alpelisib (Rx)

Brand and Other Names:Piqray
  • Print

Dosing & Uses

AdultPediatricGeriatric

Dosage Forms & Strengths

tablet

  • 50mg
  • 150mg
  • 200mg

Breast Cancer

Kinase inhibitor indicated in combination with fulvestrant for treatment of postmenopausal women, and men, with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, PIK3CA-mutated, advanced or metastatic breast cancer following progression on or after an endocrine-based regimen

Alpelisib 300 mg PO qDay AND

Fulvestrant 500 mg IM on Days 1, 15, and 29, and once monthly thereafter

Continue treatment until disease progression or unacceptable toxicity occurs

Refer to the full prescribing information for fulvestrant

Dosage Modifications

Dose reduction guidelines for adverse reactions

  • First-dose reduction: 250 mg PO qDay
  • Second-dose reduction: 200 mg PO qDay
  • Only 1 dose reduction permitted for pancreatitis
  • If dose reduction below 200 mg qDay required, discontinue treatment

Hyperglycemia

  • Grade 1 (fasting plasma glucose [FPG] >ULN to 160mg/dL OR >ULN to 8.9 mmol/L): No dosage adjustment required; initiate/intensify antidiabetic therapy
  • Grade 2 (FPG >160-250 mg/dL OR >8.9-13.9 mmol/L)
    • No dosage adjustment required
    • Initiate or further intensify antidiabetic treatment
    • If FPG not decreased ≤160 mg/dL or 8.9 mmol/L within 21 days under appropriate antidiabetic treatment, reduce dose by 1 dose level and follow FPG value specific recommendation
  • Grade 3 (FPG >250-500 mg/dL OR >13.9-27.8 mmol/L)
    • Interrupt alpelisib Initiate or intensify oral antidiabetic therapy and consider additional antidiabetic medications (eg, insulin) for 1-2 days until hyperglycemia improves
    • Administer IV hydration and consider appropriate treatment (eg, intervention for electrolyte/ketoacidosis/hyperosmolar disturbances)
    • If FPG decreases to ≤160 mg/dL or 8.9 mmol/L within 3-5 days under appropriate antidiabetic treatment, resume at 1 lower dose level
    • If FPG does not decrease to ≤160 mg/dL or 8.9 mmol/L within 3-5 days under appropriate antidiabetic treatment, consultation with a physician with expertise in the treatment of hyperglycemia is recommended
    • If FPG does not decrease to ≤160 mg/dL or 8.9 mmol/L within 21 days following appropriate antidiabetic treatment, permanently discontinue treatment
  • Grade 4 (FPG >500 mg/dL or ≤27.8 mmol/L
    • Interrupt alpelisib Initiate or intensify appropriate antidiabetic treatment
    • Administer IV hydration and consider appropriate treatment (eg, intervention for electrolyte/ketoacidosis/hyperosmolar disturbances); recheck FPG within 24 hr and as clinically indicated
    • If FPG decreases to ≤500 mg/dL or 27.8 mmol/L, follow recommendations for Grade 3 hyperglycemia
    • If FPG is confirmed at >500 mg/dL or 27.8 mmol/L, permanently discontinue treatment

Rash

  • Consider consulting with a dermatologist for all grades of rash
  • Grade 1 (<10% BSA with active skin toxicity): No dosage adjustment required; initiate topical corticosteroid treatment; consider adding oral antihistamine to manage symptoms
  • Grade 2 (10-30% BSA with active skin toxicity): No dosage adjustment required; initiate or intensify topical corticosteroid and oral antihistamine treatment; consider low-dose systemic corticosteroid treatment
  • Grade 3 (eg, severe rash not responsive to medical management; >30% BSA with active skin toxicity): Interrupt dose; initiate or intensify topical/systemic corticosteroid and oral antihistamine treatment; once improved to grade ≤1, resume alpelisib at same dose level for first occurrence, or at next lower dose level if second occurrence
  • 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 treatment

Diarrhea

  • All grades: Initiate or intensify appropriate medical therapy and monitor as clinically indicated
  • Grade 1: No dosage adjustment required
  • Grade 2: Interrupt dose until recovery to grade ≤1, then resume at same dose level
  • Grade 3 and 4: Interrupt dose until recovery to grade ≤1, then resume at the next lower dose level

Other toxicities

  • Grade 1 or 2: No dosage adjustment required; initiate appropriate medical therapy and monitor as clinically indicated
  • Grade 2 and 3 pancreatitis: Interrupt dose until recovery to grade <2 and resume at next lower dose level; only 1 dose reduction is permitted; if toxicity recurs, permanently discontinue treatment
  • Grade 2 elevated total bilirubin: Interrupt dose until recovery to grade ≤1 and resume at the same dose if resolved in ≤14 days or resume at next lower dose level if resolved in >14 days
  • Grade 3: Interrupt dose until recovery to grade ≤1, then resume at the next lower dose level
  • Grade 4: Permanently discontinue treatment

Renal impairment

  • Mild-to-moderate (CrCl 30 to <90 mL/min): No dosage adjustment required
  • Severe (CrCl <30 mL/min): Pharmacokinetic data are unknown

