Prescribing information

 

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Safety profile for PIQRAY® + fulvestrant from the SOLAR-1 Phase 3 clinical trial.

If you would like to discuss management of your patients on PIQRAY® + fulvestrant, please click here to contact a Novartis representative.

The safety profile of PIQRAY® + fulvestrant can be managed through dose reductions or interruptions or proactive treatment of adverse events (AEs)1

  • Serious AEs associated with PIQRAY® include hyperglycaemia, hypersensitivity (including anaphylactic reaction), severe cutaneous reactions, pneumonitis, osteonecrosis of the jaw and diarrhoea1,2
  • Hyperglycaemia is an expected, on-target effect of PI3K inhibition. Consequently, PIQRAY® should not be prescribed to Type 1 or uncontrolled Type 2 diabetes patients1–4†

Type 1 and Type 2 diabetes defined by the Diabetes UK.

AEs occurring in the SOLAR-1  Phase 3 trial1

Median duration of exposure in the PIQRAY® arm was 5.5 months and 8.2 months for PIQRAY® and fulvestrant, respectively. Median duration of exposure in the placebo arm was 5.6 months and 5.6 months for placebo and fulvestrant, respectively.5

Adverse event Any grade (%) Grade 3 or 4 (%)
Infections and infestations
Urinary tract infectiona Very common 29 (10.2) 2 (0.7)*
Blood and lymphatic system disorders
Anaemia Very common 125 (44.0) 14 (4.9)*
Lymphocyte count decreased Very common 157 (55.3) 26 (9.2)
Platelet count decreased Very common 43 (15.1) 4 (1.4)*
Immune system disorders
Hypersensitivityb Common 11 (3.9) 2 (0.7)*
Metabolism and nutrition disorders
Glucose plasma increased Very common 225 (79.2) 111 (39.1)
Glucose plasma decreased Very common 76 (26.8) 1 (0.4)
Decreased appetite Very common 102 (35.9) 2 (0.7)*
Hypokalaemia Very common 42 (14.8) 18 (6.3)
Hypocalcaemia Very common 79 (27.8) 6 (2.1)
Magnesium decreased Very common 34 (12.0) 1 (0.4)
Dehydration Common 10 (3.5) 1 (0.4)*
Ketoacidosisc Uncommon 2 (0.7) 2 (0.7)
Hyperglycaemic hyperosmolar
nonketotic syndrome (HHNKS)#
Not known Not known Not known
Psychiatric disorders
Insomnia Common 22 (7.7)  
Nervous system disorders
Headache Very common 55 (19.4) 2 (0.7)*
Dysgeusiad Very common 44 (15.5) 1 (0.4)*
Eye disorders
Vision blurred Common 15 (5.3) 1 (0.4)*
Dry eye Common 10 (3.5)  
Vascular disorders
Hypertension Common 27 (9.5) 13 (4.6)
Lymphoedema Common 16 (5.6)  
Respiratory, thoracic and mediastinal disorders
Pneumonitise Common 5 (1.8) 1 (0.4)*
Gastrointestinal disorders
Diarrhoea Very common 169 (59.5) 20 (7.0)*
Nausea Very common 133 (46.8) 8 (2.8)*
Stomatitisf Very common 86 (30.3) 7 (2.5)*
Vomiting Very common 81 (28.5) 2 (0.7)*
Abdominal pain Very common 50 (17.6) 4 (1.4)*
Dyspepsia Very common 33 (11.6)  
Toothache Common 13 (4.6) 1 (0.4)*
Gingivitis Common 11 (3.9) 1 (0.4)*
Gingival pain Common 9 (3.2)  
Cheilitis Common 8 (2.8)  
Pancreatitis Uncommon 1 (0.4) 1 (0.4)
Skin and subcutaneous tissue disorders
Rashg Very common 147 (51.8) 55 (19.4)*
Alopecia Very common 58 (20.4)  
Pruritus Very common 53 (18.7) 2 (0.7)*
Dry skinh Very common 53 (18.7) 1 (0.4)*
Erythemai Common 18 (6.3) 2 (0.7)*
Dermatitisj Common 10 (3.5) 2 (0.7)*
Palmar-plantar erythrodysaesthesia
syndrome
Common 5 (1.8)  
Erythema multiforme Common 3 (1.1) 2 (0.7)*
Stevens–Johnson syndrome Uncommon 1 (0.4) 1 (0.4)*
Drug reaction with eosinophilia
and systemic symptoms (DRESS)#
Not known Not known Not known
Musculoskeletal and connective tissue disorders
Muscle spasms Common 22 (7.7)  
Myalgia Common 19 (6.7) 1 (0.4)*
Osteonecrosis of jaw Common 16 (5.6) 5 (1.8)*
Renal and urinary disorders
Acute kidney injury Common 16 (5.6) 5 (1.8)
General disorders and administration site conditions
Fatiguek Very common 123 (43.3) 16 (5.6)*
Mucosal inflammation Very common 56 (19.7) 6 (2.1)*
Oedema peripheral Very common 47 (16.5)  
Pyrexia Very common 45 (15.8) 2 (0.7)
Mucosal drynessl Very common 36 (12.7) 1 (0.4)
Oedemam Common 18 (6.3)  
Investigations
Weight decreased Very common 79 (27.8) 15 (5.3)*
Blood creatinine increased Very common 192 (67.6) 8 (2.8)*
Gamma-glutamyltransferase increased Very common 151 (53.2) 34 (12.0)
Alanine aminotransferase increased Very common 125 (44.0) 12 (4.2)*
Lipase increased Very common 121 (42.6) 20 (7.0)
Activated partial thromboplastin time
(aPTT) prolonged
Very common 63 (22.2) 2 (0.7)
Albumin decreased Very common 41 (14.4) 1 (0.4)
Glycosylated haemoglobin increased Common 8 (2.8) 0
a. Urinary tract infection: also includes a single case of urosepsis h. Dry skin: also includes skin fissures, xerosis, xeroderma
b. Hypersensitivity: also includes allergic dermatitis i. Erythema: also includes erythema generalised
c. Ketoacidosis: also includes diabetic ketoacidosis j. Dermatitis: also includes dermatitis acneiform
d. Dysgeusia: also includes ageusia, hypogeusia k. Fatigue: also includes asthenia
e. Pneumonitis: also includes interstitial lung disease l. Mucosal dryness: also includes dry mouth, vulvovaginal dryness
f. Stomatitis: also includes aphthous ulcer and mouth ulceration m. Oedema: also includes face swelling, face oedema, eyelid oedema
g. Rash: also includes rash maculopapular, rash macular, rash generalised, rash papular, rash pruritic  

