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Medical Disclaimer: This information is for educational purposes only and is not a substitute for professional medical advice.
Other
Alpelisib is a kinase inhibitor used specifically for HR-positive, HER2-negative, PIK3CA-mutated advanced breast cancer and PIK3CA-Related Overgrowth Spectrum (PROS). It works by targeting the PI3K pathway to inhibit tumor growth and cellular proliferation.
Name
Alpelisib
Raw Name
ALPELISIB
Category
Other
Drug Count
3
Variant Count
9
Last Verified
February 17, 2026
RxCUI
2169300, 2169307, 2169310, 2169311, 2169313, 2169314, 2169316, 2169318, 2169319, 2169320, 2169321, 2169322, 2598459, 2598461, 2598463, 2598464, 2598465, 2598466, 2598467, 2598469, 2598470, 2680135, 2680138, 2680139, 2680140
UNII
08W5N2C97Q
About Alpelisib
Alpelisib is a kinase inhibitor used specifically for HR-positive, HER2-negative, PIK3CA-mutated advanced breast cancer and PIK3CA-Related Overgrowth Spectrum (PROS). It works by targeting the PI3K pathway to inhibit tumor growth and cellular proliferation.
Detailed information about Alpelisib
This page is for informational purposes only and does not replace medical advice. Consult a qualified healthcare professional before using any medication containing Alpelisib.
Alpelisib (brand name Piqray) is a potent, alpha-specific phosphoinositide 3-kinase (PI3K) inhibitor. It belongs to a class of medications known as antineoplastic agents (cancer-fighting drugs) and specifically functions as a kinase inhibitor. In clinical terms, it is designed to target and inhibit the p110α subunit of the PI3K enzyme, which is frequently mutated or overactive in various types of cancer and overgrowth disorders. The U.S. Food and Drug Administration (FDA) first approved Alpelisib in May 2019, marking a significant milestone as the first PI3K inhibitor approved for the treatment of breast cancer. Its approval was based on the landmark SOLAR-1 clinical trial, which demonstrated improved progression-free survival in patients with specific genetic mutations.
Your healthcare provider may prescribe Alpelisib in combination with fulvestrant (an estrogen receptor antagonist) for the treatment of postmenopausal women, and men, with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, PIK3CA-mutated, advanced or metastatic breast cancer. Additionally, in April 2022, the FDA granted accelerated approval for Alpelisib (under the brand name Vijoice) for the treatment of adult and pediatric patients with PIK3CA-Related Overgrowth Spectrum (PROS), a group of rare genetic disorders characterized by overgrowth of various body parts.
To understand how Alpelisib works, one must first understand the PI3K/Akt/mTOR signaling pathway. This pathway is a critical regulator of cell growth, proliferation (multiplication), and survival. In many cancers, a mutation in the PIK3CA gene leads to a hyperactive PI3K alpha enzyme. This hyperactivity acts like a stuck gas pedal, telling cells to divide uncontrollably and survive even when they should naturally die.
Alpelisib acts as a precision key that fits into the p110α catalytic subunit of the PI3K enzyme. By binding to this site, Alpelisib blocks the enzyme's ability to phosphorylate (activate) downstream signaling molecules. This inhibition effectively shuts down the overactive growth signals. In breast cancer cells that harbor PIK3CA mutations, Alpelisib has been shown to induce an increase in estrogen receptor (ER) transcription, which is why it is used in combination with fulvestrant to provide a dual-blockade of both the PI3K and ER pathways. In patients with PROS, Alpelisib helps to reduce the volume of overgrowth by slowing down the excessive cellular signaling that drives the condition.
The pharmacokinetics of Alpelisib describe how the body absorbs, distributes, metabolizes, and excretes the medication. Understanding these parameters is vital for optimizing therapeutic efficacy while minimizing toxicity.
Alpelisib is currently FDA-approved for two primary clinical indications:
Off-label uses are currently being explored in clinical trials for other solid tumors (such as head and neck squamous cell carcinoma or ovarian cancer) where PIK3CA mutations are prevalent, though these are not yet standard of care.
