in label — unassessed | serious PRR 10.3 · 100% clinician | no trial data cached |
| Myelodysplastic syndrome | 26 | 14.3 9.7–21.0ROR 14.4 · χ² 308 / p 3e-69 | 13.8 EB05 9.6 · IC025 +2.9 3/3 methods agree | Likely indication confounding term in indications | serious PRR 8.5 · 100% clinician | no trial data cached |
| Acute myeloid leukaemia | 26 | 13.3 9.1–19.5ROR 13.4 · χ² 283 / p 9e-64 | 12.8 EB05 8.8 · IC025 +2.8 3/3 methods agree | Likely indication confounding term in indications | serious PRR 7.8 · ♀ 9% (drug 44%) · 100% clinician | no trial data cached |
| Hyperbilirubinaemia | 16 | 12.4 7.6–20.1ROR 12.4 · χ² 156 / p 5e-36 | 11.2 EB05 6.7 · IC025 +2.4 3/3 methods agree | Not in label — unassessed | serious PRR 7.4 | no trial data cached |
| Febrile neutropenia | 96 | 11.5 9.5–14.0ROR 11.9 · χ² 914 / p 4e-201 | 11.4 EB05 9.5 · IC025 +3.1 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 6.8 · 100% clinician | no trial data cached |
| Pericardial effusion | 33 | 11.4 8.1–16.0ROR 11.5 · χ² 303 / p 4e-68 | 10.9 EB05 7.9 · IC025 +2.7 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 6.8 · ♀ 19% (drug 44%) · 100% clinician | no trial data cached |
| Haematotoxicity | 13 | 11.2 6.5–19.2ROR 11.2 · χ² 110 / p 5e-26 | 9.6 EB05 5.4 · IC025 +2.1 3/3 methods agree | Likely indication confounding shares a disease stem with the indications wording | serious PRR 6.7 | no trial data cached |
| Viral infection | 46 | 11.0 8.3–14.7ROR 11.2 · χ² 409 / p 4e-91 | 10.6 EB05 8.1 · IC025 +2.8 3/3 methods agree | Not in label — unassessed | serious PRR 5.5 · 100% clinician | no trial data cached |
| Candida infection (yeast infection) | 23 | 11.0 7.3–16.5ROR 11.0 · χ² 198 / p 2e-45 | 10.1 EB05 6.8 · IC025 +2.5 3/3 methods agree | Not in label — unassessed | serious PRR 9.2 · 100% clinician | no trial data cached |
| Drug resistance | 35 | 10.8 7.8–15.1ROR 11.0 · χ² 303 / p 4e-68 | 10.3 EB05 7.5 · IC025 +2.7 3/3 methods agree | Reporting / coding artifact | serious PRR 7.1 · ♀ 23% (drug 44%) · 94% clinician | no trial data cached |
| Neurotoxicity | 23 | 10.5 7.0–15.8ROR 10.6 · χ² 189 / p 3e-43 | 9.7 EB05 6.5 · IC025 +2.4 3/3 methods agree | Not in label — unassessed | serious PRR 6.3 · 96% clinician | no trial data cached |
| Nephropathy toxic | 14 | 10.0 5.9–16.9ROR 10.0 · χ² 104 / p 8e-25 | 8.5 EB05 5.0 · IC025 +2.0 3/3 methods agree | Not in label — unassessed | serious PRR 6.0 | no trial data cached |
| Impaired gastric emptying | 16 | 10.0 6.1–16.3ROR 10.0 · χ² 120 / p 3e-28 | 8.7 EB05 5.3 · IC025 +2.1 3/3 methods agree | Not in label — unassessed | serious PRR 6.6 | no trial data cached |
| Clostridium difficile colitis | 13 | 9.7 5.7–16.7ROR 9.8 · χ² 93 / p 2e-22 | 8.1 EB05 4.7 · IC025 +1.9 3/3 methods agree | Not in label — unassessed | serious PRR 5.8 | no trial data cached |
| Ascites | 34 | 9.2 6.6–12.8ROR 9.3 · χ² 240 / p 2e-54 | 8.6 EB05 6.3 · IC025 +2.5 3/3 methods agree | Not in label — unassessed | serious PRR 5.5 · 100% clinician | no trial data cached |
| Acute respiratory failure | 22 | 9.1 6.0–13.9ROR 9.2 · χ² 151 / p 4e-35 | 8.2 EB05 5.5 · IC025 +2.2 3/3 methods agree | Labeled (related wording) related wording | serious PRR 5.4 · 100% clinician | no trial data cached |
| Fungal infection | 38 | 9.1 6.6–12.4ROR 9.2 · χ² 265 / p 7e-60 | 8.5 EB05 6.4 · IC025 +2.5 3/3 methods agree | Not in label — unassessed | serious PRR 9.7 · 97% clinician | no trial data cached |
| Toxic epidermal necrolysis (severe skin peeling reaction) | 17 | 9.0 5.6–14.4ROR 9.0 · χ² 112 / p 1e-26 | 7.7 EB05 4.9 · IC025 +2.1 3/3 methods agree | Not in label — unassessed | serious PRR 5.3 | no trial data cached |
