Mitotane side effects: what 1,782 FDA adverse event reports show

Mitotane · Lysodren · 48 reaction terms · 1,061 drug–reaction co-reports · data 2026-09-14

Drug class

Cytochrome P450 3A4 Inducers

FDA label (mechanism-of-action class)

Brand names

Lysodren

openFDA label

Who reports

1,782 reports · 70% serious · 230 with death outcome · 66% female

openFDA FAERS counts, all years, deduplication not applied

Used for

LYSODREN is indicated for the treatment of patients with inoperable, functional or nonfunctional, adrenocortical carcinoma (ACC). LYSODREN is an adrenal cytotoxic agent indicated for the treatment of patients with inoperable, functional or nonfunctional, adrenocortical carcinoma (ACC). ( 1 )

FDA label, Indications and Usage

What it is

LYSODREN (mitotane) is an oral adrenal cytotoxic agent.

FDA label, Description section

Boxed warning

ADRENAL CRISIS IN THE SETTING OF SHOCK, SEVERE TRAUMA OR INFECTION Patients treated with LYSODREN are at increased risk for developing adrenal crisis in the setting of shock, severe trauma or infection that may lead to death. If shock, severe trauma or infection occurs or develops, temporarily discontinue LYSODREN and administer exogenous steroids.

FDA label

How to read this page. FAERS is a spontaneous-reporting system: counts are not incidence rates and a signal is not proof of causation. Each reaction below is run through an automated screen — is the term in the FDA label (known), in the indications (the disease being treated), an administrative/coding term, or none of these (unlabeled)? That screen is mechanical text matching, not a causality assessment. The 30 hand-written Bradford Hill assessments are on the causality assessment page. Not medical advice.

Causality screen of the 27 strongest signals

Labeled — boxed warning 2Labeled adverse reaction 4Labeled (related wording) 1Reporting / coding artifact 6Lab value / disease marker 1Not in label — unassessed 13

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.
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.
Lab value / disease marker A laboratory result, investigation or disease-activity marker (antibody positive, CRP abnormal, swollen joint count) not described in the label. These usually mirror the monitored disease or testing protocol rather than a drug effect; not screened further.
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. 21 further terms are in the interactive explorer. Reaction links open the term's cross-drug page.

Show: hide coding/lab/outcome terms hide indication terms unlabeled only hide PRR-only

