Itovebi Inavolisib 9 mg Tablet, Film Coated, 28-count
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the Kinase Inhibitor class.
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🏭 Manufacturer & labeler
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🩺 Clinical
Patient education
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💊 What it looks like
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🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
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UNII 1K09F3G675
Ferric oxide red is an inorganic iron compound used as a colorant in medicines. It gives tablets, capsules, or other dosage forms a red or reddish tint for identification and appearance.
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UNII EX438O2MRT
Ferric oxide yellow is a naturally occurring iron compound used as a colorant in medications. It gives tablets, capsules, and other forms a yellow or golden hue for identification and appearance.
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UNII EWQ57Q8I5X
Lactose monohydrate is a natural sugar derived from milk. It serves as a filler and binder in tablets and capsules, helping create the proper size, texture, and consistency of the medicine.
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UNII 70097M6I30
Magnesium stearate is a salt made from magnesium and stearic acid, a fatty substance. It's used in tablets and capsules as a lubricant and glidant to help ingredients flow smoothly during manufacturing and prevent sticking.
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UNII OP1R32D61U
Microcrystalline cellulose is a purified form of cellulose, a natural fiber from plant sources. It acts as a binder and filler in tablets and capsules, helping hold ingredients together and give the medicine its shape and size.
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UNII 3WJQ0SDW1A
Polyethylene glycol is a synthetic liquid or solid polymer used in medicines as a solvent, lubricant, and humectant. It helps dissolve active ingredients, reduces friction during manufacturing, and retains moisture in the final product.
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UNII 532B59J990
Polyvinyl alcohol is a synthetic polymer made from plant-derived materials. It's used as a binder to hold ingredients together, a film-former in coatings, and a thickener in liquid formulations.
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A modified starch derived from potato or corn starch. It absorbs water quickly and helps tablets or capsules break apart and dissolve in the stomach, acting as a disintegrant to ensure the medicine releases its active ingredients properly.
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UNII 7SEV7J4R1U
A powder made from a naturally occurring mineral. In medicines, talc works as a glidant and anti-caking agent, helping tablets and capsules flow smoothly during manufacturing and preventing clumping.
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UNII 15FIX9V2JP
Titanium dioxide is a bright white mineral powder commonly used as a colorant and opacifying agent. It makes pills and tablets white or lighter in color and helps make coatings non-transparent.
10 inactive ingredients listed in the exact product block matched to this NDC.
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ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per each | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | $817.02 | $22,876.60 / 28 tablets |
| Medicare drug plans payPart D · Q2 2026 | $829.40 | $23,223.07 / 28 tablets |
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Itovebi 9 mgthis 50242-0079-08 | Genentech, | 28 tablets | — | — | FDA listed | — |
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⏳ Availability & generic status
We did not find an FDA-approved generic match for this exact strength, form and route. Patent/protection dates below may affect future generic timing.
Why the date isn’t exact: Generic timing can change because patents may be challenged, settled, licensed, added, removed, or worked around with a narrower label — and FDA approval does not always mean a pharmacy can get the generic today.
🛈 What do these terms mean?
- Patent
- Legal protection listed in the Orange Book that may delay generic approval or launch. Issued by the U.S. Patent & Trademark Office.
- Substance patent
- Covers the active drug molecule itself — the hardest to design around. A generic generally can’t launch until it expires.
- Formulation (product) patent
- Covers a specific formulation or dosage form. A generic can sometimes work around it with a different formulation.
- Method-of-use patent
- A patent covering one specific approved use of the drug — not necessarily the whole molecule. A generic can sometimes launch with a “skinny label” that carves out the protected use and keeps the others.
- Skinny label
- A generic label that omits a still-patented use when the FDA allows it — letting a generic reach the market for the unprotected uses.
- Exclusivity
- FDA-granted marketing protection, separate from patents — e.g. 5-yr new chemical entity, 7-yr orphan drug, or a +6-month pediatric extension.
