Version July 2025
Dosage guidance:
Safety: Optimize fasting glucose prior to treatment initiation. Patients with a history of well-controlled type 2 diabetes mellitus may require intensified antihyperglycemic treatment and close monitoring. For patients with hyperglycemia (or are at risk for hyperglycemia), consider consultation with a health care professional experienced in hyperglycemia management.
Clinical considerations: For pre- and perimenopausal patients, administer a luteinizing hormone–releasing hormone (LHRH) agonist in accordance with local clinical practice; for males, consider administering an LHRH agonist in accordance with local practice.
Breast cancer, locally advanced or metastatic, endocrine resistant, hormone receptor positive, HER2 negative, PIK3CA mutated: Oral: 9 mg once daily (in combination with palbociclib and fulvestrant); continue until disease progression or unacceptable toxicity.
Missed dose: If a dose is missed, administer the missed dose as soon as possible within 9 hours. After >9 hours, skip the missed dose and administer the next dose at the scheduled time. If a dose is vomited, do not administer a replacement dose on that day; resume the usual dosing schedule the next day.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Altered kidney function prior to treatment initiation:
Note: Kidney function estimated with Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.
eGFR ≥60 mL/minute: No dosage adjustment recommended.
eGFR 30 to <60 mL/minute: Reduce initial dose to 6 mg once daily.
eGFR <30 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Altered liver function prior to treatment initiation:
Mild hepatic impairment (total bilirubin > ULN to ≤1.5 times ULN or AST > ULN and total bilirubin ≤ ULN): There are no dosage adjustments provided in the manufacturer's labeling; however, there were no clinically significant differences in inavolisib pharmacokinetics in patients with mild hepatic impairment.
Moderate or severe hepatic impairment: There are no dosage adjustments provided in the manufacturer's labeling (effect of moderate or severe hepatic impairment on inavolisib pharmacokinetics is unknown).
Note: Other concomitant anticancer therapies may also require treatment interruption, dosage reduction, and/or discontinuation.
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Usual (initial) dose |
9 mg once daily |
|
First dose reduction level |
6 mg once daily |
|
Second dose reduction level |
3 mg once daily |
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If unable to tolerate the second dose reduction level, permanently discontinue inavolisib. | |
|
Adverse reaction |
Severity |
Inavolisib dosage modification |
|---|---|---|
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a FPG = fasting plasma glucose; FBG = fasting blood glucose. | ||
|
Hematologic toxicities |
Grade 1, 2, or 3 |
No inavolisib dosage adjustment required. Monitor CBC and for signs/symptoms of hematologic toxicities as indicated. |
|
Grade 4 |
Withhold inavolisib until recovery to ≤ grade 2; then resume inavolisib at the same dose level or reduce by 1 dose level as clinically indicated. | |
|
GI toxicity: Diarrhea |
Advise patients to increase oral fluids and start antidiarrheal treatment at the first sign of diarrhea. | |
|
Grade 1 |
No inavolisib dosage adjustment required. Initiate appropriate medical management and monitor as clinically indicated. | |
|
Grade 2 |
Withhold inavolisib until recovery to ≤ grade 1, then resume inavolisib at the same dose level. Initiate or intensify appropriate medical therapy and monitor as clinically indicated. Recurrence: For recurrent grade 2 diarrhea, withhold inavolisib until recovery to ≤ grade 1, then resume inavolisib with the dose reduced by 1 dose level. | |
