Table 1. Alpelisib Dose Adjustments for Hyperglycemia.
| Grade | Fasting blood glucose | Dosage adjustments |
|---|---|---|
| 1 | FPG > ULN to 160 mg/dL | • No alpelisib dosage adjustment required; initiate or intensify antidiabetic therapy |
| 2 | FPG > 160 to 250 mg/dL | • No alpelisib dosage adjustment required; initiate or intensify antidiabetic therapy as described below |
| • If FPG does not decrease to ≤ 160 mg/dL within 21 days with appropriate antidiabetic therapy, reduce alpelisib dose by one dose level and continue to follow FPG-specific recommendations | ||
| 3 | FPG > 250 to 500 mg/dL | • Interrupt alpelisib therapy |
| • Initiate or intensify antidiabetic therapy; may consider additional antidiabetic medications for 1 to 2 days until hyperglycemia improves | ||
| • Administer IV hydration and consider appropriate intervention for electrolyte, ketoacidosis, hyperosmolar disturbances | ||
| • If FPG decreases to ≤160 mg/dL within 3 to 5 days with appropriate antidiabetic therapy, resume alpelisib with the dose reduced by one dose level | ||
| • If FPG does not decrease to ≤160 mg/dL within 3 to 5 days with appropriate antidiabetic therapy, consultation with a clinician with expertise in hyperglycemia management is recommended. Permanently discontinue alpelisib if FPG does not decrease to ≤ 160 mg/dL within 21 days following appropriate antidiabetic therapy | ||
| 4 | FPG > 500 mg/dL | • Interrupt alpelisib therapy |
| • Initiate or intensify antidiabetic therapy | ||
| • Administer IV hydration and consider appropriate intervention for electrolyte, ketoacidosis, hyperosmolar disturbances | ||
| • Recheck FPG within 24 hours (and as clinically indicated). If FPG decreases to ≤ 500 mg/dL, follow FPG value-specific recommendations for grade 3 hyperglycemia | ||
| • Permanently discontinue alpelisib if FPG is confirmed at > 500 mg/dL |
Note. Metformin recommendations: Initiate metformin at 500 mg once daily; based on tolerance, may increase to 500 mg twice daily (with meals), and further increase to 500 mg with breakfast and 1,000 mg with dinner, followed by a further increase to 1,000 mg twice daily (with meals). FBG = fasting blood glucose; ULN = upper limit of normal. Information from Novartis Pharmaceuticals Corporation (2019).