Important safety information
Important note: Before
prescribing, consult full prescribing information.
Presentation:
Film-coated tablets (FCT) containing 50 mg, 150 mg and
200 mg of alpelisib.
Indications:
PIQRAY® is an alpha-specific class I
phosphatidylinositol-3-kinase (PIK3CA) inhibitor
indicated for the treatment of postmenopausal women, and
men, with hormone receptor positive, HER2-negative,
advanced breast cancer with a PIK3CA mutation in
combination with fulvestrant after disease progression
following an endocrine-based regimen.*
Dosage and administration:
Adults: The
recommended dose of Piqray is 300 mg taken orally, once
daily on a continuous basis. Piqray should be taken
immediately following food, at approximately the same
time each day. If a dose of Piqray is missed, it can be
taken up to 9 hours after the time it is normally
administered. After more than 9 hours, the dose should
be skipped for that day. On the next day, Piqray should
be taken at its usual time. If patient vomits after
taking the Piqray dose, the patient should not take an
additional dose on that day, and should resume the usual
dosing schedule the next day, at the usual time.
Special populations:
♦Renal impairment: Mild or moderate: No
dose adjustment is necessary. ♦Severe:
Caution is recommended. ♦Hepatic impairment:
Mild, moderate or severe: No dose adjustment is
necessary. ♦Geriatrics (≥65 years): No
dose adjustment is required. ♦Pediatrics (≤18 years):
Safety and efficacy have not been established.
Contraindications:
♦Patients with hypersensitivity to the active
substance or to any of the excipients.
Warnings and precautions:
♦Hypersensitivity (including anaphylactic
reaction):
Serious hypersensitivity reactions (including
anaphylactic reaction and anaphylactic shock),
manifested by symptoms including, but not limited to,
dyspnea, flushing, rash, fever or tachycardia were
reported in patients treated with Piqray in clinical
studies. Angioedema has been reported in the post
marketing setting in patients treated with Piqray.
Piqray should be permanently discontinued and should not
be re-introduced in patients with serious
hypersensitivity reactions. Appropriate treatment should
be promptly initiated.
♦Severe cutaneous reactions:
Cases of severe cutaneous reactions, including
Stevens-Johnson syndrome (SJS), erythema multiforme (EM)
and drug reaction with eosinophilia and systemic
symptoms (DRESS) were reported in patients treated with
Piqray. Piqray treatment should not be initiated in
patients with history of severe cutaneous reactions.
Patients should be advised of the signs and symptoms of
severe cutaneous reactions. If symptoms or signs of
severe cutaneous reactions are present, Piqray should be
interrupted until the etiology of the reaction has been
determined. A consultation with dermatologist is
recommended. If a severe cutaneous reaction is
confirmed, Piqray should be permanently discontinued.
Piqray should not be re-introduced in patients who have
experienced previous severe cutaneous reactions.
♦Hyperglycemia:
Severe hyperglycemia, in some cases associated with
hyperglycemic hyperosmolar nonketotic syndrome (HHNKS)
or ketoacidosis, has been observed in patients treated
with Piqray. Some cases of ketoacidosis with fatal
outcome have been reported in the post marketing
setting. Patients with poor glycemic control may be at a
higher risk of developing severe hyperglycemia and
associated complications (e.g. ketoacidosis). Patients
with risk factors for hyperglycemia such as obesity (BMI
≥30), elevated FPG, HbA1c at or above the upper limit
of normal, or age ≥75 are at a higher risk of
developing severe hyperglycemia. Those patients should
be monitored for fasting glucose more frequently for the
first few weeks of treatment. Patients should be advised
of the signs and symptoms of hyperglycemia. Based on the
severity of the hyperglycemia, Piqray may require
treatment interruption, dose reduction, or treatment
discontinuation.
♦Pneumonitis:
Pneumonitis including serious cases of pneumonitis/acute
interstitial lung disease have been reported in Piqray
treated patients in clinical studies. Patients should be
advised to promptly report any new or worsening
respiratory symptoms. In patients who have new or
worsening respiratory symptoms or are suspected to have
developed pneumonitis, Piqray treatment should be
interrupted immediately and the patient should be
evaluated for pneumonitis. A diagnosis of non-infectious
pneumonitis should be considered. Piqray should be
permanently discontinued in all patients with confirmed
pneumonitis.
♦Diarrhea or colitis:
Severe diarrhea and clinical consequences, such as
dehydration and acute kidney injury, have been reported
during treatment with Piqray in clinical studies.
Colitis has been reported in the post marketing setting.
Patients should be monitored for diarrhea and additional
symptoms of colitis, such as abdominal pain and mucus or
blood in stool. In case of colitis, additional treatment
such as steroids may be considered. Based on the
severity of the diarrhea or colitis, Piqray may require
dose interruption, reduction, or discontinuation.
Patients should be advised to notify their healthcare
provider if diarrhea or colitis occurs while taking
Piqray.
