Important Safety Information


PIQRAY® (alpelisib) tablets is contraindicated in patients with severe hypersensitivity to it or any of its components. Severe Hypersensitivity: Severe hypersensitivity reactions, including anaphy...

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Indication
PIQRAY is indicated in combination with fulvestrant 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 as detected by an FDA-approved test following progression on or after an endocrine-based regimen.

Safety Profile

Adverse Reactions

  • Serious adverse reactions (ARs) associated with PIQRAY include severe hypersensitivity, severe cutaneous reactions, hyperglycemia, pneumonitis, diarrhea, and embryo-fetal toxicity1

ARs occurring in >20% of the total populationn ARs occurring in >20% of the total populationn
ARs
PIQRAY + fulvestrant (n=284)
All grades (%)
Grade 3-4 (%)
Placebo + fulvestrant (n=287)
All grades (%)
Grade 3-4 (%)
Gastrointestinal disorders
Diarrhea
Nausea
Stomatitisa
Vomiting
General disorders and administration site conditions
Fatigueb
Investigations
Weight decreased
Metabolism and nutrition disorders
Decreased appetite
Skin and subcutaneous tissue disorders
Rashc
 
58
45
30
27
 
42
 
27
 
36
 
52
 
7*
2.5*
2.5*
0.7*
 
5*
 
3.9*
 
0.7*
 
20*
 
16
22
6
10
 
29
 
2.1
 
10
 
7
 
0.3*
0.3*
0*
0.3*
 
1*
 
0*
 
0.3*
 
0.3*

 


*No grade 4 ARs were reported.
aIncluding stomatitis, aphthous ulcer, mouth ulceration.
bIncluding fatigue, asthenia.
cIncluding rash, rash maculo-papular, rash macular, rash generalized, rash papular, rash pruritic.

Laboratory abnormalities occurring in >30% of the total population Laboratory abnormalities occurring in >30% of the total population
Laboratory Abnormality
PIQRAY + fulvestrant (n=284)
All grades (%)
Grade 3-4 (%)
Placebo + fulvestrant (n=287)
All grades (%)
Grade 3-4 (%)
Hematological parameters
Lymphocyte count decreased
Hemoglobin decreased
Biochemical parameters
Glucose increaseda
Creatinine increased
Gamma Glutamyl Transferase (GGT) increased
Alanine Aminotransferase (ALT) increased
Lipase increased
 
52
42
 
79
67
52
44
42
 
8
4.2
 
39
2.8
11
3.5
7
 
40
29
 
34
25
44
34
25
 
4.5
1
 
1
0.7
10
2.4
6

 


No grade 4 ARs were reported.
aGlucose increase is an expected laboratory abnormality of PI3K inhibition.

  • Glucose increase, including hyperglycemia, is an expected, on-target effect of PI3K inhibition1,3
  • Hyperglycemia, a laboratory-related AR, was reported in 65% of patients treated with PIQRAY (grade 3=33%; grade 4=3.9%)
  • Among patients treated with PIQRAY and fulvestrant, 5% permanently discontinued both therapies and 21% permanently discontinued PIQRAY alone due to ARs1
    • The most common ARs leading to discontinuation of PIQRAY were hyperglycemia (6% of patients), rash (4%), diarrhea (3%), and fatigue (3%)1
  • Dose reductions due to ARs occurred in 55% of patients receiving PIQRAY and fulvestrant1
    • The most common ARs leading to a dose reduction of PIQRAY were hyperglycemia (29% of patients), rash (9%), diarrhea (6%), stomatitis (4%), and mucosal inflammation (2%)1

 

Considerations for Select Adverse Reactions

The only laboratory monitoring needed for patients on PIQRAY is for FPG and HbA1c1

 

FPG/HbA1c monitoring1

Recommended monitoring for hyperglycemia

*Blood glucose can also be monitored after initiating treatment.

  • Optimize blood glucose prior to initiating treatment

 

Frequency of monitoring changes in the event of hyperglycemia1

Frequency of monitoring changes in the event of hyperglycemia

Consider consultation with a healthcare provider with expertise in the treatment of hyperglycemia and counsel patients on lifestyle changes.

FPG, fasting plasma glucose; HbA1c, hemoglobin A1c.

 

Contact a representative for additional AR management information

 

 

In the SOLAR-1 trial:

  • A subgroup of 86 patients received prophylaxis, including antihistamines (eg, cetirizine), prior to onset of rash
  • In these patients, rash was reported less frequently than in the overall population as shown in the table below

Effects of prophylactic treatment, including antihistamines, prior to onset of rash in patients receiving PIQRAY plus fulvestrant1

Event
Patients receiving prophylactic treatment prior to onset of rash (n=86)
Overall population (n=284)
All grades rash
Grade 3 rash
Rash leading to permananent discontinuation of PIQRAY
27%
12%
3.5%
54%
20%
4.2%

 

Contact a representative for additional AR management information

 

References: 1. Piqray [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2019. 2. Data on file. Novartis Pharmaceuticals Corp; 2019. 3. Goncalves MD, Hopkins BD, Cantley LC. Phosphatidylinositol 3-kinase, growth disorders, and cancer. N Engl J Med. 2018;379(21):2052-2062.

Indication

PIQRAY® (alpelisib) tablets is indicated in combination with fulvestrant 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 as detected by an FDA-approved test following progression on or after an endocrine-based regimen.

