Alpelisib (Piqray) is a phosphatidylinositol-3-kinase (PI3K) inhibitor administered orally, and strict adherence to dosage adjustments and adverse reaction monitoring is required.

Precautions for the Administration of Alpelisib (Piqray)

Administration Regimen and Pretreatment

(1) Dosage and Administration: The recommended dosage for adult patients is 250 mg taken orally once daily.

(2) Management of Missed Doses: If a dose is missed, it should be taken within 9 hours before the next scheduled dose; if more than 9 hours have passed, skip the missed dose and take the next dose at the originally planned time. Do not make up for the missed dose after vomiting.

Contraindications

Absolute Contraindication: Contraindicated in patients with a severe allergy to alpelisib.

High-Risk Populations

(1) Hepatic Impairment: For patients with moderate to severe hepatic impairment (Child-Pugh B/C), the dosage needs to be reduced to 200 mg per day.

(2) Pregnancy: Alpelisib has embryotoxicity, and contraceptive measures must be taken during treatment and within 1 week after drug discontinuation.

Hyperglycemia

(1) Monitoring Requirements: Measure fasting blood glucose and HbA1c before treatment; monitor fasting blood glucose weekly for the first month of treatment, and at least once a month thereafter.

(2) Management Measures:

Fasting blood glucose > 160 mg/dL: Initiate or optimize glucose-lowering therapy.

Fasting blood glucose > 250 mg/dL: Withhold the drug and administer intravenous fluid replacement.

Fasting blood glucose > 500 mg/dL: Discontinue the drug permanently.

Severe Cutaneous Reactions

(1) These include Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN).

(2) If suspected symptoms occur, interrupt treatment immediately; discontinue the drug permanently if the diagnosis is confirmed.

Diarrhea

(1) Grade 2 diarrhea: Withhold the drug until symptoms resolve to Grade ≤ 1.

(2) Grade 3 diarrhea: Withhold the drug, and resume treatment at a reduced dosage of 250 mg per day once symptoms improve.

(3) Grade 4 diarrhea: Discontinue the drug permanently.

Principles of Dosage Adjustment

Toxicity-Based Adjustment

(1) First Dose Reduction: 250 mg per day.

(2) Second Dose Reduction: 200 mg per day.

(3) Indications for Permanent Discontinuation: Intolerance to 200 mg per day or occurrence of Grade 4 toxicity.

Drug Interactions

(1) Strong CYP3A4 Inducers: Avoid concurrent use (e.g., rifampicin).

(2) BCRP Inhibitors: May increase alpelisib exposure; monitor for adverse reactions.

(3) CYP2C9 Substrates: May reduce the efficacy of drugs such as warfarin.

Key Points for Patient Monitoring of Alpelisib (Piqray)

Baseline Assessment

(1) Confirm the PIK3CA mutation status.

(2) Measure fasting blood glucose and assess liver and renal function.

(3) Evaluate skin conditions.

Monitoring During Treatment

(1) Adjust the frequency of blood glucose monitoring based on the grade of hyperglycemia.

(2) Regularly assess skin and mucosal conditions.

(3) Monitor changes in body weight and nutritional status.

Patient Education

(1) Instruct patients to recognize symptoms of hyperglycemia and cutaneous reactions.

(2) Provide a management plan for diarrhea.

(3) Advise patients to avoid grapefruit and St. John's Wort.

(4) Emphasize the requirement for strict contraception.