mitotane

Absorption: 30–40% absorbed following oral administration.

Distribution: Widely distributed to all body tissues; accumulates in fatty tissue.

Metabolism/Excretion: Slowly released from fatty tissue. Mostly metabolized by the liver; 10% excreted by the kidneys; 15% excreted in bile.

Half-Life: 18–159 days.

Time/Action Profile ⬆ ⬇

(clinical effects‡)

ROUTE	ONSET	PEAK	DURATION
PO	2–4 wk	6 wk	unknown

‡Onset = inhibition of adrenocortical function; peak = tumor response.

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity;
OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

Obesity (↑ risk of adverse reactions);
Premenopausal women (↑ risk of ovarian macrocysts);
Rep: Women of reproductive potential;
Pedi: Safety and effectiveness not established in children.

Shock, severe trauma, or infection (↑ risk of adrenal crisis).

Adv. Reactions/Side Effects ⬆ ⬇

CV: hypertension, hypotension

Derm: maculopapular rash, flushing

EENT: ↓hearing, blurred vision, diplopia, lens opacities, optic neuritis, toxic retinopathy

Endo: adrenal suppression, ADRENAL CRISIS, gynecomastia, hypothyroidism

GI: anorexia, diarrhea, nausea, vomiting, HEPATOTOXICITY, ↑liver enzymes, ↑salivation

GU: albuminuria, hematuria, hemorrhagic cystitis, ovarian macrocysts

Hemat: anemia, ↑bleeding time, leukopenia, thrombocytopenia

Metab: hypercholesterolemia, hypouricemia

MS: arthralgia, myalgia

Neuro: lethargy, somnolence, brain damage, dizziness, fatigue, functional impairment (high-dose, long-term therapy), headache, irritability, mental depression, tremors, vertigo, weakness

Resp: dyspnea, wheezing

Misc: fever

Interactions ⬆ ⬇

Drug-drug:

May ↓ levels and effectiveness of CYP3A4 substrates; avoid concomitant use with narrow therapeutic index substrates; if concurrent use is unavoidable, ↑ dose of CYP3A4 substrate.
May ↓ levels and effectiveness of warfarin.
Additive CNS depression with other CNS depressants, includingalcohol, antihistamines, antidepressants, opioid analgesics, or sedative/hypnotics.

Route/Dosage ⬆ ⬇

Adrenocortical Carcinoma

PO (Adults ): 2–6 g/day in 3–4 divided doses; may be ↑ as tolerated (range 2–16 g/day).

Cushing’s Syndrome

PO (Adults ): 3–6 g/day in 3–4 divided doses initially; ↓ to maintenance dose of 500 mg twice weekly to 2 g/day.

Availability ⬆ ⬇

Assessment ⬆ ⬇

Monitor for symptoms of adrenal insufficiency (anorexia, nausea and vomiting, diarrhea, fatigue, weakness, hypotension, darkening of skin), especially with infection, trauma, obesity, or shock (increased risk for this side effect). Withhold drug and administer corticosteroid with supportive care.
Monitor for development of dose-limiting side effects (severe nausea, vomiting, anorexia, or diarrhea). Antiemetics may be needed. Adjust diet as tolerated to maintain nutritional intake and fluid and electrolyte balance.
Monitor neurologic status; report depression, lethargy, dizziness, or any changes from baseline; withhold drug for severe adverse neurological effects.
Monitor for liver toxicity (jaundice, dark urine, abdominal discomfort, ascites); dose may need to be ↓ or discontinued.
Premenopausal women should have a pelvic ultrasound prior to and regularly during therapy. Monitor premenopausal women for signs of ovarian macrocyst or ovarian torsion (pelvic pain, fullness, bloating, irregular bleeding). Dose may need to be ↓ or discontinued.

Lab Test Considerations:

Verify negative pregnancy test prior to starting therapy.
Obtain baseline CBC with differential, LFTs, BUN, serum creatinine, and lipid panel prior to and regularly during therapy.
- Monitor for leukopenia and anemia; dose adjustment may be needed.
- If hepatic or renal impairment occurs, initial dose may be ↓; discontinue therapy if severe. If renal impairment occurs, may continue therapy if on hemodialysis.
Monitor platelets, PT/INR or aPTT as clinically indicated; if bleeding time prolonged, dose adjustment may be needed.
- Withhold use of mitotane prior to surgery; may prolong bleeding time.
Monitor serum mitotane levels every 2–3 wk for the first mo and regularly during therapy once plateau reached
8-hr plasma cortisol concentrations and 24-hr urine tests for 17-hydroxycorticosteroid concentrations should be obtained prior to and periodically during therapy to determine degree of adrenal suppression. May be decreased because of adrenocortical inhibition.
- Monitor free cortisol and ACTH levels to determine optimal dose.
- May decrease serum uric acid and protein-bound iodine concentrations.

Implementation ⬆ ⬇

Treatment should be instituted in the hospital until a stable dose regimen is achieved.
Wear gloves when handling pills and bottles of mitotane. Wear gloves and face/eye shield during administration.
PO: Administer tablets with fatty food, if possible. Premedication with an antiemetic may be necessary. DNC: Do not crush or break tablets.

Patient/Family Teaching ⬆ ⬇

Instruct patient to take medication exactly as directed. Take missed doses as soon as remembered unless almost time for next dose. Notify health care provider of missed doses.
Teach patient that taking the medication regularly with fatty food aids absorption. Advise to not crush or chew the tablets; tablets should be swallowed whole.
Caregivers and family that assist in medication administration should be advised to wear disposable gloves. Medication should be kept away from children.
Explain to patient that this drug suppresses the adrenal glands and therefore impairs the body’s ability to cope with stress. Concurrent corticosteroid and mineralocorticoid therapy may be ordered to ensure that adequate amounts of adrenal hormones are present. Health care provider should be notified if an infection, illness, or injury occurs; supplemental steroids may be necessary or mitotane may need to be discontinued in the event of severe trauma or shock.
May cause drowsiness. Caution patient to avoid driving or other activities requiring alertness until response to medication is known.
Instruct patient to notify health care provider if vaginal bleeding, pelvic pain, abdominal pain or bloating, depression, dizziness/vertigo, nausea, vomiting, anorexia, diarrhea, skin rash, or darkening of skin or urine occurs or if muscle aches, fever, flushing, or muscle twitching become pronounced.
Instruct patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care provider before taking other medications. Avoid taking alcohol or other CNS depressants with this medication.
Rep: May cause fetal harm. Advise females of reproductive potential to use an effective nonhormonal form of contraception during and following therapy for as long as instructed by health care provider. Advise patient to notify health care provider if pregnancy is planned or suspected and to avoid breastfeeding during therapy.
Advise patient to carry identification describing medication regimen in the event of an emergency in which patient cannot relate medical history.
Explain need for continued medical follow-up, including neurologic exam to assess effectiveness and possible side effects of medication.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