:
o,p'-DDD
LYSODREN(r)
:
Miscellaneous
Special pediatric considerations are noted when applicable, otherwise adult provisions apply.
:
[1]
Mitotane is a derivative of the insecticide DDT and causes direct necrosis and atrophy of the adrenal cortex.
:
[2,3,4,5,6,7,8]
| Oral Absorption | 40% | |
| Distribution | found in all body tissues, but primarily in fat | |
| cross blood brain barrier? | mitotane: no; metabolite: trace | |
| Vd | no information found | |
| PPB | no information found | |
| Metabolism | both liver and kidney metabolize small portions | |
| active metabolite(s) | no information found | |
| inactive metabolite(s) | yes | |
| Excretion | 60% excreted unchanged in feces; small portion excreted in bile as metabolites | |
| urine | 10-25% as metabolites | |
| t1/2 | 18-159 days | |
| Cl | no information found | |
:
[9]
Adrenal cortical cancer Health Protection Branch approved indication.
:
[9]
The mutagenic, carcinogenic and teratogenic effects of mitotane are not known. Its safe use in pregnancy and its effects on fertility have not been established. Breast feeding is not recommended due to the potential secretion into breast milk.
:
[9,10,11,12]
| ORGAN SITE | SIDE EFFECT | ONSET | |||
| cardiovascular | hypertension (rare) | E | |||
| orthostatic hypotension (rare) | E | ||||
| central nervous system | lethargy (25%) | E | D | ||
| dizziness (15%) | E | D | |||
| endocrine | adrenal insufficiency | E | |||
| gastrointestinal | nausea and vomiting | I | |||
| diarrhea | E | ||||
| anorexia | E | ||||
| hypersensitivity | allergic skin rash (15%, transient) | E | |||
| ocular | blurred vision, double vision (rare) | E | |||
| toxic retinopathy (rare) | E | ||||
| cataracts (rare) | E | D | |||
| renal/metabolic | hematuria, hemorrhagic cystitis (rare) | D | |||
| albuminuria (rare) | D | ||||
| other | minor aches (rare) | E | |||
| fever (rare) | E | ||||
Dose-limiting side effects are underlined. I = immediate (onset in hours to days); E = early (days to weeks); D = delayed (weeks to months); L = late (months to years) Mitotane's main action is adrenocortical suppression. Supplementation with exogenous steroids is necessary (eg, prednisone 5 mg qam and 2.5 mg qpm or cortisone acetate 25 mg qam and 12.5 mg qpm). Occasional patients will require fludrocortisone (FLORINEF(r)) 0.1 mg po daily for mineralocorticoid deficiency causing orthostatic hypotension. If shock, severe trauma or infection occurs, mitotane should be temporarily discontinued and steroids immediately given. When mitotane is discontinued, the steroid should be tapered slowly, but may need to be continued indefinitely. Patients should use a medical alert tag or bracelet warning of adrenal suppression.
Gastrointestinal toxicity
occurs in 80% of patients.
Adverse CNS effects
occur in 40% of patients and are manifested as lethargy, somnolence, dizziness, depression, irritability, confusion and tremors. More rare CNS side effects, consisting of speech difficulty,
memory loss, ataxia and halllucinations, have been reported. Long-term use can cause brain damage. Behavioral and neurological assessments should be performed periodically when continuous mitotane exceeds 2 years.
:
[4,13,14]
| AGENT | EFFECT | MECHANISM | MANAGEMENT |
| measurement of urinary adrenal steroids | false negative for cortisol secretion rate | mitotane increases extra-adrenal metabolism of cortisol so less is excreted in urine | obtain both urine and plasma levels of cortisol |
| barbiturates, phenytoin | increased metabolism of these drugs | mitotane induces hepatic microsomal enzyme oxidation system | monitor pharmacological effects; adjust dose of barbiturate or phenytoin prn |
| CNS depressants | enhanced CNS depression | additive | caution |
| spironolactone | blocks effect of mitotane | uncertain | avoid |
| thyroid function test | decrease in serum protein-bound iodine | mitotane binds thyroxine-binding globulin | Resin triodothyronine uptake tests are not affected. Free thyroxine concentrations apparently remain in the normal range. |
| warfarin | decreased pharmacological response to warfarin | enhanced metabolism of warfarin by hepatic microsomal enzyme oxidation system | monitor prothrombin times and adjust warfarin dose prn whenever mitotane is stopped or started |
: [9]
Tablets:
500 mg; store at room temperature.
