Piqray

Q: Who makes Piqray?

Piqray is listed by 1 labeler in the FDA NDC directory, including Novartis Pharmaceuticals Corporation.

Alpelisib · Tablet · Oral

Prescription (Rx)

Uses

1 INDICATIONS AND USAGE PIQRAY is indicated in combination with fulvestrant for the treatment of adults with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, PIK3CA-mutated, advanced or metastatic breast cancer as detected by an FDA-approved test following progression on or after an endocrine-based regimen. PIQRAY is a kinase inhibitor indicated in combination with fulvestrant for the treatment of adults with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, PIK3CA-mutated, advanced or metastatic breast cancer as detected by an FDA-approved test following progression on or after an endocrine-based regimen.

Dosage and administration

Recommended Dose: 300 mg (two 150 mg tablets) taken orally once daily with food. ( 2.2 ) For adverse reactions, consider dose interruption, dose reduction, or discontinuation. ( 2.3 ) 2.1 Patient Selection Select patients for the treatment of HR-positive, HER2-negative advanced or metastatic breast cancer with PIQRAY, based on the presence of one or more PIK3CA mutations in tumor tissue or plasma specimens [see Clinical Studies (14)] . If no mutation is detected in a plasma specimen, test tumor tissue. Information on FDA-approved tests for the detection of PIK3CA mutations in breast cancer is available at: http://www.fda.gov/CompanionDiagnostics. 2.2 Dosage and Administration The recommended dose of PIQRAY is 300 mg (two 150 mg film-coated tablets) taken orally, once daily, with food [see Clinical Pharmacology (12.3)] . Continue treatment until disease progression or unacceptable toxicity occurs [see Dosage and Administration (2.3)] . Patients should take their dose of PIQRAY at approximately the same time each day. Swallow PIQRAY tablets whole (tablets should not be chewed, crushed or split prior to swallowing). No tablet should be ingested if it is broken, cracked, or otherwise not intact. If a dose of PIQRAY 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 PIQRAY 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. When given with PIQRAY, the recommended dose of fulvestrant is 500 mg administered on Days 1, 15, and 29, and once monthly thereafter. Refer to the Full Prescribing Information for fulvestrant. 2.3 Dose Modifications for Adverse Reactions The recommended dose modifications for adverse reactions are listed in Table 1. Table 1: PIQRAY Dose Reduction Guidelines for Adverse Reactions 1 1 Only one dose reduction is permitted for pancreatitis. 2 If further dose reduction below 200 mg once daily is required, discontinue PIQRAY. PIQRAY dose level Dose and schedule Number and strength of tablets Starting dose 300 mg once daily Two 150 mg tablets First-dose reduction 250 mg once daily One 200 mg tablet and one 50 mg tablet Second-dose reduction 200 mg once daily 2 One 200 mg tablet Tables 2, 3, 4, and 5 summarize recommendations for dose interruption, reduction, or discontinuation of PIQRAY in the management of specific adverse reactions. Cutaneous Adverse Reactions If a severe cutaneous adverse reaction (SCAR) is confirmed, permanently discontinue PIQRAY. Do not reintroduce PIQRAY in patients who have experienced previous SCAR during PIQRAY treatment [see Warnings and Precautions (5.2)] . Table 2: Dose Modification and Management for Rash and Severe Cutaneous Adverse Reactions (SCARs) 1 Grading according to Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. 2 For all grades of rash, consider consultation with a dermatologist. 3 Antihistamines administered prior to rash onset may decrease incidence and severity of rash based on the SOLAR-1 trial. [see Warnings and Precautions (5.1, 5.2)] Grade 1,2 Recommendation 3 Grade 1 (< 10% body surface area (BSA) with active skin toxicity) No PIQRAY dose adjustment required. Initiate topical corticosteroid treatment. Consider adding oral antihistamine to manage symptoms. If active rash is not improved within 28 days of appropriate treatment, add a low dose systemic corticosteroid. If the etiology is SCAR, permanently discontinue PIQRAY. Grade 2 (10%-30% BSA with active skin toxicity) No PIQRAY dose adjustment required. Initiate or intensify topical corticosteroid and oral antihistamine treatment. Consider low dose systemic corticosteroid treatment. If rash improves to Grade ≤ 1 within 10 days, systemic corticosteroid may be discontinued. If the etiology is SCAR, permanently discontinue PIQRAY. Grade 3 (e.g., severe rash not responsive to medical management) (> 30% BSA with active skin toxicity) Interrupt PIQRAY. Initiate or intensify topical/systemic corticosteroid and oral antihistamine treatment. If the etiology is SCAR, permanently discontinue PIQRAY. If the etiology is not a SCAR, interrupt dose until improvement to Grade ≤ 1, then resume PIQRAY at next lower dose level. Grade 4 (e.g., severe bullous, blistering or exfoliating skin conditions) (any % BSA associated with extensive superinfection, with IV antibiotics indicated; life-threatening consequences) Permanently discontinue PIQRAY. Hyperglycemia Before initiating treatment with PIQRAY, test fasting plasma glucose (FPG), HbA1c, and optimize blood glucose. Consider premedication with metformin prior to the initiation of PIQRAY in combination with fulvestrant based on patient risk factors for hyperglycemia, gastrointestinal tolerability, and clinical situation [see Warnings and Precautions (5.3) and Adverse Reactions (6.1)] . After initiating treatment with PIQRAY, 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. In patients with risk factors for hyperglycemia, monitor fasting glucose more closely and as clinically indicated [see Warnings and Precautions (5.3)] . Table 3: Dose Modification and Management for Hyperglycemia Abbreviation: ULN, upper limit of normal. 1 FPG/Fasting Blood Glucose/Grade levels reflect hyperglycemia grading according to Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03. 2 Initiate applicable anti-hyperglycemic medications, including metformin, SGLT2 inhibitors or insulin sensitizers (such as thiazolidinediones or dipeptidyl peptidase-4 inhibitors), and review respective prescribing information for dosing and dose titration recommendations, including local hyperglycemic treatment guidelines.

