Inavolisib
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From MedlinePlus, U.S. National Library of Medicine
Kinase Inhibitor
Dosing in kidney impairment
Recommended Dosage in Patients with Moderate or Severe Renal Impairment The recommended 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. The recommended dosage of ITOVEBI for patients with severe renal impairment (eGFR < 30 mL/min) is 3 mg orally once daily [see Use in Specific Populations and Clinical Pharmacology ] .
Preparation and administration
| Adverse Reaction | Severity | Dosage Modification |
|---|---|---|
| HyperglycemiaBefore initiating treatment with ITOVEBI, test FPG or FBG, and HbA1C 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 1Based 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. |
Contraindications
None. None. ( 4 )
Pregnancy and lactation
Pregnancy
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.
For breastfeeding, also see LactMed (National Library of Medicine), which summarizes milk levels and infant effects.
Supply and cost
Drug shortage status
Recalls (last 24 months)
Therapeutic equivalence (Orange Book)
Price ladder
Not the price at the counterThese are not what a patient pays at the pharmacy counter. They are what pharmacies, health plans, and government buyers pay, before manufacturer rebates. A patient's cost depends on their insurance (copay, coinsurance, or deductible) or the pharmacy's cash price.