Usual Adult Dose for Adrenal Cortical Carcinoma

2 to 6 g orally daily in 3 to 4 divided doses; increase dose incrementally to achieve a blood concentration of 14 to 20 mg/L, or as tolerated

Comments:

• Initiate this drug in a hospital until a stable dosage regimen is achieved.
• Data suggests continuous treatment with the maximum possible dosage is the best approach; patients who have been treated intermittently (i.e., therapy restarted when severe symptoms have reappeared) often do not respond after the third or fourth course.

Renal Dose Adjustments

Data not available

Liver Dose Adjustments

Use with caution.

Dose Adjustments

Adrenal crisis in the setting of shock or severe trauma:

• Discontinue therapy until recovery.

• Discontinue therapy until symptoms resolve. Seven to 10 days after symptoms resolve, restart at a lower dose (i.e., decrease by 500 to 1000 mg).

Precautions

US BOXED WARNINGS:
ADRENAL CRISIS IN THE SETTING OF SHOCK OR SEVERE TRAUMA:

• In patients taking this drug, 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 therapy until recovery.

• None

Dialysis

Data not available; however, this drug is not likely to be dialyzable because of its lipophilic nature.

Other Comments

Administration Advice:

• Drug tablets should not be crushed.
• If contact with crushed and/or broken tablets occurs, the affected area should be immediately washed.

• Handling and disposal of this drug should be performed in a manner consistent with safe procedures for cytotoxic agents.
• Impervious gloves should be worn when handling bottles containing this drug to minimize the risk of dermal exposure.

• Clinical benefits/effectiveness may include maintenance of clinical status; slowing of metastatic lesion growth; tumor mass reduction; pain reduction, weakness or anorexia; reduction of symptoms and signs due to excessive steroid production.
• If no clinical benefits are observed after 3 months at the maximum tolerated dose (MTD), the case would be considered a clinical failure; however, 10% of patients who showed a measurable response required more than 3 months at the MTD.
• Early diagnosis and prompt treatment institution improve the probability of a positive clinical response.
• No proven antidotes have been established for overdosage with this drug. Prolonged observation for toxicity is required due to this drug's long half-life.

• Endocrine: Signs/symptoms of adrenal insufficiency; free cortisol and corticotropin (ACTH) levels (if steroid replacement therapy needed)
• Hematological: Red blood cell, white blood cell, and platelet counts (during treatment)
• Hepatic: Liver function tests (periodically, especially during the first months of treatment or during dose increases)
• Nervous System: Behavioral and neurological assessments (regular intervals, especially when plasma levels of this drug exceed 20 mg/L)
• Toxicity: Plasma levels of drug (during treatment to avoid toxic levels; after treatment discontinuation to determine when contraception use can be stopped)

• Talk with your doctor if you have a fever, infection, surgery, or are hurt while taking this drug as you may need extra doses of oral steroids to help your body deal with these stresses.
• This drug may cause harm to an unborn baby; talk to your doctor about birth control that you should use during treatment and how long you need to use this birth control after you stop taking this drug.
• Rise slowly from a sitting or lying down position and use care when climbing stairs to lower the chances of feeling dizzy or passing out while taking this drug.
• If any area of your body comes into contact with broken or crushed tablets, wash that area right away and contact your doctor.
• You should not take extra doses or 2 doses at the same time; talk to your doctor about how to handle missed doses.
• This drug may cause side effects such as drowsiness and confusion that can affect your ability to perform certain activities; avoid driving and activities such as operating machinery until you know how this drug affects you.
• Caregivers should wear disposable gloves when handling this drug.
• Pregnant women should not touch or have any contact with this drug.