Alpelisib: Drug information

(For additional information see "Alpelisib: Patient drug information" and see "Alpelisib: Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)

Brand Names: US

Piqray (200 MG Daily Dose);
Piqray (250 MG Daily Dose);
Piqray (300 MG Daily Dose);
Vijoice

Brand Names: Canada

Piqray (200 MG Daily Dose);
Piqray (250 MG Daily Dose);
Piqray (300 MG Daily Dose)

Pharmacologic Category

Antineoplastic Agent, Phosphatidylinositol 3-Kinase Inhibitor;
Phosphatidylinositol 3-Kinase (PI3K) Inhibitor

Dosing: Adult

Note: Optimize blood glucose prior to initiating alpelisib. Alpelisib is available as 2 different brand names (Piqray and Vijoice); the indications and dosages differ between products.

Breast cancer, advanced or metastatic, HR-positive, HER2-negative, PIK3CA-mutated

Breast cancer, advanced or metastatic, HR-positive, HER2-negative, PIK3CA-mutated: Males and postmenopausal females: Piqray: Oral: 300 mg once daily (in combination with fulvestrant); continue until disease progression or unacceptable toxicity (Ref).

PIK3CA-related overgrowth spectrum

PIK3CA-related overgrowth spectrum: Vijoice: Oral: 250 mg once daily; continue until disease progression or unacceptable toxicity.

Missed doses: A missed dose may be administered (with food) within 9 hours after the usual administration time; if beyond 9 hours, skip the dose for that day and administer the dose for the next day at the usual time. If a dose is vomited, do not administer an additional dose on that day; resume the dosing schedule the next day at the usual time.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

Note: Kidney function estimated with the Cockcroft-Gault formula.

CrCl ≥30 mL/minute:

Breast cancer: No dosage adjustment necessary.

PIK3CA-related overgrowth spectrum: There are no dosage adjustments provided in the manufacturer's labeling; however, no clinically significant differences in alpelisib pharmacokinetics were noted based on CrCl 30 to <90 mL/minute.

CrCl <30 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling (effect on alpelisib pharmacokinetics is unknown).

Dosing: Hepatic Impairment: Adult

Hepatic impairment at baseline: Child-Pugh classes A, B, or C: There are no dosage adjustments provided in the manufacturer's labeling; however, no clinically significant differences in pharmacokinetics are expected.

Hepatotoxicity during treatment: Grade 2 total bilirubin elevation: Interrupt alpelisib treatment until improvement to ≤ grade 1, then resume at the same dose level if resolved in ≤14 days or resume at the next lower dose level if improved in >14 days. For dosage adjustment levels and other toxicity grades, follow dosage adjustment for “other toxicities” (see Dosing – Adjustment for Toxicity).

Dosing: Adjustment for Toxicity: Adult

**Breast Cancer: Recommended Alpelisib Dosage Reduction Levels^a,b**
^aOnly one dose reduction is permitted for pancreatitis.
^bRefer to Fulvestrant monograph for information on fulvestrant toxicities.
Initial (usual) dose	300 mg once daily
First dose reduction level	250 mg once daily
Second dose reduction level	200 mg once daily
If further dose reductions are required, discontinue alpelisib.

**PIK3CA- Related Overgrowth Spectrum: Recommended Alpelisib Dosage Reduction Levels^a**
^aOnly 1 dose reduction is permitted for pancreatitis.
Initial (usual) dose	250 mg once daily
First dose reduction level	125 mg once daily
Second dose reduction level	50 mg once daily
If unable to tolerate 50 mg once daily, discontinue alpelisib.