- Paragraph IV
- A generic applicant’s formal challenge to a listed patent. It can potentially lead to earlier generic entry, but often involves litigation or a settlement.
- RLD / RS
- Reference Listed Drug — the brand product the FDA uses as the reference for generic applications. Reference Standard — the product the FDA expects generics to compare against in bioequivalence testing.
- TE / AB rating
- FDA therapeutic-equivalence rating. An AB rating generally means the FDA considers a generic therapeutically equivalent to — and substitutable for — the brand.
- LOE (loss of exclusivity)
- The latest patent or exclusivity currently listed — the loss-of-exclusivity / latest-listed-protection date shown on this page. Paragraph-IV challenges and settlements can move the real date earlier; FDA approval and a manufacturer’s decision to market can move it later.
Built from the FDA Orange Book. The bars above are scaled to each protection’s expiry; the red LOE marker is the last one to lapse.
| Patent | Type | Use code | Expires |
|---|---|---|---|
| US 11760753 ↗ | Method of use | U-4024 | Jul 1, 2036 |
| US 11760753 ↗ | Method of use | U-4024 | Jul 1, 2036 |
| US 12410189 ↗ | Method of use | U-4024 | Jun 14, 2038 |
| US 12410189 ↗ | Method of use | U-4024 | Jun 14, 2038 |
| US 9650393 ↗ | Drug substance | U-4024 | Jul 1, 2036 |
| US 9650393 ↗ | Drug substance | U-4024 | Jul 1, 2036 |
| US 8343955 ↗ | Method of use | U-4024 | Sep 27, 2030 |
| US 8343955 ↗ | Method of use | U-4024 | Sep 27, 2030 |
| US 8242104 ↗ | Drug substance | — | Sep 27, 2030 |
| US 10851091 ↗ | Drug substance | — | Jul 1, 2036 |
| US 11028100 ↗ | Drug substance | — | Apr 26, 2038 |
| US 10851091 ↗ | Drug substance | — | Jul 1, 2036 |
| US 8242104 ↗ | Drug substance | — | Sep 27, 2030 |
| US 11028100 ↗ | Drug substance | — | Apr 26, 2038 |
| Code | What it grants | Expires |
|---|---|---|
| NCE | New Chemical Entity (5-year) | Oct 10, 2029 |
| NCE | New Chemical Entity (5-year) | Oct 10, 2029 |
Is there a generic version of ITOVEBI 9 MG TABLET?
The FDA approved a generic — why can’t I get it at my pharmacy yet?
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🗺️ Medicaid utilization & spend
💊 Medicaid utilization by pack size
📊 Medicare Part D spend CMS · PART D · 2026 (Q1)
🔬 Reported adverse events (FAERS)
Top reported reactions
Age at onset
Reporter sex
Serious outcomes
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📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 50242-0079-08 You're viewing this | 1 BOTTLE in 1 CARTON (50242-079-08) / 28 TABLET, FILM COATED in 1 BOTTLE | 2024-10-14 | Active |
| 50242-0079-86 | 1 BOTTLE in 1 CARTON (50242-079-86) / 28 TABLET, FILM COATED in 1 BOTTLE | 2025-01-06 | Active |
Pack size FAQ
What quantity is in NDC 50242-0079-08?
What is the difference between NDC 50242-0079-08 and NDC 50242-0079-86?
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🧭 About this NDC listing & data coverage
What data is (and isn’t) available for this NDC — tap to expand
| NDC identity (package / product / labeler codes) | ✓ Available |
| Labeler | ✓ Available |
| Product & package description | ✓ Available |
| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | ✓ Available |
| Inactive ingredients (structured) | ✓ Available |
| NADAC pharmacy acquisition price (CMS) | — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey. |
| Orange Book / therapeutic-equivalence data | ✓ Available |
| HCPCS J-code billing crosswalk | — Not published for this NDC Most self-administered / retail products have no J-code — that is normal. |
| Medicaid utilization (CMS SDUD) | ✓ Available |
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📄 Full prescribing information FDA SPL
🎯 Indications and Usage ▾
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) ] . ITOVEBI is a kinase inhibitor indicated in combination with palbociclib and fulvestrant 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.