Alpelisib is available in the following oral dosage forms:
> Important: Only your healthcare provider can determine if Alpelisib is right for your specific condition. Genetic testing to confirm a PIK3CA mutation is required before starting treatment for breast cancer.
For the treatment of HR+/HER2- Advanced Breast Cancer, the standard recommended dose of Alpelisib is 300 mg (two 150 mg tablets) taken orally once daily. This is typically administered in combination with fulvestrant (500 mg intramuscularly on Days 1, 15, and 29, and once monthly thereafter). Treatment should continue until disease progression or unacceptable toxicity occurs.
For PIK3CA-Related Overgrowth Spectrum (PROS) in adults, the starting dose is typically 250 mg taken orally once daily. Healthcare providers may adjust this dose based on individual patient response and tolerability.
Alpelisib is approved for pediatric patients aged 2 years and older for the treatment of PROS. The dosage is weight-based and age-based:
Alpelisib is not approved for the treatment of breast cancer in pediatric patients.
No dosage adjustment is required for patients with mild or moderate renal impairment (estimated glomerular filtration rate [eGFR] 30 to 89 mL/min). There is no recommended dose for patients with severe renal impairment (eGFR < 30 mL/min) as the drug has not been sufficiently studied in this population.
No dosage adjustment is necessary for patients with mild hepatic impairment (Child-Pugh A) or moderate hepatic impairment (Child-Pugh B). Alpelisib has not been studied in patients with severe hepatic impairment (Child-Pugh C); therefore, it should be used with extreme caution in these individuals.
No overall differences in safety or effectiveness have been observed between patients 65 years of age and older and younger patients. No specific dose adjustments are required based solely on age, though close monitoring for side effects like dehydration and hyperglycemia is recommended in the elderly.
If you miss a dose of Alpelisib, you may take it with food within 9 hours of the time you usually take it. If more than 9 hours have passed, skip the missed dose and take your next dose at the regular scheduled time. Do not take two doses at once to make up for a missed dose. If you vomit after taking a dose, do not take an additional dose that day; simply wait until your next scheduled dose.
Symptoms of Alpelisib overdose may include severe hyperglycemia (high blood sugar), nausea, vomiting, and fatigue. In the event of a suspected overdose, contact your local poison control center or seek emergency medical attention immediately. Treatment is generally supportive, focusing on managing blood glucose levels and maintaining hydration.
> Important: Follow your healthcare provider's dosing instructions exactly. Do not adjust your dose or stop the medication without medical guidance, as this can affect the success of your treatment.
Alpelisib is associated with several common side effects, many of which are manageable with supportive care or dose modifications. According to clinical trial data (SOLAR-1), the most frequent adverse reactions include:
> Warning: Stop taking Alpelisib and call your doctor immediately if you experience any of the following serious symptoms:
Prolonged use of Alpelisib requires ongoing monitoring of metabolic health. Long-term hyperglycemia, if not properly managed with medications like metformin, can lead to chronic complications similar to type 2 diabetes. Additionally, there is a potential for long-term changes in kidney function, necessitating regular blood tests (creatinine and BUN) for the duration of therapy.
As of 2026, there are no FDA black box warnings for Alpelisib. However, the warnings for severe hyperglycemia and severe cutaneous adverse reactions are considered "major warnings" that appear prominently in the prescribing information due to their potential for fatality.
Report any unusual symptoms or side effects to your healthcare provider promptly. Early intervention often allows patients to continue treatment at a lower dose.
Alpelisib is a high-potency medication that requires careful medical supervision. Before starting treatment, patients must undergo genetic testing to confirm the presence of a PIK3CA mutation. It is also essential to have a baseline blood glucose and HbA1c test, as Alpelisib can rapidly and significantly increase blood sugar levels, even in patients without a history of diabetes.