**Breast Cancer and PIK3CA-Related Overgrowth Spectrum: Alpelisib Dosage Reduction and Toxicity Management**
^aSCARs = severe cutaneous adverse reactions.
Dermatologic toxicity: Rash and SCARs^a
Grade 1 (<10% BSA with active skin toxicity)	No alpelisib dosage adjustment required (unless etiology determined to be a SCAR). Initiate topical corticosteroid therapy; consider adding an oral antihistamine to manage symptoms. If active rash is not improved within 28 days of appropriate therapy, add a low-dose systemic corticosteroid. Permanently discontinue alpelisib if a SCAR is confirmed.
Grade 2 (10% to 30% BSA with active skin toxicity)	No alpelisib dosage adjustment required (unless etiology determined to be a SCAR). Initiate or intensify topical corticosteroid therapy and oral antihistamine treatment; consider low-dose systemic corticosteroid treatment. If rash improves to ≤ grade 1 within 10 days, systemic corticosteroid may be discontinued. Permanently discontinue alpelisib if a SCAR is confirmed.
Grade 3 (eg, severe rash not responsive to medical management; >30% BSA with active skin toxicity)	Interrupt alpelisib treatment; initiate or intensify topical/systemic corticosteroid therapy and oral antihistamine treatment. If the etiology is not a SCAR, once improved to ≤ grade 1, resume alpelisib at the next lower dosage level. Permanently discontinue alpelisib if a SCAR is confirmed.
Grade 4 (eg, severe bullous, blistering or exfoliating skin conditions; any % BSA associated with extensive superinfection, with IV antibiotics indicated; life-threatening consequences)	Permanently discontinue alpelisib.
Consider dermatology consultation for all grades of rash. Antihistamine administration prior to rash onset may decrease the rash incidence/severity. Do not reinitiate alpelisib if previous SCAR occurred during therapy.
GI toxicity: Diarrhea or colitis
Grade 1	No alpelisib dosage adjustment required; initiate appropriate medical therapy and monitor as clinically indicated.
Grade 2	Interrupt alpelisib treatment until improvement to ≤ grade 1, then resume at the same dose level. For recurrent ≥ grade 2, interrupt alpelisib treatment until improvement to ≤ grade 1, then resume at the next lower dose level. Initiate or intensify appropriate medical therapy and monitor as clinically indicated.
Grade 3	Interrupt alpelisib treatment until improvement to ≤ grade 1, then resume at the next lower dose level. Initiate or intensify appropriate medical therapy and monitor as clinically indicated.
Grade 4	Permanently discontinue alpelisib.
Consider additional treatment (eg, enteric-acting and/or systemic steroids) for grade 2 and 3 colitis. Consider stopping lactose-containing foods, alcohol, laxatives, bulk fiber, stool softeners, and high-osmolar food supplements; encourage hydration and frequent small meals (Nunnery 2019).
Hyperglycemia: Based on fasting plasma glucose (FPG)/fasting blood glucose values.
Grade 1 (fasting glucose > ULN to 160 mg/dL or > ULN to 8.9 mmol/L)	No alpelisib dosage adjustment required; initiate or intensify antihyperglycemic therapy as described below.
Grade 2 (fasting glucose >160 to 250 mg/dL or >8.9 to 13.9 mmol/L)	No alpelisib dosage adjustment required; initiate or intensify antihyperglycemic therapy as described below. If fasting glucose does not decrease to ≤160 mg/dL or 8.9 mmol/L within 21 days with appropriate antihyperglycemic therapy, reduce alpelisib dose by 1 dose level and continue to follow fasting glucose value-specific recommendations.
Grade 3 (fasting glucose >250 to 500 mg/dL or >13.9 to 27.8 mmol/L)	Interrupt alpelisib therapy; initiate or intensify antihyperglycemic therapy as described below and consider additional antihyperglycemic medications for 1 to 2 days as clinically indicated (if needed; may not be necessary due to alpelisib half-life) until hyperglycemia improves. Administer IV hydration and consider appropriate intervention for electrolyte/ketoacidosis/hyperosmolar disturbances. If fasting glucose decreases to ≤160 mg/dL or 8.9 mmol/L within 3 to 5 days with appropriate antihyperglycemic therapy, resume alpelisib with the dose reduced by 1 dose level. If fasting glucose does not decrease to ≤160 mg/dL or 8.9 mmol/L within 3 to 5 days with appropriate antihyperglycemic therapy, consultation with a clinician with expertise in hyperglycemia management is recommended. Permanently discontinue alpelisib if fasting glucose does not decrease to ≤160 mg/dL or 8.9 mmol/L within 21 days following appropriate antihyperglycemic therapy.
Grade 4 (fasting glucose >500 mg/dL or >27.8 mmol/L)	Interrupt alpelisib therapy; initiate or intensify appropriate antihyperglycemic therapy as described below. Administer IV hydration and consider appropriate intervention for electrolyte/ketoacidosis/hyperosmolar disturbances. Recheck fasting glucose within 24 hours (and as clinically indicated). If fasting glucose decreases to ≤500 mg/dL or 27.8 mmol/L, follow fasting glucose value specific recommendations for grade 3 hyperglycemia. Permanently discontinue alpelisib if fasting glucose is confirmed at >500 mg/dL or 27.8 mmol/L.
Antihyperglycemic therapy recommendations	Initiate or intensify antihyperglycemic therapy, including metformin, SGLT2 inhibitors, or insulin sensitizers (eg, thiazolidinediones, dipeptidyl peptidase-4 inhibitors). Also refer to local treatment guidelines for hyperglycemia. For patients with breast cancer, short-term insulin (1 to 2 days) may also be considered until hyperglycemia resolves (although may not be necessary due to the short alpelisib half-life). Antihyperglycemic therapy recommendations (for patients with breast cancer) based on FPG (Rugo 2020): FPG > ULN and <140 mg/dL: Consider metformin. FPG 140 to 160 mg/dL: Initiate or intensify metformin. FPG >160 to 250 mg/dL: Initiate metformin; if FPG continues to rise beyond the maximum tolerated metformin dose, add an insulin sensitizer (eg, pioglitazone). FPG >250 to 500 mg/dL: Consider diabetes specialist consultation. Initiate metformin and add pioglitazone; rescue insulin may be used for 1 to 2 days. FPG >500 mg/dL: Obtain diabetes specialist consultation. Initiate metformin and add pioglitazone; rescue insulin may be used for 1 to 2 days. Recheck glucose levels in 24 hours.
Metformin recommendations (for patients with breast cancer)	Initiate metformin at 500 mg once daily; based on tolerance, may increase to 500 mg twice daily (with meals), and further increase to 500 mg with breakfast and 1,000 mg with dinner, followed by a further increase to 1,000 mg twice daily (with meals) if needed.
Consider consultation with a clinician with expertise in hyperglycemia management and lifestyle modifications.
Hypersensitivity
Severe	Permanently discontinue alpelisib.
Pancreatitis
Grades 2 and 3	Interrupt alpelisib treatment until improvement to < grade 2, then resume at the next lower dose level. Only 1 dose reduction is permitted for pancreatitis. If toxicity recurs, permanently discontinue alpelisib.
Grade 4	Permanently discontinue alpelisib.
Pneumonitis
New or worsening respiratory symptoms or suspected pneumonitis (any grade)	Immediately interrupt alpelisib treatment and evaluate for pneumonitis.
Confirmed	Permanently discontinue alpelisib. Pneumonitis may also require systemic corticosteroids (Nunnery 2019).
Other toxicities
Grade 1 or 2	No alpelisib dosage adjustment required; initiate appropriate medical therapy and monitor as clinically indicated.
Grade 3	Initiate or intensify appropriate medical therapy and monitor as clinically indicated. Interrupt alpelisib treatment until improvement to ≤ grade 1, then resume at the next lower dose level.
Grade 4	Permanently discontinue alpelisib.