:
[2,4,8,15]
Refer to protocol by which patient is being treated.
Adults:
Oral
: not to be taken with a fatty meal
daily: start 500 mg qid, escalate by 1000 mg/day every 1-2 weeks to maximum tolerated dose
Maximum tolerated dose:
usual: 8-10 g/day (range 2-19 g)
Adequate trial
: 3 months at maximum tolerated dose (10% of patients with measurable
response required >3 months).
Adrenal replacement:
Should be given with steroids - eg, prednisone 5 mg qam and 2.5 mg qpm or
cortisone acetate 25 mg qam and 12.5 mg qpm. Occasional patients will require fludrocortisone (FLORINEF(r)) 0.1 mg daily for mineralocorticoid deficiency causing orthostatic hypotension. If shock, severe trauma or infection occurs mitotane should be temporarily discontinued and steroids immediately given. When mitotane is discontinued, the steroid should be tapered slowly, but may need to be continued indefinitely. Patients should use medical alert tag or bracelet warning of adrenal suppression.
Dosage in myelosuppression:
no adjustment required
Dosage in renal failure:
adjustment required, no details found
Dosage in hepatic failure:
adjustment required, no details found
Children:
Oral
: daily: (2-8 year olds) 0.5-1 g, escalate to 1-4 g/day
MITOTANE FACT SHEET
FOR THE HEALTH CARE PROFESSIONAL | |
|---|---|
| OTHER NAMES | o,p'-DDD, LYSODREN(r) |
| USES * HPB approved | adrenal cortical cancer * |
| DOSAGE FORMS | oral tablet: 500 mg (not to be taken with a fatty meal) |
| USUAL DOSE RANGE | Adults: initial: 500 mg po qid, escalate by 1000 mg/day q1-2w to maximum tolerated dose usual: 8-10 g/day divided range: 2-19 g/day divided adequate trial: 3 months at maximum tolerated dose Children: (2-8 year olds) 0.5-1 g po daily, escalate to 1-4 g/day |
| DOSE REDUCTIONS | liver (hepatic) failure kidney (renal) failure central nervous system toxicity |
| ONSET | SIDE EFFECT * may be life-threatening side effects in bold, italic type are common |
| IMMEDIATE (hours to days) | nausea and vomiting |
| EARLY (days to weeks) | * adrenal insufficiency (glucocorticoid and sometimes mineralocorticoid replacement required) gastrointestinal problems ( anorexia , diarrhea) central nervous system problems (40%, lethargy 25%, dizziness 15%, depression, irritability, confusion, tremors) skin problems (transient rash 15-20%) minor aches (rare) fever (rare) blood pressure problems (hypertension, orthostatic hypotension) eye problems (blurred or double vision, toxic retinopathy, cataracts) |
| DELAYED/LATE (weeks to years) | central nervous system problems eye problems (cataracts) bladder problems (hematuria, hemorrhagic cystitis, albuminuria) |
CONTRAINDICATIONS
known hypersensitivity to mitotane
pregnancy and breast feeding
| SIGNIFICANT INTERACTIONS *increases toxicity | barbiturates, *CNS depressants, phenytoin (DILANTIN(r)), spironolactone (ALDACTONE(r)), warfarin (COUMADIN(r)) |
| MONITORING | periodically: mitotane levels, electrolytes, DHEAS (dihydroepiandrostenedione), liver function, kidney function, blood pressure, neurological assessment (>2 years treatment) |
TEACHING AIDS * For the Patient: Mitotane
For the Patient: Nausea
NOTES:
* Glucocorticoid replacement (eg, prednisone 5 mg po qam and 2.5 mg po qpm or cortisone acetate 25 mg po qam and 12.5 mg qpm) is required to avoid an adrenal crisis.