| Hepatic failure | 34 | 8.9 6.4–12.5ROR 9.0 · χ² 232 / p 1e-52 | 8.3 EB05 6.1 · IC025 +2.4 3/3 methods agree | Not in label — unassessed | serious PRR 5.3 · ♀ 10% (drug 44%) · 100% clinician | no trial data cached |
| Multi-organ failure | 19 | 8.6 5.5–13.5ROR 8.7 · χ² 120 / p 3e-28 | 7.5 EB05 4.9 · IC025 +2.1 3/3 methods agree | Not in label — unassessed | serious PRR 5.1 | no trial data cached |
| Hepatotoxicity (liver damage) | 24 | 8.6 5.8–12.8ROR 8.7 · χ² 154 / p 1e-35 | 7.7 EB05 5.3 · IC025 +2.2 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 5.2 · 100% clinician | no trial data cached |
| Encephalopathy | 25 | 8.1 5.5–12.0ROR 8.2 · χ² 149 / p 2e-34 | 7.3 EB05 5.1 · IC025 +2.2 3/3 methods agree | Not in label — unassessed | serious PRR 4.8 · ♀ 80% (drug 44%) · 100% clinician | no trial data cached |
| Product use in unapproved indication | 225 | 7.3 6.5–8.3ROR 7.9 · χ² 1,235 / p 8e-271 | 7.2 EB05 6.5 · IC025 +2.6 3/3 methods agree | Reporting / coding artifact | serious PRR 9.0 · 100% clinician | no trial data cached |
| Sepsis (blood infection) | 99 | 7.1 5.8–8.6ROR 7.3 · χ² 510 / p 3e-113 | 6.9 EB05 5.8 · IC025 +2.4 3/3 methods agree | Not in label — unassessed | serious PRR 4.2 · 99% clinician | no trial data cached |
| Gastroenteritis viral | 16 | 7.0 4.3–11.4ROR 7.1 · χ² 77 / p 1e-18 | 6.0 EB05 3.9 · IC025 +1.7 3/3 methods agree | Not in label — unassessed | serious PRR 7.8 | no trial data cached |
| Drug ineffective for unapproved indication | 48 | 6.8 5.2–9.1ROR 7.0 · χ² 234 / p 4e-53 | 6.5 EB05 5.1 · IC025 +2.2 3/3 methods agree | Reporting / coding artifact | serious PRR 9.0 · 98% clinician | no trial data cached |
| Neutropenia (low neutrophils (infection-fighting cells)) | 116 | 6.8 5.7–8.1ROR 7.1 · χ² 572 / p 1e-126 | 6.6 EB05 5.7 · IC025 +2.4 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 4.2 · 98% clinician | no trial data cached |
| Therapy non-responder | 38 | 6.8 4.9–9.3ROR 6.9 · χ² 182 / p 1e-41 | 6.3 EB05 4.8 · IC025 +2.1 3/3 methods agree | Reporting / coding artifact | serious PRR 6.5 · 100% clinician | no trial data cached |
| Cytopenia | 10 | 6.7 3.6–12.3ROR 6.7 · χ² 43 / p 4e-11 | 5.3 EB05 3.0 · IC025 +1.3 3/3 methods agree | Labeled — boxed warning exact term | serious PRR 4.0 | no trial data cached |
| Hyperthyroidism | 12 | 6.6 3.7–11.6ROR 6.6 · χ² 51 / p 4e-13 | 5.4 EB05 3.3 · IC025 +1.5 3/3 methods agree | Not in label — unassessed | serious PRR 4.2 | no trial data cached |
| Intentional product use issue | 72 | 6.5 5.2–8.2ROR 6.7 · χ² 331 / p 3e-74 | 6.3 EB05 5.1 · IC025 +2.3 3/3 methods agree | Reporting / coding artifact | serious PRR 5.5 | no trial data cached |
Trial evidence (ClinicalTrials.gov)
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) | 637 | 5.8 5.5–6.2ROR 7.4 · χ² 2,654 / p <1e-300 | 5.8 EB05 5.4 · IC025 +2.4 3/3 methods agree | Reporting / coding artifact | serious PRR 6.4 · 98% clinician | no trial data cached |
| Cytomegalovirus infection | 262 | 127.1 113.2–142.7ROR 141.0 · χ² 32,159 / p <1e-300 | 124.0 EB05 111.9 · IC025 +6.5 3/3 methods agree | Not in label — unassessed | serious PRR 74.4 · 98% clinician | no trial data cached |
| Mucosal inflammation | 234 | 72.0 63.6–81.4ROR 78.9 · χ² 16,174 / p <1e-300 | 70.9 EB05 63.6 · IC025 +5.7 3/3 methods agree | Labeled (related wording) related wording | serious PRR 44.6 · 100% clinician | no trial data cached |
| Product use in unapproved indication | 225 | 7.3 6.5–8.3ROR 7.9 · χ² 1,235 / p 8e-271 | 7.2 EB05 6.5 · IC025 +2.6 3/3 methods agree | Reporting / coding artifact | serious PRR 9.0 · 100% clinician | no trial data cached |
| Multiple organ dysfunction syndrome | 127 | 36.3 30.6–43.0ROR 38.1 · χ² 4,311 / p <1e-300 | 36.0 EB05 31.0 · IC025 +4.7 3/3 methods agree | Not in label — unassessed | serious PRR 21.2 · 95% clinician | no trial data cached |
