Piqray (alpelisib)

Temporary interruption of therapy, dosage reduction, and/or permanent discontinuance of alpelisib may be necessary in patients experiencing certain adverse effects.

The following tables on dosage modifications for alpelisib toxicity indicate the recommended dosage modifications in adults and pediatric patients receiving alpelisib (see Table 1 and Table 2).

Table 1. Adults: Recommended Dosage Reduction for Alpelisib Toxicity.

Dosage Reduction after Dosage Reduction after Recovery from Toxicity Recovery from Toxicity Dose Reduction Level Breast Cancer (Dosage = PROS (Dosage = 250 mg 300 mg once daily) once daily) First Reduce dosage to 250 mg Reduce dosage to 125 mg (one 200 mg and one 50 once daily mg tablet) once daily Second Reduce dosage to 200 mg Reduce dosage to 50 mg once daily once daily Third Permanently discontinue Permanently discontinue drug drug

Table 2. Pediatric Patients: Recommended Dosage Reduction for Alpelisib Toxicity in Patients with PROS.

Dosage Reduction after Dosage Reduction after Recovery from Toxicity Recovery from Toxicity Dose Reduction Level Dosage = 50 mg once Dosage = 125 mg once daily daily First Permanently discontinue Reduce dosage to 50 mg drug once daily Second Permanently discontinue drug

Alpelisib is commercially available as oral tablets (Piqray(R), Vijoice(R)) or oral granules (Vijoice(R)). The Vijoice(R) tablets may also be administered as an oral suspension for patients who have difficulty swallowing the whole tablets.

The most appropriate dosage form of Vijoice(R) (tablets or granules) should be prescribed based on patient needs and dosage requirements.

The oral granules are single use and only for patients prescribed a 50 mg daily dose. Clinicians should not use multiple packets to achieve a prescribed dose of 125 mg or 250 mg, and should not use partial quantities of the oral granule packets to prepare a dose. The oral granules should not be used if the packet seal is broken.

The tablets should be swallowed whole; do not chew, crush, or split. Do not use tablets that are cracked, broken, or otherwise not intact.

Administer orally with food. Take at approximately the same time each day.

If a dose of alpelisib is missed and cannot be taken within 9 hours of the regularly scheduled time, skip the missed dose and take the next dose at the regularly scheduled time.

If a dose of alpelisib is vomited, do not take an extra dose; take the next dose at the regularly scheduled time.

Store alpelisib at 20-25degreesC (excursions permitted between 15-30degreesC).

No dosing information is available for this tab.

Alpelisib is metabolized principally by chemical and enzymatic hydrolysis and to a lesser extent by cytochrome P-450 (CYP) isoenzyme 3A4.

In vitro studies indicate that alpelisib inhibits CYP isoenzyme 3A4 in a time-dependent manner and also induces CYP isoenzymes 2B6, 2C9, and 3A4.

In vitro studies also indicate that alpelisib inhibits the efflux transporter P-glycoprotein (P-gp), but has a low potential to inhibit breast cancer resistance protein (BCRP), multidrug resistance protein 2 (MRP2), bile salt export pump (BSEP), organic anion transport protein (OATP) 1B1, OATP1B3, organic anion transporter (OAT) 1, OAT3, organic cation transporter (OCT) 1, OCT2, multidrug and toxin extrusion (MATE) transporter 1, and MATE2-K at clinically relevant concentrations. In vitro, alpelisib is a substrate of BCRP.

There are no contraindication interactions for this drug.

Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

Alpelisib/Strong Cyp3a4 Inducers

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Agents that induce the CYP3A4 isoenzyme may induce the metabolism of alpelisib.(1,2)

CLINICAL EFFECTS: Concurrent use of strong CYP3A4 inducers may decrease the levels and effectiveness of alpelisib.(1,2)

PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks.

