NDC 0015-3080 Lysodren

Mitotane

NDC Product Code 0015-3080

NDC Code: 0015-3080

Proprietary Name: Lysodren What is the Proprietary Name?
The proprietary name also known as the trade name is the name of the product chosen by the medication labeler for marketing purposes.

Non-Proprietary Name: Mitotane What is the Non-Proprietary Name?
The non-proprietary name is sometimes called the generic name. The generic name usually includes the active ingredient(s) of the product.

Product Characteristics

Color(s):
WHITE (C48325)
Shape: ROUND (C48348)
Size(s):
13 MM
Imprint(s):
BL;L1
Score: 2

NDC Code Structure

  • 0015 - E.r. Squibb & Sons, L.l.c.
    • 0015-3080 - Lysodren

NDC 0015-3080-60

Package Description: 100 TABLET in 1 BOTTLE

NDC Product Information

Lysodren with NDC 0015-3080 is a a human prescription drug product labeled by E.r. Squibb & Sons, L.l.c.. The generic name of Lysodren is mitotane. The product's dosage form is tablet and is administered via oral form.

Labeler Name: E.r. Squibb & Sons, L.l.c.

Dosage Form: Tablet - A solid dosage form containing medicinal substances with or without suitable diluents.

Product Type: Human Prescription Drug What kind of product is this?
Indicates the type of product, such as Human Prescription Drug or Human Over the Counter Drug. This data element matches the “Document Type” field of the Structured Product Listing.

Lysodren Active Ingredient(s)

What is the Active Ingredient(s) List?
This is the active ingredient list. Each ingredient name is the preferred term of the UNII code submitted.

  • MITOTANE 500 mg/1

Inactive Ingredient(s)

About the Inactive Ingredient(s)
The inactive ingredients are all the component of a medicinal product OTHER than the active ingredient(s). The acronym "UNII" stands for “Unique Ingredient Identifier” and is used to identify each inactive ingredient present in a product.

  • CELLULOSE, MICROCRYSTALLINE (UNII: OP1R32D61U)
  • POLYETHYLENE GLYCOL 3350 (UNII: G2M7P15E5P)
  • SILICON DIOXIDE (UNII: ETJ7Z6XBU4)

Administration Route(s)

What are the Administration Route(s)?
The translation of the route code submitted by the firm, indicating route of administration.

  • Oral - Administration to or by way of the mouth.

Pharmacological Class(es)

What is a Pharmacological Class?
These are the reported pharmacological class categories corresponding to the SubstanceNames listed above.

  • Cytochrome P450 3A4 Inducers - [MoA] (Mechanism of Action)

Product Labeler Information

What is the Labeler Name?
Name of Company corresponding to the labeler code segment of the Product NDC.

Labeler Name: E.r. Squibb & Sons, L.l.c.
Labeler Code: 0015
FDA Application Number: NDA016885 What is the FDA Application Number?
This corresponds to the NDA, ANDA, or BLA number reported by the labeler for products which have the corresponding Marketing Category designated. If the designated Marketing Category is OTC Monograph Final or OTC Monograph Not Final, then the Application number will be the CFR citation corresponding to the appropriate Monograph (e.g. “part 341”). For unapproved drugs, this field will be null.

Marketing Category: NDA - A product marketed under an approved New Drug Application. What is the Marketing Category?
Product types are broken down into several potential Marketing Categories, such as NDA/ANDA/BLA, OTC Monograph, or Unapproved Drug. One and only one Marketing Category may be chosen for a product, not all marketing categories are available to all product types. Currently, only final marketed product categories are included. The complete list of codes and translations can be found at www.fda.gov/edrls under Structured Product Labeling Resources.

Start Marketing Date: 06-01-2009 What is the Start Marketing Date?
This is the date that the labeler indicates was the start of its marketing of the drug product.

End Marketing Date: 03-31-2021 What is the End Marketing Date?
This is the date the product will no longer be available on the market. If a product is no longer being manufactured, in most cases, the FDA recommends firms use the expiration date of the last lot produced as the EndMarketingDate, to reflect the potential for drug product to remain available after manufacturing has ceased. Products that are the subject of ongoing manufacturing will not ordinarily have any EndMarketingDate. Products with a value in the EndMarketingDate will be removed from the NDC Directory when the EndMarketingDate is reached.