*No grade 4 AEs were observed

#AEs reported during post-marketing experience. These are derived from spontaneous reports for which it is not always possible to reliably establish frequency or a causal relationship to exposure to the medicinal product.

  • AEs were managed with additional therapy (97.5% vs 70.0% of patients),5 dose interruptions (68.6% vs 15.8%) and dose reductions (62.1% vs 4.7%) in patients treated with PIQRAY® + fulvestrant (n=169) vs placebo + fulvestrant (n=171), respectively6
    • In the 190 patients with hyperglycaemia, 87.4% (166/190) were managed with antidiabetic medication, and 75.8% (144/190) of patients reported use of metformin as single agent or in combination with other antidiabetic medication (e.g. insulin, dipeptidyl peptidase-4 (DPP-4) inhibitors, SGLT2 inhibitors and sulfonylureas)1
    • Among the 169 patients who experienced diarrhoea, antidiarrhoeal medications (e.g. loperamide) were required to manage symptoms in 64.5% (109/169)1
      • Concomitant treatment with metformin did not increase the incidence or severity of diarrhoea7
    • Of the 134 patients in the PIQRAY® + fulvestrant arm who received antirash medication, corticosteroids and antihistamines were the most used (in 84.3% and 76.9%, respectively)7
  • Certain AEs may require dose modifications
    • Dose interruptions may be required prior to dose reductions
  • Among patients treated with PIQRAY® + fulvestrant, 25.0% of patients discontinued treatment due to AEs compared with 4.2% treated with placebo + fulvestrant3
  • Severe hyperglycaemia, in some cases associated with hyperglycaemic hyperosmolar nonketotic syndrome (HHNKS) or ketoacidosis, has been observed in patients treated with Piqray. Some cases of ketoacidosis with fatal outcome have been reported in the post-marketing setting.1

 

 

No patients discontinued placebo + fulvestrant due to these AEs.

 

Screenshot from the video: Professor Caroline Robert discusses the landmark 5-year data with Tafinlar + Mekinist

THERAPY MANAGEMENT GUIDE

Please see the therapy management guide for more details on managing AEs with PIQRAY® + fulvestrant.

View resources 

 

AEs, adverse events; PI3K, phosphoinositide 3-kinase.

References   

  1. PIQRAY® (alpelisib) Summary of Product Characteristics. Novartis Pharma; 2021.     
  2. PIQRAY® (alpelisib) Core Data Sheet: Version 1.0. Novartis Pharma AG; November 2018.     
  3. André F, et al. N Engl J Med 2019;380(20):1929−1940.     
  4. Goncalves MD, Hopkins BD, Cantley LC. N Engl J Med 2018;379(21):2052−2062.     
  5. SOLAR-1 Clinical Study Report. Novartis data on file.     
  6. André F, et al. N Engl J Med 2019;380(20):1929–1940. Supplementary Appendix.     
  7. Rugo HS, et al. 324P. Presented at ESMO; 27 September−1 October 2019; Barcelona, Spain.
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UK | June 2021 | 134756
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Adverse events should be reported. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard. Adverse events should also be reported to Novartis via [email protected] or online through the pharmacovigilance intake (PVI) tool at www.report.novartis.com
If you have a question about the product, please contact Medical Information on 01276 698370 or by email at [email protected]