Alpelisib

Mechanism of action

✂PI3Kα, catalytic subunit p110α of phosphoinositide 3-kinaseAlpelisib

ⓘ The crystal structure shows alpelisib in the ATP site of human PI3Kα (p110α with its p85α regulatory subunit).

Alpelisib inhibits the α isoform of PI3K with high selectivity over the other isoforms, including mutant forms produced by PIK3CA mutations. PIP3 is no longer formed, AKT-mTOR signalling falls and cell growth slows. PIK3CA mutations are common in hormone receptor-positive, HER2-negative breast cancer and can cause resistance to endocrine therapy; blocking PI3Kα also blunts insulin signalling, which explains the hyperglycaemia.

1. PIK3CA mutation keeps PI3Kα switched on
2. Alpelisib blocks the PI3Kα kinase site
3. Less PIP3: AKT-mTOR signalling falls
4. Tumour growth slows; insulin signalling falls too

Indications

• Hormone receptor-positive, HER2-negative, PIK3CA-mutated advanced or metastatic breast cancer that progressed on or after endocrine therapy, with fulvestrant, in postmenopausal women and men. Breast cancer →
• Severe PIK3CA-related overgrowth spectrum (PROS) in adults and children aged 2 or older who need systemic treatment.

Adverse effects

Common

• Hyperglycaemia
• Diarrhoea, nausea, vomiting, decreased appetite, weight loss
• Rash and itching
• Mouth sores, taste changes
• Fatigue, hair loss

Contraindications

• Severe allergy to the drug
• Caution in diabetes or pre-existing hyperglycaemia and in a history of severe skin reactions

Key interactions

Strong CYP3A4 inducers (e.g. rifampicin, St John's wort)

Lower alpelisib levels.

Antidiabetic drugs (e.g. metformin, insulin)

Often needed to control the hyperglycaemia; their doses are adjusted to the glucose readings.

What is monitored

• Fasting glucose and HbA1c before starting; glucose often in the first weeks, then regularly
• Skin for rash or blisters
• Breathing symptoms
• Stool frequency and hydration
• Test showing a PIK3CA mutation before starting (breast cancer)

Administration and safety

• Oral, once a day with food at about the same time.
• For overgrowth, some tablets may be dispersed in water as the product instructions describe.
• Hazardous oral chemotherapy: handled with gloves and kept away from children; caregivers who are pregnant avoid handling it.

Pregnancy and breastfeeding

May harm the fetus; a pregnancy test is done before treatment and effective contraception is used during and shortly after; breastfeeding is not advised.

Nursing care

• Check blood glucose as ordered and report readings above the target.
• Ask about thirst, frequent urination, blurred vision and rash.
• Check for diarrhoea and dehydration.
• Teaching: home glucose monitoring, report rash, blisters, cough or breathlessness; avoid St John's wort; use effective contraception.

Pharmacokinetics

Absorption

Oral, taken with food.

Metabolism

Liver, by CYP3A.

Half-life

About 8 to 9 hours.

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Connections

← Back to the class: PI3K inhibitors

Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.

Sources: Alpelisib: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); Alpelisib - NCI (National Cancer Institute, 2026); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).

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Representative model, for educational purposes only.