Dosing Considerations

Patient selection

  • Select patients for treatment based on presence of ≥1 PIK3CA mutations in tumor tissue or plasma specimens
  • 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

Safety and efficacy not established

Patients aged ≥65 years had higher incidence of grade 3-4 hyperglycemia compared with patients aged <65 years

Patients aged ≥75 years: Insufficient number of patients to assess differences in safety and efficacy

Next:

Interactions

Interaction Checker

and alpelisib

No Results

     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

            All Interactions Sort By:
             activity indicator 
            Previous
            Next:

            Adverse Effects

            >10% (In Combination with Fulvestrant)

            Glucose increased (79%)

            Creatinine increased (67%)

            Diarrhea (58%)

            Rash (52%)

            Lymphocyte count decreased (52%)

            GGT increased (52%)

            Nausea (45%)

            ALT increased (44%)

            Fatigue (42%)

            Hemoglobin decreased (42%)

            Lipase increased (42%)

            Glucose increased, grade 3-4 (39%)

            Decreased appetite (36%)

            Stomatitis (30%)

            Vomiting (27%)

            Decreased weight (27%)

            Calcium (corrected) decreased (27%)

            Glucose decreased (26%)

            aPTT prolonged (21%)

            Alopecia (20%)

            Rash, grade 3-4 (20%)

            Mucosal inflammation (19%)

            Pruritus (18%)

            Dry skin (18%)

            Dysgeusia (18%)

            Headache (18%)

            Abdominal pain (17%)

            Peripheral edema (15%)

            Pyrexia (14%)

            Platelet count decreased (14%)

            Potassium decreased (14%)

            Albumin decreased (14%)

            Mucosal dryness (12%)

            Dyspepsia (11%)

            Magnesium decreased (11%)

            GGT increased, grade 3-4 (11%)

            1-10% (In Combination with Fulvestrant)

            Urinary tract infection (10%)

            Lymphocyte count decreased, grade 3-4 (8%)

            Diarrhea, grade 3-4 (7%)

            Lipase increased, grade 3-4 (7%)

            Potassium decreased, grade 3-4 (2.1%)

            Fatigue, grade 3-4 (5%)

            Hemoglobin decreased, grade 3-4 (4.2%)

            Decreased weight, grade 3-4 (3.9%)

            ALT increased, grade 3-4 (3.5%)

            Creatinine increased, grade 3-4 (2.8%)

            Nausea, grade 3-4 (2.5%)

            Stomatitis, grade 3-4 (2.5%)

            Mucosal inflammation, grade 3-4 (2.1%)

            Calcium (corrected) decreased (2.1%)

            Abdominal pain, grade 3-4 (1.4%)

            Platelet count decreased, grade 3-4 (1.1%)

            >1% (In Combination with Fulvestrant)

            Pruritus, grade 3-4 (0.7%)

            Urinary tract infection, grade 3-4 (0.7%)

            Headache, grade 3-4 (0.7%)

            Decreased appetite, grade 3-4 (0.7%)

            Vomiting, grade 3-4 (0.7%)

            aPTT prolonged, grade 3-4 (0.7%)

            Dry skin, grade 3-4 (0.4%)

            Dysgeusia, grade 3-4 (0.4%)

            Mucosal dryness, grade 3-4 (0.4%)

            Glucose decreased, grade 3-4 (0.4%)

            Magnesium decreased, grade 3-4 (0.4%)

            Previous
            Next:

            Warnings

            Contraindications

            Hypersensitivity to alpelisib or any of its components

            Cautions

            Severe hypersensitivity reactions (eg, anaphylaxis, anaphylactic shock) reported; reactions manifested by symptoms including, but not limited to, dyspnea, flushing, rash, fever, or tachycardia

            Severe cutaneous reactions, including Stevens-Johnson syndrome (SJS) and erythema multiforme (EM) reported; do not initiate with history of SJS, EM, or toxic epidermal necrolysis (TEN); if SJS, TEN, or EM confirmed, permanently discontinue; do not reintroduce in patients who have experienced previous severe cutaneous reactions during treatment

            Severe pneumonitis, including acute interstitial pneumonitis and interstitial lung disease, reported; consider noninfectious pneumonitis in patients presenting with nonspecific respiratory signs and symptoms (eg, hypoxia, cough, dyspnea, or interstitial infiltrates on radiologic examinations) and in whom infectious, neoplastic, and other causes have been excluded

            Severe diarrhea, including dehydration and acute kidney injury, occurred; advise patients to start antidiarrheal treatment, increase oral fluids, and notify their healthcare provider if diarrhea occurs

            Based on findings in animals and its mechanism of action, fetal harm may occur when administered to pregnant women

            Severe hyperglycemia

            • Severe hyperglycemia, including ketoacidosis, reported
            • Before initiating treatment, test FPG and HbA1c, and optimize blood glucose
            • After initiation, monitor blood glucose and/or FPG at least qWeek for the first 2 weeks, then at least q4Weeks, and as clinically indicated; monitor HbA1c every 3 months and as clinically indicated
            • During treatment with antidiabetic medication, continue monitoring blood glucose or FPG at least once a week for 8 weeks, followed by once q2Weeks and as clinically indicated