|
Grade 3 |
Withhold inavolisib until recovery to ≤ grade 1, then resume inavolisib with the dose reduced by 1 dose level. Initiate or intensify appropriate medical therapy and monitor as clinically indicated. | |
|
Grade 4 |
Permanently discontinue inavolisib. | |
|
GI toxicity: Stomatitis |
Grade 1 |
No inavolisib dosage adjustment required. Initiate or intensify appropriate medical therapy (eg, corticosteroid-containing mouthwash). |
|
Grade 2 |
Withhold inavolisib until recovery to ≤ grade 1, then resume inavolisib at the same dose level. Initiate or intensify appropriate medical therapy. Recurrence: For recurrent grade 2 stomatitis, withhold inavolisib until recovery to ≤ grade 1, then resume inavolisib with the dose reduced by 1 dose level. | |
|
Grade 3 |
Withhold inavolisib until recovery to ≤ grade 1, then resume inavolisib with the dose reduced by 1 dose level. Initiate or intensify appropriate medical therapy. | |
|
Grade 4 |
Permanently discontinue inavolisib. | |
|
Hyperglycemia |
Fasting glucose levels (FPG or FBG) > ULN to 160 mg/dL (> ULN to 8.9 mmol/L) |
No inavolisib dosage adjustment required. Consider dietary modifications and ensure adequate hydration. Initiate or intensify oral antihyperglycemic medications for patients with risk factors for hyperglycemia. |
|
Fasting glucose levels (FPG or FBG) >160 to 250 mg/dL (>8.9 to 13.9 mmol/L) |
Withhold inavolisib until FPG or FBG ≤160 mg/dL (≤8.9 mmol/L). Initiate or intensify antihyperglycemic medications. Resume inavolisib at the same dose level. If FPG or FBG persists >200 to 250 mg/dL (>11.1 to 13.9 mmol/L) for 7 days under appropriate antihyperglycemic therapy, consider consultation with a health care professional experienced in hyperglycemia management. | |
|
Fasting glucose levels (FPG or FBG) >250 to 500 mg/dL (>13.9 to 27.8 mmol/L) |
Withhold inavolisib. Initiate or intensify antihyperglycemic medications. Administer appropriate hydration if required. If FPG or FBG decreases to ≤160 mg/dL (≤8.9 mmol/L) within 7 days, resume inavolisib at the same dose level. If FPG or FBG decreases to ≤160 mg/dL (≤8.9 mmol/L) in ≥8 days, resume inavolisib with the dose reduced by 1 dose level. Recurrence: If FPG or FBG >250 to 500 mg/dL (>13.9 to 27.8 mmol/L) recurs within 30 days, withhold inavolisib until FPG or FBG decreases to ≤160 mg/dL (≤8.9 mmol/L), resume inavolisib with the dose reduced by 1 dose level. | |
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Fasting glucose levels (FPG or FBG) >500 mg/dL (>27.8 mmol/L) |
Withhold inavolisib. Initiate or intensify antihyperglycemic 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 inavolisib with the dose reduced by 1 dose level. Recurrence: If FPG or FBG >500 mg/dL (>27.8 mmol/L) recurs within 30 days, permanently discontinue inavolisib. | |
|
Other adverse reactions |
Grade 1 |
No inavolisib dosage adjustment required. |
|
Grade 2 |
Consider withholding inavolisib (if clinically indicated) until recovery to ≤ grade 1, then resume at the same dose level. | |
|
Grade 3 (first event) |
Withhold inavolisib until recovery to ≤ grade 1, then resume at the same dose level or at 1 dose level lower based on clinical assessment. | |
|
Grade 3 (recurrence) |
Withhold inavolisib until recovery to ≤ grade 1, then resume at 1 dose level lower. | |
|
Grade 4 |
Permanently discontinue inavolisib. | |
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Reported adverse reactions are for combination therapy with palbociclib and fulvestrant in adults.
