Vijoice
Alpelisib · Tablet · Oral
Uses
1 INDICATIONS AND USAGE VIJOICE 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 a confirmatory trial(s). VIJOICE is a kinase inhibitor 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 a confirmatory trial(s). ( 1 )
Dosage and administration
Recommended Dose: Pediatric patients (2 to less than 18 years of age): 50 mg taken orally once daily with food. ( 2.1 ) Adult patients: 250 mg taken orally once daily with food. ( 2.1 ) Administration: Swallow tablets whole. Do not chew, divide, or crush. ( 2.4 ) For patients who cannot swallow tablets whole, use tablets or oral granules to create a suspension or a mixture. ( 2.4 ) VIJOICE suspension made with water can be administered orally or via a nasogastric or gastric tube. ( 2.4 ) See full prescribing information for preparation and administration instructions. 2.1 Recommended Dosage Adult Patients The recommended dosage of VIJOICE in adult patients is 250 mg orally, once daily, administered as recommended [see Dosage and Administration (2.2, 2.3, 2.4)] until disease progression or unacceptable toxicity. Pediatric Patients (2 to less than 18 years of age) The recommended initial dosage of VIJOICE in pediatric patients is 50 mg orally, once daily, administered as recommended [see Dosage and Administration (2.2, 2.3, 2.4)] until disease progression or unacceptable toxicity. Consider a dose increase to 125 mg once daily in pediatric patients ≥ 6 years old for response optimization (clinical/radiological) after 24 weeks of treatment with VIJOICE at 50 mg once daily. When a pediatric patient turns 18 years old, consider a gradual dose increase up to 250 mg. Recommended dose increases by age group are listed in Table 1. Table 1: Recommended Daily VIJOICE Dose Levels for Pediatric Patients (2 to less than 18 years of age) a Dose can be administered as VIJOICE tablets or VIJOICE oral granules. b A recommended increased dose has not been established. Patient age (years) Initial dose Dose increase 2 to < 6 50 mg a Not applicable b 6 to < 18 50 mg a 125 mg 2.2 VIJOICE Dosage Form Overview VIJOICE is available in two dosage forms: tablets and oral granules. Prescribe the most appropriate dosage form of VIJOICE according to the dose required and patient needs. VIJOICE Tablets (50 mg, 125 mg, and 200 mg) may be administered as: Whole tablets: For patients who can swallow whole tablets. Tablets prepared as an oral suspension: For patients who have difficulty swallowing whole tablets [see Dosage and Administration (2.4)] . VIJOICE Oral Granules (50 mg per packet): For patients who are prescribed a 50 mg daily dose only [see Dosage and Administration (2.1)] . Do not use multiple 50 mg packets or a partial packet of oral granules for patients prescribed a 125 mg or a 250 mg dose [see Clinical Pharmacology (12.3)] . Do not combine VIJOICE tablets and VIJOICE oral granules to achieve the prescribed dose. 2.3 VIJOICE Administration Overview Take VIJOICE with food at approximately the same time each day [see Clinical Pharmacology (12.3)] . If a dose of VIJOICE is missed, it can be taken with food within 9 hours after the time it is usually taken. After more than 9 hours, skip the dose for that day. The next day, take VIJOICE at the usual time. If the patient vomits after taking the dose, advise the patient not to take an additional dose on that day, and to resume the dosing schedule the next day at the usual time. 2.4 VIJOICE Preparation and Administration Instructions VIJOICE Tablets Swallow VIJOICE tablets whole, or prepare as a suspension to administer orally, or via feeding tubes. VIJOICE Tablets, Whole Swallow VIJOICE tablets whole and take with food. Do not chew, divide, or crush. Do not use broken, cracked, or damaged tablets. VIJOICE Tablets Prepared as a Suspension for Oral use, or Feeding Tubes (Nasogastric or Gastric Tube) Administration For patients who are not able to swallow tablets, or who are using a feeding tube, prepare and administer VIJOICE as a suspension and take with food [see Clinical Pharmacology (12.3)] . To prepare VIJOICE tablets as a suspension for oral use, place VIJOICE tablets in a cup containing 2 to 4 ounces of water. To prepare VIJOICE tablets as a suspension for feeding tubes administration, place VIJOICE tablets in a cup containing 1 to 2 ounces