Mitotane

Mitotane (brand name Lysodren) is approved for one specific indication:

• Lysodren tablets are indicated for the treatment of inoperable adrenocortical carcinoma (ACC) — cancer of the outer layer of the adrenal gland — in both functional tumors (those that overproduce hormones) and nonfunctional tumors (those that do not).

Mitotane is classified as an adrenal cytotoxic agent, meaning it directly damages and suppresses the cells of the adrenal cortex (the outer part of the adrenal gland). It also alters the way the body metabolizes steroid hormones, reducing the activity of the adrenal gland overall. The precise way it kills cancer cells is not fully known, but its suppressive effects on adrenal tissue are well documented.

Because mitotane reduces the adrenal gland's ability to produce hormones, many patients need steroid replacement therapy to compensate — especially during periods of physical stress.

Lysodren is taken by mouth as a tablet, typically in three or four doses spread throughout the day, always with food. Taking it with a high-fat meal may enhance how well the body absorbs it. Timing relative to meals should be consistent each day.

• Swallow Lysodren tablets whole — never crush, chew, or split them.
• If you miss a dose or vomit after taking a dose, take the next scheduled dose as planned; do not take an extra dose.
• Do not take any tablet that appears deteriorated.
• Caregivers should wear disposable gloves when handling tablets and avoid contact with crushed or broken tablets.

Your doctor will regularly measure mitotane levels in your blood and adjust the dose to find the right balance between effectiveness and tolerability. Blood levels are typically checked every two weeks early in treatment and monthly once stable.

Lysodren commonly causes a range of side effects, particularly related to the stomach, nervous system, and hormones:

Serious reactions requiring prompt medical attention include signs of adrenal crisis (sudden severe weakness or collapse), severe neurological symptoms, liver problems (yellowing of the skin or eyes), unusual bleeding, signs of infection, or pelvic pain and abnormal bleeding in premenopausal women.

• Adrenal crisis during shock, severe infection, or injury: This is the most dangerous risk. Lysodren suppresses the adrenal glands, so your body may not be able to respond to major physical stress. This can be fatal. Stop Lysodren and seek emergency steroid treatment immediately if this occurs.
• CNS toxicity: High mitotane blood levels (above 20 mg/L) can cause serious sedation, confusion, difficulty walking, and other neurological effects. Do not drive or operate heavy machinery if you experience these symptoms.
• Adrenal insufficiency: Even without a crisis, Lysodren can cause low adrenal hormone levels day-to-day. Steroid replacement is often needed.
• Ovarian cysts (premenopausal women): Lysodren can cause large, non-cancerous ovarian cysts that may cause pelvic pain, menstrual changes, or serious complications like cyst rupture. Regular pelvic imaging is required.
• Liver toxicity: Lysodren can injure the liver; liver function tests must be monitored regularly.
• Low blood counts: Lysodren can cause anemia, low white blood cells, and low platelets. Blood counts should be checked regularly.
• Bleeding risk: Lysodren can impair platelet function, increasing bleeding risk — especially important before any surgery or dental procedure.
• Fetal harm: Lysodren can cause serious harm to an unborn baby, including preterm birth and pregnancy loss. Effective nonhormonal contraception is required during treatment and until mitotane clears from the blood completely.

Lysodren interacts with several important medications. Tell your doctor and pharmacist about everything you take:

• Spironolactone (a diuretic used for fluid retention or blood pressure): may block mitotane's effectiveness — avoid combining these.
• Warfarin (a blood thinner): mitotane speeds up warfarin's breakdown, reducing its ability to prevent clots — avoid if possible, or monitor INR very closely and adjust the warfarin dose.
• Hormonal contraceptives (pills, patches, rings, injections): mitotane can make these ineffective at preventing pregnancy — switch to a nonhormonal method.
• CYP3A substrates (many common medications including certain seizure drugs, immunosuppressants, and others): mitotane strongly accelerates how the body breaks down these drugs, potentially making them ineffective — your doctor may need to adjust those medications.

Not a complete list. The label covers the interactions the manufacturer studied or reported, and our own interaction database does not cover every medicine either. Bring your full medication list, including vitamins and herbal products, to your pharmacist.

• Pregnancy: Lysodren can cause fetal harm, including preterm birth and early pregnancy loss. A pregnancy test is required before starting. Avoid pregnancy during treatment and until mitotane is fully cleared from the blood.
• Breastfeeding: Mitotane passes into breast milk. Do not breastfeed while taking Lysodren or until mitotane is no longer detectable in your blood.
• Females of reproductive potential: Use effective nonhormonal contraception throughout treatment and afterward, for as long as mitotane remains detectable — hormonal contraceptives may not work.
• Severe liver impairment: Lysodren is not recommended; the drug is metabolized by the liver and levels can build up dangerously.
• Severe kidney impairment: Lysodren is not recommended; the drug is partially cleared by the kidneys.
• Mild or moderate liver or kidney impairment: Use with caution and more frequent blood-level monitoring.
• Older adults: Start at the lower end of the dosing range; older patients are more likely to have reduced liver, kidney, or heart function or to be on multiple medications.
• Children and adolescents: Effectiveness has not been established. Mitotane may negatively affect neurological development, growth, and hormones in younger patients.
• Overweight patients or those with recent weight loss: Mitotane accumulates in fat tissue and levels can change unexpectedly — closer monitoring of blood levels is recommended.

If mitotane blood levels rise above 20 mg/L, it is considered an overdose range and can cause severe central nervous system effects — including significant sedation, extreme dizziness, muscle weakness, and difficulty walking. Because mitotane is stored in fat tissue and has a very long half-life (weeks to months), blood levels can remain elevated for a long time even after stopping the medication, and the drug is not effectively removed by dialysis. If toxicity occurs, the medication is withheld and blood levels are monitored more frequently until they fall to a safe range.

Mitotane directly suppresses the adrenal cortex and alters how the body breaks down steroid hormones. It reduces certain hormone byproducts in the body and increases the formation of others, reflecting its impact on adrenal and steroid metabolism. The precise exposure-response relationship — meaning exactly how a given blood level translates to a clinical effect — has not been fully characterized, but blood levels above 20 mg/L are clearly associated with a greater risk of serious side effects.

After taking Lysodren by mouth, about 40% of the dose is absorbed into the bloodstream; taking it with a high-fat meal appears to improve absorption. Mitotane distributes throughout the body but accumulates most heavily in fat (adipose) tissue — which means it can be slowly released back into the blood even after stopping the drug. It is broken down by the liver into metabolites that are excreted mainly in the urine and bile; no unchanged mitotane is found in urine or bile. The half-life (the time it takes blood levels to fall by half) is extremely variable, ranging from 18 to 159 days, with a median of about 53 days — meaning significant levels can persist in the body for weeks or even months after the last dose.

Store bottles at 25°C (77°F); excursions permitted between 15°C and 30°C (59°F-86°F).