Dosing: Older Adult

Refer to adult dosing.

Dosing: Pediatric

(For additional information see "Alpelisib: Pediatric drug information")

Note: Alpelisib is available as 2 different brand names (Vijoice [only product FDA approved for use in pediatric patients] and Piqray); the indications and dosages differ between products.

PIK3CA-related overgrowth spectrum, severe manifestations

PIK3CA-related overgrowth spectrum (PROS), severe manifestations:

Children 2 to <6 years: Vijoice: Oral: 50 mg once daily; continue therapy until disease progression or unacceptable toxicity.

Children ≥6 years and Adolescents <18 years: Vijoice: Oral: Initial: 50 mg once daily; after 6 months of treatment, consider increasing dose to 125 mg once daily to optimize clinical and/or radiologic response. Continue therapy until disease progression or unacceptable toxicity.

Adolescents ≥18 years: Vijoice: Oral: 250 mg once daily; continue therapy until disease progression or unacceptable toxicity.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosage adjustment for toxicity:

PIK3CA-related overgrowth spectrum (PROS), treatment: Vijoice: Oral:

**Recommended Alpelisib Dosage Reduction Levels^a**
	Children ≥2 years and Adolescents <18 years		Adolescents ≥18 years
^aOnly 1 dose reduction is permitted for pancreatitis.
Current dose	50 mg once daily	125 mg once daily	250 mg once daily
First dose reduction level	If 50 mg dose is not tolerated, discontinue alpelisib.	50 mg once daily	125 mg once daily
Second dose reduction level	If 50 mg dose is not tolerated, discontinue alpelisib.	If further dose reductions are required, discontinue alpelisib.	50 mg once daily
			If further dose reductions are required, discontinue alpelisib.