Reaction	Reports	PRR 95% CI · ROR · χ²/p	EBGM EB05 · IC025	Label screen	Serious-only & strata	Trial cross-check
Adrenal insufficiency	132	131.2 111.2–154.7ROR 141.6 · χ² 16,744 / p <1e-300	127.4 EB05 110.2 · IC025 +6.2 3/3 methods agree	Labeled — boxed warning exact term	serious PRR 106.7	no trial data cached
Hypercholesterolaemia	21	25.9 16.9–39.6ROR 26.2 · χ² 477 / p 5e-106	25.3 EB05 17.4 · IC025 +3.3 3/3 methods agree	Not in label — unassessed	serious PRR 20.3	no trial data cached
Product use complaint	28	21.3 14.7–30.8ROR 21.6 · χ² 521 / p 1e-115	21.0 EB05 15.2 · IC025 +3.3 3/3 methods agree	Reporting / coding artifact	serious n=3 · ♀ 100% (drug 66%) · 100% consumer	no trial data cached
Malnutrition	19	20.2 12.9–31.5ROR 20.4 · χ² 327 / p 3e-73	19.7 EB05 13.2 · IC025 +3.0 3/3 methods agree	Not in label — unassessed	serious PRR 17.1	no trial data cached
Haematotoxicity	13	16.5 9.6–28.4ROR 16.6 · χ² 174 / p 5e-40	15.5 EB05 8.9 · IC025 +2.5 3/3 methods agree	Not in label — unassessed	serious PRR 13.9	no trial data cached
Metastases to lung	16	16.3 10.0–26.6ROR 16.5 · χ² 215 / p 6e-49	15.6 EB05 9.7 · IC025 +2.6 3/3 methods agree	Not in label — unassessed	serious PRR 13.5	no trial data cached
Brain fog	18	14.5 9.2–23.0ROR 14.7 · χ² 213 / p 1e-48	13.8 EB05 8.7 · IC025 +2.6 3/3 methods agree	Not in label — unassessed	serious PRR 3.8	no trial data cached
Gamma-glutamyltransferase increased	25	13.3 9.0–19.6ROR 13.4 · χ² 272 / p 3e-61	12.7 EB05 8.7 · IC025 +2.7 3/3 methods agree	Lab value / disease marker	serious PRR 10.9	no trial data cached
Hypothyroidism	35	12.9 9.3–18.0ROR 13.2 · χ² 374 / p 1e-83	12.6 EB05 9.2 · IC025 +2.9 3/3 methods agree	Labeled adverse reaction exact term	serious PRR 11.3	no trial data cached
Ataxia	11	10.9 6.0–19.6ROR 10.9 · χ² 89 / p 2e-21	9.0 EB05 4.8 · IC025 +1.9 3/3 methods agree	Labeled adverse reaction exact term	serious PRR 8.8	no trial data cached
Device related infection	13	9.9 5.8–17.1ROR 10.0 · χ² 96 / p 7e-23	8.3 EB05 4.8 · IC025 +2.0 3/3 methods agree	Reporting / coding artifact	serious PRR 8.3	no trial data cached
Electrocardiogram qt prolonged	30	9.8 6.9–14.0ROR 10.0 · χ² 229 / p 5e-52	9.1 EB05 6.5 · IC025 +2.5 3/3 methods agree	Not in label — unassessed	serious PRR 8.2	no trial data cached
Cardiomyopathy	12	9.5 5.4–16.8ROR 9.6 · χ² 83 / p 3e-20	7.8 EB05 4.5 · IC025 +1.9 3/3 methods agree	Not in label — unassessed	serious PRR 7.2	no trial data cached
Neurotoxicity	14	9.5 5.6–16.0ROR 9.6 · χ² 98 / p 2e-23	8.0 EB05 4.8 · IC025 +2.0 3/3 methods agree	Not in label — unassessed	serious PRR 7.9	no trial data cached
Malignant neoplasm progression	80	9.2 7.5–11.5ROR 9.6 · χ² 583 / p 5e-129	9.0 EB05 7.4 · IC025 +2.8 3/3 methods agree	Reporting / coding artifact	serious PRR 7.7	no trial data cached
Hepatocellular injury	11	9.1 5.1–16.4ROR 9.2 · χ² 71 / p 1e-17	7.3 EB05 4.1 · IC025 +1.7 3/3 methods agree	Labeled (related wording) related wording	serious PRR 7.5	no trial data cached
Febrile neutropenia	50	8.9 6.8–11.7ROR 9.1 · χ² 343 / p 7e-77	8.5 EB05 6.6 · IC025 +2.6 3/3 methods agree	Not in label — unassessed	serious PRR 7.3 · 96% clinician	no trial data cached
Hyponatraemia (low sodium)	42	8.8 6.5–11.9ROR 9.0 · χ² 283 / p 8e-64	8.3 EB05 6.3 · IC025 +2.5 3/3 methods agree	Not in label — unassessed	serious PRR 7.0	no trial data cached
Disease progression	73	7.3 5.8–9.1ROR 7.6 · χ² 392 / p 2e-87	7.0 EB05 5.7 · IC025 +2.4 3/3 methods agree	Reporting / coding artifact	serious PRR 6.6	no trial data cached
Product dose omission issue	138	5.7 4.9–6.7ROR 6.1 · χ² 538 / p 3e-119	5.6 EB05 4.9 · IC025 +2.2 3/3 methods agree	Reporting / coding artifact	serious PRR 4.2 · 88% consumer	no trial data cached
Disturbance in attention	26	5.7 3.9–8.3ROR 5.7 · χ² 95 / p 8e-23	5.2 EB05 3.7 · IC025 +1.7 3/3 methods agree	Not in label — unassessed	serious PRR 6.7	no trial data cached
Neutropenia (low neutrophils (infection-fighting cells))	63	5.5 4.3–7.0ROR 5.6 · χ² 227 / p 1e-51	5.3 EB05 4.3 · IC025 +2.0 3/3 methods agree	Not in label — unassessed	serious PRR 4.7	no trial data cached
Hepatotoxicity (liver damage)	10	5.3 2.9–9.9ROR 5.3 · χ² 31 / p 1e-8	4.4 EB05 2.6 · IC025 +1.1 3/3 methods agree	Labeled — boxed warning exact term	serious PRR 4.4	no trial data cached
Intentional dose omission	12	5.2 2.9–9.1ROR 5.2 · χ² 36 / p 9e-10	4.4 EB05 2.7 · IC025 +1.2 3/3 methods agree	Reporting / coding artifact	serious PRR 2.2	no trial data cached
Mucosal inflammation	11	5.0 2.8–9.0ROR 5.0 · χ² 31 / p 1e-8	4.2 EB05 2.5 · IC025 +1.1 3/3 methods agree	Labeled adverse reaction exact term	serious PRR 4.3	no trial data cached
Neoplasm progression	14	4.7 2.8–7.9ROR 4.7 · χ² 37 / p 6e-10	4.1 EB05 2.6 · IC025 +1.2 3/3 methods agree	Not in label — unassessed	serious PRR 5.3	no trial data cached
Gynaecomastia (male breast enlargement)	12	4.5 2.6–7.9ROR 4.5 · χ² 29 / p 3e-8	3.9 EB05 2.4 · IC025 +1.0 3/3 methods agree	Labeled adverse reaction exact term	serious PRR 11.9	no trial data cached

Trial evidence (ClinicalTrials.gov)

Trial cross-check not yet run for this drug (ClinicalTrials.gov pull covers the 800 most-reported drugs first).