>10%:
Dermatologic: Alopecia (19%), skin rash (26%), xeroderma (13%)
Endocrine & metabolic: Decreased serum calcium (42%), decreased serum magnesium (27%), decreased serum potassium (38%), decreased serum sodium (28%), increase in fasting plasma glucose (85%), weight loss (17%)
Gastrointestinal: Decreased appetite (24%), diarrhea (48%; grades 3: 4%), increased serum lipase (16%; fasting), nausea (28%; grade 3: <1%), stomatitis (51%; grade 3: 6%), vomiting (15%; grade 3: <1%)
Genitourinary: Urinary tract infection (15%)
Hematologic & oncologic: Decreased hemoglobin (88%; grades 3: 8%), decreased neutrophils (grades 3/4: 82%), decreased platelet count (84%; grades 3/4: 16%), lymphocytopenia (72%; grades 3/4: 9%)
Hepatic: Increased serum alanine aminotransferase (34%)
Nervous system: Fatigue (38%), headache (22%)
Renal: Increased serum creatinine (38%)
1% to 10%:
Gastrointestinal: Abdominal pain, dysgeusia, dyspepsia
Ophthalmic: Dry eye syndrome
There are no contraindications listed in the manufacturer's labeling.
Concerns related to adverse effects:
• GI toxicity: Severe stomatitis can occur with inavolisib. Stomatitis occurred in approximately half of patients treated with inavolisib (in combination with palbociclib and fulvestrant), including some grade 3 events. The median time to first onset of stomatitis was 13 days (range: 1 to 610 days). In patients who received inavolisib (in combination with palbociclib and fulvestrant), over one-third used a corticosteroid-containing mouthwash for stomatitis prophylaxis and management. Severe diarrhea, including dehydration and acute kidney injury, may occur with inavolisib. Diarrhea occurred in nearly half of patients treated with inavolisib (in combination with palbociclib and fulvestrant); some events were grade 3. The median time to first onset of diarrhea was 15 days (range: 2 to 602 days). Antidiarrheal medicines were used in over one-fourth of patients to manage symptoms. Advise patients to increase oral fluids and start antidiarrheal treatment at the first sign of diarrhea.
• Hyperglycemia: Severe hyperglycemia can occur with inavolisib. Increased fasting glucose occurred in a majority of patients, including grade 2 (fasting plasma glucose [FPG] >160 to 250 mg/dL), grade 3 (FPG >250 to 500 mg/dL), and rare grade 4 (FPG >500 mg/dL) events. In a clinical trial of patients who received inavolisib, increased fasting glucose was managed with oral antihyperglycemic agents in nearly half of patients and in some patients, insulin was used to manage increased fasting glucose. Among patients with hyperglycemia, the median time to first onset was 7 days (range: 2 to 955 days). In patients who experienced grade 2 increased fasting glucose, most experienced a fasting glucose improvement of at least 1 grade level with a median time to improvement from the first event of 8 days (range: 2 to 43 days). The safety of inavolisib in patients with type 1 diabetes mellitus or type 2 diabetes mellitus requiring ongoing antihyperglycemic treatment have not been studied. Counsel patients on lifestyle changes if applicable.
Special populations:
• Older adults: There was a higher incidence of dosage modifications or treatment interruptions due to adverse reactions in patients ≥65 years of age, compared to patients <65 years of age.
Other warnings/precautions:
• Appropriate use: Select patients for the treatment of endocrine-resistant, hormone receptor (HR)–positive, HER2-negative, PIK3CA-mutated, locally advanced or metastatic breast cancer based on the presence of one or more PIK3CA mutations in plasma specimens. Information on FDA-approved tests for the detection of PIK3CA mutations in breast cancer is available at https://www.fda.gov/companiondiagnostics.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Itovebi: 3 mg, 9 mg
No
Tablets (Itovebi Oral)
3 mg (per each): $490.01
9 mg (per each): $980.01
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Oral: Administer at approximately the same time each day, with or without food. Swallow whole; do not chew, crush, or split prior to swallowing.
This medication is not on the NIOSH (2024) list; however, it may meet the criteria for a hazardous drug. Inavolisib may cause teratogenicity.
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (Ref).
Note: Facilities may perform risk assessment of some hazardous drugs to determine if appropriate for alternative handling and containment strategies (Ref). Refer to institution-specific handling policies/procedures.
