Source: FDA, National Drug Code (US) Revision Year: 2020
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.
Select patients for the treatment of HR-positive, HER2-negative advanced or metastatic breast cancer with PIQRAY, based on the presence of one or more PIK3CA mutations in tumor tissue or plasma specimens [see Clinical Studies (14)]. If no mutation is detected in a plasma specimen, test tumor tissue. Information on FDA-approved tests for the detection of PIK3CA mutations in breast cancer is available at: http://www.fda.gov/CompanionDiagnostics.
The recommended dose of PIQRAY is 300 mg (two 150 mg film-coated tablets) taken orally, once daily, with food [see Clinical Pharmacology (12.3)].
Continue treatment until disease progression or unacceptable toxicity occurs [see Dosage and Administration (2.3)].
Patients should take their dose of PIQRAY at approximately the same time each day.
Swallow PIQRAY tablets whole (tablets should not be chewed, crushed or split prior to swallowing). No tablet should be ingested if it is broken, cracked, or otherwise not intact.
If a dose of PIQRAY is missed, it can be taken with food within 9 hours after the time it is usually taken. After more than 9 hours, skip the dose for that day. The next day, take PIQRAY at the usual time.
If the patient vomits after taking the dose, advise the patient not to take an additional dose on that day, and to resume the dosing schedule the next day at the usual time.
When given with PIQRAY, the recommended dose of fulvestrant is 500 mg administered on Days 1, 15, and 29, and once monthly thereafter. Refer to the Full Prescribing Information for fulvestrant.
The recommended dose modifications for adverse reactions (ARs) are listed in Table 1.
Table 1. PIQRAY Dose Reduction Guidelines for Adverse Reactions 1:
| PIQRAY Dose Level | Dose and Schedule | Number and Strength of Tablets |
|---|---|---|
| Starting dose | 300 mg once daily | Two 150 mg tablets |
| First-dose reduction | 250 mg once daily | One 200 mg tablet and one 50 mg tablet |
| Second-dose reduction | 200 mg once daily 2 | One 200 mg tablet |
1 Only one dose reduction is permitted for pancreatitis
2 If further dose reduction below 200 mg once daily is required, discontinue PIQRAY.
Tables 2, 3, 4, and 5 summarize recommendations for dose interruption, reduction, or discontinuation of PIQRAY in the management of specific ARs.
If a severe cutaneous adverse reaction (SCAR) is confirmed, permanently discontinue PIQRAY. Do not reintroduce PIQRAY in patients who have experienced previous SCAR during PIQRAY treatment [see Warnings and Precautions (5.2)].
Table 2. Dose Modification and Management for Rash and Severe Cutaneous Adverse Reactions (SCARs):
[see Warnings and Precautions (5.1, 5.2)]
| Grade 1,2 | Recommendation3 |
|---|---|
| Grade 1 (< 10% body surface area (BSA) with active skin toxicity) | No PIQRAY dose adjustment required. Initiate topical corticosteroid treatment. Consider adding oral antihistamine to manage symptoms. If the etiology is SCAR, permanently discontinue PIQRAY. |
| Grade 2 (10%-30% BSA with active skin toxicity) | No PIQRAY dose adjustment required. Initiate or intensify topical corticosteroid and oral antihistamine treatment. Consider low dose systemic corticosteroid treatment. If the etiology is SCAR, permanently discontinue PIQRAY. |
| Grade 3 (e.g., severe rash not responsive to medical management) (> 30% BSA with active skin toxicity) | Interrupt PIQRAY. Initiate or intensify topical/systemic corticosteroid and oral antihistamine treatment. If the etiology is SCAR, permanently discontinue PIQRAY. If the etiology is not a SCAR, interrupt dose until recovery to Grade ≤ 1, then resume PIQRAY at same dose level for first occurrence of rash, or at next lower dose level in case of second occurrence. |
| Grade 4 (e.g., severe bullous, blistering or exfoliating skin conditions) (any % BSA associated with extensive superinfection, with IV antibiotics indicated; life-threatening consequences) | Permanently discontinue PIQRAY. |
1 Grading according to Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0.
2 For all grades of rash, consider consultation with a dermatologist.
3 Antihistamines administered prior to rash onset may decrease incidence and severity of rash based on the SOLAR-1 trial.
