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PIQRAY is a brand name for Alpelisib, supplied as a tablet. The medicine, its uses, side effects and dosage are the same regardless of brand.
Verbatim from this product's HC label. Tap a section to expand.
, Table 4-2). g. metformin), 40% of patients with dose interruption, 43% of patients with dose reduction, and 10% of patients with permanent discontinuation. In patients with hyperglycemia, 166/191 (87%) were managed with anti-diabetic medication and 145/191 (76%) reported use of metformin as single agent or in combination with other anti-diabetic medication.
The maximum dose of metformin recommended in phase III clinical study was 2,000 mg per day. In the phase III clinical study, patients with a history of diabetes mellitus intensified anti-diabetic medication(s) while on treatment with PIQRAY; therefore, these patients require monitoring and possibly intensified anti-diabetic treatment.
Patients with poor glycemic control may be at a higher risk of developing severe hyperglycemia and associated complications. Patients with risk factors for hyperglycemia such as obesity (BMI ≥30), elevated FPG or HbA1c at or above the upper limit of normal, or age ≥75 are at a higher risk of developing severe hyperglycemia.
Schedule for monitoring fasting glucose is presented in Table 7-1 (see Monitoring and Laboratory Tests). g. excessive thirst, urinating more often than usual or higher amount of urine than usual, increased appetite with weight loss).
Correct glucose levels in patients with abnormal glucose levels before initiating PIQRAY, and closely monitor glucose levels to enable early detection and early treatment of hyperglycemia. In the METALLICA study, premedication with metformin, initiated 7 days prior to the start of treatment with PIQRAY, appeared to decrease the incidence and severity of hyperglycemia events, but increase the incidence of diarrhea, nausea, and vomiting, including Grade 3 diarrhea (see 4 DOSAGE AND ADMINISTRATION and 8 ADVERSE REACTIONS).
Premedication with metformin prior to PIQRAY plus fulvestrant treatment should be considered based on patient risk factors for hyperglycemia and gastrointestinal tolerability. Gastrointestinal Diarrhea or Colitis, nausea and vomiting Severe diarrhea and clinical consequences, such as dehydration and acute kidney injury, have been reported during treatment with PIQRAY (see 8 ADVERSE REACTIONS).
In the phase III clinical study, Grade 2 and 3 diarrhea was reported in 20% and 7% of patients treated with PIQRAY, respectively. There were no reported cases of Grade 4 diarrhea. Grade 3 gastrointestinal events (mostly diarrhea) were reported in 10% of patients and serious gastrointestinal events in 5% of patients.
Among patients with Grade 2 or 3 diarrhea, median time to onset of the first event was 54 days (range: 1 to 1731 days). , loperamide) were used in 19% and 65% of patients to manage gastrointestinal symptoms. In the phase III clinical study, dose reductions of PIQRAY were required in 6% of patients and 3% of patients permanently discontinued PIQRAY due to diarrhea.
). 2. Recommended Dose and Dosage Adjustment The recommended dose of PIQRAY is 300 mg (2×150 mg film-coated tablets) taken orally, once daily on a continuous basis. PIQRAY should be taken immediately following food, at approximately the same time each day (see 10 CLINICAL PHARMACOLOGY and 9.
DRUG INTERACTIONS). The maximum recommended daily dose of PIQRAY is 300 mg. If the 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.
When co-administered with PIQRAY, the recommended dose of fulvestrant is 500 mg administered intramuscularly on days 1, 15 and 29 and every 28 days thereafter. Please refer to the full prescribing information in the fulvestrant Product Monograph.
Treatment should continue as long as clinical benefit is observed or until unacceptable toxicity occurs. Dosing modifications may be necessary to improve tolerability. Dose modifications Management of severe or intolerable adverse drug reactions (ADRs) may require temporary dosing interruption, reduction, and/or discontinuation of PIQRAY.
The dosing reduction guidelines for ADRs are listed in Table 4-1. A maximum of 2 dosing reductions are recommended, after which the patient should be discontinued from treatment with PIQRAY (see also 14 CLINICAL TRIALS). Dose reduction should be based on worst preceding toxicity.
