Approved Drug Label (PDF)
5
Warnings and Precautions
5.1 Severe Hypersensitivity
Newly added information:
Angioedema has been reported in the postmarketing setting in patients
treated with PIQRAY [see Adverse Reactions (6.2)].
5.5 Diarrhea or Colitis
Additions and revisions
underlined:
Severe diarrhea, resulting in dehydration and in some cases in
acute kidney injury,
can occur in patients treated with PIQRAY. Most patients (58%)
experienced diarrhea during treatment with PIQRAY. Grade 3 diarrhea occurred in
7% (n = 19) of patients. Among patients with Grade 2 or 3 diarrhea (n = 71),
the median time to onset was 46 days (range, 1 to 442 days).
In clinical trials, 63% of patients
who experienced diarrhea
required antidiarrheal medications (e.g., loperamide) to
manage symptoms. Dose reductions of PIQRAY were required in 6% of patients,
and 2.8% of patients permanently discontinued PIQRAY due to diarrhea.
Colitis has been reported in the postmarketing setting in patients
treated with PIQRAY
[see Adverse Reactions (6.2)]
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, PIQRAY may require dose interruption,
reduction, or discontinuation as described in Table 4 [see Dosage and Administration (2.3)].
Advise patients to start
antidiarrheal treatment, increase
oral fluids, and notify their healthcare provider
if diarrhea occurs while taking PIQRAY.
For patients with colitis,
additional treatment, such as enteric-acting and/or systemic steroids,
may be required.
6
Adverse Reactions
Additions and revisions
underlined:
The following adverse reactions are discussed in greater detail
in other sections
of the labeling:
Severe Hypersensitivity [see Warnings
and Precautions (5.1)]
Severe Cutaneous Adverse
Reactions [see Warnings and Precautions (5.2)]
Hyperglycemia [see Warnings and Precautions (5.3)]
Pneumonitis [see Warnings and Precautions (5.4)]
Diarrhea or Colitis [see Warnings and Precautions (5.5)]
6.2 Postmarketing Experience
Additions and revisions
underlined:
The following adverse reactions
have been identified during postapproval use of PIQRAY.
Because these reactions are
reported voluntarily from a population of uncertain size, it is not always
possible to reliably estimate their frequency or establish a causal
relationship to drug exposure.
Gastrointestinal disorders: Colitis
Metabolism and nutrition disorders: Hyperglycemic hyperosmolar
nonketotic syndrome (HHNKS).
Skin and subcutaneous tissue
disorders: Angioedema, Drug reaction with eosinophilia and systemic symptoms (DRESS).
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING INFORMATION
Additions and revisions
underlined:
Hyperglycemia
Advise patients
that PIQRAY may cause hyperglycemia and
requires monitoring of fasting blood glucose periodically during therapy. Advise
patients to contact
their healthcare provider
immediately for signs and
symptoms of hyperglycemia [see Warnings
and Precautions (5.3)].
Pneumonitis
Inform patients that
PIQRAY may cause
pneumonitis and to immediately contact
their healthcare provider
if they experience respiratory problems [see Warnings and Precautions (5.4)].
Diarrhea or Colitis
Advise patients that PIQRAY may
cause diarrhea, which may be severe, and to start antidiarrheal treatment,
increase oral fluids, and notify
their healthcare provider
if diarrhea occurs
while taking PIQRAY
[see Warnings and Precautions (5.5)].
Advise patients that PIQRAY may
cause colitis and to notify their healthcare provider immediately of any
symptoms of colitis, such as abdominal pain and mucus
or blood in stool, while
taking PIQRAY [see Warnings and Precautions (5.5)].
Patient Information
Additions and revisions
underlined:
PIQRAY may cause serious side effects, including:
breathing, swelling of the face or throat, flushing,
rash, fever, or fast heart rate during treatment with
PIQRAY.
severe. Severe diarrhea can lead to the loss of too much
body water (dehydration) and kidney injury. Tell
your healthcare provider right away if you develop
diarrhea, stomach-area (abdominal) pain, or see mucus or
blood in your stool during treatment with PIQRAY.