( 1 , 14.1 )
⏱️ Dosage and Administration ▾
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 and severe renal impairment. ( 2.5 )
2.1Patient 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.
2.2Recommended 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) ].
2.3Recommended 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.
2.4Dosage 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-hy…
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Tablets: 3 mg: red and round convex-shaped with an "INA 3" debossing on one side. 9 mg: pink and oval-shaped with an "INA 9" debossing on one side. Tablets: 3 mg and 9 mg ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS None. None. ( 4 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS Hyperglycemia : ITOVEBI can cause severe or fatal hyperglycemia including ketoacidosis. Before initiating treatment with ITOVEBI, test fasting plasma glucose (FPG), HbA1c, and optimize blood glucose. Initiate or optimize anti-hyperglycemic medications as clinically indicated.
Interrupt, reduce dose, or discontinue ITOVEBI if severe hyperglycemia occurs. ( 2.4 , 5.1 ) Stomatitis : ITOVEBI can cause severe stomatitis. Consider treating with a corticosteroid-containing mouthwash if stomatitis occurs.
Monitor patients for signs and symptoms of stomatitis. Withhold, reduce dose, or permanently discontinue ITOVEBI based on severity. ( 2.4 , 5.2 ) Diarrhea : ITOVEBI can cause diarrhea, which may be severe, and result in dehydration and acute kidney injury.
Advise patients to start anti-diarrheal treatment, increase oral fluids, and notify their healthcare provider if severe diarrhea occurs. Interrupt, reduce dose, or discontinue ITOVEBI if severe diarrhea occurs. ( 2.4 , 5.3 ) Embryo-Fetal Toxicity : ITOVEBI can cause fetal harm.
Advise patients of potential risk to a fetus and to use effective non-hormonal contraception. ( 5.4 , 8.1 , 8.3 ) Refer to the Full Prescribing Information of palbociclib and fulvestrant for pregnancy and contraception information.
5.1Hyperglycemia Severe or fatal hyperglycemia, including ketoacidosis, can occur in patients treated with ITOVEBI. Ketoacidosis with a fatal outcome has occurred in the postmarketing setting. 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 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 [see Dosage and Administration (2.4) ] .
5.2 Stomatitis Severe stomatitis can occur in patient…
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of the label: Hyperglycemia [see Warnings and Precautions (5.1) ] Stomatitis [see Warnings and Precautions (5.2) ] Diarrhea [see Warnings and Precautions (5.3) ] 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.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Genentech at 1-888-835-2555 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1Clinical Trial Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Locally Advanced or Metastatic Breast Cancer INAVO120 The safety of ITOVEBI was evaluated in a randomized, double-blind, placebo-controlled study (INAVO120) in 324 patients with PIK3CA -mutated, HR-positive, HER2-negative, locally advanced or metastatic breast cancer [see Clinical Studies (14.1) ] .
Patients received either ITOVEBI 9 mg (n=162) or placebo (n=162) with palbociclib and fulvestrant. The median duration of treatment with ITOVEBI was 9 months (range: 0 to 39 months) in the ITOVEBI with palbociclib and fulvestrant arm. Serious adverse reactions occurred in 24% of patients who received ITOVEBI with palbociclib and fulvestrant.
Serious adverse reactions in ≥ 1% of patients included anemia (1.9%), diarrhea (1.2%), and urinary tract infection (1.2%). Fatal adverse reactions occurred in 3.7% of patients who received ITOVEBI with palbociclib and fulvestrant, including (0.6% each) acute coronary syndrome, cerebral hemorrhage, cerebrovascular accident, COVID-19 infection, and gastrointestinal hemorrhage. Permanent discontinuation of ITOVEBI due to an adverse reaction occurred in 6% of patients.
