Alpelisib

Indications

Alpelisib is used for: Breast Cancer

Adult Dose

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

Child Dose

Renal Dose

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

Administration

Take orally with food Administer dose at approximately same time each day

Contra Indications

Hypersensitivity to alpelisib or any of its components

Precautions

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

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

Interactions

Adverse Effects

Side effects of Alpelisib : >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%)

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