of water. Make the suspension with water only. Let tablets stand in water for approximately 5 minutes. Crush the tablets with a spoon and stir until a suspension is obtained. Immediately after preparation, administer the suspension as directed below. If not administered immediately after preparation, stir the suspension with the same spoon to re-suspend any particles before administration. Discard the suspension if it is not administered within 60 minutes after preparation. Oral Administration Administer the suspension from the cup. After administration of the suspension, add approximately 1 to 2 ounces of water to the same cup. Stir with the same spoon to re-suspend any remaining particles and administer the entire contents of the cup orally. Repeat if particles remain. Feeding Tubes Administration Administer VIJOICE tablets prepared as a suspension via French size 5 to 12 diameter silicone or polyurethane nasogastric tubes, or via French size 12 to 24 diameter silicone gastric tubes. Withdraw VIJOICE suspension from the cup into an enteral syringe and administer it via the nasogastric or gastric tube. After administration, add approximately 1 to 2 ounces (approximately 30 to 60 mL) of water to the same cup. Stir with the same spoon to re-suspend any remaining particles. Withdraw the contents of the cup into the same enteral syringe and administer it via the nasogastric or gastric tube. Repeat if particles remain. VIJOICE Oral Granules Administer VIJOICE oral granules directly onto the tongue with water, or prepare as a suspension or a mixture for oral use. To administer via feeding tubes prepare the suspension with water only. Each packet is for single use only. No packet should be used if the packet seal is broken. Do not attempt to use partial quantities of oral granules from 50 mg granules packets to prepare a dose.
Dosage forms and strengths
Tablets 50 mg: Light yellow, unscored, round and curved with beveled edges film-coated tablet, debossed with “C7” on one side and “NVR” on the other side. 125 mg: Dark yellow, unscored, ovaloid and curved with beveled edges film-coated tablet, debossed with “Y7” on one side and “NVR” on the other side. 200 mg: Pale yellow, unscored, ovaloid and curved with beveled edges film-coated tablet, debossed with “CL7” on one side and “NVR” on the other side. Oral Granules 50 mg: White to almost white free flowing mixture of powder and granules in packets. Tablets: 50 mg, 125 mg, and 200 mg ( 3 ) Oral Granules: 50 mg ( 3 )
Contraindications
4 CONTRAINDICATIONS VIJOICE is contraindicated in patients with severe hypersensitivity to alpelisib or any of its ingredients [see Warnings and Precautions (5.1)] . Severe hypersensitivity to VIJOICE or to any of its ingredients. ( 4 )
Warnings and precautions
Severe Hypersensitivity : Permanently discontinue VIJOICE. Promptly initiate appropriate treatment. ( 5.1 ) Severe Cutaneous Adverse Reactions (SCARs) : VIJOICE can cause SCARs, including Stevens-Johnson syndrome (SJS), erythema multiforme (EM), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS). Interrupt VIJOICE for signs or symptoms of SCARs. Permanently discontinue VIJOICE if SCARs are confirmed. ( 2.5 , 5.2 ) Hyperglycemia : VIJOICE can cause severe hyperglycemia, in some cases associated with hyperglycemic hyperosmolar non-ketotic syndrome (HHNKS) or ketoacidosis. The safety of VIJOICE in patients with Type 1 or uncontrolled Type 2 diabetes has not been established. Before initiating treatment with VIJOICE, test fasting plasma glucose (FPG), HbA1c, and optimize blood glucose. After initiating treatment, monitor periodically. Initiate or optimize anti-hyperglycemic medications as clinically indicated. Interrupt, reduce dose, or discontinue VIJOICE if severe hyperglycemia occurs. ( 2.5 , 5.3 ) Pneumonitis : VIJOICE can cause severe pneumonitis and interstitial lung disease. Monitor for clinical symptoms or radiological changes. Permanently discontinue VIJOICE if pneumonitis occurs. ( 2.5 , 5.4 ) Diarrhea or Colitis : VIJOICE can cause severe diarrhea, resulting in dehydration and in some cases in acute kidney injury, as well as colitis. Monitor for diarrhea and additional symptoms of colitis, including abdominal pain and mucus or blood in stool. Interrupt, reduce dose, or permanently discontinue VIJOICE based on severity