PIQRAY

Metabolic Agents, Phosphatidylinositol-3-Kinase (PI3K) Inhibitors
Small Molecule Antineoplastic Phosphatidylinositol-3-Kinase (PI3K) Inhibitors

Emetic Risk
Minimal/Low
Administer prn antiemetics as necessary.

Administer alpelisib with food at approximately the same time each day.
Do not crush, chew, or split alpelisib tablets; administer alpelisib tablets whole. Do not administer any tablet that is broken, cracked, or otherwise not intact.
If vomiting occurs, do not administer an additional dose on that day. Resume dosing the following day at the usual time.
Missed Dose: If a dose 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 and resume dosing on the following day at the usual time.[64248]
 
Preparation of oral suspension from tablets
For patients receiving alpelisib for PIK3CA-Related Overgrowth Spectrum (PROS) and not able to swallow tablets, administer as an oral suspension with food.
Place the tablet(s) in a glass containing 2 to 4 ounces of water and let stand for approximately 5 minutes; only use water to prepare the suspension.
Crush the tablets with a spoon and stir until an oral suspension is obtained. Administer immediately after preparation; discard if it is not administered within 60 minutes after preparation.
After administration, add approximately 2 to 3 tablespoons of water to the same glass, stir with the same soon to re-suspend remaining particles, and administer the entire contents of the glass. Repeat if particles remain.

hyperglycemia / Delayed / 36.9-56.0
rash / Early / 12.0-20.0
elevated hepatic enzymes / Delayed / 3.5-11.0
diarrhea / Early / 7.0-7.0
fatigue / Early / 5.0-5.0
weight loss / Delayed / 3.9-3.9
renal failure (unspecified) / Delayed / 2.8-2.8
stomatitis / Delayed / 2.5-2.5
nausea / Early / 2.5-2.5
hyperbilirubinemia / Delayed / 2.0-2.0
abdominal pain / Early / 1.4-1.4
erythema multiforme / Delayed / 1.1-1.1
pruritus / Rapid / 0.7-0.7
infection / Delayed / 0.7-0.7
fever / Early / 0.7-0.7
diabetic ketoacidosis / Delayed / 0.7-0.7
vomiting / Early / 0.7-0.7
anorexia / Delayed / 0.7-0.7
headache / Early / 0.7-0.7
prolonged bleeding time / Delayed / 0.7-0.7
xerosis / Delayed / 0.4-0.4
Stevens-Johnson syndrome / Delayed / 0.4-0.4
hypoglycemia / Early / 0.4-0.4
dysgeusia / Early / 0.4-0.4
toxic epidermal necrolysis / Delayed / Incidence not known
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) / Delayed / Incidence not known
angioedema / Rapid / Incidence not known
anaphylactic shock / Rapid / Incidence not known
anaphylactoid reactions / Rapid / Incidence not known
osteonecrosis / Delayed / Incidence not known
pancreatitis / Delayed / Incidence not known
hyperkalemia / Delayed / Incidence not known

peripheral edema / Delayed / 15.0-15.0
hypoalbuminemia / Delayed / 13.0-14.0
dehydration / Delayed / 0-5.0
pneumonitis / Delayed / 1.8-1.8
dyspnea / Early / Incidence not known
interstitial lung disease / Delayed / Incidence not known
colitis / Delayed / Incidence not known
anemia / Delayed / Incidence not known
lymphopenia / Delayed / Incidence not known
leukopenia / Delayed / Incidence not known
thrombocytopenia / Delayed / Incidence not known
hypertriglyceridemia / Delayed / Incidence not known
hypomagnesemia / Delayed / Incidence not known
hyponatremia / Delayed / Incidence not known
hypophosphatemia / Delayed / Incidence not known
hypokalemia / Delayed / Incidence not known
hypocalcemia / Delayed / Incidence not known

alopecia / Delayed / 5.0-20.0
dyspepsia / Early / 11.0-11.0
xerostomia / Early / 0-5.0
maculopapular rash / Early / Incidence not known
acneiform rash / Delayed / Incidence not known
flushing / Rapid / Incidence not known
asthenia / Delayed / Incidence not known

PIQRAY, Vijoice

Rx

Phosphatidylinositol 3-kinase inhibitor
Used in combination with fulvestrant in adults for certain types of breast cancer; used in adult and pediatric patients 2 years and older with severe manifestations of PIK3CA-related overgrowth spectrum (PROS)
If possible, optimize blood glucose prior to starting therapy; safety in patients with Type 1 and uncontrolled Type 2 diabetes has not been established