Your healthcare provider may tell you to drink more fluids
or take medicines to treat diarrhea or colitis.
Approved Drug Label (PDF)
5
Warnings and Precautions
5.3 Hyperglycemia
Additions and/or
revisions underlined:
‘hyperglycemic’
replaces ‘diabetic’ throughout subsection.
Severe
hyperglycemia, in some cases associated with hyperglycemic hyperosmolar
non-ketotic syndrome (HHNKS) or ketoacidosis has occurred in
patients treated with PIQRAY. Some fatal cases of ketoacidosis have occurred
in the post marketing setting …
… After initiating
treatment with PIQRAY, 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 PIQRAY in patients
with risk factors for hyperglycemia such as obesity (BMI greater than or equal to 30), elevated FPG,
HbA1c at the upper limit of normal or above, use of concomitant systemic
corticosteroids, or age greater than or equal to 75 [see Use in
Specific Populations (8.5)] …
… 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 controlled Type 2
diabetes were included …
6
Adverse Reactions
6.2 Postmarketing Experience
Additions
and/or revisions underlined:
Metabolism and
nutrition disorders: Hyperglycemic
hyperosmolar nonketotic syndrome (HHNKS).
Skin and
sub-cutaneous tissue disorders: Drug reaction
with eosinophilia and systemic symptoms (DRESS).
8
Use in Specific Populations
8.5 Geriatric Use
Additions
and/or revisions underlined:
… There are an insufficient number of patients greater than or equal to 75 years of age to
assess whether there are differences in safety or effectiveness. However, in
the SOLAR-1 trial, an increase in the hyperglycemia adverse reactions (74% vs
66%) and Grade 3-4 (56% vs 36%) hyperglycemia were observed in patients > 75
years of age compared to patients < 75 years of age, respectively [see
Warnings and Precautions (5.3)].
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
MEDICATION GUIDE
What are the
possible side effects of PIQRAY?
PIQRAY may cause
serious side effects, including:
High blood sugar
levels (hyperglycemia) …
Addition of the
following under the bulleted line listing:
Confusion
Nausea
Vomiting
Fruity
odor on breath
Difficulty
breathing
Dry
or flushed skin
PATIENT COUNSELING INFORMATION
Additions
and/or revisions underlined:
Severe Cutaneous Adverse Reactions
Inform
patients of the signs and symptoms of severe cutaneous adverse reactions
(SCARs) …
Approved Drug Label (PDF)
5
Warnings and Precautions
5.1 Severe Hypersensitivity
(Additions and/or revisions underlined)
Severe hypersensitivity reactions, including
anaphylaxis and anaphylactic shock, can occur 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% [see
Adverse Reactions (6)].
Advise patients of the signs and symptoms of severe
hypersensitivity reactions. Permanently discontinue PIQRAY in the event of
severe hypersensitivity.
5.2 Severe Cutaneous Adverse Reactions
(Subsection title
revised; Additions and/or revisions underlined)
Severe
cutaneous adverse reactions (SCARs) including Stevens-Johnson
Syndrome (SJS), erythema multiforme (EM), toxic epidermal necrolysis (TEN),
and drug reaction with eosinophilia and systemic symptoms (DRESS) can occur
in patients treated with PIQRAY.
In
the SOLAR-1 study, SJS
and EM were reported in 0.4% and 1.1% of the patients, respectively [see Adverse Reactions (6.1)]. Drug
reaction with eosinophilia and systemic symptoms (DRESS) was reported in patients
treated with PIQRAY in the postmarketing setting [see Adverse Reactions (6.2)].
If
signs or symptoms of SCARs occur, interrupt PIQRAY until the etiology of
the reaction has been determined. Consultation with a dermatologist is
recommended.
