ans of appropriate investigations.
Permanently discontinue PIQRAY in all patients with confirmed pneumonitis.
Advise patients to immediately report new or worsening respiratory symptoms.
5.5 Diarrhea
Severe diarrhea, including dehydration and acute kidney injury, occurred in patients treated with PIQRAY.
Most patients (58%) experienced diarrhea during treatment with PIQRAY. Grade 3 diarrhea occurred in 7%(n = 19) of patients. Among patients with Grade 2 or 3 diarrhea (n = 71), the median time to onset was 46 days(range: 1 to 442 days).
Dose reductions of PIQRAY were required in 6% of patients and 2.8% of patients permanently discontinuedPIQRAY due to diarrhea. In the 164 patients that experienced diarrhea, anti-diarrheal medications(e.g., loperamide) were required to manage symptoms in 63% (104/164) of these patients.
Based on the severity of the diarrhea, PIQRAY may require dose interruption, reduction, or discontinuation asdescribed in Table 4 [see Dosage and Administration (2.3)].
Advise patients to start antidiarrheal treatment, increase oral fluids, and notify their healthcare provider ifdiarrhea occurs while taking PIQRAY.
5.6 Embryo-Fetal Toxicity
Based on findings in animals and its mechanism of action, PIQRAY can cause fetal harm when administered toa pregnant woman. In animal reproduction studies, oral administration of alpelisib to pregnant rats and rabbitsduring organogenesis caused adverse developmental outcomes including embryo-fetal mortality (postimplantation
loss), reduced fetal weights, and increased incidences of fetal malformations at maternal exposuresbased on area under the curve (AUC) that were ≥ 0.8 times the exposure in humans at the recommended dose of300 mg/day. Advise pregnant women and females of reproductive potential of the potential risk to a fetus.
Advise females of reproductive potential to use effective contraception during treatment with PIQRAY and for1 week after the last dose. Advise male patients with female partners of reproductive potential to use condomsand effective contraception during treatment with PIQRAY and for 1 week after the last dose [see Use in
Specific Populations (8.1, 8.3) and Clinical Pharmacology (12.1)].
Refer to the Full Prescribing Information of fulvestrant for pregnancy and contraception information.
6 ADVERSE REACTIONS
The following adverse reactions are discussed in greater detail in other sections of the labeling:
Severe Hypersensitivity [see Warnings and Precautions (5.1)]
Severe Cutaneous Reactions [see Warnings and Precautions (5.2)]
Hyperglycemia [see Warnings and Precautions (5.3)]
Pneumonitis [see Warnings and Precautions (5.4)]
Diarrhea [see Warnings and Precautions (5.5)]
6.1 Clinical Trial Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in theclinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may notreflect the rates observed in practice.
The safety of PIQRAY was eva luated in a randomized, double-blind, placebo-controlled trial (SOLAR-1) in571 patients with HR-positive, HER2-negative, advanced or metastatic breast cancer enrolled into two cohorts,with or without a PIK3CA mutation [see Clinical Studies (14)].
Patients received either PIQRAY 300 mg plus fulvestrant (n = 284) or placebo plus fulvestrant (n |