of diarrhea or colitis. Patients with colitis may require additional treatment, such as enteric-acting and/or systemic steroids. ( 2.5 , 5.5 ) Embryo-Fetal Toxicity : VIJOICE can cause fetal harm. Advise patients of potential risk to a fetus and to use effective contraception. ( 5.6 , 8.1 , 8.3 ) 5.1 Severe Hypersensitivity Severe hypersensitivity reactions, including anaphylaxis, anaphylactic shock, and angioedema, have occurred in adult patients treated with alpelisib in the oncology setting and in patients treated with VIJOICE [see Adverse Reactions (6.1)] . VIJOICE is not approved for use in the oncology setting. Permanently discontinue VIJOICE in the event of severe hypersensitivity [see Contraindications (4)] . 5.2 Severe Cutaneous Adverse Reactions Severe cutaneous adverse reactions (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. VIJOICE is not approved for use in the oncology setting. 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 or systemic corticosteroids, or oral antihistamine treatment as described in Table 4 [see Dosage and Administration (2.5)] . 5.3 Hyperglycemia Severe hyperglycemia, in some cases associated with hyperglycemic hyperosmolar non-ketotic 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. VIJOICE is not approved for use in the oncology setting. In the EPIK-P1 study, Grade 1 or 2 hyperglycemia was reported in 12% of patients treated with VIJOICE [see Adverse Reactions (6.1)] . 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 (BMI ≥ 30), elevated FPG, HbA1c at the upper limit of normal or above, use of concomitant systemic corticosteroids, or age ≥ 75 [see Use in Specific Populations (8.5)] . 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 anti-hyperglycemic 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 healthcare practitioner 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, or permanently discontinue VIJOICE based on the severity as described in Table 5 [see Dosage and Administration (2.5)] . 5.4 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. VIJOICE is not approved for use in the oncology setting. 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.
Side effects
The following clinically significant adverse reactions are discussed elsewhere in the labeling: Severe Hypersensitivity [see Warnings and Precautions (5.1)] Severe Cutaneous Adverse Reactions [see Warnings and Precautions (5.2)] Hyperglycemia [see Warnings and Precautions (5.3)] Pneumonitis [see Warnings and Precautions (5.4)] Diarrhea or Colitis [see Warnings and Precautions (5.5)] Most common adverse reactions (Grades 1 to 4, incidence ≥ 10%) were diarrhea, stomatitis, and hyperglycemia. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Novartis Pharmaceuticals Corporation at 1-888-669-6682 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. The safety of VIJOICE was evaluated in EPIK-P1 (NCT04285723), a single-arm clinical study in patients who were treated as part of an expanded access program for compassionate use. Fifty-seven patients 2 years of age and older with severe or life-threatening PIK3CA-Related Overgrowth Spectrum (PROS) received VIJOICE based on age at dosages ranging from 50 mg to 250 mg orally once daily [see Clinical Studies (14)] . Among patients who received VIJOICE, 95% were exposed for 6 months or longer and 79% were exposed for greater than one year. The median age of patients who received VIJOICE was 14 years (range, 2 to 50); 58% were female; 12% were White and race was not reported for 88%. Serious adverse reactions occurred in 12% of patients who received VIJOICE. Serious adverse reactions occurring in two or more patients included dehydration (n = 2) and cellulitis (n = 2). Dosage interruption of VIJOICE due to an adverse reaction occurred in 11% of patients. Adverse reactions which required dosage interruption in two or more patients included dizziness (n = 2) and vomiting (n = 2). Dose reductions of VIJOICE due to an adverse reaction occurred in 5% of patients. Adverse reactions which required dose reduction included alopecia, memory impairment, and soft tissue infection. The most common adverse reactions (≥ 10%) were diarrhea, stomatitis, and hyperglycemia. The most common Grade 3 or 4 laboratory abnormalities (≥ 2%) were increased glucose, decreased hemoglobin, decreased