No FDA black box warnings for Alpelisib. However, the risk of severe hyperglycemia is the primary safety concern and is managed with a strict monitoring protocol.
To ensure safety, your healthcare provider will require the following tests:
Alpelisib may cause fatigue or blurred vision in some patients. If you experience these symptoms, avoid driving or operating heavy machinery until you know how the medication affects you.
There is no direct contraindication for alcohol use with Alpelisib; however, alcohol can affect blood sugar levels and liver function. It is generally advised to limit alcohol consumption to avoid complicating the management of hyperglycemia and potential hepatotoxicity.
Do not stop Alpelisib abruptly unless you are experiencing a severe allergic reaction or skin rash. If treatment must be stopped due to side effects, your doctor will provide a plan for either a dose reduction or a permanent discontinuation. There is no known withdrawal syndrome associated with Alpelisib, but stopping the drug will allow the PI3K pathway to become active again, potentially leading to disease progression.
> Important: Discuss all your medical conditions, especially a history of diabetes or skin disorders, with your healthcare provider before starting Alpelisib.
While there are few absolute contraindications, certain drugs should be avoided entirely to prevent treatment failure or extreme toxicity:
For each major interaction, the mechanism usually involves the modulation of metabolic enzymes (CYP450) or transport proteins (BCRP). The clinical consequence is either an increased risk of toxicity (if levels are too high) or reduced efficacy (if levels are too low).
> Important: Tell your doctor about ALL medications, supplements, and herbal products you are taking, including over-the-counter vitamins.
Alpelisib must NEVER be used in the following circumstances:
These are conditions where the risks may outweigh the benefits, requiring a careful risk-benefit analysis by a specialist:
There is no established cross-sensitivity between Alpelisib and other kinase inhibitors (like Ribociclib or Palbociclib). However, patients sensitive to other sulfonamide-derived medications should be monitored closely, although Alpelisib itself is not a classic sulfonamide antibiotic.
> Important: Your healthcare provider will evaluate your complete medical history, including past skin reactions and metabolic health, before prescribing Alpelisib.
Alpelisib is classified as having Embryo-Fetal Toxicity. Based on its mechanism of action and animal studies, it can cause fetal harm when administered to a pregnant woman. In animal reproduction studies, oral administration during organogenesis caused adverse developmental outcomes, including embryo-fetal death and reduced fetal weight at doses lower than the recommended human dose.
It is not known if Alpelisib or its metabolites are excreted in human milk. Because of the potential for serious adverse reactions in a breastfed child, women are advised not to breastfeed during treatment and for at least 1 week after the last dose.
Alpelisib (as Vijoice) is approved for pediatric patients 2 years of age and older for the treatment of PROS. The safety and effectiveness in pediatric patients for other indications, including cancer, have not been established. In the PROS population, growth and development should be monitored, although currently, there is no evidence of permanent growth plate inhibition in humans at clinical doses.
In the SOLAR-1 clinical trial, approximately 45% of patients were 65 years of age or older. No overall differences in the efficacy or safety of Alpelisib were observed between these patients and younger patients. However, elderly patients may be more susceptible to dehydration resulting from diarrhea or hyperglycemia, and they often have a higher incidence of comorbid conditions (like renal insufficiency) that require closer monitoring.
For patients with mild to moderate renal impairment, no dose adjustment is necessary. However, for those with severe renal impairment (eGFR < 30 mL/min), there is no established safe dose. These patients should be monitored very closely for any signs of increased drug toxicity, as the kidneys are responsible for excreting approximately 14% of the drug and its metabolites.
No dose adjustment is needed for patients with mild or moderate hepatic impairment (Child-Pugh A and B). The drug has not been studied in patients with severe hepatic impairment (Child-Pugh C). In these cases, the risk of impaired drug metabolism could lead to higher systemic exposure and increased side effects. Treatment in this population is generally not recommended unless the potential benefit outweighs the risk.
> Important: Special populations, particularly pregnant women and those with severe organ impairment, require individualized medical assessment and frequent follow-up.