Adverse reactions which resulted in permanent discontinuation of ITOVEBI included hyperglycemia (1.2%), and (0.6% each) stomatitis, gastric ulcer, intestinal perforation, anal abscess, increased ALT, decreased weight, bone pain, musculoskeletal pain, transitional cell carcinoma, and acute kidney injury. Dosage interruptions of ITOVEBI due to an adverse reaction occurred in 69% of patients. Adverse reactions which required dosage interruption in ≥ 2% of patients included hyperglycemia (28%), neutropenia (23%), COVID-19 infection (16%), stomatitis (10%), diarrhea (7%), thrombocytopenia (4.9%), anemia (4.3%), upper respiratory tract infection (4.3%), decreased white blood cell count (3.7%), pyrexia (3.1%), nausea (2.5%), and fatigue (2.5%).
Dose reductions of ITOVEBI due to adverse reactions occurred in 14% of patients. Adverse reactions which required dose reduction of ITOVEBI in ≥ 2% of patients were stomatitis (3.7%) and hyperglycemia (2.5%). 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.
Adverse reactions and laboratory abnormalities in INAVO120 are summarized in Table 3 and Table 4 , respectively. Patient-reported symptoms are summarized in Table 5 . Table 3: Adverse Reactions (≥ 10% with ≥ 5% [All Grades] or ≥ 2% [Grade 3-4] Higher Incidence in the ITOVEBI Arm) in INAVO120 Adverse Reaction ITOVEBI + Palbociclib + Fulvestrant N=162 Placebo + Palbociclib + Fulvestrant N=162 All Grades (%…
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS Lactation : Advise not to breastfeed. ( 8.2 )
8.1Pregnancy Risk Summary ITOVEBI is used in combination with palbociclib and fulvestrant. Refer to the Full Prescribing Information of palbociclib and fulvestrant for pregnancy information. Based on animal data and its mechanism of action, ITOVEBI can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1) ] .
There are no available data on the use of ITOVEBI in pregnant women to inform a drug-associated risk. 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 AUC (see Data ) . Advise pregnant women and females of reproductive potential of the potential risk to a fetus.
The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects is 2% to 4% and of miscarriage is 15% to 20% of clinically recognized pregnancies in the U.S. general population. Data Animal Data In an embryo-fetal development study, pregnant rats received oral doses of inavolisib up to 6 mg/kg/day during the period of organogenesis.
Administration of doses ≥ 2 mg/kg/day resulted in decreases in fetal body weight and placental weight, post-implantation loss, lower fetal viability, fetal malformations (including kyphosis of vertebral column, fused thoracic arch, microphthalmia) and variations (including dilated renal pelvis, short supernumerary rib, wavy rib). At a dose of 2 mg/kg/day, maternal exposures were 0.9 times the human exposure at the recommended dose of 9 mg/day based on AUC.
8.2Lactation Risk Summary ITOVEBI is used in combination with palbociclib and fulvestrant. Refer to the Full Prescribing Information of palbociclib and fulvestrant for lactation information. There are no data on the presence of inavolisib or its metabolites in human milk, its effects on milk production or a breastfed child.
Because of the potential for serious adverse reactions in a breastfed child, advise lactating women to not breastfeed during treatment with ITOVEBI and for 1 week after the last dose.
8.3Females and Males of Reproductive Potential ITOVEBI is used in combination with palbociclib and fulvestrant. Refer to the Full Prescribing Information of palbociclib and fulvestrant for contraception and infertility information. ITOVEBI can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1) ] .
Pregnancy Testing Verify pregnancy status in females of reproductive potential prior to initiating treatment with ITOVEBI. Contraception Females Advise females of reproductive potential to use effective non-hormonal contraception during treatment with ITOVEBI and for 1 week after the last dose. Males 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.
Infertility Based on animal studies, ITOVEBI may impair fertility in females and males of reproductive potential [see Nonclinical Toxicology (13.1) ] .
