Important Safety Information:

VIJOICE® (alpelisib) tablets is contraindicated in patients with severe hypersensitivity to alpelisib or any of its ingredients...

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Indication: VIJOICE® (alpelisib) tablets is indicated for the treatment of adult and pediatric patients 2 years of age and older with severe manifestations of PIK3CA-Related Overgrowth Spectrum (PROS) who require systemic therapy.

This indication is approved under accelerated approval based on response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Safety Profile

Serious and Common Adverse Reactions

  • VIJOICE® (alpelisib) tablets may cause severe hypersensitivity reactions, severe cutaneous adverse reactions, hyperglycemia, severe pneumonitis, diarrhea, and embryo-fetal toxicity1

Safety profile in PIK3CA-Related Overgrowth Spectrum (PROS)1

ARs and laboratory abnormalities occurring in all patients (N=57)
AR (≥5% of patients) All grades (%) Grades 3-4 (%)
Diarrhea 16 0
Stomatitisa 16 0
Hyperglycemia 12 0
Eczema 7 0
Dry skin 7 0
Cellulitis 5 3.5
Alopecia 5 0
Headache 5 0
Laboratory abnormality (>20% of patients)b All grades (%) Grades 3-4 (%)
Chemistry    
Decreased calcium (corrected) 60 0
Decreased phosphate 59 5e
Increased glucosec 56 11e
Increased glycosylated
hemoglobin (HbA1c)d
38d NAd
Increased creatinine 31 0
Increased bilirubin 29 2e
Increased potassium 24 0
Hematology    
Decreased leukocyte 22 0
Decreased hemoglobin 20 6e
Decreased lymphocyte 20

 

Grading according to CTCAE version 4.03.
a
Stomatitis, including stomatitis and aphthous ulcer.
bThe denominator used to calculate the rate varied from 9 to 50 based on the number of patients with a baseline value and at least 1 posttreatment value.
cGlucose increase is an expected laboratory abnormality of PI3K inhibition.
dNo CTCAE grade available. For HbA1c, baseline values increasing posttreatment to a value above the upper limit of the normal range (≥5.7%) are considered increased.
eNo grade 4 laboratory abnormalities were reported.
AR, adverse reaction; NA, not available; CTCAE, Common Terminology Criteria for Adverse Events; PI3K, phosphatidylinositol-3-kinase.

The most commonly reported ARs were diarrhea (16%), stomatitis (16%), and hyperglycemia (12%)

  • All ARs occurring in ≥10% of patients were mild to moderate (grade 1 or 2)
  • Serious ARs occurred in 12% of patients who received VIJOICE. Dehydration (n=2) and cellulitis (n=2) were the only serious ARs that occurred in multiple patients

No patients permanently discontinued treatment due to ARs

  • 95% of all patients received VIJOICE for 6 months or longer
  • 79% of all patients received VIJOICE for >12 months

Additional safety data

  • 5% of patients required dose reductions due to ARs. Alopecia, memory impairment, and soft tissue infection were the only ARs that required dose reduction
  • Dose interruption due to an AR occurred in 11% of patients. Vomiting (n=2) and dizziness (n=2) were the only ARs that required dose interruption in 2 or more patients
Strategies for managing your patient before and during treatment are available in the downloadable guide below

Pediatric and adult safety profiles2

ARs occurring in >10% of either pediatric or adult patients
AR All grades (%) Grades 3-4 (%)
Pediatric (n=39) Adult (n=18) Pediatric (n=39) Adult (n=18)
Diarrhea 12.8 22.2 0 0
Vascular malformation 10.3 0 0 0
Aphthous ulcer 7.7 16.7 0 0
Inflammation 7.7 11.1 0 5.6
Hyperglycemia 5.1 27.8 0 0
Disseminated intravascular coagulation 5.1 16.7 0 5.6
Dry skin 2.6 16.7 0 0
Eczema 2.6 16.7 0 0
Cellulitis 2.6 11.1 2.6 5.6
Pain in extremity 2.6 11.1 0 5.6
Headache 0 16.7 0 0
Alopecia 0 16.7 0 0
ARs occurring in >10% of either pediatric or adult patients
AR All grades (%)
Pediatric (n=39) Adult (n=18)
Diarrhea 12.8 22.2
Vascular malformation 10.3 0
Aphthous ulcer 7.7 16.7
Inflammation 7.7 11.1
Hyperglycemia 5.1 27.8
Disseminated intravascular coagulation 5.1 16.7
Dry skin 2.6 16.7
Eczema 2.6 16.7
Cellulitis 2.6 11.1
Pain in extremity 2.6 11.1
Headache 0 16.7
Alopecia 0 16.7
AR Grades 3-4 (%)
Pediatric (n=39) Adult (n=18)
Diarrhea 0 0
Vascular malformation 0 0
Aphthous ulcer 0 0
Inflammation 0 5.6
Hyperglycemia 0 0
Disseminated intravascular coagulation 0 5.6
Dry skin 0 0
Eczema 0 0
Cellulitis 2.6 5.6
Pain in extremity 0 5.6
Headache 0 0
Alopecia 0 0

 

Grading according to CTCAE version 4.03.

 

Patient Management Guide

Managing Your Patient on VIJOICE

Download this guide to help you manage potential adverse reactions during treatment.