Alpelisib is an orally bioavailable, small-molecule inhibitor of the Class I PI3K, with specific potency against the p110α subunit. PI3Kα is a lipid kinase that plays a central role in the PI3K/Akt/mTOR signaling pathway. In many cancers, the PIK3CA gene (which encodes p110α) undergoes 'gain-of-function' mutations. These mutations lead to the constitutive (constant) activation of the pathway, promoting cell transformation, proliferation, and resistance to apoptosis (programmed cell death).
By binding to the ATP-binding pocket of p110α, Alpelisib prevents the conversion of PIP2 to PIP3. This prevents the recruitment and activation of Akt. In HR+ breast cancer, inhibiting PI3K has been shown to increase the expression of the estrogen receptor, making the cells more sensitive to endocrine therapies like fulvestrant. This synergistic effect is the rationale for the combination therapy.
Alpelisib demonstrates dose-dependent inhibition of the PI3K pathway. In clinical studies, inhibition of the pathway was confirmed by measuring the phosphorylation of downstream targets (like p-Akt) in tumor biopsies. A significant pharmacodynamic effect is the elevation of plasma glucose. Because PI3Kα is a major mediator of insulin signaling in the liver, muscle, and adipose tissue, inhibiting it leads to insulin resistance and subsequent hyperglycemia. This effect is usually observed within the first few days of treatment.
| Parameter | Value |
|---|---|
| Bioavailability | Increased ~73% with high-fat meal |
| Protein Binding | 88.9% |
| Half-life | 8 to 9 hours (steady state) |
| Tmax | 2 to 4 hours |
| Metabolism | Primarily hydrolysis; minor CYP3A4 |
| Excretion | Fecal 81%, Renal 14% |
Alpelisib is classified as a Kinase Inhibitor and more specifically an Alpha-selective Phosphoinositide 3-kinase (PI3K) Inhibitor. It is distinct from 'pan-PI3K inhibitors' which target all four isoforms (alpha, beta, delta, and gamma) and often carry higher toxicity profiles. Related medications in the broader kinase inhibitor class include Ribociclib and Abemaciclib, though their mechanisms (CDK4/6 inhibition) are different.
Common questions about Alpelisib
Alpelisib is primarily used to treat a specific type of advanced or metastatic breast cancer that is hormone receptor (HR)-positive and HER2-negative. It is only used if the cancer has a specific mutation in the PIK3CA gene, which must be confirmed by an FDA-approved test. In these cases, it is taken in combination with another medication called fulvestrant. Additionally, Alpelisib is approved for adults and children aged 2 and older who have PIK3CA-Related Overgrowth Spectrum (PROS). This is a rare condition where certain parts of the body grow excessively due to the same genetic mutation found in some cancers. Your doctor will determine if your specific condition meets the criteria for this treatment.
The most frequent side effect of Alpelisib is hyperglycemia, or high blood sugar, which affects more than half of all patients. This occurs because the drug interferes with the body's normal response to insulin. Other very common side effects include diarrhea, nausea, and a skin rash. Many patients also report feeling unusually tired (fatigue) or experiencing a decreased appetite and weight loss. Laboratory tests often show an increase in creatinine levels, which monitors kidney function, and a decrease in certain white blood cells. Most of these side effects can be managed with other medications or by adjusting the dose of Alpelisib, but they require close monitoring by your healthcare team.
There is no known direct chemical interaction between alcohol and Alpelisib that would make the drug ineffective. However, alcohol can significantly impact blood sugar levels, either raising or lowering them depending on the amount consumed and whether you have eaten. Since Alpelisib frequently causes high blood sugar, drinking alcohol can make it much harder for your doctor to manage this side effect. Alcohol can also put additional strain on the liver, which is responsible for processing many medications. It is generally recommended to limit or avoid alcohol while on Alpelisib to ensure your blood sugar remains stable and your liver stays healthy. Always discuss your alcohol consumption habits with your oncologist.