8.4Pediatric Use The safety and efficacy of ITOVEBI in pediatric patients have not been established.
8.5Geriatric Use Of the 162 patients who received ITOVEBI in INAVO120, 15% were ≥ 65 years of age, and 3% were ≥ 75 years of age. Dosage modifications or interruptions of ITOVEBI due to adverse reactions occurred at a higher incidence for patients ≥ 65 years of age compared to younger patients (79% versus 68%, respectively). Clinical studies of ITOVEBI did not include sufficient numbers of patients ≥ 65 years of age to determine whether they respond differently from younger patients.
8.6 Renal Impairment Re…
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary ITOVEBI is used in combination with palbociclib and fulvestrant. Refer to the Full Prescribing Information of palbociclib and fulvestrant for pregnancy information. Based on animal data and its mechanism of action, ITOVEBI can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1) ] .
There are no available data on the use of ITOVEBI in pregnant women to inform a drug-associated risk. 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 AUC (see Data ) . Advise pregnant women and females of reproductive potential of the potential risk to a fetus.
The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects is 2% to 4% and of miscarriage is 15% to 20% of clinically recognized pregnancies in the U.S. general population. Data Animal Data In an embryo-fetal development study, pregnant rats received oral doses of inavolisib up to 6 mg/kg/day during the period of organogenesis.
Administration of doses ≥ 2 mg/kg/day resulted in decreases in fetal body weight and placental weight, post-implantation loss, lower fetal viability, fetal malformations (including kyphosis of vertebral column, fused thoracic arch, microphthalmia) and variations (including dilated renal pelvis, short supernumerary rib, wavy rib). At a dose of 2 mg/kg/day, maternal exposures were 0.9 times the human exposure at the recommended dose of 9 mg/day based on AUC.
🧒 Pediatric Use ▾
8.4Pediatric Use The safety and efficacy of ITOVEBI in pediatric patients have not been established.
🧓 Geriatric Use ▾
8.5Geriatric Use Of the 162 patients who received ITOVEBI in INAVO120, 15% were ≥ 65 years of age, and 3% were ≥ 75 years of age. Dosage modifications or interruptions of ITOVEBI due to adverse reactions occurred at a higher incidence for patients ≥ 65 years of age compared to younger patients (79% versus 68%, respectively). Clinical studies of ITOVEBI did not include sufficient numbers of patients ≥ 65 years of age to determine whether they respond differently from younger patients.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action Inavolisib is an inhibitor of phosphatidylinositol 3-kinase (PI3K) with inhibitory activity predominantly against PI3Kα. In vitro, inavolisib induced the degradation of mutated PI3K catalytic alpha subunit p110α (encoded by the PIK3CA gene), inhibited phosphorylation of the downstream target AKT, reduced cellular proliferation, and induced apoptosis in PIK3CA -mutated breast cancer cell lines. In vivo, inavolisib reduced tumor growth in PIK3CA -mutated, estrogen receptor-positive, breast cancer xenograft models.
The combination of inavolisib with palbociclib and fulvestrant increased tumor growth inhibition compared to each treatment alone or the doublet combinations.
12.2Pharmacodynamics Exposure-Response Relationships The exposure-response relationship for the efficacy of inavolisib has not been fully characterized. Inavolisib time course of pharmacodynamic response is unknown. Higher systemic exposure of inavolisib was associated with higher incidence of Grade ≥ 2 anemia, Grade ≥ 2 hyperglycemia, and inavolisib dosage modifications due to adverse reactions.
Cardiac Electrophysiology At the recommended approved dosage, a mean increase in the QTc interval of > 20 ms is unlikely.
12.3Pharmacokinetics Inavolisib pharmacokinetics are presented as geometric mean (geometric coefficient of variation [geo CV]%) following administration of the approved recommended dosage unless otherwise specified. The inavolisib steady-state AUC is 1,010 h*ng/mL (25%) and C max is 69 ng/mL (27%). Steady-state concentrations are predicted to be attained by day 5.