300 mg PO once daily with food, in combination with fulvestrant (500 mg IM on days 1, 15, 29 and once monthly thereafter) until disease progression or unacceptable toxicity. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. In a randomized, double-blind clinical trial (SOLAR-1), treatment with fulvestrant plus alpelisib significantly improved progression-free survival (PFS) compared with fulvestrant plus placebo in patients with HR-positive, HER2-negative, advanced or metastatic breast cancer in patients with a PIK3CA mutation in tumor tissue, whose disease had progressed or recurred on or after aromatase inhibitor-based treatment (11 months vs. 5.7 months); similar results were seen in patients with tissue or plasma PIK3CA mutations. No PFS benefit was observed in patients whose tumors did not have a PIK3CA tissue mutation. The overall response rate was 35.7% in patients who were treated with fulvestrant plus alpelisib compared with 16.2% in those who received fulvestrant plus placebo. There was no significant difference in overall survival between treatment groups.

250 mg PO once daily with food until disease progression or unacceptable toxicity.

50 mg PO once daily, initially. After 24 weeks, consider increasing dose to 125 mg PO once daily for response optimization (clinical/radiological). Administer with food. Continue until disease progression or unacceptable toxicity.

50 mg PO once daily with food until disease progression or unacceptable toxicity.

Baseline Hepatic Impairment
Dose adjustments are not necessary.
 
Treatment-Related Hyperbilirubinemia
Grade 1: Initiate appropriate medical therapy and monitor as clinically indicated. No dose adjustment of alpelisib is required.
Grade 2: Interrupt alpelisib therapy and initiate appropriate medical therapy; monitor as clinically indicated.
In adults with breast cancer, if the bilirubin level recovers to grade 1 or less within 14 days, resume alpelisib therapy at the same dose level. If the bilirubin level recovers to grade 1 or less in more than 14 days, resume therapy at the next lower dose level. If dose reduction below 200 mg once daily is required, discontinue alpelisib.
In adults with PROS, if the bilirubin level recovers to grade 1 or less within 14 days, resume alpelisib therapy at the same dose level. If the bilirubin level recovers to grade 1 or less in more than 14 days, resume therapy at the next lower dose level.
In pediatric patients with PROS, if the bilirubin level recovers to grade 1 or less within 14 days, resume alpelisib therapy at the same dose level. If the bilirubin level recovers to grade 1 or less in more than 14 days, resume alpelisib 50 mg PO once daily.
Grade 3: Interrupt alpelisib therapy and initiate appropriate medical therapy; monitor as clinically indicated.
In adults with breast cancer, if the bilirubin level recovers to grade 1 or less, resume alpelisib therapy at the next lower dose level. If dose reduction below 200 mg once daily is required, discontinue alpelisib.
In adults with PROS, if the bilirubin level recovers to grade 1 or less, resume alpelisib therapy at the next lower dose level.
In pediatric patients with PROS, if the bilirubin level recovers to grade 1 or less either resume alpelisib 50 mg PO once daily or permanently discontinue alpelisib. For the second occurrence, consider permanently discontinuing alpelisib treatment. Consultation with a physician with expertise in the treatment of the specific adverse reaction is recommended.
Grade 4: Permanently discontinue alpelisib.

Baseline Renal Impairment
Dose adjustments are not necessary.

