Mitotane
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From MedlinePlus, U.S. National Library of Medicine
Boxed warning
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 [see Dosage and Administration (2.3) and Warnings and Precautions (5.1)].
WARNING: ADRENAL CRISIS IN THE SETTING OF SHOCK, SEVERE TRAUMA OR INFECTION See full prescribing information for complete boxed warning. 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 ( 2.3 , 5.1 ).
Dosing in kidney impairment
Renal Impairment Mitotane is eliminated through the kidney and mitotane plasma levels may increase if renal function is impaired. Because of the increased risk of adverse reactions in patients with mild and moderate renal impairment, monitor mitotane plasma levels more frequently and modify the dosage as needed [see Dosage and Administration ].
LYSODREN is not recommended for use in patients with severe renal impairment.
| Adverse Reaction | Severity Severity defined by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0. | Dosage Modification |
|---|---|---|
| Adrenal Crisis and Adrenal Insufficiency [see Warnings and Precautions (5.1)] | 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 severity. |
| Central Nervous System (CNS) Toxicity [see Warnings and Precautions (5.2)] | 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. | |
| 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. |
| Hepatotoxicity [see Warnings and Precautions (5.4)] | 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. |
| Hematologic Toxicity [see Warnings and Precautions (5.5)] | 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. | |
| Other Adverse Reactions [see Adverse Reactions (6.1)] | 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. |
Dosing in liver impairment
Hepatic Impairment Mitotane is metabolized through the liver and mitotane plasma levels may increase if liver function is impaired. Because of the increased risk of adverse reactions in patients with mild or moderate hepatic impairment, monitor mitotane plasma levels more frequently and modify the dosage as needed [see Dosage and Administration ].
LYSODREN is not recommended for use in patients with severe hepatic impairment [see Warnings and Precautions ] .
Preparation and administration
Recommended Dosage and Administration Recommended Dosage The recommended initial dose of LYSODREN is 2000 mg to 6000 mg orally, in three or four divided doses per day. Monitor mitotane plasma levels and increase the dose based on patient tolerance and clinical response incrementally to achieve a mitotane plasma level of 14 to 20 mg/L, or as tolerated.
Consider monitoring mitotane plasma levels every 2 weeks after starting treatment and after each dose adjustment. The target plasma level is usually reached within a period of 3 to 5 months. Monitor mitotane plasma levels periodically (e.g., monthly). Severe neurotoxicity may occur with levels > 20 mg/L. Dose Adjustments, Monitoring and Discontinuation In case of mitotane plasma levels above 20 mg/L without toxicities, consider reducing the dose by 50 to 75%.
Monitor mitotane plasma levels regularly (e.g., every two months) after discontinuation of treatment. Due to the prolonged half-life, significant levels may persist for weeks after cessation of therapy. LYSODREN is lipophilic and accumulates in adipose tissue. Despite maintaining a constant dose, mitotane levels may suddenly increase.
Monitor mitotane plasma levels even when LYSODREN has been withheld as adipose tissue may continue to release mitotane [see Clinical Pharmacology ] . Due to adipose tissue accumulation of mitotane, close monitoring of mitotane plasma levels is recommended in overweight patients and patients with recent weight loss. Administration Swallow LYSODREN tablets whole; do not crush, chew or split.
Take LYSODREN with food. Timing of the dose relative to meals must be consistent. Administration with high fat food enhances absorption [See Clinical Pharmacology Section ]. Do not take tablets showing signs of deterioration. Caregivers should wear disposable gloves when handling the tablets. Avoid exposure to crushed and/or broken tablets.
If contact with crushed/broken tablets occurs, wash the contaminated skin immediately and thoroughly. If a patient misses a dose, instruct the patient to take the next dose as scheduled. If a patient vomits after taking a dose, instruct the patient to take the next dose as scheduled.
Drug interactions
Check mitotane against a medication listLabel text (4 paragraphs)
Spironolactone: Avoid concomitant use with LYSODREN. ( 7.1 ) Certain CYP3A Substrates: Avoid concomitant use with LYSODREN. ( 7.2 ) Hormonal contraceptives: Avoid concomitant use with LYSODREN. ( 7.2 ) Warfarin: Avoid concomitant use with LYSODREN. ( 7.2 )
7.1 Effects of Other Drugs on LYSODREN Spironolactone Spironolactone may block the action of mitotane. Avoid concomitant use of mitotane with spironolactone [see Clinical Pharmacology (12.3) ].
7.2 Effects of LYSODREN on Other Drugs Certain CYP3A substrates Mitotane is a strong CYP3A inducer. Concomitant use of LYSODREN may decrease the levels of CYP3A substrates, which may reduce the activity of these substrates [see Clinical Pharmacology (12.3) ]. Avoid concomitant use of LYSODREN with other CYP3A substrates, where minimal level changes may lead to serious therapeutic failures. If concomitant use cannot be avoided, modify the dosage of the CYP3A substrate in accordance with the approved product labeling. Hormonal Contraceptives Avoid concomitant use of LYSODREN with hormonal contraceptives [see Warnings and Precautions (5.8) , Use in Specific Populations (8.3) ].
Warfarin Mitotane may induce the metabolism of warfarin, which may reduce its level and its efficacy [see Clinical Pharmacology (12.3) ] . Avoid concomitant use of LYSODREN with warfarin. If concomitant use cannot be avoided, monitor INR more frequently and adjust warfarin dose as recommended in accordance with the recommendations in the warfarin Prescribing Information.
Contraindications
None. None. ( 4 )
Pregnancy and lactation
Pregnancy
8.1 Pregnancy Risk Summary LYSODREN can cause fetal harm. Limited postmarketing cases report preterm births and early pregnancy loss in women treated with LYSODREN during pregnancy. Animal reproduction studies have not been conducted with mitotane. Advise pregnant women of the potential risk to a fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
For breastfeeding, also see LactMed (National Library of Medicine), which summarizes milk levels and infant effects.
Supply and cost
Drug shortage status
Recalls (last 24 months)
Therapeutic equivalence (Orange Book)
Price ladder
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