Dosage forms and strengths

Tablets: 50 mg, 150 mg, and 200 mg alpelisib 50 mg: Light pink, unscored, round and curved with beveled edges film-coated tablet, imprinted with “L7” on one side and “NVR” on the other side. 150 mg: Pale red, unscored, ovaloid and curved with beveled edges film-coated tablet, imprinted with “UL7” on one side and “NVR” on the other side. 200 mg: Light red, unscored, ovaloid and curved with beveled edges film-coated tablet, imprinted with “YL7” on one side and “NVR” on the other side. Tablets: 50 mg, 150 mg, and 200 mg

Contraindications

4 CONTRAINDICATIONS PIQRAY is contraindicated in patients with severe hypersensitivity to it or any of its components [see Warnings and Precautions (5.1)] . Severe hypersensitivity to PIQRAY or to any of its components. ( 4 )

Warnings and precautions

Severe Hypersensitivity : Permanently discontinue PIQRAY. Promptly initiate appropriate treatment. ( 5.1 ) Severe Cutaneous Adverse Reactions (SCARs) : PIQRAY 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 PIQRAY for signs or symptoms of SCARs. Permanently discontinue PIQRAY if SCARs are confirmed. ( 5.2 ) Hyperglycemia : PIQRAY can cause severe hyperglycemia, in some cases associated with hyperglycemic hyperosmolar non-ketotic syndrome (HHNKS) or ketoacidosis. Before initiating treatment with PIQRAY, test fasting plasma glucose (FPG), HbA1c, and optimize blood glucose. Consider premedication with metformin prior to the initiation of PIQRAY based on patient risk factors for hyperglycemia, gastrointestinal tolerability, and clinical situation. Use of metformin premedication prior to the initiation of PIQRAY decreases the incidence and severity of hyperglycemia, but increases the incidence and severity of nausea, vomiting, and diarrhea adverse reactions. After initiating treatment, monitor FPG and HbA1c periodically. Initiate or optimize anti-hyperglycemic medications as clinically indicated. Interrupt, reduce dose, or discontinue PIQRAY if severe hyperglycemia occurs. ( 2.3 , 5.3 , 6.1 ) Pneumonitis : PIQRAY can cause severe pneumonitis and interstitial lung disease. Monitor for clinical symptoms or radiological changes. Interrupt or discontinue PIQRAY if severe pneumonitis occurs. ( 2.3 , 5.4 ) Diarrhea or Colitis : PIQRAY causes diarrhea in most patients and may be severe, resulting in dehydration and acute kidney injury. Advise patients to start antidiarrheal treatment, increase oral fluids, and notify their healthcare provider if diarrhea occurs. Colitis has been reported in patients treated with PIQRAY. Monitor for diarrhea and additional symptoms of colitis, including abdominal pain and mucus or blood in stool. Interrupt, reduce dose, or discontinue PIQRAY if severe diarrhea or colitis occurs. Patients with colitis may require additional treatment, such as enteric-acting and/or systemic steroids. ( 2.3 , 5.5 , 6.2 ) Embryo-Fetal Toxicity : PIQRAY can cause fetal harm. Advise patients of potential risk to a fetus and to use effective contraception. ( 5.6 , 8.1 , 8.3 ) Refer to the Full Prescribing Information of fulvestrant for pregnancy and contraception information. 