lesions or progressive skin rash).
5.3 Hyperglycemia
Severe hyperglycemia, including ketoacidosis, has been reported in patients treated with PIQRAY.
Hyperglycemia was reported in 65% of patients treated with PIQRAY. Grade 3 (FPG > 250-500 mg/dL) andGrade 4 (FPG > 500 mg/dL) hyperglycemia was reported in 33% and 3.9% of patients, respectively.
Ketoacidosis was reported in 0.7% of patients (n = 2) treated with PIQRAY.
Among the patients who experienced Grade ≥ 2 (FPG 160-250 mg/dL) hyperglycemia, the median time to firstoccurrence of hyperglycemia was 15 days (range: 5 to 517 days).
In the 187 patients with hyperglycemia, 87% (163/187) were managed with anti-diabetic medication, and 76%(142/187) reported use of metformin as single agent or in combination with other anti-diabetic medication[i.e., insulin, dipeptidyl peptidase-4 (DPP-4) inhibitors, and sulfonylureas]. In patients with Grade ≥ 2hyperglycemia with at least 1 grade improvement (n = 153), median time to improvement from the first eventwas 8 days (range: 2 to 65 days).
In all patients with elevated FPG who continued fulvestrant treatment after discontinuing PIQRAY (n = 54),96% (n = 52) of patients had FPG levels that returned to baseline.
Before initiating treatment with PIQRAY, test FPG, HbA1c, and optimize blood glucose. After initiatingtreatment with PIQRAY, monitor blood glucose and/or FPG at least once every week for the first 2 weeks, thenat least once every 4 weeks, and as clinically indicated. Monitor HbA1c every 3 months and as clinicallyindicated.
If a patient experiences hyperglycemia after initiating treatment with PIQRAY, monitor blood glucose and/orFPG as clinically indicated, and at least twice weekly until blood glucose or FPG decreases to normal levels.
During treatment with anti-diabetic medication, continue monitoring blood glucose or FPG at least once a weekfor 8 weeks, followed by once every 2 weeks and as clinically indicated. Consider consultation with ahealthcare practitioner with expertise in the treatment of hyperglycemia and counsel patients on lifestylechanges.
The safety of PIQRAY in patients with Type 1 and uncontrolled Type 2 diabetes has not been established asthese patients were excluded from the SOLAR-1 trial. Patients with a medical history of Type 2 diabetes wereincluded. Patients with a history of diabetes mellitus may require intensified diabetic treatment. Closely monitor
patients with diabetes.
Based on the severity of the hyperglycemia, PIQRAY may require dose interruption, reduction, ordiscontinuation as described in Table 2 [see Dosage and Administration (2.3)].
Advise patients of the signs and symptoms of hyperglycemia (e.g., excessive thirst, urinating more often thanusual or higher amount of urine than usual, or increased appetite with weight loss).
5.4 Pneumonitis
Severe pneumonitis, including acute interstitial pneumonitis and interstitial lung disease, has been reported inpatients treated with PIQRAY.
Pneumonitis was reported in 1.8% of patients treated with PIQRAY.
In patients who have new or worsening respiratory symptoms or are suspected to have developed pneumonitis,interrupt PIQRAY immediately and eva luate the patient for pneumonitis. Consider a diagnosis of non-infectiouspneumonitis in patients presenting with non-specific respiratory signs and symptoms such as hypoxia, cough,
dyspnea, or interstitial infiltrates on radiologic exams and in whom infectio |
