[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Pharmacology](https://durgical.com/en/pharmacology/) › [Adrenal steroid synthesis inhibitors](https://durgical.com/en/pharmacology/classes/adrenal-steroid-synthesis-inhibitors/) › Mitotane

# Mitotane

## Adrenal steroid synthesis inhibitors?

Adrenal steroid synthesis inhibitors

## High alert?

An error with this medicine can cause serious harm: double checks and protocols are used.

## Pregnancy: avoid?

Avoid in pregnancy. It may harm the fetus. Pregnancy is excluded before starting and avoided during treatment and for as long as advised after the last dose; breastfeeding is…

An oral drug that destroys adrenal cortex cells and blocks steroid synthesis. Used for inoperable adrenal cancer; it causes adrenal insufficiency.

Updated Nov 1, 2026

Also called: o,p'-DDD

## Quick facts

**Group**
[Adrenal steroid synthesis inhibitors](https://durgical.com/en/pharmacology/classes/adrenal-steroid-synthesis-inhibitors/)

**Target**
Adrenal cortex mitochondria (activated to a toxic metabolite) and cholesterol side-chain cleavage enzyme (CYP11A1)

**Used for**
Adrenocortical carcinoma · Sometimes

**Key effects**
Anorexia · Drowsiness · Skin rash

**Monitor**
Signs of adrenal insufficiency · Neurological status

**ATC**
L01XX23

No doses: the clinician sets them by the current guideline.

On this page

- The basics Mechanism of action
- Indications
- Adverse effects
- Pharmacokinetics
- Memory aid

- Clinical What the labels mean

- Safety Contraindications
- Key interactions
- What is monitored
- Administration and safety
- Pregnancy and breastfeeding
- Nursing care

- Study Test yourself

- Connections Connections

## Mechanism of action

Mitotane is a relative of the insecticide DDT. Mitochondrial cytochrome P450 enzymes of the adrenal cortex convert it into a reactive acyl chloride that binds cell proteins and destroys adrenocortical cells (an adrenolytic effect). It also inhibits CYP11A1, the first step of steroid synthesis, so cortisol and other adrenal steroids fall. The effect builds up over weeks to months, and adrenal insufficiency is expected, so glucocorticoid replacement is given.

- Adrenal mitochondrial P450 enzymes activate mitotane
- The reactive metabolite damages adrenocortical cells
- CYP11A1 inhibition lowers steroid synthesis
- Cortisol falls; replacement glucocorticoid is needed

## Indications

- Adrenocortical carcinoma that cannot be removed surgically [Adrenocortical carcinoma →](https://durgical.com/en/conditions/adrenocortical-carcinoma/)
- Sometimes, hypercortisolism in Cushing's syndrome [Cushing syndrome →](https://durgical.com/en/conditions/cushing-syndrome/)

## Adverse effects

### Common

- Anorexia, nausea, vomiting and diarrhoea
- Drowsiness, lethargy, dizziness and unsteady gait (ataxia)
- Skin rash
- Visual changes
- Breast enlargement in men

### Serious (rare, important)

- Adrenal insufficiency, which can become an adrenal crisis during infection, injury or surgery (boxed warning)
- Confusion, memory loss and other central nervous system toxicity
- Liver injury (jaundice, dark urine)
- Ovarian cysts in premenopausal women
- Bleeding or bruising

## Contraindications

- Hypersensitivity to mitotane
- Shock, severe trauma or serious infection: treatment is interrupted (risk of adrenal crisis)

## Key interactions

**Spironolactone**
Interferes with the adrenal suppression produced by mitotane; the two are not given together

**Hormonal contraceptives**
Mitotane may make them less effective; a non-hormonal barrier method is advised

**Many other medicines**
Their doses may need adjusting during and after mitotane treatment

## What is monitored

- Signs of adrenal insufficiency; glucocorticoid replacement adjusted
- Neurological status (drowsiness, confusion, gait)
- Liver tests and blood counts
- Ovarian ultrasound in women who have not reached menopause

## Administration and safety

- Oral cytotoxic: tablets are swallowed whole and not crushed or broken
- Gloves are used to handle broken tablets
- Given with a high-fat meal or snack
- The person and every treating team know that mitotane causes adrenal insufficiency, so stress-dose glucocorticoids are considered in emergencies

## Pregnancy and breastfeeding

Avoid in pregnancy. It may harm the fetus. Pregnancy is excluded before starting and avoided during treatment and for as long as advised after the last dose; breastfeeding is avoided.

## Nursing care

- Teach the signs of adrenal insufficiency: extreme tiredness, weakness, dizziness, vomiting, salt craving
- Before surgery, dental surgery or with severe illness or injury, the treating team is informed
- Advise against driving until the effect on alertness is known
- Pregnancy test before starting and barrier contraception during treatment
- Report jaundice, unusual bleeding or abnormal vaginal bleeding or pelvic pain

## Pharmacokinetics

**Absorption**
Taken by mouth with a high-fat meal or snack, which improves absorption

**Onset and duration**
Weeks to months

## Memory aid

MITOtane MELTS the adrenal cortex: give cortisol back, and keep spironolactone away.

## Test yourself

Think of the answer, then tap the question to see it.

## How does mitotane damage the adrenal cortex?

Adrenal mitochondrial P450 enzymes convert it to a reactive acyl chloride that binds cell proteins and destroys adrenocortical cells; it also inhibits CYP11A1.

## Why do patients taking mitotane need glucocorticoid replacement?

Destruction of the adrenal cortex causes adrenal insufficiency, which can become a crisis during stress.

## Which diuretic should not be given with mitotane and why?

Spironolactone, because it interferes with the adrenal suppression produced by mitotane.

## Why is mitotane taken with a high-fat meal?

It is very fat-soluble, and fat improves its absorption.

[Add to my cards (4)](https://durgical.app/estudiar/?add=/en/pharmacology/mitotane/)

[More Pharmacology questions →](https://durgical.com/en/practice/?f=pharmacology)

## What the labels mean

**High alert**
An error with this medicine can cause serious harm: double checks and protocols are used.

**Pregnancy: avoid**
Avoid in pregnancy. It may harm the fetus. Pregnancy is excluded before starting and avoided during treatment and for as long as advised after the last dose; breastfeeding is…

## Connections

## Related drugs 4

- [Metyrapone](https://durgical.com/en/pharmacology/metyrapone/)
- [Osilodrostat](https://durgical.com/en/pharmacology/osilodrostat/)
- [Hydrocortisone](https://durgical.com/en/pharmacology/hydrocortisone/)
- [Spironolactone](https://durgical.com/en/pharmacology/spironolactone/)

## Related conditions 2

- [Adrenocortical carcinoma](https://durgical.com/en/conditions/adrenocortical-carcinoma/)
- [Cushing syndrome](https://durgical.com/en/conditions/cushing-syndrome/)

[← Back to the class: Adrenal steroid synthesis inhibitors](https://durgical.com/en/pharmacology/classes/adrenal-steroid-synthesis-inhibitors/)

Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.

Sources: [Mitotane: MedlinePlus Drug Information](https://medlineplus.gov/druginfo/meds/a608050.html) (MedlinePlus (U.S. National Library of Medicine), 2026); [ATCDDD - ATC/DDD Index](https://atcddd.fhi.no/atc_ddd_index/?code=L01XX23) (WHO Collaborating Centre for Drug Statistics Methodology, 2026).

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Representative model, for educational purposes only.

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Source: https://durgical.com/en/pharmacology/mitotane/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/pharmacology/mitotane/