Dose modification and management for hyperglycemia with alpelisib

FPG/Fasting blood glucose values*	Recommendation
Dose modifications and management should only be based on fasting glucose values (FPG or fasting blood glucose)
Grade 1 Fasting glucose >ULN –160 mg/dL or >ULN –8.9 mmol/L	No alpelisib dose adjustment required. Initiate or intensify antihyperglycemic treatment^¶
Grade 2 Fasting glucose >160 to 250 mg/dL or >8.9 to 13.9 mmol/L	No alpelisib dose adjustment required. Initiate or intensify antihyperglycemic treatment.^¶ If fasting glucose does not decrease to ≤160 mg/dL or 8.9 mmol/L within 21 days under appropriate antihyperglycemic treatment^¶^Δ, reduce alpelisib dose by 1 dose level and follow fasting glucose value-specific recommendations.
Grade 3 >250 to 500 mg/dL or >13.9 to 27.8 mmol/L	Interrupt alpelisib. Initiate or intensify oral antihyperglycemic treatment^¶ and consider additional antihyperglycemic medications^Δ for 1 to 2 days until hyperglycemia improves, as clinically indicated. Administer intravenous hydration and consider appropriate treatment (eg, intervention for electrolyte/ketoacidosis/hyperosmolar disturbances). If fasting glucose decreases to ≤160 mg/dL or 8.9 mmol/L within 3 to 5 days under appropriate antihyperglycemic treatment, resume alpelisib at 1 lower dose level. If fasting glucose does not decrease to ≤160 mg/dL or 8.9 mmol/L within 3 to 5 days under appropriate antihyperglycemic treatment, consultation with a clinician with expertise in the treatment of hyperglycemia is recommended. If fasting glucose does not decrease to ≤160 mg/dL or 8.9 mmol/L within 21 days following appropriate antihyperglycemic treatment^¶^Δ, permanently discontinue alpelisib treatment.
Grade 4 >500 mg/dL or ≥27.8 mmol/L	Interrupt alpelisib. Initiate or intensify appropriate antihyperglycemic treatment^¶^Δ (administer intravenous hydration and consider appropriate treatment [eg, intervention for electrolyte/ketoacidosis/hyperosmolar disturbances]), recheck fasting glucose within 24 hours and as clinically indicated. If fasting glucose decreases to ≤500 mg/dL or 27.8 mmol/L, follow fasting glucose value-specific recommendations for grade 3. If fasting glucose is confirmed at >500 mg/dL or 27.8 mmol/L, permanently discontinue alpelisib treatment.

FPG: fasting plasma glucose; ULN: upper limit of normal; CTCAE: Common Terminology Criteria for Adverse Events.
* FPG/fasting blood glucose/grade levels reflect hyperglycemia grading according to CTCAE Version 4.03.
¶ Initiate applicable antihyperglycemic medications, including metformin, SGLT2 inhibitors, or insulin sensitizers (such as thiazolidinediones or dipeptidyl peptidase-4 inhibitors), and review respective prescribing information for dosing and dose titration recommendations, including local hyperglycemic treatment guidelines. Metformin was recommended in the SOLAR-1 trial with the following guidance: Initiate metformin 500 mg once daily. Based on tolerability, metformin dose may be increased to 500 mg twice daily, followed by 500 mg with breakfast, and 1000 mg with dinner, followed by further increase to 1000 mg twice daily if needed.
Δ As recommended in the SOLAR-1 trial, insulin may be used for 1 to 2 days until hyperglycemia resolves. However, this may not be necessary in the majority of alpelisib-induced hyperglycemia, given the short half-life of alpelisib and the expectation of glucose levels normalizing after interruption of alpelisib.

Reproduced from: Alpelisib tablets. United States Prescribing Information. US National Library of Medicine. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/212526Orig1s004lbl.pdf (Accessed on July 23, 2021).

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Dose modification and management for hyperglycemia with alpelisib