II. Indications
- Mantle Cell Lymphoma (Acalabrutinib's only FDA approved indication)
- Chronic Lymphocytic Leukemia (17p deletion)
- Waldenstrom's Macroglobulinemia
- Marginal Zone Lymphoma
- Chronic Graft versys host disease
III. Contraindications
- Baseline hepatic Insufficiency (Ibrutinib)
IV. Mechanism
- Bruton's Tyrosine Kinase (BTK)
- BTK is part of group of src-related BTK/Tec, cytoplasmic Tyrosine Kinases
- BTK is key to B Cell receptor signaling and B Cell maturation
- BTK Is overexpressed in some B Cell malignancies, which facilitates their proliferation
- BTK Inhibitor (Bruton Tyrosine Kinase Inhibitor)
- Orally active, small molecules that irreversibly bind and inhibit BTK
- Blocks B-Cell Activation and B-Cell mediated signaling
- Greatest effect is on malignant B Cells that overexpress BTK
- BTK Inhibitors also affect normal B Cells, and are used in chronic Graft Versus Host Disease
V. Medications
- Acalabrutinib (Calquence)
- Risks include secondary malignancy, myelosuppression (bleeding and infection risk), Atrial Fibrillation
- Avoid with strong CYP3A Inhibitors and Inducers (and adjust dose with moderate agents)
- Avoid Proton Pump Inhibitors (and spaced dosing of H2 Blockers) with Acalabrutinib
- Ibrutinib (Imbruvica)
- Risks include secondary malignancy, myelosuppression (bleeding and infection risk), Atrial Fibrillation
- Other risks include Tumor Lysis Syndrome
- Avoid with strong CYP3A Inhibitors and Inducers (and adjust dose with moderate agents)
- Avoid in hepatic insufficiency
VI. Dosing
- See other references for disease specific dosing protocols
VII. Adverse Effects
- Myelosuppression (all agents)
- Neutropenia (and infection risk)
- Thrombocytopenia (and Bleeding Diathesis)
- Secondary primary malignancies including Skin Cancer (all agents)
- Atrial Fibrillation or Atrial Flutter (all agents)
- Hypertension (Ibrutinib)
- Tumor Lysis Syndrome (Ibrutinib)
- Other adverse effects
VIII. Safety
- Avoid in Lactation
- Avoid in pregnancy (all trimesters, pregnancy category X)
- Use reliable Contraception
- Monitoring
- Complete Blood Count
- Electrocardiogram (EKG) for Atrial Fibrillation or flutter
- Secondary malignancy surveillance including skin exams
IX. Drug Interactions
- Strong CYP3A Inhibitors and Inducers
- Avoid strong inhibitor and inducers with Acalabrutinib or Ibrutinib
- Adjust dosing with moderate inhibitors and inducers
-
Antacids
- Avoid Proton Pump Inhibitors (and spaced dosing of H2 Blockers) with Acalabrutinib
X. Resources
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Related Studies
Definition (NCI) | An orally bioavailable, small-molecule inhibitor of Bruton's tyrosine kinase (BTK) with potential antineoplastic activity. Upon oral administration, ibrutinib binds to and irreversibly inhibits BTK activity, thereby preventing both B-cell activation and B-cell-mediated signaling. This leads to an inhibition of the growth of malignant B cells that overexpress BTK. BTK, a member of the src-related BTK/Tec family of cytoplasmic tyrosine kinases, is required for B cell receptor signaling, plays a key role in B-cell maturation, and is overexpressed in a number of B-cell malignancies. The expression of BTK in tumor cells is also associated with increased proliferation and survival. |
Concepts | Pharmacologic Substance (T121) , Organic Chemical (T109) |
MSH | C551803 |
English | ibrutinib, 2-Propen-1-one, 1-((3R)-3-(4-amino-3-(4-phenoxyphenyl)-1h-pyrazolo(3,4-d)pyrimidin-1-yl)-1-piperidinyl)-, Ibrutinib, IBRUTINIB |