5.1 Severe Hypersensitivity Severe hypersensitivity reactions, including anaphylaxis and anaphylactic shock, can occur in patients treated with PIQRAY. Severe hypersensitivity reactions were manifested by symptoms, including, but not limited to, dyspnea, flushing, rash, fever, or tachycardia. The incidence of Grade 3 and 4 hypersensitivity reactions was 0.7% [see Adverse Reactions (6)] . Angioedema has been reported in the postmarketing setting in patients treated with PIQRAY [see Adverse Reactions (6.2)] . Advise patients of the signs and symptoms of severe hypersensitivity reactions. Permanently discontinue PIQRAY in the event of severe hypersensitivity. 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) can occur in patients treated with PIQRAY. In the SOLAR-1 study, SJS and EM were reported in 0.4% and 1.1% of the patients, respectively [see Adverse Reactions (6.1)] . Drug reaction with eosinophilia and systemic symptoms (DRESS) was reported in patients treated with PIQRAY in the postmarketing setting [see Adverse Reactions (6.2)] . If signs or symptoms of SCARs occur, interrupt PIQRAY until the etiology of the reaction has been determined. Consultation with a dermatologist is recommended. If a SCAR is confirmed, permanently discontinue PIQRAY. Do not reintroduce PIQRAY in patients who have experienced previous severe cutaneous adverse reactions during PIQRAY treatment. If a SCAR is not confirmed, PIQRAY may require dose modifications, topical corticosteroids, or oral antihistamine treatment as described in Table 2 [see Dosage and Administration (2.3)] . Advise patients of the signs and symptoms of SCARs (e.g., a prodrome of fever, flu-like symptoms, mucosal lesions, progressive skin rash, or lymphadenopathy). 5.3 Hyperglycemia Severe hyperglycemia, in some cases associated with hyperglycemic hyperosmolar non-ketotic syndrome (HHNKS) or ketoacidosis has occurred in patients treated with PIQRAY. Fatal cases of ketoacidosis have occurred in the postmarketing setting. Hyperglycemia was reported in 65% of patients treated with PIQRAY. Grade 3 (FPG > 250 to 500 mg/dL) and Grade 4 (FPG > 500 mg/dL) hyperglycemia was reported in 33% and 3.9% of patients, respectively. Ketoacidosis was reported in 0.7% of patients (n = 2) treated with PIQRAY. Among the patients who experienced Grade ≥ 2 (FPG 160 to 250 mg/dL) hyperglycemia, the median time to first occurrence of hyperglycemia was 15 days (range, 5 to 517 days). In the 187 patients with hyperglycemia, 87% (163/187) were managed with anti-hyperglycemic medication, and 76% (142/187) reported use of metformin as single agent or in combination with other anti-hyperglycemic medication [i.e., insulin, dipeptidyl peptidase-4 (DPP-4) inhibitors, and sulfonylureas]. In patients with Grade ≥ 2 hyperglycemia with at least 1 grade improvement (n = 153), median time to improvement from the first event was 8 days (range, 2 to 65 days). In all patients with elevated FPG who continued fulvestrant treatment after discontinuing PIQRAY (n = 54), 96% (n = 52) of patients had FPG levels that returned to baseline. Before initiating treatment with PIQRAY, test fasting plasma glucose (FPG), HbA1c, and optimize blood glucose.

