Lysodren

LYSODREN- mitotane tablet
HRA Pharma Rare Diseases

WARNING: 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 (2.2) and Warnings and Precautions (5.1)].

1 INDICATIONS AND USAGE

LYSODREN is indicated for the treatment of patients with inoperable, functional or nonfunctional, adrenal cortical carcinoma.

2 DOSAGE AND ADMINISTRATION

2.1 Recommended Dose

The recommended initial dose of LYSODREN is 2 g to 6 g orally, in three or four divided doses per day. Increase doses incrementally to achieve a blood concentration of 14 to 20 mg/L, or as tolerated.

LYSODREN is a cytotoxic drug. Follow applicable special handling and disposal procedures.

2.2 Dose Modifications

Adrenal Crisis in the Setting of Shock or Severe Trauma

Discontinue LYSODREN until recovery [see Warnings and Precautions (5.1)].

Central Nervous System (CNS) Toxicity

Discontinue LYSODREN until symptoms resolve. Seven to 10 days after symptoms resolve, restart at a lower dose (for example, decrease by 500-1000 mg) [see Warnings and Precautions (5.2)].

3 DOSAGE FORMS AND STRENGTHS

500 mg white, round, biconvex, scored tablets, bisected on one side and impressed with “BL” over “L1″ on the other side.

4 CONTRAINDICATIONS

None.

5 WARNINGS AND PRECAUTIONS

5.1 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 (2.2)].

5.2 CNS Toxicity

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.

5.3 Adrenal Insufficiency

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.

5.4 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 contraception during treatment with LYSODREN and after discontinuation of treatment for as long as mitotane plasma levels are detectable [see Use in Specific Populations (8.1, 8.3)].

5.5 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 [seeAdverse Reactions (6)].

6 ADVERSE REACTIONS

The following adverse reactions are discussed in greater detail in other sections of the label:

• Adrenal Crisis in the Setting of Shock or Severe Trauma [see Warnings and Precautions (5.1)]

• CNS Toxicity [ see Warnings and Precautions (5.2)]

• Adrenal Insufficiency [see Warnings and Precautions (5.3)]
• Ovarian macrocysts [see Warnings and Precautions (5.5)]

The following adverse reactions associated with the use of LYSODREN were identified in clinical trials or postmarketing reports. Because these reactions were reported voluntarily from a population of uncertain size, it is not always possible to estimate their frequency reliably or to establish a causal relationship to drug exposure.

Common adverse reactions occurring with LYSODREN treatment include:

•Anorexia, nausea, vomiting, and diarrhea (80%)

•Depression, dizziness, or vertigo (15%-40%)

•Rash (15%)•Neutropenia•Growth retardation, hypothyroidism

•Confusion, headache, ataxia, mental impairment, weakness, dysarthria

•Maculopathy•Hepatitis, elevation of liver enzymes•Gynecomastia

• Hypercholesterolemia, hypertriglyceridemia

• Decreased blood androstenedione and decreased blood testosterone in females, increased sex hormone binding globulin in females and males, decreased blood free testosterone in males.

Less common adverse reactions include: visual blurring, diplopia, lens opacity, retinopathy, prolonged bleeding time, hematuria, hemorrhagic cystitis, albuminuria, hypertension, orthostatic hypotension, flushing, generalized aching, and fever.

7 DRUG INTERACTIONS

7.1 CYP3A4 Substrates

Mitotane is a strong inducer of cytochrome P450 3A4 (CYP3A4). Monitor patients for a change in dosage requirements for the concomitant drug when administering LYSODREN to patients receiving drugs that are substrates of CYP3A4.

7.2 Warfarin

When administering coumarin-type anticoagulants to patients receiving LYSODREN, monitor coagulation tests and adjust the anticoagulant dose as needed.

8 USE IN SPECIFIC POPULATIONS

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. 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.

8.2 Lactation

Risk Summary

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.

Page 1 of 2 1 2

All MedLibrary.org resources are included in as near-original form as possible, meaning that the information from the original provider has been rendered here with only typographical or stylistic modifications and not with any substantive alterations of content, meaning or intent.

This site is provided for educational and informational purposes only, in accordance with our Terms of Use, and is not intended as a substitute for the advice of a medical doctor, nurse, nurse practitioner or other qualified health professional.

Privacy Policy | Copyright © 2020. All Rights Reserved.