In the phase III study, patients who discontinued PIQRAY were to continue taking fulvestrant as per the treating physician’s clinical judgment. Table 4-1 Recommended dose reduction guidelines for adverse drug reactions PIQRAY dose level Dose and schedule Number and strength of tablets Starting dose 300 mg/day continuously 2 x 150 mg tablets First dose reduction 250 mg/day continuously1 1 x 200 mg tablet and 1 x 50 mg tablet Second dose reduction 200 mg/day continuously2 1 x 200 mg tablet 1 Only one dose reduction is permitted for pancreatitis 2 If further dose reduction below 200 mg/day is required, discontinue PIQRAY Tables 4-2, 4-3, 4-4 and 4-5 summarize recommendations for dosing interruption, reduction or discontinuation of PIQRAY in the management of specific ADRs.
, Special Populations, Geriatrics). 2. Contraindications PIQRAY is contraindicated in patients who are hypersensitive to this drug or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container.
For a complete listing, see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING. 3. Serious Warnings and Precautions Box The following serious adverse reactions were reported in patients treated with PIQRAY. • Hypersensitivity, including anaphylactic reaction (see 7 WARNINGS AND PRECAUTIONS, Immune) • Severe cutaneous adverse reactions including Stevens-Johnson Syndrome, Drug Reaction with Eosinophilia and Systemic Symptoms and Erythema Multiforme (see 7 WARNINGS AND PRECAUTIONS, Skin) • Hyperglycemia, including hyperglycemic hyperosmolar non-ketotic syndrome and some fatal cases of diabetic ketoacidosis (see 7 WARNING AND PRECAUTIONS, Endocrine and Metabolism) • Pneumonitis (see 7 WARNINGS AND PRECAUTIONS, Respiratory) 4.
Dosage and Administration Treatment with PIQRAY should be initiated by a physician experienced in the use of anticancer therapies. 1. Dosing Considerations Patients with hormone receptor (HR) positive, HER2-negative advanced breast cancer, should be selected for treatment with PIQRAY based on the presence of a PIK3CA mutation using a validated test.
There was no treatment benefit demonstrated in breast cancer patients without a PIK3CA mutation, in PIQRAY (alpelisib) Page 5 of 46 Protected B / Protégé B the phase III clinical study; therefore, treatment with PIQRAY is not recommended for these patients (see 14 CLINICAL TRIALS).
Correct glucose levels in patients with abnormal glucose levels before initiating PIQRAY, and closely monitor glucose levels to enable early detection and early treatment of hyperglycemia. , 500 mg twice daily on days 1-3, then increased to 1000 mg twice daily based on tolerability), administered 7 days prior to initiation of PIQRAY in combination with fulvestrant, should be considered based on patient risk factors for hyperglycemia and gastrointestinal tolerability (see 7 WARNINGS AND PRECAUTIONS and
). Monitoring and Laboratory Tests Patients should be monitored for Hyperglycemia. Table 7-1 Schedule of fasting glucose monitoring Recommended schedule for the monitoring of fasting glucose and HbA1c levels in all patients treated with PIQRAY Recommended schedule of monitoring of fasting glucose and HbA1c levels in patients with diabetes, pre-diabetes, BMI ≥30 or age ≥75 years treated with PIQRAY At screening, before initiating treatment with PIQRAY Test for fasting plasma glucose (FPG), HbA1c, and optimize the patient’s level of blood glucose.
After initiating treatment with PIQRAY Monitor/self-monitor fasting glucose at least once every week for the first 2 weeks, then at least once every 4 weeks, and as clinically indicated, according to the instructions of a healthcare professional*.
Monitor/self-monitor fasting glucose more frequently for the first few weeks of treatment. Then continue to monitor fasting glucose as frequently as needed to manage hyperglycemia according to the instructions of a healthcare professional*.
HbA1c should be monitored every 3 months as clinically indicated. If hyperglycemia develops after initiating treatment with PIQRAY Monitor fasting glucose regularly, as per local standard of care and at least until fasting glucose decreases to normal levels.
During treatment with antidiabetic medication, continue monitoring fasting glucose at least once a week for 8 weeks, followed by once every 2 weeks, and monitor fasting glucose according to the instructions of a healthcare professional with expertise in the treatment of hyperglycemia.
* All glucose monitoring should be performed at the physician’s discretion as clinically indicated. PIQRAY (alpelisib) Page 14 of 46 Protected B / Protégé B Musculoskeletal Osteonecrosis of the jaw (ONJ) In the phase III clinical study, osteonecrosis of the jaw (ONJ) was reported in 6% of patients in the PIQRAY plus fulvestrant arm, including 3% with a serious event.