**Alpelisib Dosage Reduction and Toxicity Management**
	Children ≥2 years and Adolescents <18 years	Adolescents ≥18 years
^aSCARs = severe cutaneous adverse reactions (eg, Stevens-Johnson syndrome, erythema multiforme, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms) ^b Metformin may be considered in patients ≥10 years of age. ^c In patients ≥18 years of age, consider medications such as metformin, SGLT2 inhibitors, or insulin sensitizers (eg, thiazolidinediones, dipeptidyl peptidase-4 inhibitors).
Dermatologic toxicity: Rash and SCARs^a Note: Dermatology consultation is recommended for all grades. Antihistamine administration prior to rash onset may decrease the rash incidence/severity. Do not reinitiate alpelisib if SCAR has occurred during therapy with alpelisib.
Grade 1 (<10% BSA with active skin toxicity)	No alpelisib dosage adjustment required. Initiate topical corticosteroid therapy; consider adding an oral antihistamine to manage symptoms. If active rash is not improved within 28 days of appropriate therapy, add a low-dose systemic corticosteroid. Permanently discontinue alpelisib if a SCAR is confirmed.
Grade 2 (10% to 30% BSA with active skin toxicity)	No alpelisib dosage adjustment required. Initiate or intensify topical corticosteroid therapy and oral antihistamine treatment; consider low-dose systemic corticosteroid treatment. If rash improves to ≤ grade 1 within 10 days, systemic corticosteroid may be discontinued. Permanently discontinue alpelisib if a SCAR is confirmed.
Grade 3 (eg, severe rash not responsive to medical management; >30% BSA with active skin toxicity)	Interrupt alpelisib treatment; initiate or intensify topical/systemic corticosteroid therapy and oral antihistamine treatment. If the etiology is not a SCAR, once improved to ≤ grade 1, either resume alpelisib at 50 mg once daily while continuing oral antihistamine treatment, or permanently discontinue alpelisib. Permanently discontinue alpelisib if a SCAR is confirmed, if patient was receiving antihistamines at the time of rash onset and antihistamine dose cannot be increased, or if ≥ grade 3 rash recurs.	Interrupt alpelisib treatment; initiate or intensify topical/systemic corticosteroid therapy and oral antihistamine treatment. If the etiology is not a SCAR, once improved to ≤ grade 1, resume alpelisib at the next lower dosage level. Permanently discontinue alpelisib if a SCAR is confirmed.
Grade 4 (eg, severe bullous, blistering or exfoliating skin conditions; any % BSA associated with extensive superinfection, with IV antibiotics indicated; life-threatening consequences)	Permanently discontinue alpelisib.
GI toxicity: Diarrhea or Colitis Note: Consider consultation with a clinician with experience in the treatment of GI conditions.
Grade 1	No alpelisib dosage adjustment required; initiate appropriate medical therapy and monitor as clinically indicated.
Grade 2	Interrupt alpelisib treatment until improvement to ≤ grade 1, then resume at the same dose level. If ≥ grade 2 diarrhea/colitis recurs, interrupt alpelisib treatment until improvement to ≤ grade 1, then resume at 50 mg once daily. Initiate or intensify appropriate medical therapy and monitor as clinically indicated; for colitis, consider additional treatment with enteric-acting and/or systemic corticosteroids.	Interrupt alpelisib treatment until improvement to ≤ grade 1, then resume at the same dose level. If ≥ grade 2 diarrhea/colitis recurs, interrupt alpelisib treatment until improvement to ≤ grade 1, then resume at the next lower dose level. Initiate or intensify appropriate medical therapy and monitor as clinically indicated; for colitis, consider additional treatment with enteric-acting and/or systemic corticosteroids.
Grade 3	Interrupt alpelisib treatment until improvement to ≤ grade 1, then either resume alpelisib at 50 mg once daily or permanently discontinue alpelisib. Initiate or intensify appropriate medical therapy and monitor as clinically indicated; for colitis, consider additional treatment with enteric-acting and/or systemic corticosteroids. If ≥ grade 3 diarrhea/colitis recurs, consider permanent discontinuation of alpelisib.	Interrupt alpelisib treatment until improvement to ≤ grade 1, then resume at the next lower dose level. Initiate or intensify appropriate medical therapy and monitor as clinically indicated; for colitis, consider additional treatment with enteric-acting and/or systemic corticosteroids.
Grade 4	Permanently discontinue alpelisib.
Hyperglycemia: Based on fasting plasma glucose/fasting blood glucose values.
Grade 1 (fasting glucose >ULN to 160 mg/dL)	No alpelisib dosage adjustment required; initiate or intensify antihyperglycemic therapy.^b,c
Grade 2 (fasting glucose >160 to 250 mg/dL)	No alpelisib dosage adjustment required; initiate or intensify antihyperglycemic therapy.^b If fasting glucose does not decrease to ≤160 mg/dL within 21 days with appropriate antihyperglycemic therapy, interrupt alpelisib dose until improvement to ≤ grade 1, then resume alpelisib at 50 mg once daily and continue to follow fasting glucose specific recommendations.	No alpelisib dosage adjustment required; initiate or intensify antihyperglycemic therapy.^c If fasting glucose does not decrease to ≤160 mg/dL within 21 days with appropriate antihyperglycemic therapy, interrupt alpelisib dose by 1 dose level and continue to follow fasting glucose specific recommendations.
Grade 3 (fasting glucose >250 to 500 mg/dL)	Interrupt alpelisib therapy; initiate or intensify antihyperglycemic therapy^b and consider additional antihyperglycemic medications for 1 to 2 days until hyperglycemia improves. Administer IV hydration and consider appropriate intervention for electrolyte/ketoacidosis/hyperosmolar disturbances. If fasting glucose decreases to ≤160 mg/dL within 3 to 5 days with appropriate antihyperglycemic therapy, resume alpelisib at 50 mg once daily. If fasting glucose does not decrease to ≤160 mg/dL within 3 to 5 days with appropriate antihyperglycemic therapy, consultation with a clinician with expertise in hyperglycemia management is recommended to determine if treatment with alpelisib can be resumed or should be permanently discontinued. Permanently discontinue alpelisib if fasting glucose does not decrease to ≤160 mg/dL within 21 days following appropriate antihyperglycemic therapy. If ≥ grade 3 hyperglycemia recurs, consider permanent discontinuation of alpelisib.	Interrupt alpelisib therapy; initiate or intensify antihyperglycemic therapy^c and consider additional antihyperglycemic medications for 1 to 2 days until hyperglycemia improves. Administer IV hydration and consider appropriate intervention for electrolyte/ketoacidosis/hyperosmolar disturbances. If fasting glucose decreases to ≤160 mg/dL within 3 to 5 days with appropriate antihyperglycemic therapy, resume alpelisib with the dose reduced by 1 dose level. If fasting glucose does not decrease to ≤160 mg/dL within 3 to 5 days with appropriate antihyperglycemic therapy, consultation with a clinician with expertise in hyperglycemia management is recommended. Permanently discontinue alpelisib if fasting glucose does not decrease to ≤160 mg/dL within 21 days following appropriate antihyperglycemic therapy.
Grade 4 (fasting glucose >500 mg/dL)	Interrupt alpelisib therapy; initiate or intensify antihyperglycemic therapy.^b,c Administer IV hydration and consider appropriate intervention for electrolyte/ketoacidosis/hyperosmolar disturbances. Recheck fasting glucose within 24 hours (and as clinically indicated). If fasting glucose decreases to ≤500 mg/dL, follow fasting glucose value specific recommendations for grade 3 hyperglycemia. Permanently discontinue alpelisib if fasting glucose is confirmed at >500 mg/dL with recheck.
Hypersensitivity
Severe	Permanently discontinue alpelisib.
Pancreatitis
Grade 2	Interrupt alpelisib treatment until improvement to < grade 2, then resume at 50 mg once daily. If toxicity recurs, permanently discontinue alpelisib.	Interrupt alpelisib treatment until improvement to < grade 2, then resume at the next lower dose level. Only 1 dose reduction is permitted for pancreatitis. If toxicity recurs, permanently discontinue alpelisib.
Grade 3	Permanently discontinue alpelisib.	Interrupt alpelisib treatment until improvement to < grade 2, then resume at the next lower dose level. Only 1 dose reduction is permitted for pancreatitis. If toxicity recurs, permanently discontinue alpelisib.
Grade 4	Permanently discontinue alpelisib.
Pneumonitis
New or worsening respiratory symptoms or suspected pneumonitis	Immediately interrupt alpelisib treatment and evaluate for pneumonitis.
Confirmed	Permanently discontinue alpelisib.
Other toxicities
Grade 1 or 2	No alpelisib dosage adjustment required; initiate appropriate medical therapy and monitor as clinically indicated.
Grade 3	Interrupt alpelisib treatment until improvement to ≤ grade 1, then either resume at 50 mg once daily or permanently discontinue alpelisib. If adverse reaction recurs at ≥ grade 3, consider permanent discontinuation of alpelisib. Initiate or intensify appropriate medical therapy and monitor as clinically indicated. Consider consultation with a qualified clinician with specific expertise in the field of the concerned adverse reaction.	Interrupt alpelisib treatment until improvement to ≤ grade 1, then resume at the next lower dose level. Initiate or intensify appropriate medical therapy and monitor as clinically indicated.
Grade 4	Permanently discontinue alpelisib.