Side effects

The following adverse reactions are discussed in greater detail in other sections of 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, including laboratory abnormalities (all Grades, incidence ≥ 20%) were glucose increased, creatinine increased, diarrhea, rash, lymphocyte count decreased, gamma-glutamyl transferase (GGT) increased, nausea, alanine aminotransferase (ALT) increased, fatigue, hemoglobin decreased, lipase increased, decreased appetite, stomatitis, vomiting, weight decreased, calcium decreased, glucose decreased, activated partial thromboplastin time (aPTT) prolonged, and alopecia. ( 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 PIQRAY was evaluated in a randomized, double-blind, placebo-controlled trial (SOLAR-1) in 571 patients with HR-positive, HER2-negative, advanced or metastatic breast cancer enrolled into two cohorts, with or without a PIK3CA mutation [see Clinical Studies (14)] . Patients received either PIQRAY 300 mg plus fulvestrant (n = 284) or placebo plus fulvestrant (n = 287). Fulvestrant 500 mg was administered intramuscularly on Cycle 1, Day 1 and 15, and then at Day 1 of each 28-day cycle during treatment phase. Two patients (0.7%) died while on treatment with PIQRAY plus fulvestrant due to causes other than the underlying malignancy. Causes of death included one cardio-respiratory arrest and one second primary malignancy. Neither was suspected to be related to study treatment. Serious adverse reactions occurred in 35% of patients receiving PIQRAY plus fulvestrant. Serious adverse reactions in > 2% of patients receiving PIQRAY plus fulvestrant included hyperglycemia (10%), rash (3.5%), diarrhea (2.8%), acute kidney injury (2.5%), abdominal pain (2.1%), and anemia (2.1%). Osteonecrosis of the jaw (ONJ) was reported in 4.2% of patients (12/284) in the PIQRAY plus fulvestrant arm compared to 1.4% of patients (4/287) in the placebo arm. All patients experiencing ONJ had prior or concomitant bisphosphonates or RANK-ligand inhibitor administration. Among patients receiving PIQRAY plus fulvestrant, 4.6% permanently discontinued both PIQRAY and fulvestrant and 21% permanently discontinued PIQRAY alone, due to adverse reactions. The most frequent adverse reactions leading to treatment discontinuation of PIQRAY in > 2% patients receiving PIQRAY plus fulvestrant were hyperglycemia (6%), rash (4.2%), diarrhea (2.8%), and fatigue (2.5%). Dose reductions due to adverse reactions occurred in 55% of patients receiving PIQRAY plus fulvestrant. The most frequent adverse reactions leading to dose reduction in > 2% patients receiving PIQRAY plus fulvestrant were hyperglycemia (29%), rash (9%), diarrhea (6%), stomatitis (3.5%), and mucosal inflammation (2.1%). The most common adverse reactions, including laboratory abnormalities (all grades, incidence ≥ 20%) were glucose increased, creatinine increased, diarrhea, rash, lymphocyte count decreased, gamma-glutamyl transferase (GGT) increased, nausea, alanine aminotransferase (ALT) increased, fatigue, hemoglobin decreased, lipase increased, decreased appetite, stomatitis, vomiting, weight decreased, calcium decreased, glucose decreased, activated partial thromboplastin time (aPTT) prolonged, and alopecia. Adverse reactions and laboratory abnormalities are listed in Table 6 and Table 7, respectively. Table 6: Adverse Reactions Occurring in ≥ 10% and ≥ 2% Higher than Placebo Arm in SOLAR-1 (All Grades) Grading according to CTCAE Version 4.03. 