HCP Managing Treatment

Adrenal Insufficiency and Adrenal Crisis

Adrenal Insufficiency
Lysodren^® can cause adrenal insufficiency or worsen existing adrenal insufficiency in patients with ACC. Monitor for both glucocorticoid and mineralocorticoid insufficiency and replace systemic corticosteroids accordingly. Due to increased steroid clearance and increase of corticosteroid-binding protein, high-dose replacement therapy may be required and free cortisol and corticotropin (ACTH) should be monitored to adapt the systemic corticosteroids. Withhold, reduce the dose, or permanently discontinue Lysodren^® based on severity.

Adrenal Crisis in the Setting of Shock, Severe Trauma or Infection
Lysodren^® can cause adrenal suppression and adrenal crisis in the setting of shock, severe trauma or infection. Advise patients of the signs and symptoms of adrenal suppression and to contact you/their healthcare provider immediately if shock, trauma, infection, or adrenal suppression occurs.

Withhold Lysodren^® before planned surgeries.

Temporarily withhold Lysodren^® during shock, trauma, infection or adrenal suppression. Provide supportive care and administer systemic corticosteroids until recovery.

Learn More About the Importance of Corticosteroid Replacement Therapy

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Recommended Dosage Modifications for Adverse Reactions

The recommended dosage reduction for adverse reactions is to decrease the usual daily dose by
500 mg – 1000 mg.

The table below describes the dosage modifications for specific adverse reactions.

Adverse Reaction	Severity	Dosage Modification
Adrenal Crisis and Adrenal Insufficiency	All Grades	• Withhold LYSODREN during shock, trauma, infection or adrenal insufficiency until recovery to Grade ≤1 or baseline. • Resume LYSODREN at a reduced dose or permanently discontinue based on severit

Adverse Reaction	Severity	Dosage Modification
Central Nervous System (CNS) Toxicity	Grade 2	• Measure mitotane plasma level and modify the dosage according to the following recommendations: – Mitotane plasma level less than 14 mg/L: reduce the daily dose by 1000 mg. – Mitotane plasma level in the therapeutic window (14 to 20 mg/L): reduce the daily dose by 1500 mg. – Mitotane plasma level above 20 mg/L: withhold LYSODREN until recovery to grade ≤1 or baseline. Seven to ten (7-10) days after symptoms resolve, resume LYSODREN at reduced dose.
	Grade 3 or 4	• Measure mitotane plasma level and modify the dosage according to the following recommendations: – Withhold LYSODREN until recovery to grade ≤1 or baseline. Seven to ten (7-10) days after symptoms resolve, resume LYSODREN at a reduced dose or permanently discontinue based on severity.

Adverse Reaction	Severity	Dosage Modification
Gastrointestinal (GI) toxicity	Grade 3 or 4	• Measure mitotane plasma level and modify the dosage according to the following recommendations: – Mitotane plasma level less than 14 mg/L: reduce the daily dose by 1000 mg. – Mitotane plasma level in the therapeutic window (14 to 20 mg/L): reduce the daily dose by 1500 mg. – Mitotane plasma level above 20 mg/L: withhold LYSODREN until recovery to grade ≤1 or baseline. – After symptoms resolve, resume LYSODREN at a reduced dose or permanently discontinue based on severity.

Adverse Reaction	Severity	Dosage Modification
Hepatotoxicity	Grade 3 or 4	• Measure mitotane plasma level and modify the dosage according to the following recommendations: – Withhold LYSODREN until recovery to Grade ≤1 or baseline. – Resume at a reduced dose or permanently discontinue based on severity.

Adverse Reaction	Severity	Dosage Modification
Hematologic Toxicity	Grade 2	• Measure mitotane plasma level and modify the dosage according to the following recommendations: – Withhold LYSODREN until recovery to Grade ≤1 or baseline. – Resume at the same dose.
	Grade 3 or 4	• Measure mitotane plasma level and modify the dosage according to the following recommendations: – Withhold LYSODREN until recovery to Grade ≤1 or baseline. – Resume at a reduced dose or permanently discontinue based on severity.

