d as clinically indicated.
If FPG decreases to ≤ 500 mg/dL or 27.8 mmol/L, follow FPG value specific recommendations forGrade 3.
If FPG is confirmed at > 500 mg/dL or 27.8 mmol/L, permanently discontinue PIQRAY treatment.
1FPG/Blood Glucose/Grade levels reflect hyperglycemia grading according to CTCAE Version 4.03 (CTCAE=Common Terminology Criteria forAdverse Events)2
Initiate applicable anti-diabetic medications, including metformin and insulin sensitizers (such as thiazolidinediones or dipeptidyl peptidase-4inhibitors), and review respective prescribing information for dosing and dose titration recommendations, including local diabetic treatmentguidelines. Metformin was recommended in the SOLAR-1 trial with the following guidance: Initiate metformin 500 mg once daily. Based ontolerability, metformin dose may be increased to 500 mg twice daily, followed by 500 mg with breakfast, and 1000 mg with dinner, followed byfurther increase to 1000 mg twice daily if needed [see Warnings and Precautions (5.3)].
3As recommended in the SOLAR-1 trial, insulin may be used for 1-2 days until hyperglycemia resolves. However, this may not be necessary inthe majority of PIQRAY-induced hyperglycemia, given the short half-life of PIQRAY and the expectation of glucose levels normalizing afterinterruption of PIQRAY.
Rash
Table 3: Dose Modification and Management for Rash
Grade1,2 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.
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.
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.
Once improved to ≤ Grade 1, resume PIQRAY at the same dose level for first occurrence ofrash, 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; lifethreatening
consequences)
Permanently discontinue PIQRAY.
1Grading according to CTCAE Version 5.0
2For all grades of rash, consider consultation with a dermatologist.
3Antihistamines administered prior to rash onset may decrease incidence and severity of rash based on the SOLAR-1 trial.
Diarrhea
Table 4: Dose Modification and Management for Diarrhea
Grade1 Recommendation
Grade 1 No PIQRAY dose adjustment is required. Initiate appropriate medical therapy and monitor as clinicallyindicated.
Grade 2 Initiate or intensify appropriate medical therapy and monitor as clinically indicated. Interrupt PIQRAY doseuntil 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 doseuntil recovery to Grade ≤ 1, then resume PIQRAY at the next lower dose level.
1Grading according to CTCAE Version 5.0.
Other Toxicities
Table 5: Dose Modifica |
