Lysodren Drug Information
Generic name: MITOTANE
Uses of 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).
Dosage & Administration of Lysodren
| Adrenal Crisis and Adrenal Insufficiency | All Grades |
|---|---|
| Central Nervous System (CNS) Toxicity | Grade 2 |
| Grade 3 or 4 |
|
| Gastrointestinal (GI) toxicity | Grade 3 or 4 |
| Hepatotoxicity | Grade 3 or 4 |
| Hematologic Toxicity | Grade 2 |
| Grade 3 or 4 |
|
| Other Adverse Reactions | Grade 2 |
| Grade 3 or 4 |
|
Side Effects of Lysodren
- 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 Esteve Pharmaceuticals, S.A. at 1-888-306-6259 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
Warnings & Cautions for Lysodren
Adrenal Insufficiency and Adrenal Crisis Adrenal Insufficiency
LYSODREN can cause adrenal insufficiency or worsen existing adrenal insufficiency in patients with adrenocortical carcinoma. Monitor for both glucocorticoid and mineralocorticoid insufficiency and replace systemic corticosteroids accordingly. Due to increased steroid clearance and increase of steroid-binding protein, high-dose replacement therapy may be required and free cortisol and corticotropin (ACTH) should be monitored to adapt the systemic corticosteroids.
Withhold, reduce the dose, or permanently discontinue LYSODREN based on severity. Adrenal Crisis in the Setting of Shock, Severe Trauma or Infection LYSODREN can cause adrenal suppression and adrenal crisis in the setting of shock, severe trauma or infection. Advise patients of the signs and symptoms of adrenal suppression and to contact their healthcare provider immediately if shock, trauma, infection, or adrenal suppression occurs.
Withhold LYSODREN before planned surgeries. Temporarily withhold LYSODREN during shock, trauma, infection or adrenal suppression. Provide supportive care and administer systemic corticosteroids until recovery.
Central Nervous System Toxicity
LYSODREN can cause central nervous system toxicity, including sedation, lethargy, and vertigo. Monitor behavioral and neurologic assessments and mitotane plasma levels at regular intervals. Mitotane plasma levels exceeding 20 mg/L are associated with a greater incidence of toxicity.
In cases of cognitive dysfunction, thyroid function should be evaluated as mitotane may induce hypothyroidism. LYSODREN can impair the ability to drive and operate machinery. Advise patients not to drive or operate hazardous machinery if they are experiencing CNS adverse reactions.
Withhold, reduce the dose, or permanently discontinue LYSODREN based on severity.
Ovarian Macrocysts in Premenopausal Women
LYSODREN can cause non-malignant, multiple and bilateral ovarian macrocysts in premenopausal women. Ovarian macrocysts can be symptomatic (e.g., pelvic pain or discomfort, or menstrual irregularities) or asymptomatic. Complications from these cysts, including adnexal torsion and hemorrhagic cyst rupture, have occurred.
Advise female patients to contact their healthcare provider immediately for gynecological symptoms such as vaginal bleeding and/or pelvic pain. Monitor pelvic imaging in premenopausal females at baseline and in regular intervals during treatment with LYSODREN. Withhold, reduce the dose, or permanently discontinue LYSODREN based on severity.
Hepatotoxicity
LYSODREN can cause hepatoxicity, including liver injury or failure. Monitor liver function tests prior to starting treatment with LYSODREN, during dose titration, and periodically during treatment as clinically indicated. Isolated gamma-glutamyl transferase (GGT) elevation may occur.
Withhold, reduce the dose, or permanently discontinue LYSODREN based on severity of hepatoxicity.
Hematologic toxicity
LYSODREN can cause leukopenia, anemia and thrombocytopenia . Monitor complete blood counts including neutrophil count prior to starting treatment with LYSODREN, during dose titration, and periodically during treatment as clinically indicated. Withhold, reduce the dose, or permanently discontinue LYSODREN based on severity of cytopenia .
Prolonged Bleeding Time
LYSODREN can cause platelet function disorders due to abnormal adenosine diphosphate (ADP)-induced platelet aggregation. Some patients may have a prolonged bleeding time, while others may have a normal bleeding time. Routine in vitro bleeding time is not suitable to detect this platelet defect and to assess bleeding risk.
Perform ADP-inducted platelet aggregometry testing prior to surgery or dental procedures to determine mitotane-induced bleeding risk. For patients with prolonged bleeding time, withhold or reduce the dose of LYSODREN as clinically indicated.
Hormone binding protein Mitotane has been shown to increase plasma levels of
hormone binding proteins (e.g., sex hormone-binding globulin (SHBG) and corticosteroid-binding globulin (CBG)). This should be taken into account when interpreting the results of hormonal assays and may result in gynecomastia.
Embryo-Fetal Toxicity
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 nonhormonal contraception, during treatment with LYSODREN and after discontinuation of treatment for as long as mitotane plasma levels are detectable, since LYSODREN can render some hormonal contraceptives ineffective.
Drug Interactions with Lysodren
Effects of Other Drugs on
LYSODREN Spironolactone Spironolactone may block the action of mitotane. Avoid concomitant use of mitotane with spironolactone.
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. 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. Warfarin Mitotane may induce the metabolism of warfarin, which may reduce its level and its efficacy . 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.
Pregnancy Safety for Lysodren
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.
Pediatric Use of Lysodren
Pediatric Use Effectiveness in pediatric patients has not been established. Based on published case reports, mitotane may negatively impact neuro-psychological development (e.g., motor and speech delay, memory impairment) in children and adolescents. In cases of cognitive dysfunction, thyroid function should be evaluated as mitotane may induce hypothyroidism.
Other effects of mitotane observed in pediatric patients that are cited in medical literature or in a pharmacovigilance database include growth delay and estrogenic-like effects such as uterine bleeding, breast development in females and gynecomastia in males.
Overdosage Information for 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.
Drug information sourced from the FDA. This content is for informational purposes only and does not constitute medical advice. Consult a healthcare professional before making any medication decisions.
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