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
Product dose omission issue	138	5.7 4.9–6.7ROR 6.1 · χ² 538 / p 3e-119	5.6 EB05 4.9 · IC025 +2.2 3/3 methods agree	Reporting / coding artifact	serious PRR 4.2 · 88% consumer	no trial data cached
Adrenal insufficiency	132	131.2 111.2–154.7ROR 141.6 · χ² 16,744 / p <1e-300	127.4 EB05 110.2 · IC025 +6.2 3/3 methods agree	Labeled — boxed warning exact term	serious PRR 106.7	no trial data cached
Malignant neoplasm progression	80	9.2 7.5–11.5ROR 9.6 · χ² 583 / p 5e-129	9.0 EB05 7.4 · IC025 +2.8 3/3 methods agree	Reporting / coding artifact	serious PRR 7.7	no trial data cached
Disease progression	73	7.3 5.8–9.1ROR 7.6 · χ² 392 / p 2e-87	7.0 EB05 5.7 · IC025 +2.4 3/3 methods agree	Reporting / coding artifact	serious PRR 6.6	no trial data cached
Neutropenia (low neutrophils (infection-fighting cells))	63	5.5 4.3–7.0ROR 5.6 · χ² 227 / p 1e-51	5.3 EB05 4.3 · IC025 +2.0 3/3 methods agree	Not in label — unassessed	serious PRR 4.7	no trial data cached
Febrile neutropenia	50	8.9 6.8–11.7ROR 9.1 · χ² 343 / p 7e-77	8.5 EB05 6.6 · IC025 +2.6 3/3 methods agree	Not in label — unassessed	serious PRR 7.3 · 96% clinician	no trial data cached
Hyponatraemia (low sodium)	42	8.8 6.5–11.9ROR 9.0 · χ² 283 / p 8e-64	8.3 EB05 6.3 · IC025 +2.5 3/3 methods agree	Not in label — unassessed	serious PRR 7.0	no trial data cached
Hypothyroidism	35	12.9 9.3–18.0ROR 13.2 · χ² 374 / p 1e-83	12.6 EB05 9.2 · IC025 +2.9 3/3 methods agree	Labeled adverse reaction exact term	serious PRR 11.3	no trial data cached
Electrocardiogram qt prolonged	30	9.8 6.9–14.0ROR 10.0 · χ² 229 / p 5e-52	9.1 EB05 6.5 · IC025 +2.5 3/3 methods agree	Not in label — unassessed	serious PRR 8.2	no trial data cached
Product use complaint	28	21.3 14.7–30.8ROR 21.6 · χ² 521 / p 1e-115	21.0 EB05 15.2 · IC025 +3.3 3/3 methods agree	Reporting / coding artifact	serious n=3 · ♀ 100% (drug 66%) · 100% consumer	no trial data cached
Disturbance in attention	26	5.7 3.9–8.3ROR 5.7 · χ² 95 / p 8e-23	5.2 EB05 3.7 · IC025 +1.7 3/3 methods agree	Not in label — unassessed	serious PRR 6.7	no trial data cached
Gamma-glutamyltransferase increased	25	13.3 9.0–19.6ROR 13.4 · χ² 272 / p 3e-61	12.7 EB05 8.7 · IC025 +2.7 3/3 methods agree	Lab value / disease marker	serious PRR 10.9	no trial data cached
Hypercholesterolaemia	21	25.9 16.9–39.6ROR 26.2 · χ² 477 / p 5e-106	25.3 EB05 17.4 · IC025 +3.3 3/3 methods agree	Not in label — unassessed	serious PRR 20.3	no trial data cached
Malnutrition	19	20.2 12.9–31.5ROR 20.4 · χ² 327 / p 3e-73	19.7 EB05 13.2 · IC025 +3.0 3/3 methods agree	Not in label — unassessed	serious PRR 17.1	no trial data cached
Brain fog	18	14.5 9.2–23.0ROR 14.7 · χ² 213 / p 1e-48	13.8 EB05 8.7 · IC025 +2.6 3/3 methods agree	Not in label — unassessed	serious PRR 3.8	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.

Hypercholesterolaemia — n=21, PRR 25.9
Electrocardiogram qt prolonged — n=30, PRR 9.8
Febrile neutropenia — n=50, PRR 8.9
Hyponatraemia — n=42, PRR 8.8
Disturbance in attention — n=26, PRR 5.7
Neutropenia — n=63, PRR 5.5

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 Mitotane?

In FDA FAERS, the most frequently co-reported reaction terms for Mitotane are adrenal insufficiency, neutropenia, febrile neutropenia, hyponatraemia, hypothyroidism, electrocardiogram qt prolonged. 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 Mitotane have an FDA boxed warning?

Yes. The current FDA label carries a boxed warning: ADRENAL CRISIS IN THE SETTING OF SHOCK, SEVERE TRAUMA OR INFECTION Patients treated with LYSODREN are at increased risk for developing adrenal crisis in the setting of shock, severe trauma or infection that may lead to death. If shock, severe trauma or infection occurs or develops, temporarily discontinue LYSODREN and administer exogenous steroids.

Do FAERS signals prove that Mitotane 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 4046a224-8832-daa2-e063-6294a90a11d7, effective 20260303; matched on openfda.generic_name.exact:"MITOTANE")
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, field patient.drug.openfda.generic_name.exact, 48 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.