Jaypirca Pirtobrutinib Tablets

1. Indications and Usage
Relapsed or Refractory Mantle Cell Lymphoma (MCL): Indicated for adult patients with relapsed or refractory MCL who have received at least two systemic therapies, including a BTK inhibitor.
Relapsed or Refractory CLL/SLL: Indicated for adult patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic leukemia (SLL) who have received at least two systemic therapies, including a BTK inhibitor and a BCL-2 inhibitor.
2. Dosage and Administration
Recommended Dosage: 200 mg orally once daily.
Administration Details: Tablets should be swallowed whole with water; they must not be cut, crushed, or chewed. It can be taken with or without food.
Missed Dose: If a dose is missed by more than 12 hours, do not make up the dose; resume with the next scheduled dose.
Discontinuation: Continued until disease progression or unacceptable toxicity. Dose interruptions, reductions, or permanent discontinuations may be required based on the severity of adverse reactions.
3. Mechanism of Action
BTK Inhibition: Pirtobrutinib is a selective, non-covalent (reversible) inhibitor of Bruton’s tyrosine kinase (BTK).
Pathway Blockade: It binds to the ATP-binding pocket of BTK, inhibiting B-cell receptor (BCR) signaling, which is critical for B-cell proliferation, survival, and migration.
Mutant Activity: It effectively inhibits both wild-type and C481S mutant forms of BTK, overcoming resistance to covalent BTK inhibitors.
4. Safety and Warnings
Embryo-Fetal Toxicity: Can cause fetal harm. Effective contraception is required for females during treatment and for 1 week after the final dose, and for males with female partners during treatment.
Hemorrhage: Monitor for signs of bleeding; severe or fatal bleeding events have been reported.
Infections: Serious infections, including fatal sepsis and pneumonia, may occur. Monitor for signs of infection.
Cardiac Disorders: Monitor for atrial fibrillation and atrial flutter.
Second Primary Malignancies: Monitor for the development of second primary malignancies.
Hepatic and Renal Impairment: No adjustment for mild to severe hepatic impairment. For severe renal impairment (eGFR 15-29 mL/min), reduce the dose to 100 mg once daily.
5. Adverse Reactions and Clinical Research
Most Common Adverse Reactions: Fatigue, musculoskeletal pain, diarrhea, edema, dyspnea, pneumonia, and ecchymosis.
Serious Adverse Reactions: Infections, hemorrhage, cytopenias (neutropenia, anemia, thrombocytopenia), and cardiac disorders.
Clinical Research Highlights: Clinical trials (e.g., BLUEBERRY-202 for MCL, BRUIN for CLL/SLL) demonstrated significant objective response rates in heavily pretreated patients who had progressed on covalent BTK inhibitors.
6. Drug Interactions
CYP3A Inhibitors: Strong CYP3A inhibitors increase pirtobrutinib exposure; avoid concomitant use or reduce the pirtobrutinib dose.
CYP3A Inducers: Strong or moderate CYP3A inducers decrease pirtobrutinib exposure; avoid concomitant use. If using moderate inducers, increase the pirtobrutinib dose.
Sensitive Drug Substrates: Pirtobrutinib is a P-gp inhibitor and moderate CYP2C8/BCRP inhibitor; monitor or adjust doses of sensitive substrates (e.g., repaglinide, digoxin).
7. Pharmaceutical Information
Chemical Composition: Active ingredient: Pirtobrutinib.
Appearance: Blue film-coated tablets (50 mg is triangular; 100 mg is round).
Packaging: Available in 50 mg and 100 mg strengths.
Storage: Store at 20°C to 25°C (68°F to 77°F); protect from moisture.