Lysodren

MITOTANE

Manufacturer: HRA Pharma Rare Diseases

Score: 144.0

Quick Summary

Lysodren (MITOTANE) is an oral adrenal cytotoxic agent used for the treatment of patients with inoperable, functional or nonfunctional, adrenocortical carcinoma (ACC). The initial dose is 2000 mg to 6000 mg orally, in three or four divided doses per day with food, and should be titrated to achieve a plasma level of 14 to 20 mg/L. Lysodren has several important safety considerations, including the risk of adrenal crisis, central nervous system toxicity, and hepatotoxicity. It is also contraindicated in patients with certain conditions, such as spironolactone use, and has several special population considerations, including use during pregnancy, pediatric use, and geriatric use.

Key Clinical Findings and Indications

Lysodren is used for the treatment of patients with inoperable, functional or nonfunctional, adrenocortical carcinoma (ACC)
The drug has an unknown mechanism of action, but modifies the peripheral metabolism of steroids and directly suppresses the adrenal cortex
Lysodren is absorbed orally, with 40% of the dose absorbed, and has a plasma terminal half-life ranging from 18 to 159 days

Important Safety Information

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

Contraindications

Spironolactone use
Certain CYP3A substrates
Hormonal contraceptives
Warfarin

Adverse Reactions

Adrenal insufficiency and adrenal crisis
Central nervous system toxicity
Ovarian macrocysts in premenopausal women
Hepatotoxicity
Hematologic toxicity
Prolonged bleeding time
Anorexia, epigastric discomfort, nausea, vomiting, diarrhea, depression, dizziness, vertigo, rash, hypercholesterolemia, hypertriglyceridemia, hypothyroidism, and decreased blood free testosterone in males

Dosing Recommendations

General Guidance

Dose adjustments should be made based on mitotane plasma levels and clinical response, with consideration of reducing the dose by 50 to 75% if plasma levels exceed 20 mg/L

Inoperable, functional or nonfunctional, adrenocortical carcinoma (ACC)

Adult Dose

2000 mg to 6000 mg orally, in three or four divided doses per day with food, titrated to achieve a plasma level of 14 to 20 mg/L

Pediatric Dose

Not established

Special Population Considerations

Pregnancy

Lysodren can cause fetal harm
Limited postmarketing cases report preterm births and early pregnancy loss in women treated with Lysodren during pregnancy

Nursing Mothers

Pediatric Use

Effectiveness in pediatric patients has not been established
Mitotane may negatively impact neuro-psychological development in children and adolescents

Geriatric Use

Clinical studies of Lysodren did not include sufficient numbers of patients aged 65 years and older to determine whether they respond differently than younger patients
Dose selection for an older patient should be cautious, usually starting at the low end of the dosing range

Similar Drugs

Spironolactone

SPIRONOLACTONE

RPK Pharmaceuticals, Inc.

Similarity: 61.5%