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Colitis has been reported in the post marketing setting in patients treated with PIQRAY (see 8 ADVERSE REACTIONS). Patients should be monitored for diarrhea and additional symptoms of colitis, such as abdominal pain and mucus or blood in stool.
Based on the severity of the diarrhoea or colitis, PIQRAY may require dose interruption, reduction, or discontinuation as described in Table 4-4 (see 4 DOSAGE AND ADMINISTRATION). Dose modifications of PIQRAY are recommended in patients with Grade ≥ 2 diarrhea.
Patients should be advised to notify their healthcare provider if diarrhea or additional symptoms of colitis occur while taking PIQRAY. Patients experiencing gastrointestinal toxicity should be managed according to local standards of care, including electrolyte monitoring, administration of anti-emetics and antidiarrheal medications and/or fluid replacement and electrolyte supplements, as clinically indicated.
In case of colitis, additional treatment, such as steroids, may be considered as clinically indicated. Immune Hypersensitivity and anaphylactic reaction Serious hypersensitivity reactions including anaphylactic reaction and anaphylactic shock, manifested by symptoms including, but not limited to, dyspnoea, flushing, rash, fever or tachycardia were reported in patients treated with PIQRAY in clinical trials.
In the phase III clinical trial, hypersensitivity events were reported in 18% of patients treated with PIQRAY. The most common adverse events reported were PIQRAY (alpelisib) Page 13 of 46 Protected B / Protégé B hypersensitivity (4%), face oedema (4%) and swelling face (2%).
The incidence of serious hypersensitivity reaction was 2%. Hypersensitivity and anaphylactic reactions were more common in Asian patients compared to other races. Angioedema has been reported in the post marketing setting in patients treated with PIQRAY (see 8 ADVERSE REACTIONS).
PIQRAY should be permanently discontinued and should not be re-introduced in patients with serious hypersensitivity reactions (see 2 CONTRAINDICATIONS). Monitoring and Laboratory Tests Patients should be monitored for Hyperglycemia.
Table 7-1 Schedule of fasting glucose monitoring Recommended schedule for the monitoring of fasting glucose and HbA1c levels in all patients treated with PIQRAY Recommended schedule of monitoring of fasting glucose and HbA1c levels in patients with diabetes, pre-diabetes, BMI ≥30 or age ≥75 years treated with PIQRAY At screening, before initiating treatment with PIQRAY Test for fasting plasma glucose (FPG), HbA1c, and optimize the patient’s level of blood glucose.
After initiating treatment with PIQRAY Monitor/self-monitor fasting glucose at least once every week for the first 2 weeks, then at least once every 4 weeks, and as clinically indicated, according to the instructions of a […]
Clinical judgment of the treating physician, including confirmation of laboratory values if deemed necessary, should guide the management plan of each patient based on the individual benefit/risk assessment for treatment with PIQRAY (alpelisib) Page 6 of 46 Protected B / Protégé B PIQRAY.
Hyperglycemia PIQRAY can cause hyperglycemia. Consultation with a health professional experienced in the treatment of hyperglycemia should always be considered and is recommended for patients with fasting glucose > 250 mg/dL. Patients should be instructed on lifestyle changes that may reduce hyperglycemia.
Dose adjustment should be based on fasting glucose values (Table 4-2). In patients with risk factors for hyperglycemia, monitor fasting glucose more closely and as clinically indicated (see 7 WARNINGS AND PRECAUTIONS). 9 mmol/L No PIQRAY dose adjustment required.
Initiate or intensify oral anti-diabetic treatment2. 9 mmol/L No PIQRAY dose adjustment required. Initiate or intensify oral anti-diabetic treatment2. 9 mmol/L within 21 days with appropriate oral anti-diabetic treatment2,3, reduce PIQRAY dose by 1 dose level, and follow FG value specific recommendations.
8 mmol/L Interrupt PIQRAY. Initiate or intensify oral anti-diabetic treatment2 and consider additional anti- diabetic medications3 for 1-2 days until hyperglycemia improves, as clinically indicated. g. intervention for electrolyte/ketoacidosis/hyperosmolar disturbances).