1 Stomatitis: including stomatitis, aphthous ulcer and mouth ulceration. 2 Abdominal pain: abdominal pain, abdominal pain upper, abdominal pain lower. 3 Fatigue: including fatigue, asthenia. 4 Mucosal dryness: including dry mouth, mucosal dryness, vulvovaginal dryness. 5 Urinary tract infection: including UTI and single case of urosepsis. 6 Dysgeusia: including dysgeusia, ageusia, hypogeusia. 7 Rash: including rash, rash maculo-papular, rash macular, rash generalized, rash papular, rash pruritic. 8 Dry skin: including dry skin, skin fissures, xerosis, xeroderma. * No Grade 4 adverse reactions were reported. PIQRAY plus fulvestrant N = 284 Placebo plus fulvestrant N = 287 Adverse reactions All Grades Grade 3-4 All Grades Grade 3-4 % % % % Gastrointestinal disorders Diarrhea 58 7 * 16 0.3 * Nausea 45 2.5 * 22 0.3 * Stomatitis 1 30 2.5 * 6 0 * Vomiting 27 0.7 * 10 0.3 * Abdominal pain 2 17 1.4 * 11 1 * Dyspepsia 11 0 * 6 0 * General disorders and administration site conditions Fatigue 3 42 5 * 29 1 * Mucosal inflammation 19 2.1 * 1 0 * Edema peripheral 15 0 * 5 0.3 * Pyrexia 14 0.7 4.9 0.3 * Mucosal dryness 4 12 0.4 * 4.2 0 * Infections and infestations Urinary tract infection 5 10 0.7 * 5 1 * Investigations Weight decreased 27 3.9 * 2.1 0 * Metabolism and nutrition disorders Decreased appetite 36 0.7 * 10 0.3 * Nervous system disorders Dysgeusia 6 18 0.4 * 3.5 0 * Headache 18 0.7 * 13 0 * Skin and subcutaneous tissue disorders Rash 7 52 20 * 7 0.3 * Alopecia 20 0 * 2.4 0 * Pruritus 18 0.7 * 6 0 * Dry skin 8 18 0.4 * 3.8 0 * Among the patients with Grade 2 or 3 rash, the median time to first onset of Grade 2 or 3 rash was 12 days. A subgroup of 86 patients received premedication, including antihistamines, prior to onset of rash.

Drug interactions

7 DRUG INTERACTIONS CYP3A4 Inducers : Avoid coadministration of PIQRAY 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 PIQRAY. If unable to use alternative drugs, closely monitor for increased adverse reactions. ( 7.1 ) 7.1 Effect of Other Drugs on PIQRAY CYP3A4 Inducer Coadministration of PIQRAY with a strong CYP3A4 inducer decreases alpelisib concentration [see Clinical Pharmacology (12.3)] , which may reduce alpelisib efficacy. Avoid concomitant use of strong CYP3A4 inducers and consider an alternative concomitant drug with no or minimal potential to induce CYP3A4. Breast Cancer Resistance Protein Inhibitors Coadministration of PIQRAY with a breast cancer resistance protein (BCRP) inhibitor may increase alpelisib concentration [see Clinical Pharmacology (12.3)] , which may increase the risk of toxicities. Avoid the use of BCRP inhibitors in patients treated with PIQRAY. If unable to use alternative drugs, when PIQRAY is used in combination with BCRP inhibitors, closely monitor for increased adverse reactions.

