Lysodren

Before taking mitotane, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.Before using this medication, tell your doctor or pharmacist your medical history, especially of: current infection (especially viral infections such as chickenpox, herpes), blood pressure problems, liver disease.This drug may make you dizzy or drowsy. Do not drive, use machinery, or do any activity that requires alertness until you are sure you can perform such activities safely. Limit alcoholic beverages.This medication can make it difficult to control your blood pressure. To minimize dizziness and lightheadedness, get up slowly when rising from a sitting or lying position.Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).If you have been using this product, your body may not produce enough natural steroids. You may need to start taking additional corticosteroids (e.g., hydrocortisone), especially if your body is stressed due to a major infection, surgery or injury. Tell your doctor immediately if a stress situation (e.g., trauma, surgery, serious infection) is occurring or any of the following side effects occur: unusual weakness, sudden weight loss, dizziness. This advice applies during and up to 8 months after stopping mitotane treatment. Carry an emergency card or bracelet with this information. Consult your doctor or pharmacist for more details.Since this drug can be absorbed through the skin and lungs and may harm an unborn baby, women who are pregnant or who may become pregnant should not handle this medication or breathe the dust from the tablets.This medication is not recommended for use during pregnancy. It may harm an unborn baby. Use reliable forms of birth control (such as condoms, birth control pills) during and after treatment with mitotane. Your doctor will use blood tests to decide when you can stop using birth control. If you become pregnant or think you may be pregnant, tell your doctor immediately.This medication passes into breast milk and may harm a nursing infant. Breast-feeding is not recommended while using this drug. Consult your doctor before breast-feeding.

Dosage Forms & Strengths

tablet

• 500mg

Adrenal Carcinoma

Indicated for inoperable adrenal cortical carcinoma of both functional and nonfunctional types

Initial: 2-6 g/day PO divided q6-8hr, THEN

Increase incrementally to 9-10 g/day divided q6-8hr

Maximum tolerated dose varies from 2-16 g/day, usually 9-10 g/day

The highest doses used in clinical trials were 18-19 g/day

Cushing's Syndrome (Off-label)

Initial: 1.5 g PO divided q6-8hr; not to exceed 3 g PO q8hr

Maintenance: 500 mg 2 x/week to 2 g/day

Administration

All tumor tissue should be surgically removed before administration

Monitor

Growth of adrenal cortex metastatic lesion

Hepatic Impairment

May need to decrease dose in patients with liver disease

Dosage Forms & Strengths

tablet

• 500mg

Adrenocortical Carcinoma (Off-label)

1-2 g/day PO in divided dose; may increase gradually not to exceed 5-7 g/day

Pregnancy Category: D

Lactation: Detected in breast milk; because of the potential for serious adverse reactions in nursing infants from mitotane, advise women to discontinue nursing during therapy and after treatment discontinuation for as long as mitotane plasma levels are detectable

Pregnancy Categories

A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA:Information not available.

If you take too much this medication, call your healthcare provider or local Poison Control Center, or seek emergency medical attention right away.

If this medication is administered by a healthcare provider in a medical setting, it is unlikely that an overdose will occur. However, if overdose is suspected, seek emergency medical attention.

Mitotane is a cancer medication. That interferes with the growth of cancer cells and slows their growth and spread in the body.

Mitotane is used to treat cancer of the adrenal gland (adrenal cortical carcinoma).

Mitotane may also be used for other purposes not listed in this medication guide.

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]
• CNS Toxicity [see WARNINGS AND PRECAUTIONS]
• Adrenal Insufficiency [see WARNINGS AND PRECAUTIONS]
• Ovarian macrocysts [see WARNINGS AND PRECAUTIONS]

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.

Read the entire FDA prescribing information for Lysodren (Mitotane)

Read More »

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

This medication may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert.

Avoid activities that may increase your risk of bleeding or injury. Use extra care to prevent bleeding while shaving or brushing your teeth.

