Itovebi

2 DOSAGE AND ADMINISTRATION Select patients for the treatment of HR-positive, HER2-negative, locally advanced or metastatic breast cancer with ITOVEBI based on the presence of one or more PIK3CA mutations in plasma specimen. ( 2.1 ) Recommended dosage: 9 mg orally once daily with or without food. ( 2.3 ) See Full Prescribing Information for dosage modifications of ITOVEBI due to adverse reactions. ( 2.4 ) Reduce the starting dose in patients with moderate renal impairment. ( 2.5 ) 2.1 Patient Selection Select patients for the treatment of HR-positive, HER2-negative, locally advanced or metastatic breast cancer with ITOVEBI based on the presence of one or more PIK3CA mutations in plasma specimens [see Clinical Studies (14.1) ] . Information on FDA-approved tests for the detection of PIK3CA mutations in breast cancer is available at: http://www.fda.gov/companiondiagnostics. 2.2 Recommended Evaluation Before Initiating ITOVEBI Evaluate fasting plasma glucose (FPG)/blood glucose (FBG) and hemoglobin A 1C (HbA 1C ) and optimize blood glucose prior to starting ITOVEBI and at regular intervals during treatment [see Warnings and Precautions (5.1) ]. 2.3 Recommended Dosage The recommended dosage of ITOVEBI is 9 mg taken orally once daily, with or without food, until disease progression or unacceptable toxicity. Advise patients to take ITOVEBI at approximately the same time each day. Swallow ITOVEBI tablet(s) whole. Do not chew, crush, or split prior to swallowing. If a patient misses a dose, instruct the patient to take the missed dose as soon as possible within 9 hours. After more than 9 hours, instruct the patient to skip the dose and take the next dose at the scheduled time. If a patient vomits a dose, instruct patients not to take an additional dose on that day and resume the usual dosing schedule the next day. Administer ITOVEBI in combination with palbociclib and fulvestrant. The recommended dosage of palbociclib is 125 mg taken orally once daily for 21 consecutive days followed by 7 days off treatment to comprise a cycle of 28 days. Refer to the Full Prescribing Information for palbociclib and fulvestrant for dosing information. For premenopausal and perimenopausal women, administer a luteinizing hormone-releasing hormone (LHRH) agonist in accordance with local clinical practice. For men, consider administering an LHRH agonist in accordance with local clinical practice. 2.4 Dosage Modifications for Adverse Reactions The recommended dose reduction levels of ITOVEBI for adverse reactions are listed in Table 1 . Permanently discontinue ITOVEBI if patients are unable to tolerate the second dose reduction. Table 1: Dose Reduction for Adverse Reactions Dose Level Dose and Schedule Recommended starting dose 9 mg daily First dose reduction 6 mg daily Second dose reduction 3 mg daily The recommended dosage modifications of ITOVEBI for adverse reactions are summarized in Table 2 . Table 2: Recommended Dosage Modifications for Adverse Reactions Adverse Reaction Severity Dosage Modification Hyperglycemia Before initiating treatment with ITOVEBI, test FPG or FBG, and HbA 1C levels, and optimize plasma/blood glucose levels in all patients. After initiating treatment with ITOVEBI, monitor FPG or FBG levels based on the recommended schedule, and as clinically indicated [see Warnings and Precautions (5.1) ]. [see Warnings and Precautions (5.1) ] Fasting glucose levels (FPG or FBG) > ULN to 160 mg/dL (> ULN – 8.9 mmol/L) No adjustment of ITOVEBI required. Consider dietary modifications and ensure adequate hydration. Initiate or intensify oral anti-hyperglycemic medications for patients with risk factors for hyperglycemia. Fasting glucose levels > 160 to 250 mg/dL (> 8.9 – 13.9 mmol/L) Withhold ITOVEBI until FPG or FBG ≤ 160 mg/dL (≤ 8.9 mmol/L). Initiate or intensify anti-hyperglycemic medications. Resume ITOVEBI at the same dose level. If FPG or FBG persists > 200 – 250 mg/dL (> 11.1 – 13.9 mmol/L) for 7 days under appropriate anti-hyperglycemic treatment, consider consultation with