Acalabrutinib: (Major) Avoid coadministration of alpelisib with acalabrutinib due to increased exposure to alpelisib and the risk of alpelisib-related toxicity. If concomitant use is unavoidable, closely monitor for alpelisib-related adverse reactions. Alpelisib is a BCRP substrate and acalabrutinib is a BCRP inhibitor.
Amlodipine; Celecoxib: (Moderate) Monitor for decreased efficacy of celecoxib during coadministration of alpelisib as plasma concentrations of celecoxib may be decreased. Celecoxib is a sensitive CYP2C9 substrate; in vitro data suggest alpelisib is a CYP2C9 inducer.
Apalutamide: (Major) Avoid coadministration of alpelisib with apalutamide due to decreased exposure to alpelisib which could decrease efficacy. Alpelisib is a CYP3A4 substrate; apalutamide is a strong CYP3A4 inducer.
Atazanavir; Cobicistat: (Major) Avoid coadministration of alpelisib with cobicistat due to increased exposure to alpelisib and the risk of alpelisib-related toxicity. If concomitant use is unavoidable, closely monitor for alpelisib-related adverse reactions. Alpelisib is a BCRP substrate and cobicistat is a BCRP inhibitor.
Brigatinib: (Major) Avoid coadministration of alpelisib with brigatinib due to increased exposure to alpelisib and the risk of alpelisib-related toxicity. If concomitant use is unavoidable, closely monitor for alpelisib-related adverse reactions. Alpelisib is a BCRP substrate and brigatinib is a BCRP inhibitor.
Capmatinib: (Major) Avoid coadministration of alpelisib with capmatinib due to increased exposure to alpelisib and the risk of alpelisib-related toxicity. If concomitant use is unavoidable, closely monitor for alpelisib-related adverse reactions. Alpelisib is a BCRP substrate and capmatinib is a BCRP inhibitor.
Carbamazepine: (Major) Avoid coadministration of alpelisib with carbamazepine due to decreased exposure to alpelisib which could decrease efficacy. Alpelisib is a CYP3A4 substrate; carbamazepine is a strong CYP3A4 inducer.
Celecoxib: (Moderate) Monitor for decreased efficacy of celecoxib during coadministration of alpelisib as plasma concentrations of celecoxib may be decreased. Celecoxib is a sensitive CYP2C9 substrate; in vitro data suggest alpelisib is a CYP2C9 inducer.
Celecoxib; Tramadol: (Moderate) Monitor for decreased efficacy of celecoxib during coadministration of alpelisib as plasma concentrations of celecoxib may be decreased. Celecoxib is a sensitive CYP2C9 substrate; in vitro data suggest alpelisib is a CYP2C9 inducer.
Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine.
Cobicistat: (Major) Avoid coadministration of alpelisib with cobicistat due to increased exposure to alpelisib and the risk of alpelisib-related toxicity. If concomitant use is unavoidable, closely monitor for alpelisib-related adverse reactions. Alpelisib is a BCRP substrate and cobicistat is a BCRP inhibitor.
Cyclosporine: (Major) Avoid coadministration of alpelisib with cyclosporine due to increased exposure to alpelisib and the risk of alpelisib-related toxicity. If concomitant use is unavoidable, closely monitor for alpelisib-related adverse reactions. Alpelisib is a BCRP substrate and cyclosporine is a BCRP inhibitor.
Daclatasvir: (Major) Avoid coadministration of alpelisib with daclatasvir due to increased exposure to alpelisib and the risk of alpelisib-related toxicity. If concomitant use is unavoidable, closely monitor for alpelisib-related adverse reactions. Alpelisib is a BCRP substrate and daclatasvir is a BCRP inhibitor.
Darolutamide: (Major) Avoid coadministration of alpelisib with darolutamide due to increased exposure to alpelisib and the risk of alpelisib-related toxicity. If concomitant use is unavoidable, closely monitor for alpelisib-related adverse reactions. Alpelisib is a BCRP substrate and darolutamide is a BCRP inhibitor.
Darunavir; Cobicistat: (Major) Avoid coadministration of alpelisib with cobicistat due to increased exposure to alpelisib and the risk of alpelisib-related toxicity. If concomitant use is unavoidable, closely monitor for alpelisib-related adverse reactions. Alpelisib is a BCRP substrate and cobicistat is a BCRP inhibitor.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) Avoid coadministration of alpelisib with cobicistat due to increased exposure to alpelisib and the risk of alpelisib-related toxicity. If concomitant use is unavoidable, closely monitor for alpelisib-related adverse reactions. Alpelisib is a BCRP substrate and cobicistat is a BCRP inhibitor.
Elacestrant: (Major) Avoid coadministration of alpelisib with elacestrant due to increased exposure to alpelisib and the risk of alpelisib-related toxicity. If concomitant use is unavoidable, closely monitor for alpelisib-related adverse reactions. Alpelisib is a BCRP substrate and elacestrant is a BCRP inhibitor.
Elbasvir; Grazoprevir: (Major) Avoid coadministration of alpelisib with elbasvir due to increased exposure to alpelisib and the risk of alpelisib-related toxicity. If concomitant use is unavoidable, closely monitor for alpelisib-related adverse reactions. Alpelisib is a BCRP substrate and elbasvir is a BCRP inhibitor. (Major) Avoid coadministration of alpelisib with grazoprevir due to increased exposure to alpelisib and the risk of alpelisib-related toxicity. If concomitant use is unavoidable, closely monitor for alpelisib-related adverse reactions. Alpelisib is a BCRP substrate and grazoprevir is a BCRP inhibitor.