This medicine can pass into body fluids (urine, feces, vomit). Caregivers should wear rubber gloves while cleaning up a patient's body fluids, handling contaminated trash or laundry or changing diapers. Wash hands before and after removing gloves. Wash soiled clothing and linens separately from other laundry.

Absorption

Bioavailability

About 40% of an oral dose is absorbed from the GI tract, with peak plasma concentrations usually attained in about 3–5 hours.a b

Onset

Inhibition of adrenocortical function usually occurs within 2–4 weeks after beginning therapy.b

Duration

Plasma and tissue concentrations of mitotane and its metabolites decline slowly.b Following discontinuance of mitotane, unchanged drug and trace amounts of metabolites detected in plasma for up to 8 months and 18 months, respectively.b

Distribution

Extent

Widely distributed throughout body; fat is the primary storage site.a b Small amounts of one metabolite detected in CSF.b

Not known whether mitotane crosses the placenta or is distributed into milk.a b

Distribution between plasma and tissues is complete within 12 hours.b

Elimination

Metabolism

Metabolized in the liver and other tissues principally to o,p′-dichlorodiphenyl-ethene and -acetate derivatives.b

Elimination Route

Excreted in urine (10%) and in bile (1–17%) as metabolites.a b

Half-life

18–159 days.a b

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Mitotane

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Tablets	500 mg	Lysodren (scored)	Bristol-Myers Squibb

Medicines used to treat cancer are very strong and can have many side effects. Before receiving this medicine, make sure you understand all the risks and benefits. It is important for you to work closely with your doctor during your treatment.

Take this medicine only as directed by your doctor. Do not take more or less of it, do not take it more often, and do not take it for a longer time than your doctor ordered.

Do not stop taking this medicine without first checking with your doctor. To do so may increase the chance of unwanted effects.

Swallow the tablet whole. Do not crush, break, or chew it. If contact with broken or crushed tablets occurs, wash your hands immediately.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For oral dosage form (tablets):
  • For cancer of the adrenal glands:
    • Adults—At first, 2 to 6 grams (g) per day, given in 3 or 4 divided doses per day. Your doctor may adjust your dose as needed and tolerated.
    • Children—Use and dose must be determined by your doctor.

Missed Dose

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

It is very important that your doctor check you at regular visits for any problems or unwanted effects that may be caused by this medicine.

Using this medicine while you are pregnant can harm your unborn baby. Use an effective form of birth control to keep from getting pregnant during treatment and for as long as this medicine is detected in your blood. If you think you have become pregnant while using the medicine, tell your doctor right away.

Check with your doctor right away if you get a serious injury, infection, or illness of any kind. This medicine may weaken your body's defenses against infection or inflammation.

Adrenal insufficiency may develop in patients using this medicine. Check with your doctor right away if you have more than one of the following symptoms: darkening of the skin, diarrhea, dizziness, fainting, loss of appetite, mental depression, nausea, skin rash, unusual tiredness or weakness, or vomiting.

This medicine may cause some people to become dizzy, drowsy, or less alert than they are normally. Make sure you know how you react to this medicine before you drive, use machines, or do anything else that could be dangerous if you are dizzy or are not alert.

This medicine may cause cysts in the ovaries in premenopausal women (have menstrual cycles). Tell your doctor if you have bloating, sudden or severe pelvic pain, or vaginal bleeding.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

• If you have an allergy to mitotane or any other part of Lysodren (mitotane).
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If you are breast-feeding. Do not breast-feed while you take this medicine. You will also need to avoid breast-feeding after you stop Lysodren until there is no more of this medicine in your body. Talk with your doctor to see how long you need to avoid breast-feeding after you stop this drug.

This medicine may interact with other drugs or health problems.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take Lysodren with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Upset stomach or throwing up.
• Loose stools (diarrhea).
• Not hungry.
• Dizziness.
• Headache.
• Feeling sleepy.
• Feeling tired or weak.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

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.

Pharmacodynamics

The pharmacodynamics of mitotane are unknown.

Pharmacokinetics

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.