Dosing: Kidney Impairment: Pediatric

Altered kidney function: Children ≥2 years and Adolescents: Vijoice: Oral:

Mild to moderate kidney impairment: There are no dosage adjustments provided in the manufacturer's labeling. No clinically significant pharmacokinetic differences were predicted in adult pharmacokinetic models for patients with mild to moderate renal impairment (CrCl 30 to <90 mL/minute).

Severe kidney impairment: There are no dosage adjustments provided in the manufacturer's labeling; has not been studied.

Dosing: Hepatic Impairment: Pediatric

Hepatic impairment at baseline: Vijoice: Oral:

Mild to severe: Children ≥2 years and Adolescents: There are no dosage adjustments provided in the manufacturer's labeling; however, no clinically significant differences in pharmacokinetics are expected, based on adult pharmacokinetic models.

Hepatotoxicity during treatment: Vijoice: Oral:

Grade 2 total bilirubin elevation: Note: For dosage adjustment levels and other toxicity grades, follow dosage adjustment for "other toxicities" (See "Dosing: Pediatric").

Children ≥2 years and Adolescents <18 years: Interrupt alpelisib treatment until improvement to ≤ grade 1; if resolved in ≤14 days, resume at the same dose level; if resolved in >14 days, resume at 50 mg once daily.

Adolescents ≥18 years: Interrupt alpelisib treatment until improvement to ≤ grade 1; if resolved in ≤14 days, resume at the same dose level; if resolved in >14 days, resume at the next lower dose level.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

Breast cancer, advanced or metastatic

Adverse reactions reported with concomitant fulvestrant in adults.

>10%:

Cardiovascular: Peripheral edema (15%)

Dermatologic: Alopecia (20%), pruritus (18%), skin rash (52%), xeroderma (18%)

Endocrine & metabolic: Decreased serum albumin (14%), decreased serum calcium (27%), decreased serum glucose (26%), decreased serum magnesium (11%), decreased serum potassium (14%), hyperglycemia (65%; including severe hyperglycemia), increased gamma-glutamyl transferase (52%), weight loss (27%)

Gastrointestinal: Abdominal pain (17%), decreased appetite (36%), diarrhea (58%; grade 3: 7%), dry mucous membranes (12%), dysgeusia (18%), dyspepsia (11%), increased serum lipase (42%), nausea (45%; grade 3: 3%), stomatitis (19% to 30%; grades 3: 2% to 3%), vomiting (27%; grade 3: <1%)

Hematologic & oncologic: Decreased platelet count (14%; grades 3/4: 1%), lymphocytopenia (52%; grades 3/4: 8%), prolonged partial thromboplastin time (21%; grades 3: <1%)

Hepatic: Increased serum alanine aminotransferase (44%)

Nervous system: Fatigue (42%), headache (18%)

Renal: Increased serum creatinine (67%)

Miscellaneous: Fever (14%)

1% to 10%:

Dermatologic: Erythema multiforme (1%)

Genitourinary: Urinary tract infection (10%; including urinary tract infection with sepsis)

Hematologic & oncologic: Anemia (2%)

Neuromuscular & skeletal: Osteonecrosis of the jaw (4%)

Renal: Acute kidney injury (3%)

Respiratory: Pneumonitis (2%)

<1%:

Dermatologic: Stevens-Johnson syndrome

Endocrine & metabolic: Ketoacidosis

Hypersensitivity: Severe hypersensitivity reaction (grades 3/4)

PIK3CA-Related Overgrowth Spectrum (PROS)

Adverse reactions reported in children, adolescents, and adults.

>10%:

Endocrine & metabolic: Decreased serum albumin, decreased serum calcium (corrected), decreased serum magnesium, decreased serum phosphate, decreased serum potassium, decreased serum sodium, elevated glycosylated hemoglobin, hyperglycemia, increased gamma-glutamyl transferase, increased serum cholesterol, increased serum potassium, increased serum triglycerides

Gastrointestinal: Diarrhea, stomatitis

Hematologic: Decreased hemoglobin, decreased neutrophils, decreased platelet count, leukopenia, lymphocytopenia, lymphocytosis

Hepatic: Increased serum aspartate aminotransferase, increased serum bilirubin

Renal: Increased serum creatinine

1% to 10%:

Dermatologic: Alopecia, cellulitis, eczema, xeroderma

Endocrine & metabolic: Dehydration

Gastrointestinal: Dry mucous membranes, nausea, vomiting

Hepatic: Increased serum alanine aminotransferase

Nervous system: Headache

Frequency not defined (any indication):

Dermatologic: Soft tissue infection, toxic epidermal necrolysis

Hypersensitivity: Anaphylactic shock, anaphylaxis

Nervous system: Dizziness, memory impairment

Respiratory: Interstitial pulmonary disease

Postmarketing (any indication):

Dermatologic: Acne vulgaris, acneiform eruption, erythematous rash, maculopapular rash, papular rash, pruritic rash

Endocrine & metabolic: Hyperglycemic hyperosmolar syndrome

Gastrointestinal: Colitis

Hypersensitivity: Angioedema, drug reaction with eosinophilia and systemic symptoms

Contraindications

Severe hypersensitivity to alpelisib or any component of the formulation

Warnings/Precautions

Concerns related to adverse effects:

• Dermatologic toxicity: Severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome, erythema multiforme, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms, have occurred with alpelisib. Inform patients of the signs/symptoms of SCARs (eg, prodrome of fever, flu-like symptoms, mucosal lesions, progressive skin rash, lymphadenopathy). Maculopapular rash (with or without pruritus and dry skin) is the most commonly occurring rash; rash generally develops within the initial 2 months of treatment (Nunnery 2019).

