• Monitor for signs and symptoms of hypersensitivity reactions (dyspnea, flushing, rash, fever, tachycardia) during therapy. If symptoms occur, permanently discontinue alpelisib.
• Assess for severe cutaneous adverse reactions including SJS, EM, TEN, and DRESS (prodrome of fever, flu-like symptoms, mucosal lesions, progressive skin rash) during therapy. If rash is Grade 1 (< 10% body surface area [BSA] with active skin toxicity); No dose adjustment needed. Initiate topical corticosteroid treatment. Consider adding oral antihistamine to manage symptoms. If rash is not improved within 28 days of treatment, add a low dose systemic corticosteroid. If the cause is SJS, EM, TEN, or DRESS, permanently discontinue alpelisib. If Grade 2 (10-30% BSA with active skin toxicity); No dose adjustment necessary. Initiate or intensify topical corticosteroid and oral antihistamines. Consider low dose systemic corticosteroid treatment. If rash improves to Grade ≤ 1 within 10 days, systemic corticosteroid may be discontinued. If the cause is SJS, EM, TEN, or DRESS, permanently discontinue alpelisib. If Grade 3 (severe rash not responsive to medical management and >30% BSA with active skin toxicity): Hold alpelisib. Initiate or intensify topical/systemic corticosteroid and oral antihistamines. If the cause is SJS, EM, TEN, or DRESS, permanently discontinue alpelisib. If the etiology is not SJS, EM, TEN, or DRESS, hold dose until improvement to Grade ≤ 1, then resume alpelisib at next lower dose. If Grade 4 (severe bullous, blistering or exfoliating skin conditions and any % BSA associated with extensive superinfection, with IV antibiotics indicated; life-threatening): Permanently discontinue alpelisib.
• Monitor for signs and symptoms of pneumonitis (hypoxia, cough, dyspnea, interstitial infiltrates) during therapy. If pneumonitis is confirmed, discontinue alpelisib permanently.
• Monitor for signs and symptoms of diarrhea and colitis (abdominal pain, mucus or blood in stool) during therapy. If Grade 1 diarrhea occurs, do not adjust alpelisib dose. Start antidiarrheal therapy and monitor symptoms. If Grade 2 diarrhea occurs, start or intensify antidiarrheal therapy and monitor symptoms. May add enteric-acting and/or systemic steroids to therapy for Grade 2 or Grade 3 colitis. Hold alpelisib until recovery to Grade ≤1, then resume at same dose. If Grade 3 diarrhea occurs, start or intensify antidiarrheal therapy and monitor symptoms. Hold alpelisib until recovery to Grade ≤1, then resume at the next lower dose. If Grade 4 diarrhea occurs, permanently discontinue alpelisib.

Lab Test Considerations:

• Verify negative pregnancy test before starting therapy.Information on FDA approved tests for the detection of PIK3CA mutations in breast cancer is available at: http://www.fda.gov/CompanionDiagnostics.
  • May cause hyperglycemia. Before starting alpelisib therapy, test fasting blood glucose (FBG) and HbA1c; optimize blood glucose. After starting therapy, monitor blood glucose at least weekly for first 2 wk, then at least once every 4 wk, and as indicated. Monitor HbA1c every 3 mo and as indicated. If hyperglycemia develops, monitor FBG at least twice weekly until FBG decreases to normal. During treatment with anti-diabetic agents, continue monitoring FBG at least weekly for 8 wk, then once every 2 wk and as needed clinically. If Grade 1 FBG >ULN-160 mg/dL, No dose adjustment needed. Begin or intensify anti-diabetic treatment. If Grade 2 FBG >160-250 mg/dL: No dose adjustment needed. Begin or further intensify anti-diabetic therapy. If FBG does not decrease to ≤ 160 mg/dL within 21 days, reduce alpelisib dose by 1 dose level and follow FBG value recommendations. If Grade 3 >250-500 mg/dL, Hold alpelisib. Begin or intensify oral anti-diabetic therapy and consider additional anti-diabetic agents for 1-2 days until hyperglycemia improves. Administer intravenous hydration and consider added intervention for electrolyte/ketoacidosis/hyperosmolar disturbances). If FBG decreases to ≤160 mg/dL within 3 to 5 days under appropriate anti-diabetic therapy, resume alpelisib at 1 lower dose level. If FBG does not decrease to ≤160 mg/dL within 3 to 5 days under appropriate anti-diabetic therapy, consult with a specialist in the treatment of hyperglycemia. If FBG does not decrease to ≤160 mg/dL within 21 days following appropriate anti-diabetic therapy, permanently discontinue alpelisib. If Grade 4 >500 m g/dL: Hold alpelisib. Begin or intensify appropriate anti-diabetic therapy (administer intravenous hydration and consider appropriate intervention for electrolyte/ketoacidosis/hyperosmolar disturbances), recheck FBG within 24 hr and as indicated. If FBG decreases to ≤500 mg/dL, follow FBG recommendations for Grade 3. If FBG is confirmed at >500 m g/dL, discontinue alpelisib permanently.