            Drug interactions overview

            • Alpelisib: CYP3A4 and BCRP substrate; CYP2C9 inducer
            • CYP3A4 inducers
              • Strong CYP3A4 inducers may decrease alpelisib concentration and/or activity
              • Avoid coadministration with strong CYP3A4 inducers
            • BCRP inhibitors
              • Coadministration with BCRP inhibitors may increase alpelisib concentration and/or risk of toxicities
              • Avoid coadministration with BCRP inhibitors; if unable to avoid or use alternant drugs, closely monitor for increased adverse effects of alpelisib
            • CYP2C9 substrates
              • Coadministration of alpelisib with CYP2C9 substrates (eg, warfarin) may reduce plasma concentration of CYP2C9 substrates
              • Closely monitor when used in combination with CYP2C9 substrates for potential reduced activity of these drugs
            Previous
            Next:

            Pregnancy & Lactation

            Pregnancy

            Based on animal data and mechanism of action, fetal harm may occur when administered to pregnant women

            No data available in pregnant women to inform the drug-associated risk

            Advise pregnant women and females of reproductive potential of fetal risk

            Verify pregnancy status in females of reproductive potential before initiating

            Animal data

            • In animal reproduction studies, oral administration to pregnant rats and rabbits during organogenesis caused adverse developmental outcomes, including embryofetal mortality (postimplantation 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

            Contraception

            • Females of reproductive potential: Use effective contraception during treatment and for 1 week after the last dose
            • Male patients with female partners of reproductive potential: Use condoms and effective contraception during treatment and for 1 week after the last dose

            Infertility

            • Based on findings from animal studies, fertility in males and females of reproductive potential may be impaired

            Lactation

            There are no data on the presence of alpelisib in human milk, its effects on milk production, or the breastfed child

            Because of potential for serious adverse reactions in the breastfed child, advise lactating women to not breastfeed during treatment and for 1 week after the last dose

            Pregnancy Categories

            A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA:Information not available.

            more...
            Previous
            Next:

            Pharmacology

            Mechanism of Action

            Phosphatidylinositol-3-kinase (PI3K) inhibitor with inhibitory activity predominantly against PI3K-alpha

            In breast cancer, alpelisib inhibits the phosphorylation of PI3K downstream targets and has shown activity in cell lines possessing a PIK3CA mutation

            PI3K inhibition has been shown to induce an increase in ER transcription in breast cancer cells

            Combination with fulvestrant demonstrates an increase in antitumor activity compared with either treatment alone

            Absorption

            Peak plasma concentration at steady-state: 2480 ng/mL

            Peak plasma time: 2-4 hr

            AUC: 33,224 ng·hr/mL

            Steady-state reached within 3 days

            Effects of food following a single dose

            • High-fat, high-calorie meal (985 calories with 58.1 grams of fat) increased AUC by 73% and peak plasma concentration by 84%
            • Low-fat, low-calorie meal (334 calories with 8.7 grams of fat) increased AUC by 77% and peak plasma concentration by 145%

            Distribution

            Vd: 114 L

            Protein bound: 89%

            Metabolism

            Primarily metabolized by chemical and enzymatic hydrolysis to form its metabolite, BZG791

            Metabolized to a lesser extent by CYP3A4

            Elimination

            Half-life: 8-9 hr

            Clearance: 9.2 L/hr

            Excretion

            • Feces: 81% (36% unchanged, 32% BZG791)
            • Urine: 14% (2% unchanged, 7.1 BZG791)
            • CYP3A4-mediated metabolites accounted for 12% of the dose
            • Glucuronides accounted for ~15% of the dose
            Previous
            Next:

            Administration

            Oral Administration

            Take orally with food

            Administer dose at approximately same time each day

            Swallow tablet whole (do not chew, crush, or split)

            Do not ingest if tablet is broken, cracked, or otherwise not intact

            Missed dose

            • Missed dose ≤9 hr of scheduled time: Take dose
            • Missed dose >9 hr of scheduled time: Skip dose for that day; the next day, take dose at usual time
            • If dose is vomited, advise not to take an additional dose on that day; resume dosing schedule the next day at the usual time

            Storage

            Store at 20-25°C (68-77°F), excursions permitted to 15-30°C (59-86°F)

            Previous
            Next:

            Images

            Previous
            Next:

            Formulary

            FormularyPatient Discounts

            Adding plans allows you to compare formulary status to other drugs in the same class.

            To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

            Adding plans allows you to:

            • View the formulary and any restrictions for each plan.
            • Manage and view all your plans together – even plans in different states.
            • Compare formulary status to other drugs in the same class.
            • Access your plan list on any device – mobile or desktop.

            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
            Additional Offers
            Email to Patient

            From:

            To:

            The recipient will receive more details and instructions to access this offer.

            By clicking send, you acknowledge that you have permission to email the recipient with this information.

            Email Forms to Patient

            From:

            To:

            The recipient will receive more details and instructions to access this offer.

            By clicking send, you acknowledge that you have permission to email the recipient with this information.

            Previous
            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.