phosphate, increased bilirubin, decreased sodium, and decreased platelets. Adverse reactions and laboratory abnormalities are listed in Table 10 and Table 11, respectively. Table 10: Adverse Reactions (≥ 5%) in Patients with PROS Who Received VIJOICE in EPIK-P1 Grading according to CTCAE Version 4.03. a Stomatitis: including stomatitis and aphthous ulcer. VIJOICE N = 57 Adverse reactions All Grades (%) Grade 3 or 4 (%) Gastrointestinal disorders Diarrhea 16 0 Stomatitis a 16 0 Metabolism and nutrition disorders Hyperglycemia 12 0 Skin and subcutaneous tissue disorders Eczema 7 0 Dry skin 7 0 Alopecia 5 0 Nervous system disorders Headache 5 0 Infections and infestations Cellulitis 5 3.5 Clinically relevant adverse reactions in < 5% of patients who received VIJOICE included nausea, vomiting, dehydration, and mucosal dryness. Table 11: Laboratory Abnormalities Worsening from Baseline in ≥ 10% of Patients with PROS Who Received VIJOICE in EPIK-P1 Grading according to CTCAE Version 4.03. Abbreviation: N/A, not available. a The denominator used to calculate the rate varied from 9 to 50 based on the number of patients with a baseline value and at least one post-treatment value. b No Grade 4 laboratory abnormalities were reported. c Glucose increase is an expected laboratory abnormality of PI3K inhibition. d No CTCAE grade available. For HbA1c, baseline values increasing post-treatment to a value above the upper limit of the normal range (≥ 5.7%) are considered increased. Laboratory abnormality VIJOICE a N = 57 All Grades % Grade 3 or 4 % Chemistry Decreased calcium (corrected) 60 0 Decreased phosphate 59 5 b Increased glucose c 56 11 b Increased glycosylated hemoglobin (HbA1c) d 38 d N/A d Increased creatinine 31 0 Increased bilirubin 29 2 b Increased potassium 24 0 Increased triglycerides 19 0 Decreased magnesium 18 0 Increased aspartate aminotransferase (AST) 17 0 Increased cholesterol 13 0 Decreased albumin 13 0 Decreased sodium 12 2 b Decreased potassium 12 0 Increased gamma glutamyl transferase (GGT) 11 0 Increased alanine aminotransferase (ALT) 10 0 Hematology Decreased leukocyte 22 0 Decreased hemoglobin 20 6 b Decreased lymphocyte 20 0 Decreased neutrophil 19 0 Increased lymphocyte 17 0 Decreased platelets 14 2 b Other Clinical Trials Experience The following additional adverse reactions and laboratory abnormality have been identified following administration of VIJOICE: hypersensitivity, lipase increased, dermatitis, and abdominal pain. 6.2 Postmarketing Experience and Other Spontaneous Adverse Reaction Reports The following adverse reactions have been identified with VIJOICE use in patients with PROS in an expanded access program for compassionate use. Because these reactions are reported from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Metabolism and nutrition disorders: Decreased appetite. Skin and subcutaneous tissue disorders: Pruritus, rash (including rash maculo-papular, rash erythematous, rash papular, and rash pruritic), acne (including dermatitis acneiform).
Drug interactions
7 DRUG INTERACTIONS CYP3A4 Inducers : Avoid coadministration of VIJOICE with a strong CYP3A4 inducer. Consider an alternative concomitant drug with no or minimal potential to induce CYP3A4. ( 7.1 ) Breast Cancer Resistance Protein (BCRP) Inhibitors : Avoid the use of BCRP inhibitors in patients treated with VIJOICE. If unable to use alternative drugs, closely monitor for increased adverse reactions. ( 7.1 ) 7.1 Effect of Other Drugs on VIJOICE CYP3A4 Inducers Avoid coadministration of VIJOICE with strong CYP3A4 inducers and consider an alternative concomitant drug with no or minimal potential to induce CYP3A4. Alpelisib is metabolized by CYP3A4. Concomitant use of VIJOICE with a strong CYP3A4 inducer may decrease alpelisib concentration [see Clinical Pharmacology (12.3)] , which may decrease alpelisib activity. Breast Cancer Resistance Protein Inhibitors (BCRP) Avoid the use of BCRP inhibitors in patients treated with VIJOICE. If unable to use alternative drugs, when VIJOICE is used in combination with BCRP inhibitors, closely monitor for increased adverse reactions. Alpelisib is transported by BCRP. Concomitant use of VIJOICE with a BCRP inhibitor may increase alpelisib exposure [see Clinical Pharmacology (12.3)] , which may increase the risk of adverse reactions.