9 mmol/L within 3 to 5 days under appropriate anti-diabetic treatment, resume PIQRAY at next lower dose level. 9 mmol/L within 3 to 5 days under appropriate anti-diabetic treatment, consultation with a physician with expertise in the treatment of hyperglycemia is recommended.
9 mmol/L within 21 days following appropriate anti-diabetic treatment2,3, permanently discontinue PIQRAY treatment. 8 mmol/L Interrupt PIQRAY. g. intervention for electrolyte/ketoacidosis/hyperosmolar disturbances)). Re-check FG within 24 hours and as clinically indicated.
8 mmol/L, then follow FG value- specific recommendations for < 500 mg/dL. 8 mmol/L, permanently discontinue PIQRAY treatment. 03. CTCAE=Common Terminology Criteria for Adverse Events. 2 Initiate applicable anti-diabetic medications, such as metformin, SGLT2 inhibitor, or insulin sensitizers (such as thiazolidinediones or dipeptidyl peptidase-4 inhibitors) and review respective prescribing information for dosing and dose titration recommendations, including local diabetic treatment guidelines.
Metformin was recommended in the phase III clinical study with the following guidance: Initiate metformin 500 mg once daily. Based on tolerability, metformin dose may be increased to 500 mg bid, […]
g. denosumab). Caution should be exercised when PIQRAY and drugs known to cause ONJ are used either simultaneously, or sequentially. PIQRAY treatment should not be initiated in patients with ongoing ONJ. Patients should be advised to promptly report any new or worsening oral symptoms (such as dental mobility, pain or swelling, non-healing of mouth sores, or discharge) during treatment with PIQRAY.
A dental examination with appropriate preventive dentistry is recommended prior to treatment with PIQRAY in patients with risk factors for ONJ, such as invasive dental procedures, concomitant therapies, poor oral hygiene and comorbid disorders.
In patients who develop ONJ, standard medical management should be initiated, including maintaining good oral hygiene, controlling pain and treating areas of infection with antibiotics and oral antibiotic mouth rinses. Patients should have appropriate nutrition and oral fluid intake.
Reproductive Health Reproduction The pregnancy status for females of reproductive potential should be verified prior to starting treatment with PIQRAY. Females of reproductive potential should be advised of the potential harm to the developing foetus (see 15 NON-CLINICAL TOXICOLOGY).
Advise sexually-active females of reproductive potential to use effective contraception (methods that result in less than 1% pregnancy rates) when using PIQRAY, during treatment and for at least 1 week after stopping treatment. It is currently unknown whether PIQRAY may reduce the effectiveness of systemically acting hormonal contraceptives.
Advise male patients with sexual partners who are pregnant, possibly pregnant, or who could become pregnant, to use condoms during sexual intercourse while taking PIQRAY and for at least 1 week after stopping treatment with PIQRAY.
Male patients are also advised not to donate or store semen during treatment and at least 1 week after the last dose of PIQRAY. Fertility There are no clinical data available on the effect of PIQRAY on human fertility. Based on repeated dose toxicity studies in animals, PIQRAY may impair fertility in males and females of reproductive potential.
In fertility studies conducted in male and female rats, similar effects were observed Respiratory Pneumonitis Pneumonitis, including serious cases of pneumonitis/acute interstitial lung disease, have been reported in clinical trials.
In the phase III clinical study, pneumonitis was reported in 5 (2%) of patients treated with PIQRAY (see 8 ADVERSE REACTIONS). Advise patients to promptly report any new or worsening respiratory symptoms. In patients who have new or worsening respiratory symptoms or are suspected PIQRAY (alpelisib) Page 15 of 46 Protected B / Protégé B to have developed pneumonitis, interrupt PIQRAY treatment 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, dyspnoea, 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. Skin Severe cutaneous adverse reactions Severe cutaneous adverse reactions have been reported with PIQRAY (see 8 ADVERSE REACTIONS). In the phase III study, Stevens-Johnson syndrome (SJS) and erythema multiforme (EM) were reported in 1 (< 1%) and 3 (1%) patients, respectively.
Drug reaction with eosinophilia and systemic symptoms (DRESS) has been reported in the post marketing setting. Do not initiate PIQRAY treatment in patients with history of severe cutaneous reactions. g. a prodrome of fever, flu-like symptoms, mucosal lesions or progressive skin rash).
If signs or symptoms of severe cutaneous adverse reactions are […]