Precautions of Alpelisib

1.Severe Hypersensitivity

Advise patients of the signs and symptoms of severe hypersensitivity reactions. Permanently discontinue Alpelisib in the event of severe hypersensitivity.

2.Severe Cutaneous Adverse Reactions

If signs or symptoms of SCARs occur, interrupt Alpelisib until the etiology of the reaction has been determined. Consultation with a dermatologist is recommended. 

If a SCAR is confirmed, permanently discontinue Alpelisib. Do not reintroduce Alpelisib in patients who have experienced previous severe cutaneous adverse reactions during Alpelisib treatment. 

If a SCAR is not confirmed, Alpelisib may require dose modifications, topical corticosteroids, or oral antihistamine treatment as described in Table 2.

Advise patients of the signs and symptoms of SCARs (e.g., a prodrome of fever, flu-like symptoms, mucosal lesions, progressive skin rash, or lymphadenopathy).

3.Hyperglycemia

Before initiating treatment with Alpelisib, test fasting plasma glucose (FPG), HbA1c, and optimize blood glucose. After initiating treatment with Alpelisib, monitor fasting glucose (FPG or fasting blood glucose) at least once every week for the first 2 weeks, then at least once every 4 weeks, and as clinically indicated. Monitor HbA1c every 3 months and as clinically indicated. Monitor fasting glucose more frequently for the first few weeks during treatment with Alpelisib in patients with risk factors for hyperglycemia, such as obesity (BMI ≥ 30), elevated FPG, HbA1c at the upper limit of normal or above, use of concomitant systemic corticosteroids, or age ≥ 75. 

If a patient experiences hyperglycemia after initiating treatment with Alpelisib, monitor fasting glucose as clinically indicated, and at least twice weekly until fasting glucose decreases to normal levels. During treatment with anti-hyperglycemic medication, continue monitoring fasting glucose at least once a week for 8 weeks, followed by once every 2 weeks and as clinically indicated. Consider consultation with a healthcare practitioner with expertise in the treatment of hyperglycemia and counsel patients on lifestyle changes.

Based on the severity of the hyperglycemia, Alpelisib may require dose interruption, reduction, or discontinuation as described in Table Advise patients of the signs and symptoms of hyperglycemia (e.g., excessive thirst, urinating more often than usual or higher amount of urine than usual, or increased appetite with weight loss).

4.Pneumonitis

In patients who have new or worsening respiratory symptoms or are suspected to have developed pneumonitis, interrupt Alpelisib immediately and evaluate the patient for pneumonitis. Consider a diagnosis of non-infectious pneumonitis in patients presenting with non-specific respiratory signs and symptoms, such as hypoxia, cough, dyspnea, or interstitial infiltrates on radiologic exams and in whom infectious, neoplastic, and other causes have been excluded by means of appropriate investigations. 

Permanently discontinue Alpelisib in all patients with confirmed pneumonitis. 

Advise patients to immediately report new or worsening respiratory symptoms.

5.Diarrhea or Colitis

Monitor patients for diarrhea and additional symptoms of colitis, such as abdominal pain and mucus or blood in stool. Based on the severity of the diarrhea or colitis, Alpelisib may require dose interruption, reduction, or discontinuation as described in Table 4.

Advise patients to start antidiarrheal treatment, increase oral fluids, and notify their healthcare provider if diarrhea occurs while taking Alpelisib. 

Patients with colitis may require additional treatment, such as enteric-acting and/or systemic steroids.

6.Embryo-Fetal Toxicity

Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with Alpelisib and for 1 week after the last dose. Advise male patients with female partners of reproductive potential to use condoms and effective contraception during treatment with Alpelisib and for 1 week after the last dose. Refer to the Full Prescribing Information of fulvestrant for pregnancy and contraception information.

from FDA,2022.11