• GI toxicity: Severe diarrhea and colitis may commonly occur with alpelisib; dehydration, acute kidney injury, and grade 3 diarrhea have been reported in patients with breast cancer. The median time to onset of grade 2 or 3 diarrhea was 46 days (range: 1 to 442 days). Some patients with PIK3CA-related overgrowth spectrum experienced grade 1 diarrhea. Antidiarrheal medication (eg, loperamide) was required to manage symptoms in a majority of patients with breast cancer who experienced diarrhea. Instruct patients with breast cancer to initiate antidiarrheal treatment, increase oral fluids, and notify their health care provider if diarrhea occurs during alpelisib treatment. Patients experiencing colitis may require additional treatment (eg, enteric-acting and/or systemic steroids).

• Hyperglycemia: Severe hyperglycemia, occasionally associated with hyperglycemic hyperosmolar state or ketoacidosis (some fatal), may occur with alpelisib. Hyperglycemia was reported in nearly two-thirds of patients with breast cancer. Grade 3 hyperglycemia occurred in one-third of those patients; grade 4 hyperglycemia and ketoacidosis (including fatal ketoacidosis cases) were reported in a small percentage of patients. Among patients who experienced grade 2 or higher hyperglycemia, the median time to first occurrence of hyperglycemia was 15 days (range: 5 to 517 days). Grade 1 or 2 hyperglycemia was reported in 12% of patients with PIK3CA-related overgrowth spectrum. Most hyperglycemia events in patients with breast cancer were managed with antihyperglycemic medication, with a majority utilizing metformin (either as single agent or in combination with other antihyperglycemic medications (eg, insulin, dipeptidyl peptidase-4 inhibitors, sulfonylureas). The median time from ≥ grade 2 hyperglycemia to at least 1 grade improvement was 8 days (range: 2 to 65 days). Most patients who continued fulvestrant but discontinued alpelisib (due to hyperglycemia) had fasting plasma glucose (FPG) levels that returned to baseline. Patients with type 1 or uncontrolled type 2 diabetes were excluded from clinical trials; the safety of alpelisib in these patients has not been established. Patients with a history of controlled type 2 diabetes were included in the breast cancer clinical trial but were not included in trials for patients with PIK3CA-related overgrowth spectrum (Nunnery 2019). Patients should be aware of signs/symptoms of hyperglycemia (eg, excessive thirst, frequent urination, increased urine volume, increased appetite with weight loss).

• Hypersensitivity: Severe hypersensitivity reactions (including anaphylaxis, anaphylactic shock, and angioedema) have occurred with alpelisib. Manifestations of severe hypersensitivity reactions included dyspnea, flushing, rash, fever, or tachycardia. Grade 3 and 4 hypersensitivity reactions have occurred rarely.

• Pulmonary toxicity: Severe pneumonitis, including acute interstitial pneumonitis and interstitial lung disease, may occur; pneumonitis was reported in a small percentage of patients with breast cancer. Patients should immediately report new or worsening respiratory symptoms.

Special populations:

• Older adults: Patients ≥65 years of age with breast cancer experienced a higher incidence of grades 3 and 4 hyperglycemia.

Other warnings/precautions:

• PIK3CA mutation status: Select patients for treatment of advanced/metastatic breast cancer based on the presence of one or more PIK3CA mutations in tumor tissue or plasma specimens; if no mutation is detected in a plasma specimen, test tumor tissue. Information on tests approved for detection of PIK3CA mutations in breast cancer is available at http://www.fda.gov/CompanionDiagnostics.

Warnings: Additional Pediatric Considerations

Based on animal toxicity data, regular monitoring of growth and development is recommended in pediatric patients receiving alpelisib. In rats administered alpelisib at doses ~1.2 to 2.8 times human doses, growth plate thickening and decreased trabeculae of the knee joint, dentin thinning, and degenerative odontoblasts were observed. In a study of 39 pediatric patients receiving alpelisib for PIK3CA-related overgrowth spectrum, no new safety signals were observed; however, the data are insufficient to determine if alpelisib adversely impacts growth and development in humans.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet Therapy Pack, Oral:

Piqray (200 MG Daily Dose): 200 mg (28 ea)

Piqray (250 MG Daily Dose): 200 mg tablets and 50 mg tablets (28 ea, 56 ea)

Piqray (300 MG Daily Dose): 2 x 150 mg (28 ea, 56 ea)

Vijoice: 50 mg (28 ea); 125 mg (28 ea); 200 mg tablets and 50 mg tablets (28 ea, 56 ea)

Generic Equivalent Available: US

Pricing: US

Tablet Therapy Pack (Piqray (200 MG Daily Dose) Oral)

200 mg (per each): $944.55

Tablet Therapy Pack (Piqray (250 MG Daily Dose) Oral)

200 & 50 mg (per each): $472.28

Tablet Therapy Pack (Piqray (300 MG Daily Dose) Oral)

2 x 150 mg (per each): $472.28

Tablet Therapy Pack (Vijoice Oral)

50 mg (per each): $1,392.86

125 mg (per each): $1,392.86

200 & 50 mg (per each): $696.43

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet Therapy Pack, Oral:

Piqray (200 MG Daily Dose): 200 mg (28 ea)

Piqray (250 MG Daily Dose): 200 mg tablets and 50 mg tablets (56 ea)

Piqray (300 MG Daily Dose): 2 x 150 mg (56 ea)

Administration: Adult

Oral: Administer with food at approximately the same time each day. Swallow tablets whole (tablets should be intact prior to ingestion); do not chew, crush, or split.

Vijoice: For patients unable to swallow tablets, may administer as an oral suspension (with food). Place tablets in a glass containing 60 to 120 mL of water (use water only) and let stand ~5 minutes, then crush tablets with a spoon and stir until a suspension forms. Administer suspension immediately after preparation (discard if not administered within 60 minutes). After administering the initial suspension, add another 30 to 45 mL of water to the same glass and stir to resuspend remaining particles and administer contents. Repeat if particles remain.