Mineralocorticoid replacement (eg, fludrocortisone 0.1 mg po daily) may be required for orthostatic hypotension.
Patients should wear a medical alert tag or bracelet warning of adrenal suppression.
If shock, severe trauma or infection occurs, mitotane should be temporarily discontinued and steroids immediately given.
Steroids should be tapered slowly when mitotane is discontinued, but may need to be continued indefinitely.
FOR THE PATIENT
Mitotane :
Other names: LYSODREN(r)
Mitotane (MITE-oh-tane) a drug that is used to treat cancer of the adrenal cortex. The adrenal cortex is the outer part of a small gland (adrenal gland) that produces steroids. Mitotane decreases the amounts of steroids produced by the adrenal cortex. It is a tablet that you take by mouth.
It is important to take mitotane exactly as directed by your doctor. Make sure you understand the directions. Mitotane may be taken with food or on an empty stomach with a glass of water or juice. Avoid taking mitotane with fatty foods.
For 3-4 times a day dosing: If you miss a dose of mitotane, take it as soon as you can if it is within 3 hours of the missed dose. If it is over 3 hours since your missed dose, skip the missed dose and go back to your usual dosing times.
Store mitotane tablets out of the reach of children, at room temperature, away from heat, light and moisture.
Other drugs such as barbiturates, CNS depressants, phenytoin (DILANTIN(r)), spironolactone (ALDACTONE(r)), warfarin (COUMADIN(r)) may interact with mitotane. Tell your doctor if you are taking these or any other drugs as your dose may need to be changed. Check with your doctor or pharmacist before you start taking any new drugs.
You will be given another drug such as prednisone (eg, DELTASONE(r)) or cortisone (eg, CORTONE(r)) to take while you are on mitotane. This helps prevent side effects caused by changes in your body's ability to produce steroids. Wear a medical alert tag or bracelet to inform doctors in an emergency as you may need extra steroids.
Alcohol may increase the side effects of mitotane. However, one drink of alcohol with food each day will not affect the usefulness of mitotane. If you are also taking other drugs (like hydrocortisone), ask your doctor about the safety of a drink of alcohol.
Mitotane has not been shown to cause problems during pregnancy in humans. However, it is best to use birth control while taking mitotane. Tell your doctor right away if you become pregnant. Do not breast feed during treatment.
Tell doctors or dentists that you are being treated with mitotane before you receive any treatment from them.
| SIDE EFFECTS | MANAGEMENT |
| You may feel drowsy and/or dizzy when you take mitotane. | *Do not drive a car or operate machinery if you are feeling drowsy, dizzy or less alert than usual. *Avoid alcohol as it may make you more drowsy or dizzy. |
| Nausea (upset stomach) may occur. | *Take your mitotane after eating. *Eat often in small amounts. *Try the ideas in For the Patient: Nausea . *You may be given an antinausea drug to take at home. It is easier to prevent nausea than treat it once it has occurred, so follow directions closely. Most antinausea drugs cause drowsiness. |
| A skin rash may occur. This should go away in a week or two even though you keep taking mitotane. | *Keep on taking your mitotane. *Take an antihistamine such as diphenhydramine (eg, Benadryl) 25 mg capsules 2-4 times a day when needed. Most antihistamines cause drowsiness. |
| Your body's ability to handle illness or injury is weakened by mitotane. You may need extra steroids to help you get better. | *Check with your doctor if you have an infection, illness or injury. |
SEE YOUR DOCTOR AS SOON AS POSSIBLE (DURING OFFICE HOURS) IF YOU HAVE:
Signs of bladder problems such as blood in urine.
Signs of low blood pressure such as dizziness when you bend over or stand up suddenly.
Signs of eye problems such as blurred or double vision.
CHECK WITH YOUR DOCTOR IF ANY OF THE FOLLOWING CONTINUE OR BOTHER YOU:
Uncontrolled nausea, vomiting, loss of appetite or diarrhea.
Mental depression.
Dizziness or drowsiness that does not improve.
Skin rash that lasts longer than 2 weeks, gets worse or is unbearable.
REPORT ADDITIONAL PROBLEMS TO YOUR DOCTOR.
Notes:
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