AL-pe-LISib

Therapeutic Classification: antineoplastics

Pharmacologic Classification: kinase inhibitors

Piqray:

• Treatment of postmenopausal women and men with hormone receptor-positive, human epidermal growth factor receptor 2-negative, PIK3CA-mutated, advanced or metastatic breast cancer (in combination with fulvestrant).

Vijoice:

• Severe manifestations of PIK3CA-related overgrowth spectrum in patients who require systemic therapy.

• Acts as an inhibitor of phosphatidylinositol 3–kinase (PI3K). 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. Activating mutations in PIK3CA may induce overgrowths and malformations in PROS.

• Decreased progression of breast cancer.
• Reduction in lesion volume in PIK3CA-related overgrowth spectrum.

Absorption: Well absorbed following oral administration.

Distribution: Widely distributed to tissues.

Metabolism/Excretion: Primarily metabolized via hydrolysis; also metabolized to a lesser extent by CYP3A4. Excreted in feces (36% as unchanged drug; 32% as metabolites) and urine (2% as unchanged drug; 7% as metabolites).

Half-life: 8–9 hr.

(plasma concentrations)

Contraindicated in:

• History of serious hypersensitivity reactions including anaphylaxis, Stevens-Johnson syndrome, erythema multiforme, or toxic epidermal necrolysis
• Concurrent use of strong CYP3A inducers
• OB: Pregnancy
• Lactation: Lactation.

Use Cautiously in:

• Diabetes or risk factors for hyperglycemia (obesity, elevated fasting plasma glucose, elevated HbA1c, concurrent use of systemic corticosteroids or age ≥75 yr)
• Severe renal impairment (CCr ≤30 mL/min) (Piqray only)
• Rep: Women of reproductive potential and men with female partners of reproductive potential
• Pedi: Safety and effectiveness not established in children <18 yr (breast cancer) or <2 yr (PIK3CA-related overgrowth spectrum)
• Geri: Older adults may be more sensitive to drug effects.

CV: peripheral edema.

Derm: Stevens-johnson syndrome (SJS), alopecia, drug reaction with eosinophilia and systemic symptoms (dress), dry skin, erythema Multiform (EM), pruritus, rash, toxic epidermal necrolysis (TEN), cellulitis, eczema.

Endo: hyperglycemia, hypoglycemia, hyperglycemic hyperosmolar non-ketotic syndrome, KETOACIDOSIS.

F and E: hyperkalemia, hypocalcemia, hypokalemia, hypomagnesemia, hyponatremia, hypophosphatemia.

GI: ↓ appetite, ↑ lipase, ↑ liver enzymes, abdominal pain, diarrhea, hyperbilirubinemia, metallic taste, nausea, stomatitis, vomiting, colitis.

GU: ↑ serum creatinine, ↓ fertility, acute kidney injury.

Hemat: anemia, lymphocytopenia, thrombocytopenia.

Metab: ↓ weight, hypercholesterolemia, hypertriglyceridemia, hypoalbuminemia.

Neuro: fatigue, headache, insomnia.

Resp: cough, PNEUMONITIS.

Misc: fever, infection, HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS AND ANGIOEDEMA).

Drug-Drug:

• Strong CYP3A4 inducers may ↓ levels and effectiveness; avoid concurrent use.
• breast cancer resistance protein inhibitors may ↑ levels and risk of toxicity; avoid concurrent use.
• May ↓ levels of CYP2C9 substrates, including warfarin.

Breast Cancer

• PO (Adults): 300 mg once daily until disease progression or unacceptable toxicity.

PIK3CA-Related Overgrowth Spectrum

• PO (Adults): 250 mg once daily until disease progression or unacceptable toxicity.
• PO (Children 6–<18 yr): 50 mg once daily until disease progression or unacceptable toxicity. After 24 wk, may ↑ to 125 mg once daily to optimize clinical/radiological response; continue until disease progression or unacceptable toxicity. Once patient becomes 18 yr old, gradually ↑ to 250 mg once daily.
• PO (Children 2–<6 yr): 50 mg once daily until disease progression or unacceptable toxicity.