PATIENT MANAGEMENT: The manufacturer of alpelisib states the use of strong CYP3A4 inducers in patients receiving therapy with alpelisib should be avoided. Consider the use of alternative agents with less enzyme induction potential.(1,2)

DISCUSSION: In a study, rifampin, a strong CYP3A4 inducer, decreased the maximum concentration (Cmax) and area-under-curve (AUC) of single-dose alpelisib (300 mg) by 38% and 57%, respectively, and of multiple doses of alpelisib (300 mg) by 59% and 74%, respectively.(1) Strong CYP3A4 inducers linked to this monograph include: apalutamide, barbiturates, carbamazepine, encorafenib, enzalutamide, fosphenytoin, ivosidenib, lumacaftor, mitotane, phenobarbital, phenytoin, primidone, rifampin, rifapentine, and St. John's wort.(3,4)

There are no moderate interactions for this drug.

*History of serious hypersensitivity reactions to alpelisib or any ingredient in the formulation.

• Lactation

• Colitis
• Dehydration
• Hyperglycemia
• Interstitial lung disease
• Interstitial pneumonitis
• Pregnancy
• Severe diarrhea

• Diabetes mellitus

Adverse effects reported in 20% or more of patients receiving alpelisib for the treatment of breast cancer include increased serum glucose, increased serum creatinine, diarrhea, rash, decreased lymphocyte count, increased gamma glutamyl transferase, nausea, increased alanine aminotransferase, fatigue, decreased hemoglobin, increased lipase, decreased appetite, stomatitis, vomiting, decreased weight, decreased calcium, decreased glucose, prolonged activated partial thromboplastin time, and alopecia.

Adverse effects reported in 10% or more of patients receiving alpelisib for the treatment of PROS include diarrhea, stomatitis, and hyperglycemia.

More Frequent

• Anemia
• Dehydration
• Hyperglycemia
• Hypocalcemia
• Increased alanine transaminase
• Lymphopenia

Less Frequent

• Abnormal hepatic function tests
• Kidney disease with reduction in glomerular filtration rate (GFr)

Rare or Very Rare

• Anaphylaxis
• Angioedema
• Colitis
• DRESS syndrome
• Erythema multiforme
• Hyperosmolar hyperglycemic state
• Hypersensitivity drug reaction
• Interstitial pneumonitis
• Ketoacidosis
• Stevens-johnson syndrome
• Toxic epidermal necrolysis

More Frequent

• Alopecia
• Anorexia
• Diarrhea
• Elevated serum lipase
• Fatigue
• Nausea
• Prolonged activated partial thromboplastin time
• Skin rash
• Stomatitis
• Vomiting
• Weight loss

Less Frequent

• Acute abdominal pain
• Dry skin
• Dysgeusia
• Headache disorder
• Peripheral edema
• Pruritus of skin
• Urinary tract infection
• Vulvovaginal dryness
• Xerostomia

Rare or Very Rare

• Skin inflammation
• Uveitis

No enhanced messaging available.

Safety and efficacy of alpelisib for the treatment of breast cancer have not been established in pediatric patients.

Safety and efficacy of alpelisib for the treatment of PROS have not been established in pediatric patients <2 years of age.

Alpelisib may cause fetal harm if administered to pregnant females based on its mechanism of action and animal findings.

It is not known whether alpelisib is distributed into milk. Because of the potential for serious adverse reactions to alpelisib in breast-fed infants, females should be advised to discontinue breast-feeding during alpelisib therapy and for one week after discontinuance of the drug. The effects of the drug on breast-fed infants or on milk production are unknown.

The manufacturer makes no specific dosage recommendations for geriatric patients.

No adults >=65 years of age were enrolled in the EPIK-P1 study evaluating alpelisib in patients with PROS.

In the SOLAR-1 study evaluating alpelisib in patients with breast cancer, 41% of patients receiving alpelisib were 65 years of age or older, while 12% were 75 years of age or older. No overall differences in efficacy were observed between geriatric patients 65 years of age or older and younger adults; however, grade 3 or 4 hyperglycemia occurred more frequently in geriatric patients (44 versus 32%). Experience with alpelisib in patients 75 years of age or older is insufficient to determine whether efficacy and safety of the drug in this age group are similar to those in younger adults. However, in the SOLAR-1 study, hyperglycemia (74 versus 66%) and grade 3-4 hyperglycemia (56 versus 36%) occurred more frequently in patients 75 years of age or older compared to patients younger than 75 years of age, respectively.