Imbruvica Ibrutinib Capsules

1. Indications and Usage
Mantle Cell Lymphoma (MCL):
Indicated for the treatment of patients with MCL who have received at least one prior therapy.
Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL):
Indicated for the treatment of patients with CLL/SLL.
Waldenström’s Macroglobulinemia (WM):
Indicated for the treatment of patients with WM.
Marginal Zone Lymphoma (MZL):
Indicated for the treatment of patients with MZL who require systemic therapy and have received at least one prior anti-CD20-based regimen.
Chronic Graft-versus-Host Disease (cGVHD):
Indicated for the treatment of adult patients with cGVHD after failure of one or more lines of systemic therapy.
2. Dosage and Administration
Recommended Dosage:
MCL: 560 mg orally once daily.
CLL/SLL, WM, MZL, cGVHD: 420 mg orally once daily.
Administration:
Swallow capsules whole with water at approximately the same time every day. Do not open, break, or chew the capsules.
Dose Modifications:
With CYP3A Inhibitors: Reduce dose when co-administered with moderate or strong CYP3A inhibitors (e.g., reduce to 280 mg or 140 mg respectively).
Toxicity: Interrupt treatment for Grade ≥ 3 toxicities (except lymphocytosis); resume at reduced dose upon recovery.
3. Mechanism of Action
BTK Inhibition:
Ibrutinib is a small molecule inhibitor that covalently binds to cysteine-481 in the ATP binding pocket of BTK.
Physiological Effect:
Ibrutinib inhibits BTK activity, which is an important signaling molecule of the B-cell antigen receptor (BCR) pathway. This inhibition blocks BCR signaling, leading to inhibition of B-cell proliferation and survival.
4. Safety and Warnings
Hemorrhage:
Severe hemorrhage, including fatalities, has occurred. Monitor for signs of bleeding. Avoid concomitant use with warfarin or other Vitamin K antagonists.
Atrial Fibrillation:
New onset or worsening atrial fibrillation (AF) can occur. Monitor patients for AF signs/symptoms.
Infections:
Severe fatal infections (e.g., invasive fungal infections, bacterial sepsis, viral encephalitis) have occurred.
Cytopenias:
Severe neutropenia and thrombocytopenia can occur. Monitor complete blood counts (CBC) monthly.
Tumor Lysis Syndrome (TLS):
TLS has occurred. Assess baseline risk and take precautions.
5. Adverse Reactions
Most Common:
Thrombocytopenia, diarrhea, neutropenia, anemia, fatigue, musculoskeletal pain, increased creatinine, nausea, diarrhea, rash, and hemorrhage.
6. Drug Interactions
CYP3A Inhibitors:
Avoid concomitant use with strong CYP3A inhibitors (e.g., ketoconazole, ritonavir). If short-term use is required, interrupt Ibrutinib.
CYP3A Inducers:
Avoid concomitant use with strong CYP3A inducers (e.g., rifampin, carbamazepine).
Antiplatelet/Anticoagulant Agents:
Use with caution with antiplatelet or anticoagulant agents due to increased bleeding risk.
7. Pharmaceutical Information
Chemical Composition:
Active Ingredient: Ibrutinib.
Storage:
Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F).