Use in specific populations

Lactation : Advise not to breastfeed. ( 8.2 ) 8.1 Pregnancy Risk Summary PIQRAY is used in combination with fulvestrant. Refer to the Full Prescribing Information of fulvestrant for pregnancy information. Based on animal data and mechanism of action, PIQRAY 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 maternal exposures ≥ 0.8 times the exposure in humans based on AUC at the recommended dose of 300 mg/day (see Data) . Advise pregnant women and females of reproductive potential 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 up to 30 mg/kg/day during the period of organogenesis. 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 times the exposure in humans at the recommended dose of 300 mg/day based on AUC). At a dose of 10 mg/kg/day (approximately 0.8 times the exposure in humans at the recommended dose of 300 mg/day based on AUC), 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 resulted in no viable fetuses (post-implantation loss). Doses ≥ 15 mg/kg/day resulted in increased embryo-fetal deaths, reduced fetal weights, and malformations, mostly related to the tail and head. At 15 mg/kg/day in rabbits, the maternal exposure was approximately 5 times the exposure achieved at the recommended human dose of 300 mg/day based on AUC. 8.2 Lactation PIQRAY is used in combination with fulvestrant. Refer to the Full Prescribing Information of fulvestrant for lactation information. There is 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 PIQRAY and for 1 week after the last dose. 8.3 Females and Males of Reproductive Potential PIQRAY is used in combination with fulvestrant. Refer to the Full Prescribing Information of fulvestrant for contraception and infertility information. Pregnancy Testing Verify the pregnancy status in females of reproductive potential prior to initiating PIQRAY. Contraception Females PIQRAY 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 PIQRAY 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 PIQRAY and for 1 week after the last dose. Infertility Based on findings from animal studies, PIQRAY may impair fertility in males and females of reproductive potential [see Nonclinical Toxicology (13.1)] . 8.4 Pediatric Use The safety and efficacy of PIQRAY in pediatric patients have not been established. 8.5 Geriatric Use Of 284 patients who received PIQRAY in the SOLAR-1 trial, 117 patients were ≥ 65 years of age and 34 patients were ≥ 75 years of age. In patients treated with PIQRAY plus fulvestrant, there was a higher incidence of Grade 3-4 hyperglycemia in patients ≥ 65 years of age (44%) compared to patients < 65 years of age (32%). No overall differences in effectiveness of PIQRAY were observed between patients ≥ 65 years of age compared to younger patients. There are an insufficient number of patients ≥ 75 years of age to assess whether there are differences in safety or effectiveness. However, in the SOLAR-1 trial, an increase in the hyperglycemia adverse reactions (74% vs 66%) and Grade 3-4 (56% vs 36%) hyperglycemia were observed in patients ≥ 75 years of age compared to patients < 75 years of age, respectively [see Warnings and Precautions (5.3)] . 8.6 Renal Impairment The effect of severe renal impairment (CLcr < 30 mL/min) on alpelisib pharmacokinetics is unknown [see Clinical Pharmacology (12.3)] . No dose adjustment is recommended for patients with mild to moderate renal impairment (CLcr 30 to < 90 mL/min).

