Selumetinib Dosage Adjustments for Adverse Reactions
If intolerance persists after two dose reductions, permanently discontinue.
Dose Reduction Scheme Based on BSA
BSA 0.55–0.69 m²: First reduction to 10 mg twice daily; second reduction to 10 mg once daily.
BSA 0.7–0.89 m²: First reduction to 20 mg in the morning + 10 mg in the evening; second reduction to 10 mg twice daily.
BSA 0.9–1.09 m²: First reduction to 25 mg in the morning + 10 mg in the evening; second reduction to 10 mg twice daily.
BSA 1.1–1.29 m²: First reduction to 25 mg in the morning + 20 mg in the evening; second reduction to 20 mg in the morning + 10 mg in the evening.
BSA 1.3–1.49 m²: First reduction to 25 mg twice daily; second reduction to 25 mg in the morning + 10 mg in the evening.
BSA 1.5–1.69 m²: First reduction to 30 mg twice daily; second reduction to 25 mg in the morning + 20 mg in the evening.
BSA 1.7–1.89 m²: First reduction to 35 mg in the morning + 30 mg in the evening; second reduction to 25 mg in the morning + 20 mg in the evening.
BSA ≥1.9 m²: First reduction to 35 mg twice daily; second reduction to 25 mg twice daily.
Selumetinib Dosage Adjustments for Hepatic Impairment
Mild (Child-Pugh A): No adjustment needed.
Moderate (Child-Pugh B): Starting dose reduced to 20 mg/m² twice daily. Specific doses as follows:
BSA 0.55–0.69 m²: 10 mg twice daily.
BSA 0.7–0.89 m²: 20 mg in the morning + 10 mg in the evening.
BSA 0.9–1.09 m²: 20 mg twice daily.
BSA 1.1–1.29 m²: 25 mg twice daily.
BSA 1.3–1.49 m²: 30 mg in the morning + 25 mg in the evening.
BSA 1.5–1.69 m²: 35 mg in the morning + 30 mg in the evening.
BSA 1.7–1.89 m²: 35 mg twice daily.
BSA ≥1.9 m²: 40 mg twice daily.
Severe (Child-Pugh C): Dose unknown or not specified.
Management of Specific Adverse Reactions to Selumetinib
1. Cardiomyopathy
Asymptomatic decrease in left ventricular ejection fraction (LVEF) ≥10% and below the lower limit of normal: Withhold until recovery, then resume at a reduced dose.
Symptomatic LVEF decline or Grade 3/4 LVEF decline: Permanently discontinue.
2. Ocular Toxicity
Retinal pigment epithelial detachment (RPED): Withhold until recovery, then resume at a reduced dose.
Retinal vein occlusion (RVO): Permanently discontinue.
3. Gastrointestinal Toxicity
Grade 3 diarrhea: Withhold until improvement to Grade 0/1, then resume at the same dose; if no improvement within 3 days, permanently discontinue.
Grade 4 diarrhea or Grade 3/4 colitis: Permanently discontinue.
4. Skin Toxicity
Grade 3/4 rash: Withhold until improvement, then resume at a reduced dose.
5. Creatine Phosphokinase (CPK) Elevation
Grade 4 CPK elevation: Withhold until improvement to Grade 0/1, then resume at a reduced dose; if no improvement within 3 weeks, permanently discontinue.
CPK elevation with myalgia: Withhold until improvement to Grade 0/1, then resume at a reduced dose; if no improvement within 3 weeks, permanently discontinue.
Rhabdomyolysis: Permanently discontinue.
6. Other Adverse Reactions
Intolerable Grade 2 or Grade 3: Withhold until improvement to Grade 0/1, then resume at a reduced dose.
Grade 4: Withhold until improvement to Grade 0/1, then resume at a reduced dose, and consider permanent discontinuation.