Use in specific populations
Lactation : Advise not to breastfeed. ( 8.2 ) 8.1 Pregnancy Risk Summary Based on animal data and mechanism of action, VIJOICE can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1)] . There are no available data in pregnant women to inform the drug-associated risk. In animal reproduction studies, oral administration of alpelisib to pregnant rats and rabbits during organogenesis caused adverse developmental outcomes, including embryo-fetal mortality (post-implantation loss), reduced fetal weights, and increased incidences of fetal malformations at doses described below ( see Data ). Advise pregnant women of the potential risk to a fetus. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. However, 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 embryo-fetal development studies in rats and rabbits, pregnant animals received oral doses of alpelisib during the period of organogenesis. In the rat study, animals were dosed at 3, 10, or 30 mg/kg/day from gestation day 6 to 17; and in the rabbit study, animals were dosed at 3, 15, 25, and 30 mg/kg/day from gestation day 7 to 20. In rats, oral administration of alpelisib resulted in maternal toxicity (body weight loss, low food consumption) and no viable fetuses (post-implantation loss) at 30 mg/kg/day (approximately 3.6 to 1.2 times the initial recommended doses of 50 mg and 250 mg in pediatric and adult patients, respectively, based on BSA). At a dose of 10 mg/kg/day (approximately 1.2 to 0.4 times the initial recommended doses of 50 mg and 250 mg in pediatric and adult patients, respectively, based on BSA), toxicities included reduced fetal weight and increased incidences of skeletal malformations (bent scapula and thickened or bent long bones) and fetal variations (enlarged brain ventricle, decreased bone ossification). In a pilot embryo-fetal development study in rabbits, a dose of 30 mg/kg/day (approximately 7 to 2.2 times the initial recommended doses of 50 mg and 250 mg in pediatric and adult patients based on BSA) resulted in no viable fetuses (post-implantation loss). Doses ≥ 15 mg/kg/day (approximately 3.5 to 1.1 times the initial recommended doses of 50 mg and 250 mg in pediatric and adult patients, respectively, based on BSA) resulted in increased embryo-fetal deaths, reduced fetal weights, and malformations, mostly related to the tail and head. 8.2 Lactation Risk Summary There are no data on the presence of alpelisib in human milk, its effects on milk production, or the breastfed child. Because of the potential for serious adverse reactions in the breastfed child, advise lactating women to not breastfeed during treatment with VIJOICE and for 1 week after the last dose. 8.3 Females and Males of Reproductive Potential Pregnancy Testing Verify the pregnancy status in females of reproductive potential prior to initiating VIJOICE. Contraception Females VIJOICE can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1)] . Advise females of reproductive potential to use effective contraception during treatment with VIJOICE and for 1 week after the last dose. Males 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. Infertility Based on findings from animal studies, VIJOICE may impair fertility in males and females of reproductive potential [see Nonclinical Toxicology (13.1)] . 8.4 Pediatric Use The safety and effectiveness of VIJOICE have been established in pediatric patients 2 to less than 18 years of age with PROS based on results from a single-arm clinical study of VIJOICE (EPIK-P1) that enrolled 39 pediatric patients: 11 patients aged 2 to 5 years, 12 patients aged 6 to 11 years, and 16 patients aged 12 to less than 18 years of age [see Adverse Reactions (6.1) and Clinical Studies (14)] . The safety and effectiveness of VIJOICE in pediatric patients below the age of 2 years have not been established. Although there were no new safety signals observed in pediatric patients, there is insufficient data to determine whether VIJOICE has an adverse impact on growth and development in pediatric patients with PROS. Based on the animal toxicity data (described below), regular monitoring of growth and development in pediatric patients treated with VIJOICE is recommended. Animal Toxicity Data In a 4-week general toxicology study, rats administered alpelisib had growth plate thickening and decreased trabeculae of the knee joint, dentin thinning, and degenerative odontoblasts at the dose of 30 mg/kg/day (approximately 2.8 to 1.2 times the initial recommended doses of 50 mg and 250 mg in pediatric and adult patients, respectively, based on BSA). Dentin thinning/irregular dentin was also observed in the 13-week toxicology study in rats at the high dose of 20 mg/kg/day (approximately 2 to 0.8 times the initial recommended doses of 50 mg and 250 mg in pediatric and adult patients, respectively, based on BSA). 8.5 Geriatric Use There were no adult patients aged 65 years of age or older who received VIJOICE in EPIK-P1.
