Mitotane

Mitotane may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:

• loss of appetite
• nausea
• vomiting
• diarrhea
• depression
• lack of energy
• unusual drowsiness
• feeling that the room is spinning
• changes in vision
• rash or changes in skin color

Some side effects can be serious. If you experience any of these symptoms, call your doctor immediately:

• abdominal or side pain
• confusion
• fast heartbeat
• high fever or shaking chills
• excessive sweating

Mitotane may cause brain or nervous system damage when taken at high doses for longer than 2 years. Talk to your doctor about the risks of taking this medication.

Mitotane may cause other side effects. Call your doctor if you have any unusual problems while taking this medication.

If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting program online (http://www.fda.gov/Safety/MedWatch) or by phone (1-800-332-1088).

>10%

Nausea (39%)

Vomiting (37%)

Lethargy/somnolence (25%)

Anorexia (24%)

Vertigo (15%)

Skin rash (15%)

Diarrhea (13%)

Weakness (12%)

Frequency Not Defined

Eye: Visual blurring, diplopia, lens opacity, toxic retinopathy

Genitourinary: Hematuria, hemorrhagic cystitis, and albuminuria

Cardiovascular: Hypertension, orthostatic hypotension, and flushing

Generalized aching and hyperpyrexia

Decreased protein bound iodine

Postmarketing Reports

Blood and lymphatic system disorders: Neutropenia

Endocrine disorders: Growth retardation, hypothyroidism

Psychiatric disorders: Confusional state

Nervous system disorders: Neuropsychological disturbance, dysarthria, headache, ataxia, mental impairment

Eye disorders: Maculopathy

Hepatobiliary disorders: Hepatitis, elevation of liver enzymes

Reproductive system and breast disorders: Gynecomastia, ovarian macrocysts

LYSODREN (mitotane) is an oral adrenal cytotoxic agent. The chemical name is (±)-1,1dichloro-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.

No Information Provided

Take the missed dose as soon as you remember. If it is almost time for your next dose, wait until then to take the medicine and skip the missed dose. Do not take extra medicine to make up the missed dose.

Mitotane is a prescription medication used to treat cancer of the adrenal gland that can not be treated with surgery. Mitotane belongs to a group of drugs called antineoplastic agents. These work by slowing growth or reducing the size of the tumor.

Mitotane comes as a tablet to take by mouth. It is usually taken three to four times a day. Take mitotane at around the same times every day.

Common side effects of mitotane include loss of appetite, nausea or vomiting, and diarrhea. Mitotane can also cause dizziness or drowsiness. Do not drive or operate machinery until you know how this medication affects you.

Mitotane should be administered under the supervision of a qualified physician experienced in the uses of cancer chemotherapeutic agents. Mitotane should be temporarily discontinued immediately following shock or severe trauma since adrenal suppression is its prime action. Exogenous steroids should be administered in such circumstances, since the depressed adrenal may not immediately start to secrete steroids.

General

• Consult specialized references for procedures for proper handling and disposal of antineoplastic drugs.a

• Individualize dosage according to patient response.b

• Replacement steroid therapy recommended when mitotane treatment is initiated.b (See Adrenal Effects under Cautions.)

• Patients should be hospitalized when therapy is initiated and until dosage regimen is stabilized (usually 5–7 days).a b

Administration

Oral Administration

Administer orally in divided doses, 3 or 4 times daily.a b

Dosage

Pediatric Patients

Generally, initiate therapy at a dosage of 0.5–1 g daily and increase according to patient’s response and tolerance.b

1–4 g daily has been used in children 2–8 years of age.b

Adults

Initially, 2–6 g daily given in 3 or 4 divided doses.101 a b

Increase dosage incrementally to 9–10 g daily in divided doses;101 a some clinicians increase dosage by 2–4 g daily, every 3–7 days.b

In patients who can tolerate higher dosage and in whom improved clinical response appears possible, dosage may be increased until intolerable adverse effects occur.a b