Eltrombopag: (Major) Avoid coadministration of alpelisib with eltrombopag due to increased exposure to alpelisib and the risk of alpelisib-related toxicity. If concomitant use is unavoidable, closely monitor for alpelisib-related adverse reactions. Alpelisib is a BCRP substrate and eltrombopag is a BCRP inhibitor.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Major) Avoid coadministration of alpelisib with cobicistat due to increased exposure to alpelisib and the risk of alpelisib-related toxicity. If concomitant use is unavoidable, closely monitor for alpelisib-related adverse reactions. Alpelisib is a BCRP substrate and cobicistat is a BCRP inhibitor.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Avoid coadministration of alpelisib with cobicistat due to increased exposure to alpelisib and the risk of alpelisib-related toxicity. If concomitant use is unavoidable, closely monitor for alpelisib-related adverse reactions. Alpelisib is a BCRP substrate and cobicistat is a BCRP inhibitor.
Enasidenib: (Major) Avoid coadministration of alpelisib with enasidenib due to increased exposure to alpelisib and the risk of alpelisib-related toxicity. If concomitant use is unavoidable, closely monitor for alpelisib-related adverse reactions. Alpelisib is a BCRP substrate and enasidenib is a BCRP inhibitor.
Encorafenib: (Major) Avoid coadministration of alpelisib with encorafenib due to increased exposure to alpelisib and the risk of alpelisib-related toxicity. If concomitant use is unavoidable, closely monitor for alpelisib-related adverse reactions. Alpelisib is a BCRP substrate and encorafenib is a BCRP inhibitor.
Enzalutamide: (Major) Avoid coadministration of alpelisib with enzalutamide due to decreased exposure to alpelisib which could decrease efficacy. Alpelisib is a CYP3A4 substrate; enzalutamide is a strong CYP3A4 inducer.
Fosphenytoin: (Major) Avoid coadministration of alpelisib with fosphenytoin due to decreased exposure to alpelisib which could decrease efficacy; fosphenytoin exposure may also decrease. Alpelisib is a CYP3A4 substrate and may induce CYP2C9; fosphenytoin is a strong CYP3A4 inducer and a CYP2C9 substrate.
Fostamatinib: (Major) Avoid coadministration of alpelisib with fostamatinib due to increased exposure to alpelisib and the risk of alpelisib-related toxicity. If concomitant use is unavoidable, closely monitor for alpelisib-related adverse reactions. Alpelisib is a BCRP substrate and fostamatinib is a BCRP inhibitor.
Fostemsavir: (Major) Avoid concomitant use of alpelisib with fostemsavir due to increased exposure to alpelisib and the risk of alpelisib-related toxicity. If concomitant use is unavoidable, closely monitor for alpelisib-related adverse reactions. Alpelisib is a BCRP substrate and fostemsavir is a BCRP inhibitor.
Futibatinib: (Major) Avoid coadministration of alpelisib with futibatinib due to increased exposure to alpelisib and the risk of alpelisib-related toxicity. If concomitant use is unavoidable, closely monitor for alpelisib-related adverse reactions. Alpelisib is a BCRP substrate and futibatinib is a BCRP inhibitor.
Gilteritinib: (Major) Avoid coadministration of alpelisib with gilteritinib due to increased exposure to alpelisib and the risk of alpelisib-related toxicity. If concomitant use is unavoidable, closely monitor for alpelisib-related adverse reactions. Alpelisib is a BCRP substrate and gilteritinib is a BCRP inhibitor.
Glecaprevir; Pibrentasvir: (Major) Avoid coadministration of alpelisib with glecaprevir due to increased exposure to alpelisib and the risk of alpelisib-related toxicity. If concomitant use is unavoidable, closely monitor for alpelisib-related adverse reactions. Alpelisib is a BCRP substrate and glecaprevir is a BCRP inhibitor. (Major) Avoid coadministration of alpelisib with pibrentasvir due to increased exposure to alpelisib and the risk of alpelisib-related toxicity. If concomitant use is unavoidable, closely monitor for alpelisib-related adverse reactions. Alpelisib is a BCRP substrate and pibrentasvir is a BCRP inhibitor.
Glimepiride: (Moderate) Monitor for decreased efficacy of glimepiride during coadministration of alpelisib as plasma concentrations of glimepiride may be decreased. Glimepiride is a sensitive CYP2C9 substrate; in vitro data suggest alpelisib is a CYP2C9 inducer.
Ibrutinib: (Major) Avoid coadministration of alpelisib with ibrutinib due to increased exposure to alpelisib and the risk of alpelisib-related toxicity. If concomitant use is unavoidable, closely monitor for alpelisib-related adverse reactions. Alpelisib is a BCRP substrate and ibrutinib is a BCRP inhibitor.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Avoid coadministration of alpelisib with rifampin due to decreased exposure to alpelisib which could decrease efficacy. Alpelisib is a CYP3A4 substrate; rifampin is a strong CYP3A4 inducer.
Isoniazid, INH; Rifampin: (Major) Avoid coadministration of alpelisib with rifampin due to decreased exposure to alpelisib which could decrease efficacy. Alpelisib is a CYP3A4 substrate; rifampin is a strong CYP3A4 inducer.
Itraconazole: (Major) Avoid coadministration of alpelisib with itraconazole due to increased exposure to alpelisib and the risk of alpelisib-related toxicity. If concomitant use is unavoidable, closely monitor for alpelisib-related adverse reactions. Alpelisib is a BCRP substrate and itraconazole is a BCRP inhibitor.
Ledipasvir; Sofosbuvir: (Major) Avoid coadministration of alpelisib with ledipasvir due to increased exposure to alpelisib and the risk of alpelisib-related toxicity. If concomitant use is unavoidable, closely monitor for alpelisib-related adverse reactions. Alpelisib is a BCRP substrate and ledipasvir is a BCRP inhibitor.
Leflunomide: (Major) Avoid coadministration of alpelisib with leflunomide due to increased exposure to alpelisib and the risk of alpelisib-related toxicity. If concomitant use is unavoidable, closely monitor for alpelisib-related adverse reactions. Alpelisib is a BCRP substrate and leflunomide is a BCRP inhibitor.