Table 3. Dose Modification and Management for Hyperglycemia:
[see Warnings and Precautions (5.3)]
| Fasting Plasma Glucose (FPG)/Fasting Blood Glucose Values1 | Recommendation |
|---|---|
| Dose modifications and management should only be based on fasting glucose values (FPG or fasting blood glucose) | |
| Grade 1 Fasting glucose > ULN -160 mg/dL or > ULN -8.9 mmol/L | No PIQRAY dose adjustment required. Initiate or intensify anti-diabetic treatment 2. |
| Grade 2 Fasting glucose > 160-250 mg/dL or > 8.9-13.9 mmol/L | No PIQRAY dose adjustment required. Initiate or further intensify anti-diabetic treatment 2. If fasting glucose does not decrease to ≤ 160 mg/dL or 8.9 mmol/L within 21 days under appropriate anti-diabetic treatment, reduce PIQRAY dose by 1 dose level and follow fasting glucose value specific recommendations. |
| Grade 3 > 250-500 mg/dL or > 13.9-27.8 mmol/L | Interrupt PIQRAY. Initiate or intensify oral anti-diabetic treatment 2 and consider additional anti-diabetic medications 3 for 1-2 days until hyperglycemia improves. Administer intravenous hydration and consider appropriate treatment (e.g., intervention for electrolyte/ketoacidosis/hyperosmolar disturbances). If fasting glucose decreases to ≤ 160 mg/dL or 8.9 mmol/L within 3 to 5 days under appropriate anti-diabetic treatment, resume PIQRAY at 1 lower dose level. If fasting glucose does not decrease to ≤ 160 mg/dL or 8.9 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. If fasting glucose does not decrease to ≤ 160 mg/dL or 8.9 mmol/L within 21 days following appropriate anti-diabetic treatment 2, permanently discontinue PIQRAY treatment. |
| Grade 4 > 500 mg/dL or ≥ 27.8 mmol/L | Interrupt PIQRAY. Initiate or intensify appropriate anti-diabetic treatment 2 (administer intravenous hydration and consider appropriate treatment (e.g., intervention for electrolyte/ketoacidosis/hyperosmolar disturbances)), re-check fasting glucose within 24 hours and as clinically indicated. If fasting glucose decreases to ≤ 500 mg/dL or 27.8 mmol/L, follow fasting glucose value specific recommendations for Grade 3. If fasting glucose is confirmed at > 500 mg/dL or 27.8 mmol/L, permanently discontinue PIQRAY treatment. |
Abbreviation: ULN, upper limit of normal.
1 FPG/Fasting Blood Glucose/Grade levels reflect hyperglycemia grading according to Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03.
2 Initiate applicable anti-diabetic medications, including metformin and 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 SOLAR-1 trial with the following guidance: Initiate metformin 500 mg once daily. Based on tolerability, metformin dose may be increased to 500 mg twice daily, followed by 500 mg with breakfast, and 1000 mg with dinner, followed by further increase to 1000 mg twice daily if needed [see Warnings and Precautions (5.3)].
3 As recommended in the SOLAR-1 trial, insulin may be used for 1-2 days until hyperglycemia resolves. However, this may not be necessary in the majority of PIQRAY-induced hyperglycemia, given the short half-life of PIQRAY and the expectation of glucose levels normalizing after interruption of PIQRAY.
Table 4. Dose Modification and Management for Diarrhea:
[see Warnings and Precautions (5.5)]
| Grade1 | Recommendation |
|---|---|
| Grade 1 | No PIQRAY dose adjustment is required. Initiate appropriate medical therapy and monitor as clinically indicated. |
| Grade 2 | Initiate or intensify appropriate medical therapy and monitor as clinically indicated. Interrupt PIQRAY dose until recovery to Grade ≤ 1, then resume PIQRAY at same dose level. |
| Grade 3 and 4 | Initiate or intensify appropriate medical therapy and monitor as clinically indicated. Interrupt PIQRAY dose until recovery to Grade ≤ 1, then resume PIQRAY at the next lower dose level. |
1 Grading according to CTCAE Version 5.0.
Table 5. Dose Modification and Management for Other Toxicities (Excluding Hyperglycemia, Rash, and Diarrhea):
| Grade1 | Recommendation |
|---|---|
| Grade 1 or 2 | No PIQRAY dose adjustment is required. Initiate appropriate medical therapy and monitor as clinically indicated 2, 3. |
| Grade 3 | Interrupt PIQRAY dose until recovery to Grade ≤ 1, then resume PIQRAY at the next lower dose level. |
| Grade 4 | Permanently discontinue PIQRAY. |
1 Grading according to CTCAE Version 5.0.
2 For Grade 2 and 3 pancreatitis, interrupt PIQRAY dose until recovery to Grade < 2 and resume at next lower-dose level. Only one dose reduction is permitted. If toxicity reoccurs, permanently discontinue PIQRAY treatment.
3 For Grade 2 total bilirubin elevation, interrupt PIQRAY dose until recovery to Grade ≤ 1 and resume at the same dose if resolved in ≤ 14 days or resume at the next lower dose level if resolved in > 14 days.
Refer to the Full Prescribing Information of fulvestrant for dose modification guidelines in the event of toxicity and for other relevant safety information.
There is limited experience of overdose with PIQRAY in clinical trials. In the clinical studies, PIQRAY was administered at doses up to 450 mg once daily.
In cases where accidental overdosage of PIQRAY was reported in the clinical studies, the adverse reactions associated with the overdose were consistent with the known safety profile of PIQRAY and included hyperglycemia, nausea, asthenia, and rash.
Initiate general symptomatic and supportive measures in all cases of overdosage where necessary. There is no known antidote for PIQRAY.
Store at 20°C to 25°C (68°F to 77°F), excursions permitted between 15°C and 30°C (59°F and 86°F) [see USP Controlled Room Temperature].
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