If severe adverse effects occur, reduce dosage until the maximum tolerated dosage (MTD) is attained.a b

MTD may range from 2–16 g daily but is usually 9–10 g daily.a

Continue as long as clinical benefits are observed (e.g., decreased cortisol secretion rate, plasma cortisol concentration, and urinary free cortisol or steroid excretion; slowed growth or regression of the tumor; maintenance of the patient’s clinical status; symptomatic relief or reduction of physical effects caused by excessive steroid production).a b

If no clinical benefits occur within 3 months of continuous therapy at the MTD, the patient may be considered unresponsive; however, 10% of patients who had measurable tumor regression required >3 months of therapy at the MTD.a

Initially, 3–6 g daily given in 3 or 4 divided doses.b Maintenance dosages range from 500 mg twice weekly to about 2 g daily.b

Mitotane has been administered for as long as 7 years.b

Prescribing Limits

Adults

Maximum 18–19 g daily has been used.a

Maximum 12 g daily has been used.b

Special Populations

Hepatic Impairment

Use with caution; however, routine dosage reduction not required.a b

Renal Impairment

No special population dosage recommendations at this time.a

Geriatric Patients

Careful dosage selection, starting at the low end of the dosing range, recommended due to possible age-related decrease in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.a

In the U.S.

• Lysodren

Available Dosage Forms:

• Tablet

Therapeutic Class: Adrenocortical Suppressant

• Tell all of your health care providers that you take this medicine. This includes your doctors, nurses, pharmacists, and dentists.
• Have blood work checked as you have been told by the doctor. Talk with the doctor.
• If you have upset stomach, throwing up, loose stools (diarrhea), or are not hungry, talk with your doctor. There may be ways to lower these side effects.
• You may have more chance of getting an infection. Wash hands often. Stay away from people with infections, colds, or flu.
• If you are taking warfarin, talk with your doctor. You may need to have your blood work checked more closely while you are taking it with mitotane.
• This medicine may cause high cholesterol and triglyceride levels. Talk with the doctor.
• This medicine may affect growth in children and teens in some cases. They may need regular growth checks. Talk with the doctor.
• This medicine may cause harm to the unborn baby or loss of the unborn baby if you take it while you are pregnant.
• Use birth control that you can trust to prevent pregnancy while you take this medicine. You will also need to use it after you stop mitotane until there is no more of this medicine in your body. Talk with your doctor to see how long you need to use birth control after you stop mitotane.
• If you get pregnant while taking this medicine or within several months after the last dose, call your doctor right away.

Use mitotane as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• You will need to take special care when handling this medicine. Check with the doctor or pharmacist to see how to handle mitotane.
• Swallow whole. Do not chew, break, or crush.
• To gain the most benefit, do not miss doses.
• Keep taking this medicine as you have been told by your doctor or other health care provider, even if you feel well.

What do I do if I miss a dose?

• Take a missed dose as soon as you think about it.
• If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
• Do not take 2 doses at the same time or extra doses.

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• Some drugs may have another patient information leaflet. Check with your pharmacist. If you have any questions about this medicine, please talk with your doctor, nurse, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take mitotane or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to mitotane. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Review Date: October 4, 2017

(MYE toe tane)

There are no contraindications listed in the manufacturer's US labeling.

Canadian labeling: Hypersensitivity to mitotane or any component of the formulation

Adrenocortical carcinoma (stage III or IV) (off-label use): Based on limited data (efficacy results are variable; optimal dose not fully established): Children and Adolescents: Oral: Initial: 0.5 to 1 g/day divided 3 times a day, increase weekly to a target dose of 4 g/m2/day (divided 3 times a day) in combination with 8 cycles of the CED regimen (cisplatin, etoposide, and doxorubicin); titrate dose to achieve a target serum concentration of 14 to 20 mcg/mL (Zancanella 2006). Additional data may be necessary to further define the role of mitotane in the treatment of adrenocortical carcinoma in pediatric patients.

There are no dosage adjustments provided in the manufacturer's labeling.

Use with caution in patients with liver disease.