Lenacapavir: (Major) Avoid coadministration of alpelisib with lenacapavir due to increased exposure to alpelisib and the risk of alpelisib-related toxicity. If concomitant use is unavoidable, closely monitor for alpelisib-related adverse reactions. Alpelisib is a BCRP substrate and lenacapavir is a BCRP inhibitor.
Leniolisib: (Major) Avoid coadministration of alpelisib with leniolisib due to increased exposure to alpelisib and the risk of alpelisib-related toxicity. If concomitant use is unavoidable, closely monitor for alpelisib-related adverse reactions. Alpelisib is a BCRP substrate and leniolisib is a BCRP inhibitor.
Lumacaftor; Ivacaftor: (Major) Avoid coadministration of alpelisib with lumacaftor; ivacaftor due to decreased exposure to alpelisib which could decrease efficacy. Alpelisib is a CYP3A4 substrate; lumacaftor is a strong CYP3A4 inducer.
Lumacaftor; Ivacaftor: (Major) Avoid coadministration of alpelisib with lumacaftor; ivacaftor due to decreased exposure to alpelisib which could decrease efficacy. Alpelisib is a CYP3A4 substrate; lumacaftor is a strong CYP3A4 inducer.
Maribavir: (Major) Avoid coadministration of alpelisib with maribavir due to increased exposure to alpelisib and the risk of alpelisib-related toxicity. If concomitant use is unavoidable, closely monitor for alpelisib-related adverse reactions. Alpelisib is a BCRP substrate and maribavir is a BCRP inhibitor.
Midostaurin: (Major) Avoid concomitant use of alpelisib with midostaurin due to increased exposure to alpelisib and the risk of alpelisib-related toxicity. If concomitant use is unavoidable, closely monitor for alpelisib-related adverse reactions. Alpelisib is a BCRP substrate and midostaurin is a BCRP inhibitor.
Mitotane: (Major) Avoid coadministration of alpelisib with mitotane due to decreased exposure to alpelisib which could decrease efficacy. Alpelisib is a CYP3A4 substrate; mitotane is a strong CYP3A4 inducer.
Osimertinib: (Major) Avoid coadministration of alpelisib with osimertinib due to increased exposure to alpelisib and the risk of alpelisib-related toxicity. If concomitant use is unavoidable, closely monitor for alpelisib-related adverse reactions. Alpelisib is a BCRP substrate and osimertinib is a BCRP inhibitor.
Oteseconazole: (Major) Avoid coadministration of alpelisib with oteseconazole due to increased exposure to alpelisib and the risk of alpelisib-related toxicity. If concomitant use is unavoidable, closely monitor for alpelisib-related adverse reactions. Alpelisib is a BCRP substrate and oteseconazole is a BCRP inhibitor.
Pacritinib: (Major) Avoid coadministration of alpelisib with pacritinib due to increased exposure to alpelisib and the risk of alpelisib-related toxicity. If concomitant use is unavoidable, closely monitor for alpelisib-related adverse reactions. Alpelisib is a BCRP substrate and pacritinib is a BCRP inhibitor.
Phenobarbital: (Major) Avoid coadministration of alpelisib with phenobarbital due to decreased exposure to alpelisib which could decrease efficacy. Alpelisib is a CYP3A4 substrate; phenobarbital is a strong CYP3A4 inducer.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Major) Avoid coadministration of alpelisib with phenobarbital due to decreased exposure to alpelisib which could decrease efficacy. Alpelisib is a CYP3A4 substrate; phenobarbital is a strong CYP3A4 inducer.
Phenytoin: (Major) Avoid coadministration of alpelisib with phenytoin due to decreased exposure to alpelisib which could decrease efficacy; phenytoin exposure may also decrease. Alpelisib is a CYP3A4 substrate and may induce CYP2C9; phenytoin is a strong CYP3A4 inducer and a CYP2C9 substrate.
Pioglitazone; Glimepiride: (Moderate) Monitor for decreased efficacy of glimepiride during coadministration of alpelisib as plasma concentrations of glimepiride may be decreased. Glimepiride is a sensitive CYP2C9 substrate; in vitro data suggest alpelisib is a CYP2C9 inducer.
Pirtobrutinib: (Major) Avoid coadministration of alpelisib with pirtobrutinib due to increased exposure to alpelisib and the risk of alpelisib-related toxicity. If concomitant use is unavoidable, closely monitor for alpelisib-related adverse reactions. Alpelisib is a BCRP substrate and pirtobrutinib is a BCRP inhibitor.
Pretomanid: (Major) Avoid coadministration of alpelisib with pretomanid due to increased exposure to alpelisib and the risk of alpelisib-related toxicity. If concomitant use is unavoidable, closely monitor for alpelisib-related adverse reactions. Alpelisib is a BCRP substrate and pretomanid is a BCRP inhibitor.
Primidone: (Major) Avoid coadministration of alpelisib with primidone due to decreased exposure to alpelisib which could decrease efficacy. Alpelisib is a CYP3A4 substrate; primidone is a strong CYP3A4 inducer.
Regorafenib: (Major) Avoid coadministration of alpelisib with regorafenib due to increased exposure to alpelisib and the risk of alpelisib-related toxicity. If concomitant use is unavoidable, closely monitor for alpelisib-related adverse reactions. Alpelisib is a BCRP substrate and regorafenib is a BCRP inhibitor.
Rifampin: (Major) Avoid coadministration of alpelisib with rifampin due to decreased exposure to alpelisib which could decrease efficacy. Alpelisib is a CYP3A4 substrate; rifampin is a strong CYP3A4 inducer.
Rifapentine: (Major) Avoid coadministration of alpelisib with rifapentine due to decreased exposure to alpelisib which could decrease efficacy. Alpelisib is a CYP3A4 substrate; rifapentine is a strong CYP3A4 inducer.