Administration: Pediatric

Oral: Vijoice: Administer with food at approximately the same time each day. Swallow intact tablet whole.

Patients unable to swallow tablet: If patient is not able to swallow tablet, may prepare as an oral suspension. Place tablet in a glass containing 60 to 120 mL water and let stand for ~5 minutes. Crush tablets with a spoon and stir until oral suspension is obtained. Administer immediately after preparation; discard if not used within 60 minutes. After administration, add ~30 to 45 mL of water to same glass, stir with same spoon, and administer entire contents of glass. Repeat if any alpelisib particles remain. Do not prepare using any other liquids; only use water.

Vomited dose: If the patient vomits after taking the dose, do not administer an additional dose; resume dosing schedule on the following day at the usual time.

Missed dose: A missed dose may be administered within 9 hours after the usual administration time. If >9 hours have passed, skip that day's dose and administer the next day's dose at the usual time.

Hazardous Drugs Handling Considerations

This medication is not on the NIOSH (2016) list; however, it may meet the criteria for a hazardous drug. Alpelisib may cause teratogenicity and reproductive toxicity.

Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).

Note: Facilities may perform risk assessment of some hazardous drugs to determine if appropriate for alternative handling and containment strategies (USP-NF 2020). Refer to institution-specific handling policies/procedures.

Use: Labeled Indications

Breast cancer, advanced or metastatic: Treatment (in combination with fulvestrant) of HR-positive, HER2-negative, PIK3CA-mutated (as detected by an approved test), advanced or metastatic breast cancer in males and postmenopausal females following progression on or after an endocrine-based regimen.

PIK3CA-related overgrowth spectrum: Treatment of severe manifestations of PIK3CA-related overgrowth spectrum in patients ≥2 years of age who require systemic therapy.

Medication Safety Issues

Sound-alike/look-alike issues:

Alpelisib may be confused with abemaciclib, acalabrutinib, afatinib, Alecensa, alectinib, avapritinib, axitinib, copanlisib, duvelisib, idelalisib.

Alpelisib is available as 2 different brand names, Piqray and Vijoice. The indications and dosages differ between products.

High alert medication:

This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.

Metabolism/Transport Effects

Substrate of BCRP/ABCG2, CYP3A4 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Antidiabetic Agents: Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy

Asciminib: May increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy

BCRP/ABCG2 Inhibitors: May increase the serum concentration of Alpelisib. Management: Avoid coadministration of BCRP/ABCG2 inhibitors and alpelisib due to the potential for increased alpelisib concentrations and toxicities. If coadministration cannot be avoided, closely monitor for increased alpelisib adverse reactions. Risk D: Consider therapy modification

CYP2C9 Substrates (High risk with Inducers): Alpelisib may decrease the serum concentration of CYP2C9 Substrates (High risk with Inducers). Risk C: Monitor therapy

CYP3A4 Inducers (Strong): May decrease the serum concentration of Alpelisib. Risk X: Avoid combination

Elacestrant: May increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy

Futibatinib: May increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy

Gilteritinib: May increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy

Leniolisib: May increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk X: Avoid combination

Pacritinib: May increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk X: Avoid combination

Pretomanid: May increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy

Sparsentan: May increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk X: Avoid combination

Taurursodiol: May increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk X: Avoid combination

Voxilaprevir: May increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk X: Avoid combination

Food Interactions

Following a single alpelisib 300 mg dose, a high-fat and high-calorie meal (985 calories with 58.1 g of fat) increased the alpelisib AUC and C_max by 73% and 84%, respectively; a low-fat and low-calorie meal (334 calories with 8.7 g of fat) increased the alpelisib AUC and C_max by 77% and 145%, respectively.

Reproductive Considerations

Verify pregnancy status prior to use in patients who could become pregnant. Patients who could become pregnant should use effective contraception during therapy and for 1 week after the last alpelisib dose. Patients with partners who could become pregnant should use condoms and effective contraception during therapy and for 1 week after the last dose of alpelisib.

Also refer to the Fulvestrant monograph for additional information.

Pregnancy Considerations

Based on the mechanism of action, and data from animal reproduction studies, in utero exposure to alpelisib may cause fetal harm.

Also refer to the fulvestrant monograph for additional information.

Breastfeeding Considerations

It is not known if alpelisib is present in breast milk.

Due to the potential for adverse events in a breastfed infant, breastfeeding is not recommended during therapy and for 1 week after the last alpelisib dose.

Also refer to the Fulvestrant monograph for additional information.

Monitoring Parameters

PIK3CA mutation status (in patients with breast cancer). Verify pregnancy status (prior to treatment in patients who could become pregnant).

Hyperglycemia: Monitor fasting plasma glucose (FPG) and HbA_1c prior to alpelisib treatment initiation; monitor fasting plasma glucose or fasting blood glucose at least once each week for the first 2 weeks, then at least once every 4 weeks, and as clinically indicated; monitor HbA_1c every 3 months and as clinically indicated. Monitor fasting glucose more closely in patients with risk factors for hyperglycemia. If hyperglycemia occurs, monitor fasting glucose as clinically indicated, and at least twice weekly until blood glucose or FPG decreases to normal levels. During treatment with antihyperglycemic medication, continue monitoring blood glucose or FPG at least once a week for 8 weeks, followed by once every 2 weeks and as clinically indicated.

The American Society of Clinical Oncology hepatitis B screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends hepatitis B virus (HBV) screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.