If
a SCAR is confirmed, permanently discontinue PIQRAY. Do not reintroduce
PIQRAY in patients who have experienced previous severe cutaneous reactions
during PIQRAY treatment.
If
a SCAR is not confirmed, PIQRAY may require dose modifications, topical
corticosteroids, or oral antihistamine treatment as described in Table 2
[see Dosage and Administration (2.3)].
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).
5.3 Hyperglycemia
(Additions and/or
revisions underlined)
Severe
hyperglycemia, including ketoacidosis, can occur 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.
Among
the patients who experienced Grade ? 2 (FPG 160-250 mg/dL) hyperglycemia, the
median time to first occurrence of hyperglycemia was 15 days (range: 5 to 517
days).
In
the 187 patients with hyperglycemia, 87% (163/187) were managed with
anti-diabetic medication, and 76% (142/187) reported use of metformin as single
agent or in combination with other anti-diabetic medication [i.e., insulin,
dipeptidyl peptidase-4 (DPP-4) inhibitors, and sulfonylureas]. In patients with
Grade ? 2 hyperglycemia with at least 1 grade improvement (n = 153), median
time to improvement from the first event was 8 days (range: 2 to 65 days).
In
all patients with elevated FPG who continued fulvestrant treatment after
discontinuing PIQRAY (n = 54), 96% (n = 52) of patients had FPG levels that
returned to baseline.
Before
initiating treatment with PIQRAY, test fasting plasma glucose (FPG),
HbA1c, and optimize blood glucose. After initiating treatment with PIQRAY,
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.
If
a patient experiences hyperglycemia after initiating treatment with PIQRAY,
monitor fasting glucose as clinically indicated, and at least twice
weekly until fasting glucose decreases to normal levels. During
treatment with anti-diabetic 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.
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 as described in Table 3 [see Dosage and Administration (2.3)].
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).
5.4 Pneumonitis
(Additions and/or
revisions underlined)
Severe
pneumonitis, including acute interstitial pneumonitis and interstitial lung
disease, can occur 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.
5.5 Diarrhea
(Additions and/or
revisions underlined)
Severe
diarrhea, including dehydration and acute kidney injury, can occur in
patients treated with PIQRAY. Most patients (58%) experienced diarrhea during
treatment with PIQRAY. Grade 3 diarrhea occurred in 7% (n = 19) of patients.
Among patients with Grade 2 or 3 diarrhea (n = 71), the median time to onset
was 46 days (range: 1 to 442 days).
Dose
reductions of PIQRAY were required in 6% of patients and 2.8% of patients
permanently discontinued PIQRAY due to diarrhea. In the 164 patients that
experienced diarrhea, anti-diarrheal medications
(e.g.,
loperamide) were required to manage symptoms in 63% (104/164) of these
patients.
Based
on the severity of the diarrhea, PIQRAY may require dose interruption,
reduction, or discontinuation as described in Table 4 [see Dosage and Administration (2.3)].
Advise
patients to start antidiarrheal treatment, increase oral fluids, and notify
their healthcare provider if diarrhea occurs while taking PIQRAY.
6
Adverse Reactions
(Additions and/or
revisions underlined)
The
following adverse reactions are discussed in greater detail in other sections
of the labeling:
Severe
Hypersensitivity [see Warnings and
Precautions (5.1)]
Severe
Cutaneous Adverse Reactions [see
Warnings and Precautions (5.2)]
Hyperglycemia
[see Warnings and Precautions (5.3)]
Pneumonitis
[see Warnings and Precautions (5.4)]
Diarrhea
[see Warnings and Precautions (5.5)]
6.2 Postmarketing Experience
(Newly added
subsection)
The
following adverse reactions have been identified during post-approval use of
PIQRAY. Because these reactions are reported voluntarily from a population of
uncertain size, it is not always possible to reliably estimate their frequency
or establish a causal relationship to drug exposure.
Skin and
sub-cutaneous tissue disorders: Drug reaction with eosinophilia and
systemic symptoms (DRESS).
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