Rolapitant: (Major) Avoid coadministration of alpelisib with rolapitant due to increased exposure to alpelisib and the risk of alpelisib-related toxicity. If concomitant use is unavoidable, closely monitor for alpelisib-related adverse reactions. Alpelisib is a BCRP substrate and rolapitant is a BCRP inhibitor.
Safinamide: (Major) Avoid coadministration of alpelisib with safinamide due to increased exposure to alpelisib and the risk of alpelisib-related toxicity. If concomitant use is unavoidable, closely monitor for alpelisib-related adverse reactions. Alpelisib is a BCRP substrate and safinamide is a BCRP inhibitor.
SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
Sodium Phenylbutyrate; Taurursodiol: (Major) Avoid coadministration of alpelisib with taurursodiol due to increased exposure to alpelisib and the risk of alpelisib-related toxicity. If concomitant use is unavoidable, closely monitor for alpelisib-related adverse reactions. Alpelisib is a BCRP substrate and taurursodiol is a BCRP inhibitor.
Sofosbuvir; Velpatasvir: (Major) Avoid coadministration of alpelisib with velpatasvir due to increased exposure to alpelisib and the risk of alpelisib-related toxicity. If concomitant use is unavoidable, closely monitor for alpelisib-related adverse reactions. Alpelisib is a BCRP substrate and velpatasvir is a BCRP inhibitor.
Sofosbuvir; Velpatasvir; Voxilaprevir: (Major) Avoid coadministration of alpelisib with velpatasvir due to increased exposure to alpelisib and the risk of alpelisib-related toxicity. If concomitant use is unavoidable, closely monitor for alpelisib-related adverse reactions. Alpelisib is a BCRP substrate and velpatasvir is a BCRP inhibitor. (Major) Avoid coadministration of alpelisib with voxilaprevir due to increased exposure to alpelisib and the risk of alpelisib-related toxicity. If concomitant use is unavoidable, closely monitor for alpelisib-related adverse reactions. Alpelisib is a BCRP substrate and voxilaprevir is a BCRP inhibitor.
Sotorasib: (Major) Avoid coadministration of alpelisib with sotorasib due to increased exposure to alpelisib and the risk of alpelisib-related toxicity. If concomitant use is unavoidable, closely monitor for alpelisib-related adverse reactions. Alpelisib is a BCRP substrate and sotorasib is a BCRP inhibitor.
Sparsentan: (Major) Avoid coadministration of alpelisib with sparsentan due to increased exposure to alpelisib and the risk of alpelisib-related toxicity. If concomitant use is unavoidable, closely monitor for alpelisib-related adverse reactions. Alpelisib is a BCRP substrate and sparsentan is a BCRP inhibitor.
St. John's Wort, Hypericum perforatum: (Major) Avoid coadministration of alpelisib with St. John's Wort due to decreased exposure to alpelisib which could decrease efficacy. Alpelisib is a CYP3A4 substrate; St. John's Wort is a strong CYP3A4 inducer.
Stiripentol: (Major) Avoid coadministration of alpelisib with stiripentol due to increased exposure to alpelisib and the risk of alpelisib-related toxicity. If concomitant use is unavoidable, closely monitor for alpelisib-related adverse reactions. Alpelisib is a BCRP substrate and stiripentol is a BCRP inhibitor.
Sulfasalazine: (Major) Avoid coadministration of alpelisib with sulfasalazine due to increased exposure to alpelisib and the risk of alpelisib-related toxicity. If concomitant use is unavoidable, closely monitor for alpelisib-related adverse reactions. Alpelisib is a BCRP substrate and sulfasalazine is a BCRP inhibitor.
Tacrolimus: (Major) Avoid coadministration of alpelisib with tacrolimus due to increased exposure to alpelisib and the risk of alpelisib-related toxicity. If concomitant use is unavoidable, closely monitor for alpelisib-related adverse reactions. Alpelisib is a BCRP substrate and tacrolimus is a BCRP inhibitor.
Tafamidis: (Major) Avoid coadministration of alpelisib with tafamidis due to increased exposure to alpelisib and the risk of alpelisib-related toxicity. If concomitant use is unavoidable, closely monitor for alpelisib-related adverse reactions. Alpelisib is a BCRP substrate and tafamidis is a BCRP inhibitor.
Tedizolid: (Major) Avoid coadministration of alpelisib with tedizolid due to increased exposure to alpelisib and the risk of alpelisib-related toxicity. If concomitant use is unavoidable, closely monitor for alpelisib-related adverse reactions. Alpelisib is a BCRP substrate and tedizolid is a BCRP inhibitor.
Teriflunomide: (Major) Avoid coadministration of alpelisib with teriflunomide due to increased exposure to alpelisib and the risk of alpelisib-related toxicity. If concomitant use is unavoidable, closely monitor for alpelisib-related adverse reactions. Alpelisib is a BCRP substrate and teriflunomide is a BCRP inhibitor.
Tolbutamide: (Moderate) Monitor for decreased efficacy of tolbutamide during coadministration of alpelisib as plasma concentrations of tolbutamide may be decreased. Tolbutamide is a sensitive CYP2C9 substrate; in vitro data suggest alpelisib is a CYP2C9 inducer.
Vemurafenib: (Major) Avoid coadministration of alpelisib with vemurafenib due to increased exposure to alpelisib and the risk of alpelisib-related toxicity. If concomitant use is unavoidable, closely monitor for alpelisib-related adverse reactions. Alpelisib is a BCRP substrate and vemurafenib is a BCRP inhibitor.
Warfarin: (Moderate) Closely monitor the INR if coadministration of warfarin with alpelisib is necessary as concurrent use may decrease the exposure of warfarin leading to reduced efficacy. Alpelisib is a weak CYP2C9 inducer and the S-enantiomer, the active metabolite of warfarin, is a CYP2C9 substrate. The S-enantiomer of warfarin exhibits 2 to 5 times more anticoagulant activity than the R-enantiomer, but the R-enantiomer generally has a slower clearance.