Monitor for diarrhea and colitis; signs/symptoms of severe cutaneous adverse reactions, hyperglycemia, hypersensitivity, respiratory symptoms (new or worsening) indicative of pneumonitis (evaluate for noninfectious pneumonitis in patients with nonspecific respiratory signs/symptoms, including hypoxia, cough, dyspnea, or interstitial infiltrates on radiologic exam after excluding infections, neoplastic or other causes). Monitor adherence.

Mechanism of Action

Alpelisib is a small-molecule phosphatidylinositol-3-kinase (PI3K) inhibitor with selective (and strong) activity against PI3Kα (André 2019). Mutations in the gene encoding the catalytic α-subunit of PI3K (PI3KCA) lead to activation of PI3Kα and Akt-signaling, cellular transformation, and tumor generation. Alpelisib inhibits phosphorylation of PI3K downstream targets (including Akt) and demonstrated activity in cell lines harboring a PIK3CA mutation. When compared with either agent alone, the combination of alpelisib with fulvestrant has synergistic antitumor activity in PIK3CA-mutated, estrogen receptor-positive models (André 2019).

Activating mutations in PIK3CA may induce a spectrum of overgrowths/malformations comprising clinically recognizable disorders commonly known as PIK3CA-related overgrowth spectrum (PROS) (Venot 2018). In an animal model PROS phenotype (congenital lipomatous overgrowth, vascular malformations, epidermal nevi, scoliosis/skeletal and spinal syndrome [CLOVES]), alpelisib inhibited the PI3K pathway, resulting in prevention or improvement of organ abnormalities associated with the disease; findings were reversed following alpelisib withdrawal.

Pharmacokinetics (Adult Data Unless Noted)

Distribution: V_dss: 114 L.

Protein binding: 89%.

Metabolism: Primarily by chemical and enzymatic hydrolysis to form its metabolite BZG791, and to a lesser extent by CYP3A4.

Half-life elimination: 8 to 9 hours.

Time to peak: 2 to 4 hours.

Excretion: Following a single 400 mg dose: Feces: 81% (36% as unchanged drug, 32% as BZG791); Urine: 14% (2% as unchanged drug, 7% as BZG791).

Clearance: 9.2 L/hour (under fed conditions).

Brand Names: International

International Brand Names by Country

For country code abbreviations (show table)

(AE) United Arab Emirates: Piqray;
(AR) Argentina: Piqray;
(AT) Austria: Piqray;
(BE) Belgium: Piqray;
(BR) Brazil: Piqray;
(CH) Switzerland: Piqray;
(CZ) Czech Republic: Piqray;
(DE) Germany: Piqray;
(ES) Spain: Piqray;
(FI) Finland: Piqray;
(FR) France: Piqray;
(GB) United Kingdom: Piqray;
(HK) Hong Kong: Piqray;
(HU) Hungary: Piqray;
(IE) Ireland: Piqray;
(IN) India: Pivikto;
(IT) Italy: Piqray;
(JO) Jordan: Piqray;
(KW) Kuwait: Piqray;
(LB) Lebanon: Piqray;
(LV) Latvia: Piqray;
(MY) Malaysia: Trezilent;
(NL) Netherlands: Piqray;
(NO) Norway: Piqray;
(PL) Poland: Piqray;
(PR) Puerto Rico: Piqray | Vijoice;
(QA) Qatar: Piqray (200 mg Daily Dose) | Piqray (250 mg Daily Dose) | Piqray (300 mg Daily Dose);
(RO) Romania: Piqray;
(RU) Russian Federation: Piqray;
(SA) Saudi Arabia: Piqray;
(SE) Sweden: Piqray;
(SI) Slovenia: Piqray;
(SK) Slovakia: Piqray;
(TR) Turkey: Pimreva;
(ZA) South Africa: Pivikto | Trezilent

<800> Hazardous Drugs—Handling in Healthcare Settings. United States Pharmacopeia and National Formulary (USP 43-NF 38). Rockville, MD: United States Pharmacopeia Convention; 2020:74-92.
André F, Ciruelos E, Rubovszky G, et al; SOLAR-1 Study Group. Alpelisib for PIK3CA-mutated, hormone receptor-positive advanced breast cancer. N Engl J Med. 2019;380(20):1929-1940. [PubMed 31091374]
Hwang JP, Feld JJ, Hammond SP, et al. Hepatitis B virus screening and management for patients with cancer prior to therapy: ASCO provisional clinical opinion update. J Clin Oncol. 2020;38(31):3698-3715. doi:10.1200/JCO.20.01757 [PubMed 32716741]
Nunnery SE, Mayer IA. Management of toxicity to isoform α-specific PI3K inhibitors. Ann Oncol. 2019;30(suppl 10):x21-x26. doi: 10.1093/annonc/mdz440 [PubMed 31626273]
Piqray (alpelisib) [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; November 2022.
Rugo HS, André F, Yamashita T, et al. Time course and management of key adverse events during the randomized phase III SOLAR-1 study of PI3K inhibitor alpelisib plus fulvestrant in patients with HR-positive advanced breast cancer. Ann Oncol. 2020;31(8):1001-1010. doi:10.1016/j.annonc.2020.05.001 [PubMed 32416251]
US Department of Health and Human Services; Centers for Disease Control and Prevention; National Institute for Occupational Safety and Health. NIOSH list of antineoplastic and other hazardous drugs in healthcare settings 2016. https://www.cdc.gov/niosh/docs/2016-161/default.html. Updated September 2016. Accessed May 29, 2019.
Venot Q, Blanc T, Rabia SH, et al. Targeted therapy in patients with PIK3CA-related overgrowth syndrome. Nature. 2018;558(7711):540-546. doi:10.1038/s41586-018-0217-9 [PubMed 29899452]
Vijoice (alpelisib) [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; November 2022.

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خرید پکیج

Alpelisib: Drug information