Itovebi (inavolisib)

If adverse reactions occur, dosage interruption and/or reduction, or discontinuance of inavolisib may be necessary (see Table 1).

If dosage reduction from 9 mg once daily is necessary, the dosage should be reduced to 6 mg daily. If the toxicity recurs at a dosage of 6 mg daily, the dosage should be reduced to 3 mg daily. If patients are unable to tolerate the second dosage reduction, inavolisib should be permanently discontinued.

Table 1: Recommended Dosage Modifications for Inavolisib Adverse Reactions

Adverse Reaction Dosage Modification Based on Severity Hyperglycemia Fasting glucose levels (FPG or FBG) >ULN to 160 mg/dL: No adjustment 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: Withhold until FPG or FBG <=160 mg/dL; initiate or intensify anti-hyperglycemic medications. Resume inavolisib at the same dose level. If FPG or FBG persists >200-250 mg/dL for 7 days under the appropriate anti-hyperglycem ic treatment, consider consultation with a healthcare professional experienced in hyperglycemia management. Fasting glucose levels >250 to 500 mg/dL: Withhold therapy. Initiate or intensify anti-hyperglycemic medications. Administer appropriate hydration i f required. If FPG or FBG decreases to <=160 mg/dL within 7 days, resume inavolisib at the same dose. If FPG or FBG decreases to <=160 mg/dL in >=8 days, resume at 1 lower dose level. If FPG or FBG >250 to 500 mg/dL recurs within 30 days, withhold until FP G or FBG decreases to <=160 mg/dL, then resume at 1 lower dose level. Fasting glucose levels >500 mg/dL: Withhold therapy. Initiate or intensify anti-hyperglycemic medications. Assess for volume depletion and ketosis and administer appropriate hydration. I f FPG or FBG decreases to <=160 mg/dL, resume inavolisib at 1 lower dose level. If FPG or FBG >500 mg/dL recurs within 30 days, permanently discontinue therapy. Stomatitis Grade 1: No adjustment necessary. Initiate or intensify appropriate medical therapy (e.g., corticosteroid-containing mouthwash) as clinically indicated. Grade 2: Withhold until improvement to grade 1 or lower. Initiate or intensify appropriate medical the rapy. Resume inavolisib at the same dose level. For recurrent grade 2 stomatitis, withhold until recovery to grade 1 or lower, then resume at one lower dose level. Grade 3: Withhold until recovery to grade 1 or lower. Initiate or intensify appropriate med ical therapy. Resume inavolisib at 1 lower dose level. Grade 4: Permanently discontinue therapy. Diarrhea Grade 1: No adjustment required. Initiate appropriate medical therapy and monitor as clinically indicated. Grade 2: Withhold until recovery to grade 1 or lower, then resume inavolisib at same dose level. Initiate or intensify appropriate medical therapy a nd monitor as clinically indicated. For recurrent grade 2 diarrhea, withhold until recovery to grade 1 or lower, then resume inavolisib at one lower dose level. Grade 3: Withhold until recovery to grade 1 or lower, then resume inavolisib at one lower dose level. Initiate or intensify appropriate medical therapy and monitor as clinically indicated. Grade 4: Permanently discontinue therapy. Hematologic toxicities Grade 1, 2, or 3: No adjustment required. Monitor CBC and for signs or symptoms of hematologic toxicities as clinically indicated. Grade 4: Withhold until recovery to grade 2 or lower. Resume inavolisib at the same dose level or reduce to one lower dose l evel as clinically indicated. Other adverse reactions Grade 1: No adjustment required. Grade 2: Consider withholding, if clinically indicated, until recovery to grade 1 or lower. Resume inavolisib at the same dose level. Grade 3 (first event): Withhold until recovery to grade 1 or lower. Resume inavolisib at the same dose level or one lower dose level based on clinical evaluation. Grade 3 (recurrent): Withhold until recovery to grade 1 or lower. Resume inavolisib at one lower dose level. Grade 4: Permanently discontinue therapy.

No dosing information is available for this tab.

No dosing information is available for this tab.

In vitro studies indicate that inavolisib induces cytochrome P-450 (CYP) isoenzyme 3A and CYP2B6.

Inavolisib is a time-dependent inhibitor of CYP3A. Inavolisib does not inhibit CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, or CYP2D6.

Inavolisib is a substrate of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), but is not a substrate of organic anion transporting polypeptide (OATP)1B1, OATP1B3, organic cation transporter (OCT)1, OCT2, multidrug and toxin extrusion transporter (MATE)1, MATE2K, or organic anion transporter (OAT)1, OAT2.

Inavolisib does not inhibit P-gp, BCRP, OATP1B1, OATP1B3, OCT1, OCT2, OAT1, OAT3, MATE1, or MATE2K.

There are no contraindication interactions for this drug.

There are no severe interactions for this drug.

There are no moderate interactions for this drug.

*None.

• Lactation

• Chronic kidney disease stage 3A (moderate) GFR 45-59 ml/min
• Chronic kidney disease stage 3B (moderate) GFR 30-44 ml/min
• Hyperglycemia
• Pregnancy
• Type 2 diabetes mellitus

• Kidney disease with likely reduction in glomerular filtration rate (GFr)

The most common adverse reactions (>= 20%) including laboratory abnormalities, reported with inavolisib in clinical studies 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.

More Frequent

• Anemia
• Diarrhea
• Hyperglycemia
• Stomatitis

Less Frequent

• Urinary tract infection

Rare or Very Rare

• Acute coronary syndrome
• Bone pain
• Gastrointestinal hemorrhage
• Gastrointestinal ulcer
• Intestinal perforation
• Intracerebral hemorrhage
• Musculoskeletal pain
• Weight loss

More Frequent

• Alopecia
• Anorexia
• COVId-19
• Dry skin
• Elevated serum lipase
• Fatigue
• Headache disorder
• Hypocalcemia
• Hypokalemia
• Hypomagnesemia
• Hyponatremia
• Increased alanine transaminase
• Kidney disease with reduction in glomerular filtration rate (GFr)
• Lymphopenia
• Nausea
• Neutropenic disorder
• Skin rash
• Thrombocytopenic disorder
• Vomiting

Less Frequent

• Fever
• Leukopenia
• Upper respiratory infection

Rare or Very Rare

• Ketoacidosis

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Safety and efficacy of inavolisib have not been established in pediatric patients.

There are no adequate and well-controlled studies of inavolisib in pregnant women; however, based on findings of animal reproductive studies and its mechanism of action, inavolisib may cause embryo-fetal harm when administered to pregnant females.

It is not known whether inavolisib is distributed into human milk, or if the drug has any effects on the breastfed infant or on milk production. Because of the potential for serious adverse reactions to inavolisib in nursing infants, advise patients to discontinue breastfeeding during and for 1 week after final dose.

The manufacturer makes no specific dosage recommendations for geriatric patients.

In the INAVO120 study, 15% of patients were >=65 years of age and 3% were >=75 years of age. Patients >=65 years of age in this study had a higher incidence of dosage modifications or interruptions of therapy due to adverse effects than younger patients (79 versus 68%). An insufficient number of patients >=65 years of age were included in clinical studies to determine whether they respond differently from younger patients.