* 2.4 0
*Pruritus 18 0.7* 6 0
*Dry skin8 18 0.4* 3.8 0
*Grading according to CTCAE Version 4.03
1 Stomatitis: including stomatitis, aphthous ulcer and mouth ulceration
2 Abdominal pain: abdominal pain, abdominal pain upper, abdominal pain lower
3 Fatigue: including fatigue, asthenia
4 Mucosal dryness: including dry mouth, mucosal dryness, vulvovaginal dryness
5 Urinary tract infection: including UTI and single case of urosepsis
6 Dysgeusia: including dysgeusia, ageusia, hypogeusia
7 Rash: including rash, rash maculo-papular, rash macular, rash generalized, rash papular, rash pruritic
8 Dry skin: including dry skin, skin fissures, xerosis, xeroderma
* No Grade 4 adverse reactions were reported.
Among the patients with Grade 2 or 3 rash, the median time to first onset of Grade 2 or 3 rash was 12 days. Asubgroup of 86 patients received prophylaxis, including anti-histamines, prior to onset of rash. In these patients,rash was reported less frequently than in the overall population, for all grades rash (27% vs 54%), Grade 3 rash(12% vs 20%) and rash leading to permanent discontinuation of PIQRAY (3.5% vs 4.2%). Of the 153 patientsho experienced rash, 141 had resolution of the rash.
Table 7: Laboratory Abnormalities Occurring in ≥ 10% of Patients in SOLAR-1
PIQRAY plus fulvestrant
N = 284
Placebo plus fulvestrant
N = 287
Laboratory Abnormality
All Grades
%
Grade 3-4
%
All Grades
%
Grade 3-4
%
Hematological parameters
Lymphocyte count decreased 52 8 40 4.5*
Hemoglobin decreased 42 4.2* 29 1
*Activated Partial Thromboplastin Time (aPTT)
prolonged
21 0.7* 16 0.3*
Platelet count decreased 14 1.1 6 0
*Biochemical parameters
Glucose increased1 79 39 34 1
Creatinine increased 67 2.8* 25 0.7*
Gamma Glutamyl Transferase (GGT) increased 52 11 44 10
Alanine Aminotransferase (ALT) increased 44 3.5 34 2.4*
Lipase increased 42 7 25 6
Calcium (corrected) decreased 27 2.1 20 1.4
Glucose decreased 26 0.4 14 0
*
Potassium decreased 14 6 2.8 0.7*
Albumin decreased 14 0
* 8 0
*Magnesium decreased 11 0.4* 4.2 0
*1Glucose increase is an expected laboratory abnormality of PI3K inhibition.
*No Grade 4 laboratory abnormalities were reported.
7 DRUG INTERACTIONS
7.1 Effect of Other Drugs on PIQRAY
CYP3A4 Inducer
Coadministration of PIQRAY with a strong CYP3A4 inducer may decrease alpelisib concentration [seeClinical Pharmacology (12.3)], which may decrease alpelisib activity. Avoid coadministration of PIQRAY withstrong CYP3A4 inducers.
BCRP Inhibitors
Coadministration of PIQRAY with a BCRP inhibitor may increase alpelisib concentration [see ClinicalPharmacology (12.3)], which may increase the risk of toxicities. Avoid the use of BCRP inhibitors in patientstreated with PIQRAY. If unable to use alternative drugs, when PIQRAY is used in combination with BCRPinhibitors, closely monitor for increased adverse reactions.
7.2 Effect of PIQRAY on Other Drugs
CYP2C9 Substrates
Coadministration of PIQRAY with CYP2C9 substrates (e.g., warfarin) may reduce plasma concentration ofthese drugs [see Clinical Pharmacology (12.3)]. Closely monitor when PIQRAY is used in combination withCYP2C9 subsstrates where decreases in the plasma concentration of CYP2C9 substrates may reduce activity ofthese drugs.
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Risk Summary
PIQRAY is used in combination with ful |