No, Alpelisib is not considered safe for use during pregnancy as it can cause significant harm or death to an unborn baby. The drug works by blocking pathways that are essential for normal cellular growth, which are critical for a developing fetus. Women who are able to become pregnant must have a negative pregnancy test before starting the medication and must use highly effective birth control during treatment. This birth control should be continued for at least one week after the final dose is taken. Male patients with female partners who can become pregnant should also use condoms during this time. If you become pregnant while taking Alpelisib, you should notify your doctor immediately to discuss the potential risks.
The time it takes for Alpelisib to show a clinical benefit can vary depending on the individual and the condition being treated. In clinical trials for breast cancer, many patients showed a response or stabilization of their disease within the first 8 to 12 weeks of treatment. For patients with PROS, improvements in overgrowth volume and related symptoms may also take several months to become clearly visible. It is important to remember that Alpelisib is often used to control the disease rather than provide an immediate cure. Your doctor will use regular imaging scans, such as CT or MRI, and blood tests to monitor how well the medication is working for you. You should continue taking the medication as prescribed even if you do not feel a difference right away.
You should not stop taking Alpelisib suddenly unless you are experiencing a severe allergic reaction or a life-threatening skin rash. Stopping the medication abruptly can allow the PI3K signaling pathway to become active again, which may lead to the rapid growth of cancer cells or a return of overgrowth symptoms in PROS. If you are struggling with side effects like severe diarrhea or high blood sugar, your doctor will usually prefer to lower your dose or temporarily pause the treatment rather than stopping it entirely. This allows your body to recover while still maintaining some level of control over the disease. Always consult your healthcare provider before making any changes to your medication schedule.
If you miss a dose of Alpelisib, you can still take it as long as it is within 9 hours of your regularly scheduled time. You must take the missed dose with food to ensure it is absorbed properly. If more than 9 hours have passed since you were supposed to take the dose, you should skip the missed dose entirely and simply take your next dose at the usual time the following day. Never take two doses at the same time to make up for a missed one, as this can significantly increase your risk of severe side effects like dangerously high blood sugar. If you vomit after taking your dose, do not take another one that day; just wait for your next scheduled dose.
Alpelisib is much more likely to cause weight loss rather than weight gain. In clinical trials, weight loss was a frequently reported side effect, often occurring because the drug can cause a decreased appetite, changes in how food tastes, and nausea. Additionally, the diarrhea associated with Alpelisib can lead to fluid loss and weight reduction. While high blood sugar (hyperglycemia) is a common side effect, it does not typically lead to weight gain in the way that some other metabolic conditions might. If you notice a sudden or significant change in your weight while taking this medication, you should report it to your doctor, as it may require a change in your supportive care or diet.
Alpelisib can interact with several other medications, so it is vital to provide your doctor with a full list of everything you take. It specifically interacts with drugs that are strong 'inducers' of the CYP3A4 enzyme, such as certain anti-seizure medications and the herbal supplement St. John's Wort; these can make Alpelisib less effective. It may also affect how your body processes blood thinners like Warfarin, requiring more frequent blood tests to ensure your blood is clotting correctly. Because Alpelisib raises blood sugar, you may also need to start or adjust doses of diabetes medications like metformin. Your pharmacist and oncologist will check for these interactions before you start treatment to ensure all your medications work safely together.
Currently, Alpelisib is not available as a generic medication. It is a relatively new drug, first approved by the FDA in 2019, and is protected by patents held by the manufacturer, Novartis. This means that only the brand-name versions, Piqray (for breast cancer) and Vijoice (for PROS), are available on the market. Generic versions typically do not become available until the original patents expire, which often takes many years. Because it is a specialized 'specialty' medication, it is usually dispensed through specialty pharmacies rather than your local neighborhood drugstore. If you are concerned about the cost of this medication, the manufacturer often provides patient assistance programs or co-pay cards to help cover the out-of-pocket expenses.