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PIK3CA Inhibitor

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PIK3CA Inhibitor, Phosphatidylinositol 3-Kinase Catalytic Alpha Inhibitor, Phosphatidylinositol 3-kinase Inhibitor, Phosphoinositide 3-Kinase Inhibitor, PI3K Inhibitor, Alpelisib, Piqray, Copanlisib, Aliqopa, Duvelisib, Copiktra, Idelalisib, Zydelig

  • See Also
  1. Small Molecule Inhibitor-Mediated Chemotherapy
  2. Chemotherapy
  • Indications
  1. Breast Cancer (PIK3CA mutation, HR positive, HER2 negative, metastatic)
    1. Alpelisib
  2. Follicular Lymphoma (relapsed)
    1. Copanlisib
    2. Duvelisib
    3. Idelalisib
  3. Chronic Lymphocytic Leukemia (relapsed or refractory)
    1. Duvelisib
    2. Idelalisib
  4. Small Lymphocytic Leukemia (relapsed or refractory)
    1. Duvelisib
    2. Idelalisib
  • Mechanism
  1. Phosphatidylinositol 3-Kinase Catalytic Alpha (PIK3CA)
    1. PIK3CA gene encodes for Phosphatidylinositol 3-kinases (PI3K), key to cell growth, development and survival
  2. Phosphatidylinositol 3-kinase (PI3K)
    1. Growth factors bind and activate PI3K Tyrosine Kinase, triggering synthesis of PIP3 as a secondary messenger
    2. PIP3 drives many cell processes, including growth, development, apoptosis, adhesion and motility
  3. PI3K Inhibitors
    1. Block various subunits (alpha, delta) to impact cancer growth, function, proliferation and antineoplastic resistance
  • Medications
  1. Alpelisib (Piqray)
    1. PI3K Inhibitor of the alpha subunit
    2. Risk of Hypersensitivity Reaction, severe rash (SJ/TEN), Hyperglycemia, pneumonitis, severe Diarrhea
    3. Take with food (absorption increased >70%)
    4. Avoid with Strong CYP3A4 Inducers
  2. Copanlisib (Aliqopa)
    1. PI3K Inhibitor of the alpha and delta subunits
    2. Inhibits B-Cell receptor-mediated signaling and B-Cell chemotaxis
    3. Also inhibits NFkB signaling
    4. Risk of Neutropenia, severe infections, Hyperglycemia, Severe Hypertension, pneumonitis and severe rash (SJ/TEN)
    5. Consider PJP Prophylaxis
    6. Avoid with Strong CYP3A4 Inducers, and reduce dose with strong CYP3A4 inhibitors
  3. Duvelisib (Copiktra)
    1. PI3K Inhibitor of the alpha and delta subunits
    2. Risk of colitis and severe Diarrhea, Neutropenia, severe infections, pneumonitis, hepatotoxicity and severe rash (SJ/TEN)
    3. Consider PJP Prophylaxis
  4. Idelalisib (Zydelig)
    1. PI3K Inhibitor of the delta subunit
    2. Risk of colitis and severe Diarrhea, Neutropenia, severe infections, pneumonitis, hepatotoxicity, Hypersensitivity, severe rash
  • Dosing
  1. See other references for disease specific dosing protocols
  • Safety
  1. Avoid in Lactation
    1. Continue to avoid Lactation for at least 1 month after last dose of Duvelisib
  2. Avoid in pregnancy (all trimesters, pregnancy category X)
    1. Use reliable Contraception
  3. Monitoring
    1. Complete Blood Count
    2. Blood Glucose
    3. Blood Pressure (Copanlisib)
    4. Liver Function Tests (Idelalisib, Duvelisib)
  • Adverse Effects
  1. Severe Hypersensitivity Reaction (Alpelisib, Idelalisib)
  2. Severe dermatologic reactions (Alpelisib, Copanlisib, Duvelisib, Idelalisib)
    1. Stevens-Johnson Syndrome or Toxic Epidermal Necrolysis
    2. DRESS Syndrome (Duvelisib)
  3. Hyperglycemia including Ketoacidosis (Alpelisib, Copanlisib)
  4. Severe Diarrhea or colitis (Alpelisib, Duvelisib, Idelalisib)
  5. Pneumonitis or Interstitial Lung Disease (Alpelisib, Copanlisib, Idelalisib)
  6. Neutropenia and Severe Infections, esp. Pneumonia, Sepsis (Copanlisib, Duvelisib, Idelalisib)
    1. Consider PJP Prophylaxis
  7. Severe Hypertension (Copanlisib)
  8. Hepatotoxicity with transaminase increase (Idelalisib, Duvelisib)
  • Drug Interactions
  1. Strong CYP3A4 Inducers
    1. Avoid with Alpelisib, Copanlisib, Duvelisib
  2. Strong CYP3A4 Inhibitors
    1. Decrease Copanlisib or Duvelisib dose
  3. CYP3A4 Substrates with narrow Therapeutic Index
    1. Observe for toxicity with Duvelisib
  4. BCRP Inhibitors
    1. Avoid with Alpelisib
  • Resources
  1. Alpelisib (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b20b4e18-7a4b-4500-a08f-06c6dab0ee5b
  2. Copanlisib (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b20b4e18-7a4b-4500-a08f-06c6dab0ee5b
  3. Duvelisib (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e3c5ac56-e1f6-473a-bc73-687836534780
  4. Idelalisib (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=efbdafa9-d18c-4e85-b4a2-1e620fc74e50
  • References
  1. Castel (2021) Nat Cancer 2(6):587-97 +PMID: 35118422 [PubMed]