a healthcare professional experienced in the treatment of hyperglycemia. Fasting glucose levels > 250 to 500 mg/dL (> 13.9 – 27.8 mmol/L) Withhold ITOVEBI. Initiate or intensify anti-hyperglycemic medications. Administer appropriate hydration if required. If FPG or FBG decreases to ≤ 160 mg/dL (≤ 8.9 mmol/L) within 7 days, resume ITOVEBI at the same dose level. If FPG or FBG decreases to ≤ 160 mg/dL (≤ 8.9 mmol/L) in ≥ 8 days, resume ITOVEBI at one lower dose level. If FPG or FBG > 250 to 500 mg/dL (> 13.9 – 27.8 mmol/L) recurs within 30 days, withhold ITOVEBI until FPG or FBG decreases to ≤ 160 mg/dL (≤ 8.9 mmol/L). Resume ITOVEBI at one lower dose level. Fasting glucose levels > 500 mg/dL (> 27.8 mmol/L) Withhold ITOVEBI. Initiate or intensify anti-hyperglycemic medications. Assess for volume depletion and ketosis and administer appropriate hydration. If FPG or FBG decreases to ≤ 160 mg/dL (≤ 8.9 mmol/L), resume ITOVEBI at one lower dose level. If FPG or FBG > 500 mg/dL (> 27.8 mmol/L) recurs within 30 days, permanently discontinue ITOVEBI. Stomatitis [see Warnings and Precautions (5.2) ] Grade 1 Based on CTCAE version 5.0. No adjustment of ITOVEBI required. Initiate or intensify appropriate medical therapy (e.g., corticosteroid-containing mouthwash) as clinically indicated. Grade 2 Withhold ITOVEBI until recovery to Grade ≤ 1. Initiate or intensify appropriate medical therapy. Resume ITOVEBI at the same dose level. For recurrent Grade 2 stomatitis, withhold ITOVEBI until recovery to Grade ≤ 1, then resume ITOVEBI at one lower dose level. Grade 3 Withhold ITOVEBI until recovery to Grade ≤ 1. Initiate or intensify appropriate medical therapy. Resume ITOVEBI at one lower dose level. Grade 4 Permanently discontinue ITOVEBI. Diarrhea [see Warnings and Precautions (5.3) ] Grade 1 No adjustment of ITOVEBI required. Initiate appropriate medical therapy and monitor as clinically indicated. Grade 2 Withhold ITOVEBI until recovery to Grade ≤ 1, then resume ITOVEBI at the same dose level. Initiate or intensify appropriate medical therapy and monitor as clinically indicated. For recurrent Grade 2 diarrhea, withhold ITOVEBI until recovery to Grade ≤ 1, then resume ITOVEBI at one lower dose level. Grade 3 Withhold ITOVEBI until recovery to Grade ≤ 1, then resume ITOVEBI at one lower dose level. Initiate or intensify appropriate medical therapy and monitor as clinically indicated. Grade 4 Permanently discontinue ITOVEBI. Hematologic Toxicities [see Adverse Reactions (6.1) ] Grade 1, 2, or 3 No adjustment of ITOVEBI required. Monitor complete blood count and for signs or symptoms of hematologic toxicities as clinically indicated. Grade 4 Withhold ITOVEBI until recovery to Grade ≤ 2. Resume ITOVEBI at the same dose level or reduce to one lower dose level as clinically indicated. Other Adverse Reactions [see Adverse Reactions (6.1) ] Grade 1 No adjustment of ITOVEBI required. Grade 2 Consider withholding ITOVEBI, if clinically indicated, until recovery to Grade ≤ 1. Resume ITOVEBI at the same dose level. Grade 3 (first event) Withhold ITOVEBI until recovery to Grade ≤ 1. Resume ITOVEBI at the same dose level or one lower dose level based on clinical evaluation. Grade 3 (recurrent) Withhold ITOVEBI until recovery to Grade ≤ 1. Resume ITOVEBI at one lower dose level. Grade 4 Permanently discontinue ITOVEBI. 2.5 Dosage Modification for Moderate Renal Impairment The recommended starting dosage of ITOVEBI for patients with moderate renal impairment (eGFR 30 to < 60 mL/min based on CKD-EPI) is 6 mg orally once daily [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3) ] .

See official label

1 INDICATIONS AND USAGE ITOVEBI, in combination with palbociclib and fulvestrant, is indicated for the treatment of adults with endocrine-resistant, PIK3CA -mutated, hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, locally advanced or metastatic breast cancer, as detected by an FDA-approved test, following recurrence on or after completing adjuvant endocrine therapy [see Clinical Studies (14.1) ] .