Pregnancy
8.1 Pregnancy Risk Summary Based on animal data and mechanism of action, VIJOICE can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1)] . There are no available data in pregnant women to inform the drug-associated risk. In animal reproduction studies, oral administration of alpelisib to pregnant rats and rabbits during organogenesis caused adverse developmental outcomes, including embryo-fetal mortality (post-implantation loss), reduced fetal weights, and increased incidences of fetal malformations at doses described below ( see Data ). Advise pregnant women of the potential risk to a fetus. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. However, 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 embryo-fetal development studies in rats and rabbits, pregnant animals received oral doses of alpelisib during the period of organogenesis. In the rat study, animals were dosed at 3, 10, or 30 mg/kg/day from gestation day 6 to 17; and in the rabbit study, animals were dosed at 3, 15, 25, and 30 mg/kg/day from gestation day 7 to 20. In rats, oral administration of alpelisib resulted in maternal toxicity (body weight loss, low food consumption) and no viable fetuses (post-implantation loss) at 30 mg/kg/day (approximately 3.6 to 1.2 times the initial recommended doses of 50 mg and 250 mg in pediatric and adult patients, respectively, based on BSA). At a dose of 10 mg/kg/day (approximately 1.2 to 0.4 times the initial recommended doses of 50 mg and 250 mg in pediatric and adult patients, respectively, based on BSA), toxicities included reduced fetal weight and increased incidences of skeletal malformations (bent scapula and thickened or bent long bones) and fetal variations (enlarged brain ventricle, decreased bone ossification). In a pilot embryo-fetal development study in rabbits, a dose of 30 mg/kg/day (approximately 7 to 2.2 times the initial recommended doses of 50 mg and 250 mg in pediatric and adult patients based on BSA) resulted in no viable fetuses (post-implantation loss). Doses ≥ 15 mg/kg/day (approximately 3.5 to 1.1 times the initial recommended doses of 50 mg and 250 mg in pediatric and adult patients, respectively, based on BSA) resulted in increased embryo-fetal deaths, reduced fetal weights, and malformations, mostly related to the tail and head.
Pediatric use
8.4 Pediatric Use The safety and effectiveness of VIJOICE have been established in pediatric patients 2 to less than 18 years of age with PROS based on results from a single-arm clinical study of VIJOICE (EPIK-P1) that enrolled 39 pediatric patients: 11 patients aged 2 to 5 years, 12 patients aged 6 to 11 years, and 16 patients aged 12 to less than 18 years of age [see Adverse Reactions (6.1) and Clinical Studies (14)] . The safety and effectiveness of VIJOICE in pediatric patients below the age of 2 years have not been established. Although there were no new safety signals observed in pediatric patients, there is insufficient data to determine whether VIJOICE has an adverse impact on growth and development in pediatric patients with PROS. Based on the animal toxicity data (described below), regular monitoring of growth and development in pediatric patients treated with VIJOICE is recommended. Animal Toxicity Data In a 4-week general toxicology study, rats administered alpelisib had growth plate thickening and decreased trabeculae of the knee joint, dentin thinning, and degenerative odontoblasts at the dose of 30 mg/kg/day (approximately 2.8 to 1.2 times the initial recommended doses of 50 mg and 250 mg in pediatric and adult patients, respectively, based on BSA). Dentin thinning/irregular dentin was also observed in the 13-week toxicology study in rats at the high dose of 20 mg/kg/day (approximately 2 to 0.8 times the initial recommended doses of 50 mg and 250 mg in pediatric and adult patients, respectively, based on BSA).
Geriatric use
8.5 Geriatric Use There were no adult patients aged 65 years of age or older who received VIJOICE in EPIK-P1.
Overdosage
There is limited experience of overdose with alpelisib in clinical trials. In cases where accidental overdosage of alpelisib was reported in the clinical studies, the adverse reactions associated with the overdose were consistent with the known safety profile of alpelisib and included hyperglycemia, nausea, asthenia, and rash. Initiate general symptomatic and supportive measures in all cases of overdosage where necessary. There is no known antidote for VIJOICE.
