Overview
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.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Mitotane is an adrenal cytotoxic agent with an unknown mechanism of action. Mitotane modifies the peripheral metabolism of steroids and directly suppresses the adrenal cortex. A reduction in 17-hydroxycorticosteroids in the absence of decreased corticosteroid levels and increased formation of 6-β-hydroxycortisol have been reported. 12.2 Pharmacodynamics Mitotane exposure-response relationships and the time course of pharmacodynamic response have not been fully characterized. 12.3 Pharmacokinetics Absorption Following oral administration of LYSODREN, 40% of the dose is absorbed. Effect of Food The effect of food on the absorption of mitotane (LYSODREN) is not known.
Indications
- 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 )
Common Doses
- 2000 mg
- 6000 mg
- 20 mg
- 1000 mg
Dosage
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.
Black Box 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)].
Contraindications
- 4 CONTRAINDICATIONS None. None. ( 4 )
Side Effects
- 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.
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.