• Tablets (Piqray): 50 mg; 150 mg; 200 mg;
• Tablets (Vijoice): 50 mg; 125 mg; 200 mg;

• Monitor for signs and symptoms of hypersensitivity reactions (dyspnea, flushing, rash, fever, tachycardia) during therapy. If symptoms occur, permanently discontinue alpelisib.
• Assess for severe cutaneous adverse reactions including SJS, EM, TEN, and DRESS (prodrome of fever, flu-like symptoms, mucosal lesions, progressive skin rash) during therapy. If rash is Grade 1 (< 10% body surface area [BSA] with active skin toxicity); No dose adjustment needed. Initiate topical corticosteroid treatment. Consider adding oral antihistamine to manage symptoms. If rash is not improved within 28 days of treatment, add a low dose systemic corticosteroid. If the cause is SJS, EM, TEN, or DRESS, permanently discontinue alpelisib. If Grade 2 (10-30% BSA with active skin toxicity); No dose adjustment necessary. Initiate or intensify topical corticosteroid and oral antihistamines. Consider low dose systemic corticosteroid treatment. If rash improves to Grade ≤ 1 within 10 days, systemic corticosteroid may be discontinued. If the cause is SJS, EM, TEN, or DRESS, permanently discontinue alpelisib. If Grade 3 (severe rash not responsive to medical management and >30% BSA with active skin toxicity): Hold alpelisib. Initiate or intensify topical/systemic corticosteroid and oral antihistamines. If the cause is SJS, EM, TEN, or DRESS, permanently discontinue alpelisib. If the etiology is not SJS, EM, TEN, or DRESS, hold dose until improvement to Grade ≤ 1, then resume alpelisib at next lower dose. If Grade 4 (severe bullous, blistering or exfoliating skin conditions and any % BSA associated with extensive superinfection, with IV antibiotics indicated; life-threatening): Permanently discontinue alpelisib.
• Monitor for signs and symptoms of pneumonitis (hypoxia, cough, dyspnea, interstitial infiltrates) during therapy. If pneumonitis is confirmed, discontinue alpelisib permanently.
• Monitor for signs and symptoms of diarrhea and colitis (abdominal pain, mucus or blood in stool) during therapy. If Grade 1 diarrhea occurs, do not adjust alpelisib dose. Start antidiarrheal therapy and monitor symptoms. If Grade 2 diarrhea occurs, start or intensify antidiarrheal therapy and monitor symptoms. May add enteric-acting and/or systemic steroids to therapy for Grade 2 or Grade 3 colitis. Hold alpelisib until recovery to Grade ≤1, then resume at same dose. If Grade 3 diarrhea occurs, start or intensify antidiarrheal therapy and monitor symptoms. Hold alpelisib until recovery to Grade ≤1, then resume at the next lower dose. If Grade 4 diarrhea occurs, permanently discontinue alpelisib.

• Verify negative pregnancy test before starting therapy.Information on FDA approved tests for the detection of PIK3CA mutations in breast cancer is available at: www.fda.gov/CompanionDiagnostics.
  • May cause hyperglycemia. Before starting alpelisib therapy, test fasting blood glucose (FBG) and HbA1c; optimize blood glucose. After starting therapy, monitor blood glucose at least weekly for first 2 wk, then at least once every 4 wk, and as indicated. Monitor HbA1c every 3 mo and as indicated. If hyperglycemia develops, monitor FBG at least twice weekly until FBG decreases to normal. During treatment with anti-diabetic agents, continue monitoring FBG at least weekly for 8 wk, then once every 2 wk and as needed clinically. If Grade 1 FBG >ULN-160 mg/dL, No dose adjustment needed. Begin or intensify anti-diabetic treatment. If Grade 2 FBG >160-250 mg/dL: No dose adjustment needed. Begin or further intensify anti-diabetic therapy. If FBG does not decrease to ≤ 160 mg/dL within 21 days, reduce alpelisib dose by 1 dose level and follow FBG value recommendations. If Grade 3 >250-500 mg/dL, Hold alpelisib. Begin or intensify oral anti-diabetic therapy and consider additional anti-diabetic agents for 1-2 days until hyperglycemia improves. Administer intravenous hydration and consider added intervention for electrolyte/ketoacidosis/hyperosmolar disturbances). If FBG decreases to ≤160 mg/dL within 3 to 5 days under appropriate anti-diabetic therapy, resume alpelisib at 1 lower dose level. If FBG does not decrease to ≤160 mg/dL within 3 to 5 days under appropriate anti-diabetic therapy, consult with a specialist in the treatment of hyperglycemia. If FBG does not decrease to ≤160 mg/dL within 21 days following appropriate anti-diabetic therapy, permanently discontinue alpelisib. If Grade 4 >500 mg/dL: Hold alpelisib. Begin or intensify appropriate anti-diabetic therapy (administer intravenous hydration and consider appropriate intervention for electrolyte/ketoacidosis/hyperosmolar disturbances), recheck FBG within 24 hr and as indicated. If FBG decreases to ≤500 mg/dL, follow FBG recommendations for Grade 3. If FBG is confirmed at >500 mg/dL, discontinue alpelisib permanently.

