Piqray

Alpelisib

In combination w/ fulvestrant for the treatment of postmenopausal women, & men, w/ hormone receptor +ve, HER2 -ve, advanced or metastatic breast cancer w/ PIK3CA mutation after disease progression following endocrine-based regimen.

Recommended dose: 300 mg Piqray once daily on continuous basis + 500 mg fulvestrant via IM on days 1, 15, 29, & once mthly thereafter. Max daily dose: 300 mg. Management of severe or intolerable adverse drug reactions: 1st dose reduction: 250 mg (one 200 mg tab & one 50 mg tab) once daily continuously. 2nd dose reduction: 200 mg (one 200 mg tab) once daily continuously. Max of 2 dose reductions (1 dose reduction for pancreatitis).

Should be taken with food: Take immediately after meals, at approx the same time each day. Swallow whole, do not chew/crush/split.

Hypersensitivity.

Permanently discontinue & do not re-introduce in patients w/ serious hypersensitivity & severe cutaneous reactions. Should not be initiated in patients w/ history of severe cutaneous reactions. Test for fasting plasma glucose, HbA1c before initiating treatment; monitor fasting glucose at wk 1, 2, 4, 6 & 8 after start of treatment & mthly thereafter; monitor HbA1c after 4 wk of treatment & every 3 mth thereafter. History of DM. Patients w/ type 1 & uncontrolled type 2 diabetes; symptomatic visceral disease. Interrupt treatment immediately on & evaluate patients w/ new or worsening resp symptoms or suspected pneumonitis. Permanently discontinue in all confirmed pneumonitis. Severe diarrhea, dehydration or acute kidney injury. Should not be initiated in patients w/ on-going jaw osteonecrosis from previous or concurrent treatment w/ bisphosphonates/denosumab. Minor influence on the ability to drive & use machines. Severe renal impairment. Females of reproductive potential should use effective contraception, & male patients w/ sexual partners who are pregnant, possibly pregnant or could become pregnant should use condoms during sexual intercourse during & for at least 1 wk after stopping treatment. Not recommended during pregnancy. Women should not breast-feed during treatment & for at least 1 wk after the last dose. Childn ≤18 yr. Elderly ≥75 yr.

UTI; anaemia, decreased lymphocyte & platelet count; increased & decreased plasma glucose, decreased appetite & Mg, hypokalaemia, hypocalcaemia; headache, dysgeusia; diarrhoea, nausea, stomatitis, vomiting, abdominal pain, dyspepsia; rash, alopecia, pruritus, dry skin; fatigue, mucosal inflammation, peripheral oedema, pyrexia, mucosal dryness; decreased wt, increased blood creatinine, γ-glutamyltransferase, ALT, lipase, prolonged activated partial thromboplastin time, decreased albumin. Hypersensitivity; dehydration; insomnia; blurred vision, dry eye; HTN, lymphoedema; pneumonitis; toothache, gingivitis, gingival pain, cheilitis; erythema, dermatitis, palmar-plantar erythrodysaesthesia syndrome, erythema multiforme; muscle spasms, myalgia, jaw osteonecrosis; acute kidney injury; oedema; increased HbA1c. SJS. DRESS.

Increased systemic exposure w/ BCRP inhibitors (eg, eltrombopag, lapatinib, pantoprazole). Decreased bioavailability & exposure w/ H₂ receptor antagonist (ranitidine). CYP3A4 substrates w/ additional time-dependent inhibition & induction potential on CYP3A4 that affects their own metabolism (eg, rifampicin, ribociclib, encorafenib). Reduce pharmacological activity of CYP2C9 substrates w/ narrow therapeutic index (eg, warfarin) & sensitive CYP2B6 substrates (eg, bupropion) or CYP2B6 substrates w/ narrow therapeutic window. Potentially inhibit activities & may increase systemic exposure of OAT3 drug transporters, intestinal BCRP & P-gp.

Targeted Cancer Therapy

L01EM03 - alpelisib ; Belongs to the class of phosphatidylinositol-3-kinase (Pi3K) inhibitors. Used in the treatment of cancer.

S