| Neutropenia (low neutrophils (infection-fighting cells)) | 116 | 6.8 5.7–8.1ROR 7.1 · χ² 572 / p 1e-126 | 6.6 EB05 5.7 · IC025 +2.4 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 4.2 · 98% clinician | no trial data cached |
| Sepsis (blood infection) | 99 | 7.1 5.8–8.6ROR 7.3 · χ² 510 / p 3e-113 | 6.9 EB05 5.8 · IC025 +2.4 3/3 methods agree | Not in label — unassessed | serious PRR 4.2 · 99% clinician | no trial data cached |
| Febrile neutropenia | 96 | 11.5 9.5–14.0ROR 11.9 · χ² 914 / p 4e-201 | 11.4 EB05 9.5 · IC025 +3.1 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 6.8 · 100% clinician | no trial data cached |
| Thrombocytopenia (low platelets) | 88 | 6.3 5.1–7.7ROR 6.5 · χ² 387 / p 2e-86 | 6.1 EB05 5.1 · IC025 +2.3 3/3 methods agree | Labeled — boxed warning exact term | serious PRR 3.8 · 100% clinician | no trial data cached |
| Product use issue | 76 | 3.2 2.6–4.0ROR 3.3 · χ² 116 / p 3e-27 | 3.2 EB05 2.6 · IC025 +1.3 3/3 methods agree | Reporting / coding artifact | serious PRR 4.2 · 97% clinician | no trial data cached |
| Intentional product use issue | 72 | 6.5 5.2–8.2ROR 6.7 · χ² 331 / p 3e-74 | 6.3 EB05 5.1 · IC025 +2.3 3/3 methods agree | Reporting / coding artifact | serious PRR 5.5 | no trial data cached |
| Staphylococcal infection | 66 | 15.9 12.5–20.1ROR 16.2 · χ² 904 / p 7e-199 | 15.7 EB05 12.8 · IC025 +3.4 3/3 methods agree | Not in label — unassessed | serious PRR 10.3 · 100% clinician | no trial data cached |
| Posterior reversible encephalopathy syndrome | 66 | 55.5 43.7–70.4ROR 56.8 · χ² 3,452 / p <1e-300 | 54.3 EB05 44.1 · IC025 +4.9 3/3 methods agree | Not in label — unassessed | serious PRR 32.4 · 100% clinician | no trial data cached |
| Respiratory failure | 59 | 6.4 5.0–8.3ROR 6.5 · χ² 266 / p 5e-60 | 6.1 EB05 4.9 · IC025 +2.2 3/3 methods agree | Labeled (related wording) related wording | serious PRR 3.8 · ♀ 11% (drug 44%) · 98% clinician | no trial data cached |
| Disease progression | 58 | 3.9 3.0–5.0ROR 4.0 · χ² 123 / p 6e-29 | 3.8 EB05 3.1 · IC025 +1.5 3/3 methods agree | Reporting / coding artifact | serious PRR 2.7 · 98% clinician | no trial data cached |
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.
- Cytomegalovirus infection — n=262, PRR 127.1
- Posterior reversible encephalopathy syndrome — n=66, PRR 55.5
- Thrombotic microangiopathy — n=57, PRR 47.0
- Multiple organ dysfunction syndrome — n=127, PRR 36.3
- Acute respiratory distress syndrome — n=44, PRR 19.8
- Lymphopenia — n=31, PRR 17.5
- Bacteraemia — n=25, PRR 16.9
- Staphylococcal infection — n=66, PRR 15.9
- Viral infection — n=46, PRR 11.0
- Candida infection — n=23, PRR 11.0
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 Treosulfan?
In FDA FAERS, the most frequently co-reported reaction terms for Treosulfan are cytomegalovirus infection, mucosal inflammation, multiple organ dysfunction syndrome, neutropenia, sepsis, febrile neutropenia. 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 Treosulfan have an FDA boxed warning?
Yes. The current FDA label carries a boxed warning: MYELOSUPPRESSION GRAFAPEX causes severe and prolonged myelosuppression at the recommended dosage. Hematopoietic stem cell transplantation is required to prevent potentially fatal complications of the prolonged myelosuppression. Monitor hematologic laboratory parameters [see Warnings and Precautions ( 5.1 )] .
Do FAERS signals prove that Treosulfan 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 2d06b03c-17aa-0492-e063-6294a90abd8f, effective 20250131; matched on
openfda.generic_name.exact:"TREOSULFAN") - 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, 93 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
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.