Breast cancer, locally advanced or metastatic, endocrine resistant, hormone receptor positive, HER2 negative, PIK3CA mutated: Treatment (in combination with palbociclib and fulvestrant) of endocrine-resistant, hormone receptor (HR)–positive, human epidermal growth factor 2 (HER2)–negative, PIK3CA-mutated (as detected by an approved test), locally advanced or metastatic breast cancer in adults following recurrence on or after completing adjuvant endocrine therapy.
Inavolisib may be confused with alpelisib, copanlisib, duvelisib, enasidenib, idelalisib, imatinib, ivosidenib, leniolisib.
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes (chemotherapeutic agent, parenteral and oral) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Acute Care, Community/Ambulatory Care, and Long-Term Care Settings).
Substrate of BCRP, P-glycoprotein (Minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential;
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Antidiabetic Agents: Hyperglycemia-Associated Agents may decrease therapeutic effects of Antidiabetic Agents. Risk C: Monitor
Verify pregnancy status prior to initiating treatment in patients who could become pregnant.
Patients who could become pregnant should use effective nonhormonal contraception during therapy and for 1 week after the last inavolisib dose. Patients with partners who could become pregnant should also use effective contraception during therapy and for 1 week after the last inavolisib dose.
Adverse effects to fertility were observed in animal toxicology studies; data are lacking on possible fertility effects in humans.
Based on the mechanism of action and data from animal reproduction studies, in utero exposure to inavolisib may cause fetal harm. Adverse events were observed following oral doses to pregnant rats during the period of organogenesis at doses equivalent to the human exposure (based on AUC).
It is not known if inavolisib is present in breast milk.
Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer during therapy and for 1 week after the last inavolisib dose. Also refer to the palbociclib and fulvestrant monographs for additional information.
PIK3CA mutation status in plasma specimens. Monitor CBC (baseline and periodic; more frequently when clinically indicated). Verify pregnancy status prior to treatment initiation (in patients who could become pregnant).
Hyperglycemia: Fasting glucose levels (fasting plasma glucose or fasting blood glucose) prior to treatment initiation; during treatment (or in patients who experience hyperglycemia or are at risk for hyperglycemia) monitor (or have patient self-monitor at home) fasting glucose levels once every 3 days for the first week (days 1 to 7), then once every week for the next 3 weeks (days 8 to 28), then once every 2 weeks for the next 8 weeks, then once every 4 weeks thereafter, and as clinically indicated. During treatment with antihyperglycemic medication, continue monitoring fasting glucose levels. HbA1C levels prior to treatment initiation, every 3 months during treatment, and as clinically indicated.
Monitor for signs/symptoms of diarrhea, hematologic toxicities, hyperglycemia, and stomatitis. Monitor adherence.
The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (Ref) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
Inavolisib is a potent, selective inhibitor of the mutated phosphatidylinositol 3-kinase (PI3K) subunit, p110α (Ref). Inavolisib reduces tumor growth in PIK3CA-mutated, estrogen receptor-positive, breast cancer models and (in vitro) induces degradation of mutated PI3K catalytic alpha subunit p110α (encoded by the PIK3CA gene), inhibits downstream AKT phosphorylation, reduces cellular proliferation, and induces apoptosis in PIK3CA-mutated breast cancer cell lines. The combination of inavolisib with palbociclib and fulvestrant increased inhibition of tumor growth, compared to each component alone or as doublet combinations.
Distribution: Vd: 155 L.
Protein binding: 37%.
Metabolism: Metabolized primarily via hydrolysis; in vitro, inavolisib was minimally metabolized by CYP3A.
Bioavailability: Oral: 76%.
Half-life elimination: 15 hours.
Time to peak: 3 hours (range: 0.5 to 4 hours).
Excretion: Urine: 49% (40% as unchanged drug); feces: 48% (11% as unchanged drug).
Clearance: 8.8 L/hour.
Altered kidney function: Inavolisib AUC was 73% higher in patients with moderate kidney impairment (eGFR 30 to <60 mL/minute) compared to patients with normal kidney function (eGFR ≥90 mL/minute).
