Alpelisib


Generic Medicine Info
Indications and Dosage
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).
Administration
Should be taken with food. Take at the same time each day. Swallow whole, do not chew/crush/split.
Contraindications
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).
Special Precautions
Patient with diabetes mellitus. Severe renal impairment.
Adverse Reactions
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.
Monitoring Parameters
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.
Overdosage
Symptoms: Asthenia, hyperglycaemia, nausea, rash. Management: Symptomatic and supportive treatment.
Drug Interactions
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.
Action
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.
Chemical Structure

Chemical Structure Image
Alpelisib

Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 56649450, Alpelisib. https://pubchem.ncbi.nlm.nih.gov/compound/Alpelisib. Accessed Aug. 25, 2021.

Storage
Store below 30°C. Protect from moisture.
ATC Classification
L01EM03 - alpelisib ; Belongs to the class of phosphatidylinositol-3-kinase (Pi3K) inhibitors. Used in the treatment of cancer.
References
Alpelisib Tablet (Novartis Pharmaceuticals Corporation). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 01/07/2021.

Anon. Alpelisib. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 01/07/2021.

Anon. Alpelisib. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 01/07/2021.

Buckingham R (ed). Alpelisib. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 01/07/2021.

Joint Formulary Committee. Alpelisib. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 01/07/2021.

Piqray 50 mg and 200 mg Film-Coated Tablets (Novartis Pharmaceuticals UK Limited). MHRA. https://products.mhra.gov.uk. Accessed 01/07/2021.

Trezilent 50 mg, 150 mg and 200 mg Film-Coated Tablets (Novartis Corporation (M) Sdn. Bhd.). MIMS Malaysia. http://www.mims.com/malaysia. Accessed 02/07/2021.

Disclaimer: This information is independently developed by MIMS based on Alpelisib from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2021 MIMS. All rights reserved. Powered by MIMS.com
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