LYSODREN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for LYSODREN (LYSODREN).
Adrenocorticolytic agent; causes adrenal cortical necrosis and suppresses adrenal steroidogenesis, especially glucocorticoids and mineralocorticoids.
| Metabolism | Hepatic metabolism to o,p'-DDA (inactive) and other metabolites; undergoes enterohepatic circulation. |
| Excretion | Primarily renal excretion of metabolites; about 10% as unchanged drug. Biliary/fecal excretion accounts for <5%. |
| Half-life | 18-159 days; clinical context: during chronic therapy, steady-state may not be reached for 3-6 months. |
| Protein binding | >99% bound, primarily to low-density lipoproteins and albumin. |
| Volume of Distribution | Estimated 150-300 L/kg (due to extensive adipose tissue sequestration); clinical meaning: very large Vd indicates extensive tissue binding. |
| Bioavailability | Oral: 40-70% (variable due to first-pass metabolism and food effects). |
| Onset of Action | Oral: 2-4 weeks for clinical effect (adrenolytic); gradual onset. |
| Duration of Action | Prolonged, up to 4-6 weeks after cessation due to long half-life and slow elimination. |
Oral, initial dose 2-6 g/day divided in 3-4 doses, increase gradually to 8-10 g/day. Maximum dose 18 g/day.
| Dosage form | TABLET |
| Renal impairment | No specific dose adjustment recommended; monitor for toxicity due to potential accumulation of metabolites in severe renal impairment. |
| Liver impairment | Contraindicated in Child-Pugh class C; dose reduction or avoidance in Child-Pugh class B due to decreased clearance. |
| Pediatric use | Safety and efficacy not established in pediatric patients; not recommended. |
| Geriatric use | No specific dose adjustment; monitor for neurotoxicity and adrenal insufficiency due to age-related reduced tolerance. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for LYSODREN (LYSODREN).
| Breastfeeding | Excreted in breast milk; M/P ratio not established. Discontinue breastfeeding due to potential for serious adverse effects in infants. |
| Teratogenic Risk | FDA Pregnancy Category C. First trimester: Risk of fetal harm based on animal studies; no adequate human studies. Second/third trimesters: Potential for fetal adrenal suppression; mitotane is adrenolytic and may cause fetal adrenocortical insufficiency. |
| Fetal Monitoring |
■ FDA Black Box Warning
None.
| Serious Effects |
Hypersensitivity to mitotane or any component; adrenal cortical insufficiency (relative).
| Precautions | Adrenal insufficiency requiring corticosteroid replacement; neurotoxicity (CNS depression, visual disturbances); hemorrhagic cystitis; hepatotoxicity; gynecomastia; lipid abnormalities; fetal harm; carcinogenicity in rats. |
| Food/Dietary | Grapefruit and star fruit inhibit CYP3A4 and may increase mitotane toxicity; avoid these fruits. High-fat meals can increase mitotane absorption; take consistently with food to maintain stable levels. Avoid alcohol as it may exacerbate CNS depression. |
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| Monitor maternal adrenal function (serum cortisol, ACTH), liver enzymes, renal function, and thyroid function. Fetal monitoring with ultrasound for growth and development; assess for fetal adrenal suppression. |
| Fertility Effects | Can cause ovarian toxicity and impaired spermatogenesis; may reduce fertility. Reversibility not established. |
| Clinical Pearls |
| Mitotane is an adrenolytic agent that requires therapeutic drug monitoring targeting plasma levels of 14-20 mg/L. Initiate therapy gradually over 4-6 weeks to improve gastrointestinal tolerability. Concomitant use of glucocorticoid and mineralocorticoid replacement is mandatory due to adrenal insufficiency. Monitor thyroid function, liver enzymes, and lipid profile regularly. CNS toxicity (somnolence, ataxia, confusion) is dose-limiting and reversible upon dose reduction. |
| Patient Advice | Take LYSODREN with food to reduce nausea; split doses only if prescribed. · You must take replacement steroids (hydrocortisone and fludrocortisone) exactly as directed; never stop them abruptly. · Report severe dizziness, slurred speech, unsteady gait, or confusion immediately. · Avoid pregnancy during treatment and for at least 2 years after stopping; use reliable contraception. · Do not consume grapefruit or star fruit while on this medication. · Wear a medical alert bracelet indicating 'adrenal insufficiency' and 'mitotane therapy'. · Have your blood levels of mitotane checked regularly to ensure they are in the therapeutic range. |