PIQRAY/Vijoice Oral Tab: 50mg, 125mg, 150mg, 200mg, 50-200mg

250 mg PO once daily for PROS; 300 mg PO once daily for breast cancer.

300 mg PO once daily for breast cancer; safety and efficacy have not been established for treatment of PROS.

125 mg PO once daily for PROS; safety and efficacy have not been established for treatment of breast cancer.

6 to 12 years: 125 mg PO once daily for PROS; safety and efficacy have not been established for treatment of breast cancer.
2 to 5 years: 50 mg PO once daily for PROS; safety and efficacy have not been established for treatment of breast cancer.
1 year: Safety and efficacy have not been established.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Alpelisib is a kinase inhibitor targeting phosphatidylinositol-3-kinase (PI3K); its inhibitory activity primarily targets PI3K-alpha. Gain-of-function mutations in the gene encoding the catalytic alpha-subunit of PI3K (PIK3CA) lead to activation of PI3K-alpha and Akt-signaling, cellular transformation, and the generation of tumors in in vitro and in vivo models.[64248]
 
In breast cancer cell lines, alpelisib inhibited the phosphorylation of PI3K downstream targets, including Akt, and showed activity in cell lines harboring a PI3KCA 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.[64248]
 
Activating mutations in PIK3CA have been found to induce a spectrum of overgrowths and malformations comprising a wide group of clinically recognizable disorders commonly known as PIK3CA-related overgrowth spectrum (PROS). In an inducible mouse model of congential lipomatous overgrowth, vascular malformations, epidermal nevi, scoliosis/skeletal and spinal syndrome (CLOVES), a phenotype of PROS, alpelisib inhibition of the PI3K pathway resulted in the prevention or improvement of organ abnormalities associated with the disease, depending on when alpelisib treatment was started. These findings were reversed after alpelisib withdrawal.

