What are the precautions for Alpelisib-Piqray?

Among the warnings and precautions that emerged from the clinical studies of Alpelisib-Piqray: Serious hypersensitivity, serious adverse skin reactions, hyperglycemia, pneumonia, diarrhea, or colitis , embryo-fetal toxicity, etc. are more common. Doctors may regularly check patients for drug treatment of locally advanced or metastatic breast cancer (mBC) progression, and based on the duration and severity of the disease, discontinue, reduce the dose, or permanently discontinue Apelvis.

1. Severe allergies: including anaphylaxis and anaphylactic shock. Severe hypersensitivity reactions manifest themselves as symptoms, including but not limited to dyspnea, flushing, rash, fever or tachycardia. Angioedema has been reported in patients treated with apelvis during postmarketing periods. Inform patients of the signs and symptoms of severe hypersensitivity reactions. In case of severe hypersensitivity reaction, permanently discontinue apelix.

2. Serious skin adverse reactions (SCARs): including Stevens-Johnson syndrome (SJS), erythema multiforme (EM), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS). Signs and symptoms may include prodrome of fever, flu-like symptoms, mucosal lesions, progressive rash or lymphadenopathy. Such adverse reactions have also appeared after marketing. If signs or symptoms of SCAR occur, interrupt PIQRAY until the cause of the reaction is determined. If SCAR is confirmed, permanently discontinue apelix. Do not reinstitute Apelvis in patients who have experienced serious cutaneous adverse reactions during Apelvis treatment. If SCAR is not confirmed, dose modification, topical corticosteroids, or oral antihistamine therapy may be required.

3. Hyperglycemia: In some cases, it is related to hyperglycemic hyperosmolar nonketotic acidosis syndrome (HHNKS) or ketoacidemia. Fatal cases of ketoacidosis have occurred in the postmarketing setting. Signs and symptoms of high blood sugar may include excessive thirst, urinating more often or peeing more than usual, or increased appetite with weight loss. Before starting apelixtreatment, test fasting plasma glucose (FPG), HbA1c, and optimize glycemia. After initiating treatment with Apelvis, monitor fasting blood glucose at least weekly for the first 2 weeks, then at least every 4 weeks, and HbA1c every 3 months, as clinically indicated. During the first few weeks of Apelixtreatment, monitor fasting blood glucose more frequently in patients with risk factors for hyperglycemia, such as obesity (BMI ≥30), elevated FPG, HbA1c at or above the upper limit of normal, concurrent use of systemic corticosteroids, or age ≥75 years.

4. Pneumonia: including acute interstitial pneumonia and interstitial lung disease. For patients who have new or worsening respiratory symptoms or who are suspected of having pneumonia, immediately interrupt Apelvis and evaluate the patient for pneumonia. Consider a diagnosis of noninfectious pneumonia in patients who present with nonspecific respiratory signs and symptoms on radiological examination (such as hypoxia, cough, dyspnea, or interstitial infiltrates) and for whom infectious, neoplastic, and other causes have been excluded by appropriate investigations. Permanently discontinue apelvis in all patients with confirmed pneumonia.

5. Diarrhea or colitis: Patients may experience severe diarrhea, leading to dehydration and, in some cases, acute kidney injury; in clinical studies, the median onset time was 46 days, and patients need antidiarrheal drugs (such as loperamide) to control symptoms. Monitor patients for diarrhea and other symptoms of colitis, such as abdominal pain and mucus or blood in the stool. Patients with colitis may require additional treatments such as enteric and/or systemic steroids.

6. Embryo-Fetal Toxicity: Based on findings in animals and its mechanism of action, Apelvis can cause harm to the fetus when administered to pregnant women. In animal reproduction studies, oral administration of Apelvis to pregnant rats and rabbits during organogenesis resulted in adverse developmental outcomes, including embryonic-fetal mortality (post-implantation loss), reduced fetal weight, and an increased incidence of fetal malformations based on maternal exposure based on area under the curve (AUC) ≥ 0.8 times the human exposure at the recommended dose of 300 mg/day.

Pregnant women and women of childbearing potential are advised to be aware of the potential risk to the fetus. It is recommended that females of childbearing potential use effective contraception during treatment with Apelvis and within 1 week after the last dose; male patients with female partners of childbearing potential are advised to use condoms and effective contraception during treatment with Apelvis and within 1 week after the last dose.