Description
(alpelisib) is a kinase inhibitor. The chemical name of alpelisib is (2 S )- N 1 -[4-Methyl-5-[2-(2,2,2-trifluoro-1,1-dimethylethyl)-4-pyridinyl]-2-thiazolyl]-1,2-pyrrolidinedicarboxamide. Alpelisib is a white to almost white powder. The molecular formula for alpelisib is C 19 H 22 F 3 N 5 O 2 S and the relative molecular mass is 441.47 g/mol. The pH of a 1.0% (m/V) solution of alpelisib in water/ethanol (50:50 V/V) is approximately 6.2. The chemical structure of alpelisib is shown below: VIJOICE film-coated tablets are supplied for oral administration with three strengths that contain 50 mg, 125 mg, and 200 mg of alpelisib. The tablets also contain hypromellose, magnesium stearate, mannitol, microcrystalline cellulose, and sodium starch glycolate. The film-coating contains hypromellose, iron oxide red (applicable only to 50 mg and 200 mg strengths), iron oxide yellow, macrogol/polyethylene glycol (PEG) 4000, talc, and titanium dioxide. VIJOICE oral granules are supplied for oral administration with one strength that contains 50 mg of alpelisib. The granules also contain hypromellose, magnesium stearate, mannitol, microcrystalline cellulose, and sodium starch glycolate. alpelisib structural formula
Mechanism of action
12.1 Mechanism of Action Alpelisib is an inhibitor of phosphatidylinositol-3-kinase (PI3K) with inhibitory activity predominantly against PI3Kα. Gain-of-function mutations in the gene encoding the catalytic α-subunit of PI3K (PIK3CA) lead to activation of PI3Kα and Akt-signaling, cellular transformation and the generation of tumors in in vitro and in vivo models. Activating mutations in PIK3CA have been found to induce a spectrum of overgrowths and malformations comprising a wide group of clinically recognizable disorders commonly known as PROS. In an inducible mouse model of Congenital Lipomatous Overgrowth, Vascular Malformations, Epidermal Nevi, Scoliosis/Skeletal and Spinal syndrome (CLOVES), a phenotype of PROS, alpelisib inhibition of the PI3K pathway resulted in the prevention or improvement of organ abnormalities associated with the disease, depending on when alpelisib treatment was started. These findings were reversed after withdrawal of alpelisib.
How supplied
(alpelisib) 50 mg, 125 mg, and 200 mg film-coated tablets are available in blister packs based on daily dose as described in Table 13. Table 13: VIJOICE Tablets Daily Dose Blister Packs Daily dose Each carton contains Each child-resistant blister pack contains Appearance of tablet NDC 50 mg daily dose One 28-day supply blister pack 28 tablets: 50 mg alpelisib per tablet Light yellow, unscored, round and curved with beveled edges, debossed with “C7” on one side and “NVR” on the other side NDC 0078-1021-84 125 mg daily dose One 28-day supply blister pack 28 tablets: 125 mg alpelisib per tablet Dark yellow, unscored, ovaloid and curved with beveled edges, debossed with “Y7” on one side and “NVR” on the other side NDC 0078-1028-84 250 mg daily dose Two 14-day supply blister packs (56 tablets total) 14 tablets: 200 mg alpelisib per tablet, and 14 tablets: 50 mg alpelisib per tablet Pale yellow, unscored, ovaloid and curved with beveled edges, debossed with “CL7” on one side and “NVR” on the other side Light yellow, unscored, round and curved with beveled edges, debossed with “C7” on one side and “NVR” on the other side NDC 0078-1035-02 Table 14: VIJOICE Oral Granules Daily dose Each carton contains Each child-resistant packet contains Appearance NDC 50 mg daily dose 28 packets (28-day supply of single-use packets) 50 mg alpelisib White to almost white free flowing mixture of powder and granules NDC 0078-1175-51 Store at 20°C to 25°C (68°F to 77°F), excursions permitted between 15°C and 30°C (59°F and 86°F) [see USP Controlled Room Temperature].
