Management of Adverse Effects of Mitotane in Medical Personnel
1. Overall Adverse Events
Common adverse reactions with an incidence ≥15%: anorexia, nausea, vomiting, diarrhea, depression, dizziness, vertigo, and rash.
2. Cardiovascular System
Reported: hypertension, orthostatic hypotension, flushing.
3. Skin
Very common (≥10%): rash.
Reported: pruritus.
4. Endocrine System
Very common (≥10%): adrenal insufficiency (incidence up to 100%).
Common (1%-10%): decreased androstenedione, decreased testosterone in females, increased sex hormone-binding globulin (SHBG) in both sexes, decreased free testosterone in males, gynecomastia.
Reported: male hypogonadism (symptoms include gynecomastia, decreased libido, erectile dysfunction, fertility impairment), hypothyroidism/thyroid damage.
Note in pediatric patients: possible estrogen-like effects such as gynecomastia in males, breast development in females, and/or vaginal bleeding.
5. Gastrointestinal System
Very common (≥10%): diarrhea (up to 80%), nausea (up to 80%), vomiting (up to 80%), upper abdominal discomfort (≥10%), stomatitis/mucositis (≥10%).
Reported: dysgeusia, dyspepsia, hypersalivation.
6. Genitourinary System
Reported: proteinuria, hematuria, hemorrhagic cystitis, non‑malignant ovarian giant cysts (may be accompanied by pelvic pain, bleeding, etc.).
7. Hematologic System
Very common (≥10%): prolonged bleeding time (up to 90%), leukopenia/neutropenia (up to 12%).
Common (1%-10%): anemia, thrombocytopenia.
8. Hepatobiliary System
Very common (≥10%): elevated liver enzymes (≥10%, including gamma‑glutamyl transferase (γ‑GT), transaminases, alkaline phosphatase).
Common (1%-10%): autoimmune hepatitis.
Reported: liver injury (including hepatocellular, cholestatic, and mixed hepatitis).
9. Hypersensitivity
Reported: hypersensitivity reactions.
10. Metabolic
Very common (≥10%): anorexia (up to 80%), elevated plasma cholesterol/hypercholesterolemia (≥10%), elevated plasma triglycerides/hypertriglyceridemia (≥10%).
Reported: decreased blood uric acid/hypouricemia.
11. Musculoskeletal
Very common (≥10%): muscle weakness.
12. Nervous System
Very common (≥10%): dizziness (up to 40%), vertigo (up to 40%), ataxia (≥10%), paresthesia (≥10%), somnolence (≥10%).
Common (1%-10%): psychiatric disorders (e.g., confusion, depression), polyneuropathy, movement disorders, headache.
Reported: balance disorders, memory deficits, central vestibular syndrome, dysarthria, parkinsonism, encephalopathy, delayed neuropsychological development (pediatric).
Note: neurological adverse reactions occur in about 40% of patients; they are usually reversible after drug discontinuation and decrease in blood concentrations. Anorexia may be an early sign of central nervous system impairment.
13. Ocular
Common (1%-10%): maculopathy.
Reported: blurred vision, diplopia, lens opacities, toxic retinopathy, visual disturbances.
14. Psychiatric System
Very common (≥10%): depression (up to 40%), confusion (≥10%).
Reported: aggressive behavior.
15. Others
Common (1%-10%): growth retardation (pediatric).
Reported: fatigue/asthenia, general malaise, fever, opportunistic fungal infections.
