Inavolisib
FDA Drug Information • Also known as: Itovebi
- Brand Names
- Itovebi
- Drug Class
- Kinase Inhibitor [EPC]
- Route
- ORAL
- Dosage Form
- TABLET, FILM COATED
- Product Type
- HUMAN PRESCRIPTION DRUG
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
What Is Inavolisib Used For?
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 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...
Side Effects (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. 6.1 Clinical 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...
Contraindications
4 CONTRAINDICATIONS None. None. ( 4 )
Pregnancy and Breastfeeding
8.1 Pregnancy 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.
How Supplied
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 in the original container and keep the bottle tightly closed in order to protect from moisture.
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.