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Mitotane

FDA Drug Information • Also known as: Lysodren

Brand Names
Lysodren
Dosage Form
POWDER
Product Type
BULK INGREDIENT

⚠ Boxed Warning (Black Box)

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 ).

Description

11 DESCRIPTION LYSODREN (mitotane) is an oral adrenal cytotoxic agent. The chemical name is (±)-1,1-dichloro-2-( o -chlorophenyl)-2-( p -chlorophenyl) ethane (also known as o,p'-DDD). The chemical structure is: Mitotane is a white granular solid composed of clear colorless crystals. It is tasteless and has a slight pleasant aromatic odor. It is soluble in ethanol and has a molecular weight of 320.05. Inactive ingredients in LYSODREN are: microcrystalline cellulose, polyethylene glycol 3350, silicon dioxide, and starch. Chemical Structure

What Is Mitotane Used For?

1 INDICATIONS AND USAGE LYSODREN is indicated for the treatment of patients with inoperable, functional or nonfunctional, adrenocortical carcinoma (ACC). LYSODREN is an adrenal cytotoxic agent indicated for the treatment of patients with inoperable, functional or nonfunctional, adrenocortical carcinoma (ACC). ( 1 )

Dosage and Administration

2 DOSAGE AND ADMINISTRATION The recommended initial dose of LYSODREN is 2000 mg to 6000 mg orally, in three or four divided doses per day with food. ( 2.3 ) Titrate LYSODREN dose to achieve a plasma level of 14 to 20 mg/L. ( 2.3 ) LYSODREN is lipophilic and accumulates in adipose tissue. ( 2.3 ) 2.1 Recommended Evaluation and Testing Before Initiating LYSODREN Before initiating LYSODREN, evaluate pelvic ultrasound in premenopausal women, liver functions tests and complete blood count [see Warnings and Precautions (5.3 , 5.4 , 5.5) ]. 2.2 General Precautions LYSODREN is a hazardous drug. Advise caregivers to wear disposable gloves when handling LYSODREN tablets [see References (15) and Storage and Handling (16) ]. 2.3 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 (12.3) ] . 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 (12.3) ]. 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. 2.4 Dosage Modifications for Adverse Reactions The recommended dosage reduction...

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling:

  • Adrenal Insufficiency and Adrenal Crisis [see Warnings and Precautions (5.1)]
  • Central Nervous System Toxicity [see Warnings and Precautions (5.2)]
  • Ovarian Macrocysts in Premenopausal Women [see Warnings and Precautions (5.3)]
  • Hepatotoxicity [see Warnings and Precautions (5.4)]
  • Hematologic Toxicity [see Warnings and Precautions (5.5)]
  • Prolonged Bleeding Time [see Warnings and Precautions (5.6)]
  • Hormone Binding Protein [see Warnings and Precautions (5.7)]
  • Embryo-Fetal Toxicity [see Warnings and Precautions (5.8)] Most common adverse reactions include: anorexia, epigastric discomfort, nausea, vomiting, diarrhea, dizziness, vertigo, rash, hypercholesterolemia, hypertriglyceridemia, hypothyroidism, and decreased blood free testosterone in males. (6) To report SUSPECTED ADVERSE REACTIONS, contact Direct Success Inc.at 1-844-597-6373 or FDA at 1-800-FDA-1088 or www.FDA.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Reported adverse reactions include: Metabolism and nutrition disorders: Anorexia Gastrointestinal disorders: Epigastric discomfort, nausea, vomiting, diarrhea, mucosal inflammation, dyspepsia Nervous system disorders: Dizziness, vertigo, confusion, headache, ataxia, mental impairment, weakness, dysarthria, paresthesia, polyneuropathy, movement disorder, balance disorder, dysgeusia Skin and subcutaneous tissue disorders: Rash, pruritus, hypersensitivity reactions Blood and lymphatic system disorders: Leukopenia, anemia, thrombocytopenia, prolonged bleeding time, hematuria, hemorrhagic cystitis Endocrine: Growth retardation, hypothyroidism Eye disorders: Maculopathy, visual blurring, diplopia, lens opacity, retinopathy Hepatobiliary disorders: Hepatitis, elevation of liver enzymes, liver injury (hepatocellular/cholestatic/mixed) Reproductive system and breast disorders: Gynecomastia, hypogonadism (in males) Investigations: Hypercholesterolemia, hypertriglyceridemia, decreased plasma androstenedione, decreased plasma testosterone in females, increased sex hormone binding globulin in females and males, decreased blood free testosterone in males, hypouricemia Musculoskeletal disorders: Muscular weakness, generalized aching General disorders: Fever Renal and urinary disorders: Albuminuria/proteinuria Vascular disorders: Hypertension, orthostatic hypotension, flushing Infections: Opportunistic infection Respiratory, thoracic and mediastinal disorders: Dyspnoea

    • Drug Interactions

    7 DRUG INTERACTIONS 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

    4 CONTRAINDICATIONS None. None. ( 4 )

    Pregnancy and Breastfeeding

    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.

    Overdosage

    10 OVERDOSAGE LYSODREN overdosage (plasma levels are above 20 mg/L) can cause central nervous system toxicity, including sedation, lethargy, and vertigo, as well as muscular weakness and gait disturbance. Withhold LYSODREN as clinically indicated for signs or symptoms of toxicity. LYSODREN is lipophilic and has a prolonged half-life; therefore, it may take weeks for plasma levels to decrease. LYSODREN is not likely to be dialyzable. Increase the frequency of mitotane plasma level monitoring, as clinically indicated.

    How Supplied

    16 HOW SUPPLIED/STORAGE AND HANDLING LYSODREN tablets are supplied as 500 mg white, round, biconvex, scored tablets, bisected on one side and impressed with "BL" over "L1" on the other side. 100 tablets per bottle: NDC 76336-080-60 Store bottles at 25°C (77°F); excursions permitted between 15°C and 30°C (59°F-86°F). Mitotane is a hazardous drug. Follow applicable special handling and disposal procedures [see References (15) ] .

    About This Information

    This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

    What are side effects?

    Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

    What are drug interactions?

    Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.