• When starting at Piqray at 300 mg once daily, two 150 mg tablets, dose adjustments for adverse reactions include First-dose reduction: 250 mg once daily, one 200 mg tablet and one 50 mg tablet. Second-dose reduction: 200 mg tablet once daily.
• Dose reductions for Vijoice include First dose reduction: 125 mg once daily. Second dose reduction: 50 mg once daily. If adult or pediatric patients cannot tolerate 50 mg, discontinue alpelisib.
• PO: Administer with food once daily at same time of day. DNC: Swallow tablets whole, do not crush, break, or chew. For patients with difficulty swallowing, administer Vijoice as an oral suspension with food. Place Vijoice tablets 2–4 ounces of water and let stand for 5 min. Make suspension with water only. Crush tablets with a spoon and stir until an oral suspension is obtained. Administer immediately after preparation. Discard oral suspension if not administered within 60 min after preparation. After administration, add 2–3 tbsp of water to same glass. Stir with same spoon to resuspend any remaining particles and administer entire contents. Repeat if particles remain.
  • When administered with fulvestrant, fulvestrant 500 mg is usually given on Days 1, 15, and 29, and once monthly thereafter.

• Instruct patient to take alpelisib as directed. Take missed doses with food within 9 hr of time usually taken. If >9 hr, omit dose and take next dose next day at usual time. If patient vomits after dose, skip dose and take next dose next day. Advise patient to read Patient Information before starting and with each Rx refill in case of changes.
• Advise patients to notify health care professional of the signs and symptoms of hypersensitivity reactions, skin reactions, hyperglycemia (e.g., excessive thirst, urinating more often than usual or higher amount of urine than usual, or increased appetite with weight loss), and lung problems occur. Advise patients to immediately report new or worsening respiratory symptoms.
• If diarrhea occurs, advise patient to start antidiarrheal treatment, increase oral fluids, and notify health care professional.
• Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional before taking any new medications.
• Rep: May cause fetal harm. Advise females of reproductive potential and males with female partners of reproductive potential to use effective contraception during and for 1 wk after last dose. Advise patient to avoid breast feeding during and for 1 wk after last dose. May impair fertility in male and female patients.

• Decreased progression of breast cancer.
• Reduction in lesion volume in PIK3CA-related overgrowth spectrum.

Piqray, Vijoice

NDC Code^*

• 0078- Novartis Pharmaceuticals Corporation
  • 0078-0701- PIQRAY
    • 0078-0701-84- 1 BLISTER PACK in 1 CARTON (0078-0701-84) > 28 TABLET in 1 BLISTER PACK (0078-0701-51)

• 0078- Novartis Pharmaceuticals Corporation
  • 0078-0708- PIQRAY
    • 0078-0708-02- 2 BLISTER PACK in 1 CARTON (0078-0708-02) > 28 TABLET in 1 BLISTER PACK (0078-0708-51)

• 0078- Novartis Pharmaceuticals Corporation
  • 0078-0708- PIQRAY
    • 0078-0708-91- 1 BLISTER PACK in 1 CARTON (0078-0708-91) > 28 TABLET in 1 BLISTER PACK (0078-0708-90)

• 0078- Novartis Pharmaceuticals Corporation
  • 0078-0715- PIQRAY
    • 0078-0715-02- 2 KIT in 1 CARTON (0078-0715-02) > 1 KIT in 1 KIT (0078-0715-61) * 14 TABLET in 1 BLISTER PACK * 14 TABLET in 1 BLISTER PACK

• 0078- Novartis Pharmaceuticals Corporation
  • 0078-0715- PIQRAY
    • 0078-0715-91- 1 KIT in 1 CARTON (0078-0715-91) > 1 KIT in 1 KIT (0078-0715-94) * 14 TABLET in 1 BLISTER PACK * 14 TABLET in 1 BLISTER PACK