Patient information
Advise the patient and their caregivers to read the FDA-approved patient labeling (Patient Information). Severe Hypersensitivity Inform patients and their caregivers of the signs and symptoms of hypersensitivity. Advise patients and their caregivers to contact their healthcare provider immediately for signs and symptoms of hypersensitivity [see Warnings and Precautions (5.1)] . Severe Cutaneous Adverse Reactions Inform patients and their caregivers of the signs and symptoms of severe cutaneous adverse reactions (SCARs). Advise patients and their caregivers to contact their healthcare provider immediately for signs and symptoms of SCARs (e.g., a prodrome of fever, flu-like symptoms, mucosal lesions, progressive skin rash, or lymphadenopathy) [see Warnings and Precautions (5.2)] . Hyperglycemia Advise patients and their caregivers that VIJOICE may cause hyperglycemia and the need to monitor fasting glucose periodically during therapy. Advise patients and their caregivers of the signs and symptoms of hyperglycemia (e.g., excessive thirst, urinating more often than usual or higher amount of urine than usual, or increased appetite with weight loss) [see Warnings and Precautions (5.3)] . Pneumonitis Inform patients and their caregivers that VIJOICE may cause pneumonitis and to immediately report new or worsening respiratory symptoms [see Warnings and Precautions (5.4)] . Diarrhea or Colitis Advise patients and their caregivers that VIJOICE 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 VIJOICE [see Warnings and Precautions (5.5)] . Advise patients and their caregivers that VIJOICE may cause colitis and to notify their healthcare provider immediately of any symptoms of colitis, such as abdominal pain and mucus or blood in stool, while taking VIJOICE [see Warnings and Precautions (5.5)] . Alopecia Advise patients and caregivers that VIJOICE may cause alopecia [see Adverse Reactions (6.1)] . Advise patients and caregivers to contact a dermatologist if alopecia becomes a concern [see Dosage and Administration (2.5)] . 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 (5.6) and Use in Specific Populations (8.1)] . Advise females of reproductive potential to use effective contraception during treatment with VIJOICE 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 condoms and effective contraception during treatment with VIJOICE and for 1 week after the last dose [see Use in Specific Populations (8.3)]. Lactation Advise women not to breastfeed during treatment with VIJOICE and for 1 week after the last dose [see Use in Specific Populations (8.2)] . Infertility Advise males and females of reproductive potential that VIJOICE may impair fertility [see Use in Specific Populations (8.3)] . Drug Interactions Advise patients and their caregivers to inform their healthcare providers of all concomitant medications, herbal and dietary supplements [see Drug Interactions (7.1)] . Dosing Instruct patients and their caregivers of the following: Take VIJOICE with food at approximately the same time each day [see Dosage and Administration (2.3)] . Swallow the tablets whole (tablets should not be crushed, chewed, or split prior to swallowing) [see Dosage and Administration (2.4)] . For patients unable to swallow tablets, advise how to prepare an oral suspension using the tablets or how to take the oral granules (if applicable) [see Dosage and Administration (2.4)] . If a dose of VIJOICE is missed, it can be taken with food within 9 hours after the time it is usually taken. After more than 9 hours, skip the dose for that day. The next day, take VIJOICE at the usual time. Instruct patients not to take 2 doses to make up for a missed dose [see Dosage and Administration (2.3)]. If vomiting occurs after taking the dose of VIJOICE, they should not take an additional dose on that day and should resume the usual dosing schedule the next day at the usual time [see Dosage and Administration (2.3)]. Distributed by Novartis Pharmaceuticals Corporation East Hanover, New Jersey 07936 © Novartis T2025-38
Label text from the FDA structured product label by Novartis Pharmaceuticals Corporation (revised Nov 4, 2025). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Alpelisib in 3 products
Vijoice NDC products (4)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 0078-1021 | Alpelisib 50 mg/1 Tablet | Novartis Pharmaceuticals Corporation | NDA |
| 0078-1028 | Alpelisib 125 mg/1 Tablet | Novartis Pharmaceuticals Corporation | NDA |
| 0078-1035 | Kit | Novartis Pharmaceuticals Corporation | NDA |
| 0078-1175 | Alpelisib 50 mg/1 Granule | Novartis Pharmaceuticals Corporation | NDA |
Frequently asked questions
What is Vijoice used for?
1 INDICATIONS AND USAGE VIJOICE 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…
What are the side effects of Vijoice?
The following clinically significant adverse reactions are discussed elsewhere in the labeling: Severe Hypersensitivity [see Warnings and Precautions (5.1)] Severe Cutaneous Adverse Reactions [see Warnings and Precautions (5.2)] Hyperglycemia [see Warnings and Precautions (5.3)] Pneumonitis [see Warnings and Precautions (5.4)] Diarrhea or Colitis [see Warnings and Precautions (5.5)] Most common… See the full label for the complete list.
Who makes Vijoice?
Vijoice is listed by 1 labeler in the FDA NDC directory, including Novartis Pharmaceuticals Corporation.