Download Guide

 

References:

  1. Vijoice [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2022.
  2. Data on file. CBYL719F12002 clinical study report. Novartis Pharmaceuticals Corp; 2021.

INDICATION

VIJOICE® (alpelisib) tablets is indicated for the treatment of adult and pediatric patients 2 years of age and older with severe manifestations of PIK3CA-Related Overgrowth Spectrum (PROS) who require systemic therapy.

This indication is approved under accelerated approval based on response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

IMPORTANT SAFETY INFORMATION

VIJOICE is contraindicated in patients with severe hypersensitivity to alpelisib or any of its ingredients.

Severe Hypersensitivity. Severe hypersensitivity reactions, including anaphylaxis and anaphylactic shock, have occurred in adult patients treated with alpelisib in the oncology setting and may occur in patients treated with VIJOICE. VIJOICE is not approved for use in the oncology setting. Permanently discontinue VIJOICE in the event of severe hypersensitivity.

Severe Cutaneous Adverse Reactions (SCARs). SCARs, including Stevens-Johnson syndrome (SJS), erythema multiforme (EM), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS), have occurred in adult patients treated with alpelisib in the oncology setting and may occur in patients treated with VIJOICE. If signs or symptoms of SCARs occur, interrupt VIJOICE until the etiology of the reaction has been determined. Consultation with a dermatologist is recommended. If a SCAR is confirmed, permanently discontinue VIJOICE. If a SCAR is not confirmed, VIJOICE may require dose modifications, topical corticosteroids, or oral antihistamine treatment.

Hyperglycemia. Severe hyperglycemia, in some cases associated with hyperglycemic hyperosmolar nonketotic syndrome (HHNKS) or fatal cases of ketoacidosis, has occurred in adult patients treated with alpelisib in the oncology setting and may occur in patients treated with VIJOICE.

In the EPIK-P1 study, grade 1 or 2 hyperglycemia was reported in 12% of patients treated with VIJOICE.

Before initiating treatment with VIJOICE, test fasting plasma glucose (FPG), HbA1c, and optimize blood glucose. After initiating treatment with VIJOICE, monitor fasting glucose (FPG or fasting blood glucose) at least once every week for the first 2 weeks, then at least once every 4 weeks, and as clinically indicated. Monitor HbA1c every 3 months and as clinically indicated. Monitor fasting glucose more frequently for the first few weeks during treatment with VIJOICE in patients with risk factors for hyperglycemia, such as obesity (body mass index ≥30), elevated FPG, HbA1c at the upper limit of normal or above, use of concomitant systemic corticosteroids, or age ≥75.

If a patient experiences hyperglycemia after initiating treatment with VIJOICE, monitor fasting glucose as clinically indicated and at least twice weekly until fasting glucose decreases to normal levels. During treatment with antihyperglycemic medication, continue monitoring fasting glucose at least once a week for 8 weeks, followed by once every 2 weeks, and as clinically indicated. Consider consultation with a health care provider with expertise in the treatment of hyperglycemia, and counsel patients on lifestyle changes.

The safety of VIJOICE in patients with type 1 and uncontrolled type 2 diabetes has not been established. Patients with a history of diabetes mellitus may require intensified hyperglycemic treatment. Closely monitor patients with diabetes.

Interrupt, reduce the dose of, or permanently discontinue VIJOICE based on severity.

Pneumonitis. Severe pneumonitis, including acute interstitial pneumonitis and interstitial lung disease, has occurred in adult patients treated with alpelisib in the oncology setting and may occur in patients treated with VIJOICE.

In patients who have new or worsening respiratory symptoms or are suspected to have developed pneumonitis, interrupt VIJOICE immediately and evaluate the patient for pneumonitis. Consider a diagnosis of noninfectious pneumonitis in patients presenting with nonspecific respiratory signs and symptoms, such as hypoxia, cough, dyspnea, or interstitial infiltrates on radiologic examinations and in whom infectious, neoplastic, and other causes have been excluded by means of appropriate investigations.

Permanently discontinue VIJOICE in all patients with confirmed pneumonitis.

Diarrhea. Severe diarrhea, including cases resulting in dehydration and acute kidney injury, has occurred in adult patients treated with alpelisib in the oncology setting and may occur in patients treated with VIJOICE. In the EPIK-P1 study, 16% of patients experienced grade 1 diarrhea during treatment with VIJOICE. Interrupt, reduce the dose of, or permanently discontinue VIJOICE based on severity.

Embryo-Fetal Toxicity. Based on findings in animals and its mechanism of action, VIJOICE can cause fetal harm when administered to a pregnant woman. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with VIJOICE and for 1 week after the last dose. Advise male patients with female partners of reproductive potential to use condoms and effective contraception during treatment with VIJOICE and for 1 week after the last dose.

The most common adverse reactions (all grades, incidence ≥10%) were diarrhea (16%), stomatitis (16%), and hyperglycemia (12%).

The most common laboratory abnormalities (all grades, incidence ≥20%) were decreased calcium (corrected) (60%), decreased phosphate (59%), increased glucose (56%), increased HbA1c (38%), increased creatinine (31%), increased bilirubin (29%), decreased magnesium (26%), increased potassium (24%), decreased leukocyte (22%), decreased lymphocyte (20%), and decreased hemoglobin (20%).

Please see full Prescribing Information for VIJOICE® (alpelisib) tablets.