Pregnancy, lactation, females and males of
reproductive potential:
Pregnancy: It is
possible that Piqray can cause fetal harm when
administered to a pregnant woman. Piqray should not be
used during pregnancy unless the benefits to the mother
outweigh the risk to the fetus. If Piqray is used during
pregnancy, the patient should be advised of the
potential risk to the fetus.
Lactation: Women
should not breast-feed during treatment and for at least
4 days after the last dose of Piqray.
Females and males of reproductive
potential:
♦Pregnancy testing: For female patients
of reproductive potential, the pregnancy status should
be verified, prior to initiating treatment with Piqray.
♦Contraception: Sexually active females
of reproductive potential (ORP) should use effective
contraception and male patients with female partners ORP
should use condoms during treatment with Piqray and for
4 days after stopping treatment with Piqray.
Infertility: Based on
animal studies, Piqray may impair fertility in females
and males of reproductive potential.
Adverse drug reactions:
Very common (≥10%):
Anaemia, diarrhoea, nausea, vomiting, stomatitis,
abdominal pain, dyspepsia, fatigue, mucosal
inflammation, oedema peripheral, pyrexia, mucosal
dryness, urinary tract infection, weight decreased,
blood creatinine increased, hyperglycaemia, decreased
appetite, headache, dysgeusia, rash, alopecia, pruritus,
dry skin, activated partial thromboplastin time
increased, hemoglobin decreased, lymphocyte count
decreased, platelet count decreased, alanine
aminotransferase increased, albumin decreased, calcium
corrected decreased, gamma-glutamyl transferase
increased, glucose plasma increased, glucose plasma
decreased, lipase increased.
Common (≥1 to <10%):
Lymphopenia, thrombocytopenia, vision blurred, dry eye,
toothache, cheilitis, gingival pain, gingivitis, oedema,
hypersensitivity, glycosylated haemoglobin increased,
hypokalemia, hypocalcaemia, dehydration, muscle spasms,
myalgia, osteonecrosis of jaw, insomnia, acute kidney
injury, pneumonitis, erythema, dermatitis,
palmar-plantar erythrodysaesthesia syndrome, erythema
multiforme, hypertension, lymphoedema, potassium
decreased, magnesium decreased.
Uncommon (≥0.1 to <1%):
Pancreatitis, ketoacidosis, Stevens-Johnson syndrome
(SJS).
♦Adverse drug reactions from post-marketing
experience (frequency not known):
colitis, hyperglycaemic hyperosmolar nonketotic syndrome
(HHNKS), angioedema, drug reaction with eosinophilia and
systemic symptoms (DRESS).
Description of select ADRs and treatment
recommendations, where applicable:
♦Rash: Topical
corticosteroid treatment should be initiated at the
first signs of rash and oral corticosteroids should be
considered for more moderate to severe rashes.
Additionally, antihistamines are recommended to manage
symptoms of rash. Oral antihistamines may be initiated
prophylactically, at the time of initiation of treatment
with Piqray. ♦
Gastrointestinal (GI) toxicity (nausea, diarrhoea,
vomiting):
Severe diarrhoea and clinical consequences, such as
dehydration and acute kidney injury, have been reported
during treatment with Piqray and resolved with
appropriate intervention. Patients should be managed
according to local standard of care medical management,
including electrolyte monitoring, administration of
anti-emetics and antidiarrhoeal medications and/or fluid
replacement and electrolyte supplements, as clinically
indicated.
Interactions:
♦BCRP (breast cancer resistance protein)
inhibitors:
Caution is advised when co-administering Piqray with a
BCRP inhibitor (e.g. eltrombopag, lapatininb,
pantoprazole), as inhibition of BCRP may lead to an
increase in systemic exposure of Piqray.
♦CYP3A4 inducers:
Co-administration of alpelisib with strong CYP3A4
inducers (e.g., apalutamide, carbamazepine,
enzalutamide, mitotane, phenytoin, rifampin, St.
John's wort) should be avoided and selection of an
alternative concomitant medicinal product, with no or
minimal potential to induce CYP3A4, should be
considered.
♦CYP3A4 substrates:
Caution is recommended when Piqray is used in
combination with CYP3A4 substrates that also possess an
additional time-dependent inhibition and induction
potential on CYP3A4 that affects their own metabolism
(e.g. rifampicin, ribociclib, encorafenib).
♦CYP2C9 substrates with narrow therapeutic
index:
No dose adjustment of Piqray is required. However, in
the absence of clinical data, caution is recommended
when Piqray is co-administered with drugs that are
CYP2C9 substrates with narrow therapeutic index
(e.g.warfarin).
♦CYP2B6 sensitive substrates with narrow
therapeutic index:
Sensitive CYP2B6 substrates (e.g. bupropion) or CYP2B6
substrates with a narrow therapeutic window should be
used with caution in combination with Piqray, as Piqray
may reduce the clinical activity of such drugs.
♦Hormonal contraceptives:
It is currently unknown whether alpelisib may reduce the
effectiveness of systemically acting hormonal
contraceptives.
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Legal classification:
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