Inavolisib accumulation is approximately 2-fold. Inavolisib steady-state AUC is proportional with dose from 6 to 12 mg (0.7 to 1.3 times the approved recommended dosage). Absorption Inavolisib absolute oral bioavailability is 76%.
Inavolisib steady-state median (min, max) time to maximum plasma concentration (T max ) is 3 hours (0.5, 4 hours). Effect of Food No clinically significant differences in inavolisib pharmacokinetics were observed following administration of inavolisib with a high-fat meal (approximately 1,000 calories, 50% fat). Distribution Inavolisib apparent (oral) volume of distribution is 155 L (26%).
Inavolisib plasma protein binding is 37% and is not concentration-dependent in vitro. Inavolisib blood-to-plasma ratio is 0.8. Elimination Inavolisib elimination half-life is 15 hours (24%) with a total clearance of
8.8L/hr (29%). Metabolism Inavolisib is primarily metabolized by hydrolysis. In vitro, inavolisib was minimally metabolized by CYP3A.
Excretion Following oral administration of a single radiolabeled dose, 49% of the administered dose was recovered in urine (40% unchanged) and 48% in feces (11% unchanged). Specific Populations No clinically significant differences in the pharmacokinetics of inavolisib were observed based on age (27 to 85 years), sex, race (Asian or White), body weight (39 to 159 kg), or mild hepatic impairment (total bilirubin > ULN to ≤ 1.5 × ULN or AST > ULN and total bilirubin ≤ ULN). The effect of moderate to severe hepatic impairment on inavolisib pharmacokinetics is unknown.
Patients with Renal Impairment Inavolisib AUC increased 1.7-fold in subjects with moderate renal impairment (eGFR 30 to < 60 mL/min based on CKD-EPI) and 2.2-fold in subjects with severe renal impairment (eGFR < 30 mL/min) compared to subjects with normal renal function (eGFR ≥ 90 mL/min). No clinically significant differences in the pharmacokinetics of inavolisib were observed in patients with mild renal impairment compared to patients with normal renal function. Drug Interaction Studies Clinical Studies and Model-Informed Approaches Proton Pump Inhibitors: No clinically significant difference in steady-state inavolisib pharmacokinetics were observed based upon concomitant use of a proton pump inhibitor (lansoprazole, omeprazole, esomeprazole, pantoprazole, or rabeprazole).
In Vitro Studies CYP450 Enzymes: Inavolisib induc…
🧬 Mechanism of Action ▾
12.1Mechanism of Action Inavolisib is an inhibitor of phosphatidylinositol 3-kinase (PI3K) with inhibitory activity predominantly against PI3Kα. In vitro, inavolisib induced the degradation of mutated PI3K catalytic alpha subunit p110α (encoded by the PIK3CA gene), inhibited phosphorylation of the downstream target AKT, reduced cellular proliferation, and induced apoptosis in PIK3CA -mutated breast cancer cell lines. In vivo, inavolisib reduced tumor growth in PIK3CA -mutated, estrogen receptor-positive, breast cancer xenograft models.
The combination of inavolisib with palbociclib and fulvestrant increased tumor growth inhibition compared to each treatment alone or the doublet combinations.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING ITOVEBI is supplied in the following strengths and package configurations: Package Configuration Tablet Strength NDC Tablet Description Bottle of 28 tablets 3 mg 50242-084-08 Red and round convex-shaped with an "INA 3" debossing on one side Bottle of 28 tablets 9 mg 50242-079-08 Pink and oval-shaped with an "INA 9" debossing on one side Store at 20°C to 25°C (68°F to 77°F), excursions permitted between 15°C and 30°C (between 59°F and 86°F) [see USP Controlled Room Temperature]. Store and dispense in original bottle.
Keep the bottle tightly closed to protect from moisture.