Important Safety Information

PIQRAY is contraindicated in patients with severe hypersensitivity to it or any of its components.

Severe Hypersensitivity: Severe hypersensitivity reactions, including anaphylaxis and anaphylactic shock, were reported in patients treated with PIQRAY. Severe hypersensitivity reactions were manifested by symptoms including, but not limited to, dyspnea, flushing, rash, fever, or tachycardia. The incidence of grade 3 and 4 hypersensitivity reactions was 0.7%. Advise patients of the signs and symptoms of severe hypersensitivity reactions. Permanently discontinue PIQRAY in the event of severe hypersensitivity.

Severe Cutaneous Reactions: Severe cutaneous reactions, including Stevens-Johnson syndrome (SJS) and erythema multiforme (EM) were reported in patients treated with PIQRAY. SJS and EM were reported in 0.4% and 1.1% of patients, respectively. Do not initiate PIQRAY treatment in patients with a history of SJS, EM, or toxic epidermal necrolysis (TEN). If signs or symptoms of severe cutaneous reactions occur, interrupt PIQRAY until the etiology of the reaction has been determined. Consultation with a dermatologist is recommended.

If SJS, TEN, or EM is confirmed, permanently discontinue PIQRAY. Do not reintroduce PIQRAY in patients who have experienced previous severe cutaneous reactions during PIQRAY treatment. If it is not confirmed, PIQRAY may require dose modifications, topical corticosteroids, or oral antihistamine treatment.

Advise patients of the signs and symptoms of severe cutaneous reactions (eg, a prodrome of fever, flu-like symptoms, mucosal lesions, or progressive skin rash).

Hyperglycemia: Severe hyperglycemia, including ketoacidosis, has been reported in patients treated with PIQRAY. Hyperglycemia was reported in 65% of patients treated with PIQRAY. Grade 3 (FPG >250-500 mg/dL) and Grade 4 (FPG >500 mg/dL) hyperglycemia was reported in 33% and 3.9% of patients, respectively. Ketoacidosis was reported in 0.7% of patients (n=2) treated with PIQRAY.

Before initiating treatment with PIQRAY, test FPG, HbA1c, and optimize blood glucose. After initiating treatment with PIQRAY, monitor blood glucose and/or FPG 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. If a patient experiences hyperglycemia after initiating treatment with PIQRAY, monitor blood glucose and/or FPG as clinically indicated, and at least twice weekly until blood glucose or FPG decreases to normal levels. During treatment with antidiabetic medication, continue monitoring blood glucose or FPG at least once a week for 8 weeks, followed by once every 2 weeks and as clinically indicated. Consider consultation with a health care practitioner with expertise in the treatment of hyperglycemia and counsel patients on lifestyle changes.

The safety of PIQRAY in patients with type 1 and uncontrolled type 2 diabetes has not been established as these patients were excluded from the SOLAR-1 trial. Patients with a medical history of type 2 diabetes were included. Patients with a history of diabetes mellitus may require intensified diabetic treatment. Closely monitor patients with diabetes.

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

Pneumonitis: Severe pneumonitis, including acute interstitial pneumonitis and interstitial lung disease, has been reported in patients treated with PIQRAY. Pneumonitis was reported in 1.8% of patients treated with PIQRAY.

In patients who have new or worsening respiratory symptoms or are suspected to have developed pneumonitis, interrupt PIQRAY 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 PIQRAY in all patients with confirmed pneumonitis. Advise patients to immediately report new or worsening respiratory symptoms.

Diarrhea: Severe diarrhea, including dehydration and acute kidney injury, occurred in patients treated with PIQRAY. Most patients (58%) experienced diarrhea during treatment with PIQRAY. Grade 3 diarrhea occurred in 7% (n=19) of patients. Based on the severity of the diarrhea, PIQRAY may require dose interruption, reduction, or discontinuation. Advise patients to start antidiarrheal treatment, increase oral fluids, and notify their health care provider if diarrhea occurs while taking PIQRAY.

Embryo-Fetal Toxicity: Based on findings in animals and its mechanism of action, PIQRAY can cause fetal harm when administered to a pregnant woman. 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 PIQRAY 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 PIQRAY and for 1 week after the last dose. Refer to the Full Prescribing Information of fulvestrant for pregnancy and contraception information.

The most common adverse reactions (all grades, incidence ≥20%) were diarrhea (58%), rash (52%), nausea (45%), fatigue (42%), decreased appetite (36%), stomatitis (30%), vomiting (27%), weight decreased (27%), and alopecia (20%). The most common grade 3/4 adverse reactions (incidence ≥2%) were rash (20%), diarrhea (7%), fatigue (5%), weight decreased (3.9%), nausea (2.5%), stomatitis (2.5%), and mucosal inflammation (2.1%).

The most common laboratory abnormalities (all grades, incidence ≥20%) were glucose increased (79%), creatinine increased (67%), lymphocyte count decreased (52%), gamma glutamyl transferase (GGT) increased (52%), alanine aminotransferase (ALT) increased (44%), hemoglobin decreased (42%), lipase increased (42%), calcium decreased (27%), glucose decreased (26%), and activated partial thromboplastin time (aPTT) prolonged (21%). The most common grade 3/4 laboratory abnormalities (incidence ≥5%) were glucose increased (39%), GGT increased (11%), lymphocyte count decreased (8%), and lipase increased (7%), and potassium decreased (6%).

Please see full Prescribing Information.