Exclude Flag: N What is the NDC Exclude Flag?
This field indicates whether the product has been removed/excluded from the NDC Directory for failure to respond to FDA’s requests for correction to deficient or non-compliant submissions. Values = ‘Y’ or ‘N’.

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Information for Patients

Mitotane

Mitotane is pronounced as (mye' toe tane)

Why is mitotane medication prescribed?
Mitotane is used to treat cancer of the adrenal gland that can not be treated with surgery. Mitotane is in a class of medications called antineoplastic agents. It works b...
[Read More]

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Lysodren Product Labeling Information

The product labeling information includes all published material associated to a drug. Product labeling documents include information like generic names, active ingredients, ingredient strength dosage, routes of administration, appearance, usage, warnings, inactive ingredients, etc.

Product Labeling Index

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.

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.

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.

5.1 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 [seeWarnings and Precautions (5.2)]•   Adrenal Insufficiency [seeWarnings and Precautions (5.3)]•   Ovarian macrocysts [seeWarnings 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.

7.1 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.

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.

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

LYSODREN can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1)]. 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 (12.3)].

8.4 Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

8.5 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. 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.

8.6 Hepatic Impairment

Hepatic impairment may interfere with the metabolism of mitotane and the drug may accumulate. Administer LYSODREN with caution to patients with hepatic impairment.

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 320.05.Inactive ingredients in LYSODREN are: microcrystalline cellulose, polyethylene glycol 3350, silicon dioxide, and starch.

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 concentrations and increased formation of 6-β-hydroxycortisol have been reported.

12.2 Pharmacodynamics

The pharmacodynamics of mitotane are unknown.

Absorption

Following oral administration of LYSODREN, 40% of the dose is absorbed.

Distribution

Mitotane is found in most tissues of the body; however, fat is the primary site of distribution.

Elimination

Following discontinuation of mitotane, the plasma terminal half-life ranges from 18 to 159 days (median 53 days).

Metabolism

Mitotane is converted to a water-soluble metabolite.

Excretion

No unchanged mitotane is found in urine or bile. Approximately 10% of the administered dose is recovered in the urine as a water-soluble metabolite. A variable amount of metabolite (1%-17%) is excreted in the bile.

13.1 Carcinogenesis, Mutagenesis, Impairment Of Fertility

The carcinogenicity and mutagenicity of mitotane are unknown.

References

15 REFERENCES1.OSHA. http://www.osha.gov/SLTC/hazardousdrugs/index.html

16 How Supplied/Storage And Handling

LYSODREN tablets are supplied as 500 mg white, round, biconvex, scored tablets, bisected on one side and impressed with “BL” over “L1” on the other side.100 tablets per bottle: NDC 0015-3080-60Store bottles at 25°C (77°F); excursions permitted between 15°C and 30°C (59°F-86°F).Mitotane is a cytotoxic drug. Follow applicable special handling and disposal procedures [see References (15)].

Adrenal Crisis

  • •Advise patients to discontinue LYSODREN in the case of shock or severe trauma and contact their healthcare provider immediately. •Advise patients to tell their healthcare provider of any planned surgeries.

Other

Ovarian Macrocysts• Advise premenopausal women to seek medical care if they experience gynecological symptoms such as vaginal bleeding and/or pelvic pain [see Warnings and Precautions(5.5)].

Manufactured for:Bristol-Myers Squibb CompanyPrinceton, New Jersey 08543 USATBD

Embryo-Fetal Toxicity

  • •Advise females of reproductive potential of the potential risk to a fetus and to inform their healthcare provider of a known or suspected pregnancy [see Warnings and Precautions (5.4) and Use in Specific Populations (8.1)]. •Advise females of reproductive potential to use effective contraception during treatment and after discontinuation of treatment for as long as instructed by their healthcare provider [see Use in Specific Populations (8.3)].

Lactation

  • •Advise females who are nursing not to breastfeed during treatment with LYSODREN [see Use in Specific Populations (8.2)].

Lysodren 500 Mg Tablets Representative Packaging

See How Supplied section for a complete list of available packages of LYSODREN.NDC 0015-3080-60100 TABLETSLYSODREN® (mitotane tablets, USP)EACH TABLET CONTAINS 500 mg Rx onlyBristol-Myers Squibb

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