Adverse Reaction	Severity	Dosage Modification
Other Adverse Reactions	Grade 2	• Measure mitotane plasma level and modify the dosage according to the following recommendations: – Withhold LYSODREN until recovery to Grade ≤1 or baseline. – Resume at the same dose.
	Grade 3 or 4	• Measure mitotane plasma level and modify the dosage according to the following recommendations: – Withhold LYSODREN until recovery to Grade ≤1 or baseline. – Resume at a reduced dose or permanently discontinue based on severity.

*Severity defined by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0.

If Lysodren^® is discontinued, continue monitoring plasma levels regularly (eg, every 2 months) for as long as mitotane plasma levels are detectable. Due to the long half-life, significant levels may persist for weeks.

Lysodren^®. US Prescribing information. ESTEVE.

INDICATION AND IMPORTANT SAFETY INFORMATION FOR LYSODREN^©

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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. Monitor patients closely for infections and instruct patients to contact their physician immediately if injury, infection, or any other concomitant illness occurs.

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

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. Monitor patients closely for infections and instruct patients to contact their physician immediately if injury, infection, or any other concomitant illness occurs.

Adrenal Insufficiency and Adrenal Crisis: Temporarily withhold LYSODREN during shock; trauma, infection or adrenal insufficiency. Steroid replacement may be necessary.

Central Nervous System (CNS) Toxicity: Monitor behavioral and neurologic assessments and mitotane plasma levels at regular intervals. Mitotane plasma levels exceeding 20 mg/L are associated with a greater incidence of toxicity. Advise patients not to drive or operate hazardous machinery if experiencing CNS adverse reactions.

Ovarian Macrocysts in Premenopausal Women: Monitor pelvic ultrasound at baseline and at regular intervals. Withhold, reduce the dose, or permanently discontinue LYSODREN based on severity.

Hematologic Toxicity: Monitor complete blood counts prior to starting LYSODREN, during dose titration and as clinically indicated. Withhold, reduce the dose or permanently discontinue based on severity.

Prolonged Bleeding Time: Prolonged bleeding time has occurred in patients treated with mitotane and this should be taken into account when surgery is considered.

Embryo-Fetal Toxicity: LYSODREN can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use effective nonhormonal contraception.

Lactation: Advise not to breastfeed.

Hepatic Impairment: LYSODREN is not recommended for patients with severe hepatic impairment. In patients with mild to moderate hepatic impairment, monitor mitotane plasma levels frequently and modify the dosage as needed.

Renal Impairment: LYSODREN^® is not recommended for patients with severe renal impairment. In patients with mild or moderate renal impairment, monitor mitotane plasma levels frequently and modify the dosage as needed.

Most common adverse reactions include: anorexia, epigastric discomfort, nausea, vomiting diarrhea, depression, dizziness, vertigo, rash, hypercholesterolemia, hypertriglyceridemia, hypothyroidism and decreased blood free testosterone in males. LYSODREN is a hazardous drug. Advise caregivers to wear disposable gloves when handling LYSODREN tablets.

Avoid concomitant use with spironolactone, certain CYP3A substrates, hormonal contraceptives and warfarin.

Please see Full Prescribing Information, including BOXED WARNING, for LYSODREN^® (mitotane) tablets.

To report SUSPECTED ADVERSE REACTIONS, contact Direct Success Pharmacy, Inc. at 1-844-LYSODREN (1-844-597-6373) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Link to US Prescribing Information including Boxed Warning.

ESTEVE.
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Tel: +34 93 446 60 00 / Fax: +34 93 347 39 44

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Last updated: October 2025; 0097-10/2026@ESTEVE

Managing Treatment

Adrenal Insufficiency and Adrenal Crisis

Recommended Dosage Modifications for Adverse Reactions

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