Included as part of the "PRECAUTIONS" Section
Adrenal Crisis In The Setting Of Shock Or Severe Trauma
In patients taking LYSODREN, adrenal crisis occurs in the setting of shock or severe trauma and response to shock is impaired. Administer hydrocortisone, monitor for escalating signs of shock, and discontinue LYSODREN until recovery [see DOSAGE AND ADMINISTRATION].
CNS toxicity, including sedation, lethargy, and vertigo, occurs with LYSODREN treatment. Mitotane plasma concentrations exceeding 20 mcg/mL are associated with a greater incidence of toxicity.
Treatment with LYSODREN can cause adrenal insufficiency. Institute steroid replacement as clinically indicated. Measure free cortisol and corticotropin (ACTH) levels to achieve optimal steroid replacement.
LYSODREN can cause fetal harm when administered to a pregnant woman. Abnormal pregnancy outcomes, such as preterm births and early pregnancy loss, can occur in patients exposed to mitotane during pregnancy. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with LYSODREN and after discontinuation of treatment for as long as mitotane plasma levels are detectable [see Use In Specific Populations].
Ovarian Macrocysts In Premenopausal Women
Ovarian macrocysts, often bilateral and multiple, have been reported in premenopausal patients receiving LYSODREN. Complications from these cysts, including adnexal torsion and hemorrhagic cyst rupture, have been reported. In some cases, improvement after mitotane discontinuation has been described. Advise female patients to seek medical care if they experience gynecological symptoms such as vaginal bleeding and/or pelvic pain [see ADVERSE REACTIONS].
Carcinogenesis, Mutagenesis, Impairment Of Fertility
The carcinogenicity and mutagenicity of mitotane are unknown.
Use In Specific Populations
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. The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.
Mitotane is excreted in human milk; however, the effect of LYSODREN on the breastfed infant, or effect on milk production is unknown. Because of the potential for serious adverse reactions in the breastfed infant, advise nursing women that breastfeeding is not recommended during treatment with LYSODREN and after discontinuation of treatment for as long as mitotane plasma levels are detectable.
Females And Males Of Reproductive Potential
LYSODREN can cause fetal harm when administered to a pregnant woman [see Pregnancy]. Advise female patients of reproductive potential to use effective contraception during treatment with LYSODREN and after discontinuation of therapy for as long as mitotane plasma levels are detectable [see CLINICAL PHARMACOLOGY].
Safety and effectiveness in pediatric patients have not been established.
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. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
Hepatic impairment may interfere with the metabolism of mitotane and the drug may accumulate. Administer LYSODREN with caution to patients with hepatic impairment.