JAYPIRCA

/ Eli Lilly

The recommended dosage of pirtobrutinib is 200 mg orally once daily until disease progression or unacceptable toxicity.
See prescribing information for full details.

Mantle Cell Lymphoma
Monotherapy is indicated for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL) who have been previously treated with a Bruton’s tyrosine kinase (BTK) inhibitor.
Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Treatment of adult patients with chronic lymphocytic leukemia or small lymphocytic
lymphoma (CLL/SLL) who have received at least two prior lines of therapy, including a BTK inhibitor and a BCL-2
inhibitor.

Hypersensitivity to the active substance or to any of the excipients

Infections
Fatal and serious infections (including bacterial, viral, or fungal infections) and opportunistic infections have occurred in patients treated with pirtobrutinib. In the clinical trial, Grade 3 or higher infections occurred in 24% of 593 patients, most
commonly pneumonia (14%), with fatal infections occurring in 4.4% of patients. Sepsis occurred in 6% of patients and febrile neutropenia in 4%. Opportunistic infections after treatment with pirtobrutinib have included, but are not limited to,
Pneumocystis jirovecii pneumonia and fungal infection. Consider prophylaxis, including vaccinations and antimicrobial prophylaxis, in patients who are at increased risk for infections, including opportunistic infections. Monitor patients for signs and symptoms of infection, evaluate promptly, and treat appropriately. Based on severity, reduce dose, temporarily withhold, or permanently discontinue.
Hemorrhage
Fatal and serious hemorrhage has occurred with pirtobrutinib. Major hemorrhage (defined as Grade 3 or higher bleeding or any central nervous system bleeding) occurred in 3% of 593 patients treated with pirtobrutinib, including gastrointestinal
hemorrhage; fatal hemorrhage occurred in 0.3% of patients. Bleeding of any grade, excluding bruising and petechiae, occurred in 17% of patients.
Major hemorrhage occurred in 2.3% of patients taking pirtobrutinib without antithrombotic agents and 0.7% of patients taking pirtobrutinib with antithrombotic agents. Consider the risks and benefits of antithrombotic agents when co-administered with pirtobrutinib. Monitor patients for signs of bleeding. Based on severity of bleeding, reduce dose, temporarily withhold, or permanently discontinue treatment.
Consider the benefit-risk of withholding pirtobrutinib for 3 to 7 days pre- and post-surgery depending upon the type of surgery and risk of bleeding.
Cytopenias
Pirtobrutinib can cause cytopenias, including neutropenia, thrombocytopenia, and anemia. Monitor complete blood counts regularly during treatment. Based on severity, reduce dose, temporarily withhold, or permanently discontinue treatment.
Cardiac Arrhythmias
Cardiac arrhythmias, including atrial fibrillation and atrial flutter were reported in recipients of pirtobrutinib. Patients with cardiac risk factors, such as hypertension, or previous arrhythmias may be at increased risk. Monitor for signs and symptoms of arrhythmias (e.g., palpitations, dizziness, syncope, dyspnea) and manage appropriately. Based on severity, reduce dose, temporarily withhold, or permanently discontinue treatment.
Second Primary Malignancies
Second primary malignancies, including non-skin carcinomas, developed in 9% of 593 patients treated with pirtobrutinib monotherapy. The most frequent malignancy was non-melanoma skin cancer, reported in 4.6% of 593 patients. Other second primary malignancies included solid tumors (including genitourinary and breast cancers) and melanoma. Advise patients to use sun protection and monitor patients for the development of second primary malignancies.
Hepatotoxicity, Including Drug-Induced Liver Injury
Hepatotoxicity, including severe, life-threatening, and potentially fatal cases of drug-induced liver injury (DILI), has occurred in patients treated with Bruton tyrosine kinase inhibitors, including pirtobrutinib. Evaluate bilirubin and transaminases at baseline and throughout treatment with pirtobrutinib. For patients who develop
abnormal liver tests after pirtobrutinib, monitor more frequently for liver test abnormalities and clinical signs and symptoms of hepatic toxicity. If DILI is suspected, withhold treatment. Upon confirmation of DILI, discontinue treatment.
See prescribing information for full details.

clinically significant adverse reactions: infections, hemorrhage, cytopenias, atrial fibrillation and atrial flutter, second primary malignancies, hepatotoxicity, including DILI.
See prescribing information for full details.

Effect of Other Drugs on pirtobrutinib
Strong CYP3A Inhibitors
Pirtobrutinib is a CYP3A substrate. Concomitant use of pirtobrutinib with a strong CYP3A inhibitor increased pirtobrutinib systemic exposure.
Strong or Moderate CYP3A Inducers
Concomitant use of pirtobrutinib with a strong or moderate CYP3A inducer decreased pirtobrutinib systemic exposure, which may reduce pirtobrutinib efficacy. Avoid concomitant use of pirtobrutinib with strong or moderate CYP3A inducers. If concomitant use of moderate CYP3A inducers is unavoidable, increase the pirtobrutinib dosage.
Effect of pirtobrutinib on Other Drugs
Sensitive CYP2C8, CYP2C19, CYP3A, P-gp, or BCRP Substrates
Pirtobrutinib is a P-gp inhibitor, a moderate CYP2C8 and BCRP inhibitor, and a weak CYP2C19 and CYP3A inhibitor. Concomitant use of pirtobrutinib with sensitive P-gp, CYP2C8, BCRP, CYP2C19, or CYP3A substrates increased their plasma concentrations, which may increase the risk of adverse reactions related to these substrates for drugs which are sensitive to minimal concentration changes. Follow recommendations for sensitive CYP2C8, CYP2C19, CYP3A, P-gp, or BCRP substrates provided in their approved product labeling.
See prescribing information for full details.

Pregnancy: There are no available data on pirtobrutinib use in pregnant women to evaluate for a drug-associated risk. Verify pregnancy status in females of reproductive potential prior to initiating treatment.
Contraception
Advise females of reproductive potential to use effective contraception during treatment with pirtobrutinib and for one week after the last dose.
Lactation: There are no data on the presence of pirtobrutinib in human milk or the effects on the breastfed child or milk production. Because of the potential for serious adverse reactions in the breastfed child, advise women not to breastfeed during treatment with pirtobrutinib and for one week after the last dose.