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Warnings and Precautions

Itovebi has warnings and precautions for hyperglycemia, stomatitis, diarrhea, and embryo-fetal toxicity.

Hyperglycemia

Severe hyperglycemia can occur in patients treated with Itovebi.

Increased fasting glucose occurred in 85% of patients treated with Itovebi, including 22% of patients with Grade 2 (FPG > 160 to 250 mg/dL), 12% with Grade 3 (FPG > 250 to 500 mg/dL), and 0.6% with Grade 4 (FPG > 500 mg/dL) events.

In INAVO120, 46% (74/162) of patients who received Itovebi were treated with oral anti-hyperglycemic medications and 7% (11/162) were treated with insulin to manage increased fasting glucose. In patients who experienced increased fasting glucose of > 160 mg/dL, 96% (52/54) had an improvement in fasting glucose of at least one grade level with a median time to improvement from the first event of 8 days (range: 2 to 43 days). Among patients with hyperglycemia, the median time to first onset was 7 days (range: 2 to 955 days). Hyperglycemia led to dose interruption in 28%, to dose reduction in 2.5%, and to discontinuation of Itovebi in 1.2% of patients.

The safety of Itovebi in patients with Type 1 diabetes mellitus, or Type 2 diabetes mellitus requiring ongoing anti-hyperglycemic treatment have not been studied.

Before initiating treatment with Itovebi, test fasting glucose levels (FPG or FBG), HbA_1C levels, and optimize fasting glucose. After initiating treatment with Itovebi or in patients who experience hyperglycemia after initiating treatment with Itovebi, monitor or self-monitor fasting glucose levels once every 3 days for the first week (Day 1 to 7), then once every week for the next 3 weeks (Day 8 to 28), then once every 2 weeks for the next 8 weeks, then once every 4 weeks thereafter, and as clinically indicated. Monitor HbA_1C every 3 months and as clinically indicated.

Manage hyperglycemia with anti-hyperglycemic medications as clinically indicated. During treatment with anti-hyperglycemic medication, continue monitoring fasting glucose levels. Patients with a history of well-controlled Type 2 diabetes mellitus may require intensified anti-hyperglycemic treatment and close monitoring of fasting glucose levels.

Consider consultation with a healthcare professional experienced in the treatment of hyperglycemia, and initiation of fasting glucose monitoring at home for patients who have risk factors for hyperglycemia or who experience hyperglycemia. Advise patients of the signs and symptoms of hyperglycemia and counsel patients on lifestyle changes.

Based on the severity of the hyperglycemia, Itovebi may require dose interruption, reduction, or discontinuation.

Stomatitis

Severe stomatitis can occur in patients treated with Itovebi.

Stomatitis occurred in 51% of patients treated with Itovebi in combination with palbociclib and fulvestrant, including Grade 3 events in 6% of patients. The median time to first onset was 13 days (range: 1 to 610 days). Stomatitis led to interruption of Itovebi in 10%, to dose reduction in 3.7%, and to discontinuation of Itovebi in 0.6% of patients.

In patients who received Itovebi in combination with palbociclib and fulvestrant, 38% used a mouthwash containing corticosteroid for management or prophylaxis of stomatitis.

Monitor patients for signs and symptoms of stomatitis. Withhold, reduce dose, or permanently discontinue Itovebi based on severity.

Diarrhea

Severe diarrhea, including dehydration and acute kidney injury, can occur in patients treated with Itovebi.

Diarrhea occurred in 48% of patients treated with Itovebi in combination with palbociclib and fulvestrant; including Grade 3 events in 3.7% of patients. The median time to first onset was 15 days (range: 2 to 602 days). Anti-diarrheal medicines were used in 28% (46/162) of patients who received Itovebi in combination with palbociclib and fulvestrant to manage symptoms. Dose interruptions were required in 7% of patients, and dose reductions occurred in 1.2%.

Monitor patients for signs and symptoms of diarrhea. Advise patients to increase oral fluids and start anti-diarrheal treatment at the first sign of diarrhea while taking Itovebi. Withhold, reduce dose, or permanently discontinue Itovebi based on severity.

Embryo-Fetal Toxicity

Based on findings in animals and its mechanism of action, Itovebi can cause fetal harm when administered to a pregnant woman. In an animal reproduction study, oral administration of inavolisib to pregnant rats during the period of organogenesis caused adverse developmental outcomes, including embryo-fetal mortality, structural abnormalities, and alterations to growth at maternal exposures approximately equivalent to the human exposure at the recommended dose of 9 mg/day based on area under the curve (AUC).

Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective non-hormonal contraception during treatment with Itovebi and for 1 week after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with Itovebi and for 1 week after the last dose.

Most Common Adverse Reactions

The most common (≥ 20%) adverse reactions, including laboratory abnormalities, were decreased neutrophils, decreased hemoglobin, increased fasting glucose, decreased platelets, decreased lymphocytes, stomatitis, diarrhea, decreased calcium, fatigue, decreased potassium, increased creatinine, increased ALT, nausea, decreased sodium, decreased magnesium, rash, decreased appetite, COVID-19 infection, and headache.

You may report side effects to the FDA at (800) FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Genentech at (888) 835-2555.

Please see the full Prescribing Information for additional Important Safety Information.