Oral Hormone receptor positive, HER2-negative, PIK3CA-mutated advanced breast cancer, Hormone receptor positive, HER2-negative, PIK3CA-mutated metastatic breast cancer
Adult: For the treatment of cases in men or postmenopausal women that has progressed after an endocrine-based regimen: 300 mg once daily, in combination with fulvestrant (see fulvestrant prescribing information for dosage details). Continue until disease progression or unacceptable toxicity occurs. Dose reduction, interruption, or discontinuation may be required according to individual safety or tolerability (refer to detailed product guideline).
Should be taken with food. Take at the same time each day. Swallow whole, do not chew/crush/split.
Hypersensitivity. History of severe cutaneous reactions; osteonecrosis of the jaw from previous or concurrent treatment with bisphosphonates or denosumab. Pregnancy and lactation. Concomitant use with strong CYP3A4 inducers (e.g. phenytoin, rifampicin).
Patient with diabetes mellitus. Severe renal impairment.
Significant: Severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome, erythema multiforme, toxic epidermal necrolysis and drug reaction with eosinophilia and systemic symptoms (DRESS); severe hypersensitivity reactions (e.g. anaphylaxis, anaphylactic shock); rash; severe pneumonitis and interstitial lung disease; severe diarrhoea (including dehydration and acute kidney injury), hepatitis B virus reactivation, severe hyperglycaemia (including ketoacidosis), osteonecrosis of the jaw. Blood and lymphatic system disorders: Anaemia. Eye disorders: Blurred vision, dry eye. Gastrointestinal disorders: Stomatitis, nausea, vomiting, dysgeusia, abdominal pain, dyspepsia, cheilitis, gingivitis, gingival pain, mucosal inflammation or dryness, toothache, pancreatitis. General disorders and administration site conditions: Fatigue, pyrexia, oedema. Investigations: Increased creatinine, gamma glutamyltransferase (GGT), ALT, lipase, glycosylated Hb; decreased Hb, Ca, Mg, albumin, lymphocyte, platelet counts; increased or decreased glucose, prolonged aPTT, decreased weight. Metabolism and nutrition disorders: Decreased appetite, hypokalaemia, hypocalcaemia. Musculoskeletal and connective tissue disorders: Muscle spasm, myalgia. Nervous system disorders: Headache. Psychiatric disorders: Insomnia. Renal and urinary disorders: UTI. Skin and subcutaneous tissue disorders: Alopecia, dry skin, pruritus, dermatitis, erythema, palmar-plantar erythrodysaesthesia syndrome. Vascular disorders: Hypertension, lymphoedema.
Patient Counseling Information
This drug may cause fatigue or blurred vision, if affected, do not drive or operate machinery.
Prior to treatment initiation, confirm PIK3CA mutation status; perform pregnancy test (in females of reproductive potential). Monitor fasting plasma glucose (FPG) and HbA1c prior to treatment initiation; fasting glucose or fasting blood glucose at least once weekly for the 1st 2 weeks, then at least once every 4 weeks, and as clinically indicated; HbA1c every 3 months and as necessary; hepatitis B virus screening with hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc), total Ig or IgG, and antibody to hepatitis B surface antigen (anti-HBs) prior to treatment initiation. Assess for diarrhoea; signs or symptoms of severe cutaneous adverse reactions, hyperglycaemia, hypersensitivity or pneumonitis.
Symptoms: Asthenia, hyperglycaemia, nausea, rash. Management: Symptomatic and supportive treatment.
Decreased serum concentrations with strong CYP3A4 inducers (e.g. phenytoin, rifampicin). Increase serum concentrations with breast cancer resistance protein (BCRP) inhibitors (e.g. eltrombopag, pantoprazole). May reduce the pharmacological activity of CYP2C9 substrates (e.g. warfarin). Increased risk of osteonecrosis of the jaw with bisphosphonates or denosumab.
Description: Alpelisib is a phosphatidylinositol-3 kinase (PI3K) inhibitor with predominant activity against PI3Kα. In breast cancer, it inhibits the phosphorylation of PI3K downstream targets (including Akt) and exhibits activity in cell lines harbouring a PIK3CA mutation. In vivo, alpelisib blocked PI3K/Akt signalling and decreased tumour growth in xenograft models. Pharmacokinetics: Absorption: Time to peak plasma concentration: 2-4 hours. Distribution: Plasma protein binding: 89%. Metabolism: Metabolised mainly via chemical and enzymatic hydrolysis to its metabolite BZG791, and partly by CYP3A4. Excretion: Mainly via faeces (81%; 36% as unchanged drug, 32% as BZG791); urine (14%; 2% as unchanged drug, 7% as BZG791). Elimination half-life: 8-9 hours.