Mitotane
Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.
| ID | DRUG-MITOTANE |
|---|---|
| Type | Drug |
| Aliases | LysodrenMitotane Esteveo,p'-DDDo,p'-dichlorodiphenyldichloroethaneМітотан |
| Status | reviewed 2026-07-11 | pending_clinical_signoff |
| Diseases | DIS-ADRENOCORTICAL-CARCINOMA |
| Sources | SRC-ADIUVO-TERZOLO-2023 SRC-ENSAT-ACC-2018 SRC-ESMO-ACC-2020 SRC-FIRM-ACT-FASSNACHT-2012 |
Drug Facts
| Class | Adrenolytic cytotoxic agent (DDT/o,p'-DDD derivative) — the only ACC-specific approved cytotoxic drug |
|---|---|
| Mechanism | Mitotane is a chlorinated hydrocarbon derivative of the insecticide DDT with selective adrenolytic activity. It accumulates in adrenocortical cells and is metabolized (partly CYP11B1-dependent) to a reactive acyl chloride metabolite that covalently binds mitochondrial and other cellular proteins, producing structural mitochondrial damage and direct cytotoxic necrosis of both normal and malignant adrenocortical tissue (zona fasciculata/reticularis predominantly). It also inhibits several steroidogenic enzymes (side-chain cleavage/CYP11A1, 3-beta-HSD, 11-beta- hydroxylase/CYP11B1) and is a potent, durable inducer of hepatic CYP3A4, which increases cortisol clearance and reduces exposure of many co-administered CYP3A4-metabolized drugs. The adrenolytic effect is not tumor-selective: essentially all patients develop drug-induced adrenal insufficiency and require glucocorticoid (+/- mineralo... |
| Typical dosing | Oral, 500 mg scored tablets. Initiated at 2-3 g/day PO in divided doses (higher starting doses of 4-6 g/day may be used when rapid disease control is urgent), taken with fatty meals to enhance absorption. Dose is increased progressively — typically at ~2-week intervals under standard conditions, or as often as weekly if expedited control is needed — guided by tolerability and mitotane blood level, toward a target therapeutic blood level of 14-20 mg/L (levels above 20 mg/L risk toxicity without additional antitumor benefit). Blood-level monitoring is required after each dose adjustment and at frequent intervals (e.g. every 2 weeks) during titration, then monthly at a stable maintenance dose,... |
| Ukraine registered | False |
| NSZU reimbursed | False |
| Ukraine last verified | 2026-07-11 |
Warnings
- Adrenal insufficiency — mitotane is adrenolytic to both normal and malignant adrenocortical tissue; essentially all patients (100% with non-functional tumors, ~75% with functional tumors per EU SmPC) develop adrenal insufficiency and require glucocorticoid (+/- mineralocorticoid) replacement; unrecognized adrenal crisis during intercurrent illness, trauma, or surgery can be fatal.
- CNS toxicity at supratherapeutic blood levels (>20 mg/L) — lethargy, dizziness, vertigo, ataxia, confusion; use blood-level monitoring to stay within the 14-20 mg/L therapeutic window.
- Embryo-fetal toxicity — contraindicated in pregnancy; effective contraception required during and after treatment given the drug's very long half-life.
Notes
STUB pending clinical co-lead sign-off (CHARTER §6.1). The only FDA/EMA-approved adrenal-cortex-specific cytotoxic agent; used as (1) adjuvant monotherapy after resection in high-recurrence-risk stage I-III ACC, and (2) continuously alongside EDP chemotherapy (etoposide + doxorubicin + cisplatin) in advanced/metastatic disease per the FIRM-ACT trial (Fassnacht 2012, NEJM). Dosing, titration cadence, target blood level (14-20 mg/L), and adrenal-insufficiency incidence figures are sourced from the EU SmPC for Mitotane Esteve 500 mg tablets (medicines.org.uk/emc/product/101074) — verify against institutional protocol and the primary ENSAT/ESMO guideline text before clinical use. The randomized ADIUVO trial (Terzolo 2023) found no significant benefit from adjuvant mitotane in a lower/intermediate-recurrence-risk resected population (stage I-III, R0, Ki-67 <=10%), so this KB restricts the adjuvant-mitotane Indication (IND-ACC-1L-RESECTION-MITOTANE) to a higher-recurrence-risk subgroup — see that Indication and RF-ACC-HIGH-RECURRENCE-RISK-BIOLOGY for detail.
Used By
Regimens
REG-EDP-M-ACC- EDP-M (etoposide + doxorubicin + cisplatin + mitotane) — FIRM-ACT regimenREG-MITOTANE-ADJUVANT-ACC- Mitotane adjuvant monotherapy (ACC)