[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Pharmacology](https://durgical.com/en/pharmacology/) › [PI3K inhibitors](https://durgical.com/en/pharmacology/classes/pi3k-inhibitors/) › Alpelisib # Alpelisib ## PI3K inhibitors? PI3K inhibitors ## High alert? An error with this medicine can cause serious harm: double checks and protocols are used. Oral PI3Kα inhibitor used with fulvestrant in PIK3CA-mutant breast cancer, and for PIK3CA-related overgrowth. Signature effect: high blood sugar. Updated Nov 1, 2026 ## Quick facts **Group** [PI3K inhibitors](https://durgical.com/en/pharmacology/classes/pi3k-inhibitors/) **Target** PI3Kα, catalytic subunit p110α of phosphoinositide 3-kinase **Used for** Hormone receptor-positive **Key effects** Hyperglycaemia · Diarrhoea · Rash and itching **Monitor** Fasting glucose · Skin for rash or blisters **ATC** L01EM03 No doses: the clinician sets them by the current guideline. On this page - The basics Mechanism of action - Indications - Adverse effects - Pharmacokinetics - Memory aid - Clinical What the labels mean - Safety Contraindications - Key interactions - What is monitored - Administration and safety - Pregnancy and breastfeeding - Nursing care - Study Test yourself - Connections Connections ## Mechanism of action ✂**PI3Kα, catalytic subunit p110α of phosphoinositide 3-kinase**Alpelisib ⓘ The crystal structure shows alpelisib in the ATP site of human PI3Kα (p110α with its p85α regulatory subunit). **Target in 3D:** PI3Kα, catalytic subunit p110α of phosphoinositide 3-kinase. PDB structure 4JPS (RCSB PDB, public domain). [View the structure at RCSB PDB](https://www.rcsb.org/structure/4JPS) · Drag to rotate · pinch to zoom 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. - PIK3CA mutation keeps PI3Kα switched on - Alpelisib blocks the PI3Kα kinase site - Less PIP3: AKT-mTOR signalling falls - 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 →](https://durgical.com/en/conditions/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 ### Serious (rare, important) - Severe hyperglycaemia and ketoacidosis - Severe skin reactions with blistering or peeling - Pneumonitis - Severe diarrhoea with dehydration - Severe allergic reactions ## 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. ## Memory aid «ALPHA-lisib hits PI3K-ALPHA»: alpelisib blocks p110α, and alpha also carries insulin's signal, so sugar rises. ## Test yourself Think of the answer, then tap the question to see it. ## Which PI3K isoform does alpelisib inhibit? PI3Kα (p110α), encoded by PIK3CA. ## Which drug is alpelisib combined with in breast cancer? Fulvestrant. ## What is the most characteristic adverse effect of alpelisib? Hyperglycaemia. ## Which test must be done on the breast tumour before alpelisib? A test showing a PIK3CA mutation. [Add to my cards (4)](https://durgical.app/estudiar/?add=/en/pharmacology/alpelisib/) [More Pharmacology questions →](https://durgical.com/en/practice/?f=pharmacology) ## What the labels mean **High alert** An error with this medicine can cause serious harm: double checks and protocols are used. ## Connections ## Related drugs 3 - [Idelalisib](https://durgical.com/en/pharmacology/idelalisib/) - [Everolimus](https://durgical.com/en/pharmacology/everolimus/) - [Metformin](https://durgical.com/en/pharmacology/metformin/) ## Related conditions 1 - [Breast cancer](https://durgical.com/en/conditions/breast-cancer/) [← Back to the class: PI3K inhibitors](https://durgical.com/en/pharmacology/classes/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](https://medlineplus.gov/druginfo/meds/a619036.html) (MedlinePlus (U.S. National Library of Medicine), 2026); [Alpelisib - NCI](https://www.cancer.gov/about-cancer/treatment/drugs/alpelisib) (National Cancer Institute, 2026); [ATCDDD - ATC/DDD Index](https://atcddd.fhi.no/atc_ddd_index/?code=L01EM03) (WHO Collaborating Centre for Drug Statistics Methodology, 2026). ## **Spotted a mistake?** We are always improving for the community. Tell us what is wrong and our team will review it. Report a mistake Representative model, for educational purposes only. --- Source: https://durgical.com/en/pharmacology/alpelisib/ License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/pharmacology/alpelisib/