Alpelisib is administered orally. It is 89% protein bound, independent of concentration. The mean apparent volume of distribution (Vd) at steady state is predicted to be 114 liters (CV, 46%). The half-life of alpelisib is predicted to be 8 to 9 hours, with a mean clearance of 9.2 liters/hour (CV, 21%) under fed conditions; steady-state plasma concentrations are reached within 3 days after daily dosage. After a single radiolabeled dose under fasted conditions, 81% of the administered dose was recovered in feces (36% unchanged, 32% as metabolite BZG791) and 14% was recovered in urine (2% unchanged, 7.1% BZG791). CYP3A4-mediated metabolites (12%) and glucuronides amounted to approximately 15% of the dose.[64248]
 
Affected cytochrome P450 isoenzymes and drug transporters: CYP2C9, CYP3A4, BCRP
Alpelisib is primarily metabolized by chemical and enzymatic hydrolysis to form its metabolite BZG791 followed by CYP3A4 mediated hydroxylation. It is also an in vitro substrate of BCRP. Alpelisib inhibits CYP3A4 in a time-dependent manner and induces CYP2B6, CYP2C9, and CYP3A4 in vitro. Alpelisib is an in vitro inhibitor of P-glycoprotein (P-gp), and has a low potential to inhibit BCRP, MRP2, BSEP, OATP1B1, OATP1B3, OCT1, OAT1, OAT3, OCT2, MATE1, and MATE2K at clinically relevant concentrations. No clinically significant differences in the pharmacokinetics of everolimus (a CYP3A4 and P-gp substrate) were observed when coadministered with alpelisib.[64248]

In adult breast cancer patients who received alpelisib at the recommended dosing in the SOLAR-1 trial, population approach derived mean steady-state alpelisib Cmax was 2,480 ng/mL (CV, 23%) and AUC was 33,224 ng x hour/mL (CV, 21%). The median time to reach peak plasma concentration (Tmax) ranged from 2 to 4 hours. Steady-state alpelisib Cmax and AUC increased proportionally over the dose range of 30 mg to 450 mg (0.1 to 1.5 times the approved recommended dosage) under fed conditions. The mean accumulation of alpelisib is 1.3 to 1.5. [64248]
 
A high-fat, high-calorie meal (985 calories, 58.1 g fat) increased the AUC of alpelisib by 73% and the Cmax by 84% after a single dose. A low-fat, low-calorie meal (334 calories, 8.7 g fat) increased the AUC of alpelisib by 77% and the Cmax by 145% after a single dose. No clinically significant differences in the AUC of alpelisib were observed between low-fat, low-calorie and high-fat, high-calorie meals. Alpelisib can be administered with acid-reducing agents since it should be taken with food. Food exhibited a more pronounced effect on the solubility of alpelisib than the effect of gastric pH value. Coadministration with ranitidine decreased the AUC and Cmax of alpelisib by 21% and 36%, respectively, with a low-fat, low-calorie meal. Under the fasted state, the AUC and Cmax of alpelisib decreased on average by 30% and 51% with ranitidine.[64248]

Pregnancy should be avoided by females of reproductive potential during alpelisib treatment and for at least 1 week after the last dose. Although there are no adequately controlled studies in pregnant women, alpelisib can cause fetal harm or death when administered during pregnancy based on its mechanism of action and animal studies. Women who are pregnant or who become pregnant while receiving alpelisib should be apprised of the potential hazard to the fetus. Oral administration of alpelisib to pregnant rats caused maternal toxicity (weight loss, decreased food consumption) and no viable fetuses (postimplantation loss) at doses approximately 3 times the exposure in humans at the recommended dose based on AUC. At approximately 0.8 times the exposure in humans at the recommended dose, 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 embryofetal development study in rabbits, a dose of 30 mg/kg/day resulted in no viable fetuses (postimplantation loss). Administering half of this dose increased embryofetal deaths, reduced fetal weights, and caused malformations mostly related to the tail and head; at this dose, the maternal exposure was approximately 5 times that achieved at the recommended human dose based on AUC.[64248]

Due to the potential for serious adverse reactions in nursing infants from alpelisib, advise women to discontinue breast-feeding during treatment and for 1 week after the final dose. It is not known whether alpelisib is present in human milk, although many drugs are excreted in human milk.