📦 Storage and Handling ▾
Store at 20°C to 25°C (68°F to 77°F), excursions permitted between 15°C and 30°C (between 59°F and 86°F) [see USP Controlled Room Temperature]. Store and dispense in original bottle. Keep the bottle tightly closed to protect from moisture.
📋 Description ▾
11 DESCRIPTION ITOVEBI contains inavolisib, a kinase inhibitor. The chemical name of inavolisib is (2S)-2-[[2-[(4S)-4-(difluoromethyl)-2-oxo-oxazolidin-3-yl]-5,6-dihydroimidazo[1,2-d][1,4]benzoxazepin-9-yl]amino]propanamide. Inavolisib is a white to off-white, greyish pink, greyish orange, or greyish yellow powder or powder with lumps.
Inavolisib demonstrates pH-dependent aqueous solubility; the greatest solubility is at low pH, and solubility decreases with increasing pH. The molecular formula for inavolisib is C 18 H 19 F 2 N 5 O 4 and the molecular weight is 407.37 g/mol. The chemical structure of inavolisib is shown below: ITOVEBI film-coated tablets are supplied for oral administration with two strengths that contain 3 mg and 9 mg of inavolisib.
The tablets also contain lactose, magnesium stearate, microcrystalline cellulose, and sodium starch glycolate. The film-coating contains the following inactive ingredients: polyvinyl alcohol (partially hydrolyzed), titanium dioxide, macrogol/polyethylene glycol, talc, iron oxide red, and iron oxide yellow (in the 9 mg tablet only). Chemical Structure
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information). Hyperglycemia Advise patients that ITOVEBI may cause severe or fatal hyperglycemia, including ketoacidosis, and that monitoring fasting glucose levels before and periodically during therapy is needed. Advise patients to contact their healthcare provider immediately for signs and symptoms of hyperglycemia (e.g., excessive thirst, urinating more often, blurred vision, confusion, difficulty breathing, or increased appetite with weight loss) [see Warnings and Precautions (5.1) ] .
Stomatitis Advise patients that ITOVEBI may cause stomatitis, which may be severe, and to notify their healthcare provider if they develop symptoms of stomatitis (e.g., painful redness, swelling, or sores in the mouth) [see Warnings and Precautions (5.2) ]. Diarrhea Advise patients that ITOVEBI may cause diarrhea, which may be severe, and to start anti-diarrheal treatment, increase oral fluids, and notify their healthcare provider if diarrhea occurs while taking ITOVEBI [see Warnings and Precautions (5.3) ]. Embryo-Fetal Toxicity Inform pregnant women and females of reproductive potential of the potential risk to a fetus.
Advise females to inform their healthcare provider of a known or suspected pregnancy [see Warnings and Precautions (5.4) and Use in Specific Populations (8.1) ] . Advise females of reproductive potential to use effective non-hormonal contraception during treatment with ITOVEBI and for 1 week after the last dose [see Use in Specific Populations (8.3) ] . 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 [see Use in Specific Populations (8.3) ] .
Refer to the Full Prescribing Information of palbociclib and fulvestrant for pregnancy and contraception information. Lactation Advise women not to breastfeed during treatment with ITOVEBI and for 1 week after the last dose [see Use in Specific Populations (8.2) ] . Refer to the Full Prescribing Information of palbociclib and fulvestrant for lactation information.
Infertility Advise females and males of reproductive potential that ITOVEBI may impair fertility [see Use in Specific Populations (8.3) ] . Refer to the Full Prescribing Information of palbociclib and fulvestrant for infertility information. Dosing Instruct patients to take ITOVEBI at approximately the same time each day [see Dosage and Administration (2.3) ] .
Instruct patients that if a dose of ITOVEBI is missed, to take the missed dose as soon as possible within 9 hours. After more than 9 hours, skip the dose and take the next dose at the scheduled time [see Dosage and Administration (2.3) ] . Instruct patients that if vomiting occurs after taking the ITOVEBI dose, do not take an additional dose on that day.
Resume the usual dosing schedule the next day [see Dosage and Administration (2.3) ] .