Pregnancy

8.1 Pregnancy Risk Summary PIQRAY is used in combination with fulvestrant. Refer to the Full Prescribing Information of fulvestrant for pregnancy information. Based on animal data and mechanism of action, PIQRAY 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 maternal exposures ≥ 0.8 times the exposure in humans based on AUC at the recommended dose of 300 mg/day (see Data) . Advise pregnant women and females of reproductive potential 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 up to 30 mg/kg/day during the period of organogenesis. 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 times the exposure in humans at the recommended dose of 300 mg/day based on AUC). At a dose of 10 mg/kg/day (approximately 0.8 times the exposure in humans at the recommended dose of 300 mg/day based on AUC), 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 resulted in no viable fetuses (post-implantation loss). Doses ≥ 15 mg/kg/day resulted in increased embryo-fetal deaths, reduced fetal weights, and malformations, mostly related to the tail and head. At 15 mg/kg/day in rabbits, the maternal exposure was approximately 5 times the exposure achieved at the recommended human dose of 300 mg/day based on AUC.

Pediatric use

8.4 Pediatric Use The safety and efficacy of PIQRAY in pediatric patients have not been established.

Geriatric use

8.5 Geriatric Use Of 284 patients who received PIQRAY in the SOLAR-1 trial, 117 patients were ≥ 65 years of age and 34 patients were ≥ 75 years of age. In patients treated with PIQRAY plus fulvestrant, there was a higher incidence of Grade 3-4 hyperglycemia in patients ≥ 65 years of age (44%) compared to patients < 65 years of age (32%). No overall differences in effectiveness of PIQRAY were observed between patients ≥ 65 years of age compared to younger patients. There are an insufficient number of patients ≥ 75 years of age to assess whether there are differences in safety or effectiveness. However, in the SOLAR-1 trial, an increase in the hyperglycemia adverse reactions (74% vs 66%) and Grade 3-4 (56% vs 36%) hyperglycemia were observed in patients ≥ 75 years of age compared to patients < 75 years of age, respectively [see Warnings and Precautions (5.3)] .

Overdosage

There is limited experience of overdose with PIQRAY in clinical trials. In the clinical studies, PIQRAY was administered at doses up to 450 mg once daily. In cases where accidental overdosage of PIQRAY was reported in the clinical studies, the adverse reactions associated with the overdose were consistent with the known safety profile of PIQRAY 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 PIQRAY.

Description

(alpelisib) is a kinase inhibitor. The chemical name of alpelisib is (2S)- 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 chemical structure of alpelisib is shown below: PIQRAY film-coated tablets are supplied for oral administration with three strengths that contain 50 mg, 150 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 black, iron oxide red, macrogol/polyethylene glycol (PEG) 4000, talc, and titanium dioxide. 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. In breast cancer cell lines, alpelisib inhibited the phosphorylation of PI3K downstream targets, including Akt and showed activity in cell lines harboring a PIK3CA mutation. In vivo, alpelisib inhibited the PI3K/Akt signaling pathway and reduced tumor growth in xenograft models, including models of breast cancer. PI3K inhibition by alpelisib treatment has been shown to induce an increase in estrogen receptor (ER) transcription in breast cancer cells. The combination of alpelisib and fulvestrant demonstrated increased anti-tumor activity compared to either treatment alone in xenograft models derived from ER-positive, PIK3CA mutated breast cancer cell lines.

How supplied

(alpelisib) 50 mg, 150 mg, and 200 mg film-coated tablets [see Dosage Forms and Strengths (3)] . Daily dose Each carton contains Each blister pack contains NDC 300 mg daily dose 2 blister packs (56 tablets total) A 14-day supply of 28 tablets (28 tablets, 150 mg alpelisib per tablet) NDC 0078-0708-02 250 mg daily dose 2 blister packs (56 tablets total) A 14-day supply of 28 tablets (14 tablets, 200 mg alpelisib per tablet and 14 tablets, 50 mg alpelisib per tablet) NDC 0078-0715-02 200 mg daily dose 1 blister pack (28 tablets total) A 28-day supply of 28 tablets (28 tablets, 200 mg alpelisib per tablet) NDC 0078-0701-84 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 to read the FDA-approved patient labeling (Patient Information). Severe Hypersensitivity Inform patients of the signs and symptoms of hypersensitivity. Advise patients to contact their healthcare provider immediately for signs and symptoms of hypersensitivity [see Warnings and Precautions (5.1)] . Severe Cutaneous Adverse Reactions Inform patients of the signs and symptoms of severe cutaneous adverse reactions (SCARs). Advise patients to contact their healthcare provider immediately for signs and symptoms of SCARs [see Warnings and Precautions (5.2)] . Hyperglycemia Advise patients that PIQRAY may cause hyperglycemia and the need to monitor fasting blood glucose periodically during therapy. Advise patients to contact their healthcare provider immediately for signs and symptoms of hyperglycemia [see Warnings and Precautions (5.3)] . Pneumonitis Inform patients that PIQRAY may cause pneumonitis and to immediately contact their healthcare provider if they experience respiratory problems [see Warnings and Precautions (5.4)] . Diarrhea or Colitis Advise patients that PIQRAY may cause diarrhea, which may be severe, and to start antidiarrheal treatment, increase oral fluids, and notify their healthcare provider if diarrhea occurs while taking PIQRAY [see Warnings and Precautions (5.5)] . Advise patients that PIQRAY 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 PIQRAY [see Warnings and Precautions (5.5)] . Uveitis Advise patients to contact their healthcare provider immediately for signs and symptoms of uveitis [see Adverse Reactions (6.2)] . 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 PIQRAY 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 PIQRAY and for 1 week after the last dose [see Use in Specific Populations (8.3)] . Refer to the Full Prescribing Information of fulvestrant for pregnancy and contraception information. Lactation Advise women not to breastfeed during treatment with PIQRAY and for 1 week after the last dose [see Use in Specific Populations (8.2)] . Refer to the Full Prescribing Information of fulvestrant for lactation information. Infertility Advise males and females of reproductive potential that PIQRAY may impair fertility [see Use in Specific Populations (8.3)] . Refer to the Full Prescribing Information of fulvestrant for infertility information. Drug Interactions Advise patients to avoid the use of strong CYP3A4 inducers in patients treated with PIQRAY. Advise patients to avoid the use of BCRP inhibitors while taking PIQRAY. If unable to use alternative drugs, closely monitor for increased adverse reactions. No dose adjustment is required when coadministering PIQRAY with CYP3A4, CYP2C8, CYP2C9, CYP2C19 and CYP2B6 substrates [see Drug Interactions (7.1, 7.2)] . Dosing Instruct patients to take PIQRAY at approximately the same time each day and to swallow the tablet(s) whole (tablets should not be chewed, crushed, or split prior to swallowing) [see Dosage and Administration (2.2)] . Advise patients to take PIQRAY with food [see Clinical Pharmacology (12.3)] . Instruct patients that if a dose of PIQRAY 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 PIQRAY at the usual time. Instruct patients not to take 2 doses to make up for a missed dose. Instruct patients that if they vomit after taking the dose of PIQRAY, they should not take an additional dose on that day, and to resume the usual dosing schedule the next day at the usual time [see Dosage and Administration (2.2)] . Distributed by: Novartis Pharmaceuticals Corporation East Hanover, New Jersey 07936 © Novartis T2024-03

Label text from the FDA structured product label by Novartis Pharmaceuticals Corporation (revised Dec 15, 2025). Long sections are shortened; the complete label is on DailyMed.

Active ingredients

Alpelisib in 2 products

Piqray NDC products (3)

NDC	Strength & form	Labeler	Type
0078-0701	Alpelisib 200 mg/1 Tablet	Novartis Pharmaceuticals Corporation	NDA
0078-0708	Alpelisib 150 mg/1 Tablet	Novartis Pharmaceuticals Corporation	NDA
0078-0715	Kit	Novartis Pharmaceuticals Corporation	NDA

Frequently asked questions

What is Piqray used for?

What are the side effects of Piqray?

Who makes Piqray?

Piqray is listed by 1 labeler in the FDA NDC directory, including Novartis Pharmaceuticals Corporation.