Jaypirca
(pirtobrutinib)Dosage & Administration
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Jaypirca Prescribing Information
Mantle Cell Lymphoma
JAYPIRCA® is indicated for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL) after at least two lines of systemic therapy, including a BTK inhibitor.
This indication is approved under accelerated approval based on response rate [see Clinical Studies ]. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
JAYPIRCA is indicated for the 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.
This indication is approved under accelerated approval based on response rate [see Clinical Studies ]. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
Recommended Dosage
The recommended dosage of JAYPIRCA is 200 mg orally once daily until disease progression or unacceptable toxicity.
Advise patients of the following:
- Swallow tablets whole with water. Do not cut, crush, or chew tablets.
- Take JAYPIRCA at the same time each day. JAYPIRCA may be taken with or without food.
- If a dose of JAYPIRCA is missed by more than 12 hours, do not make up the dose and take the next dose as scheduled.
Dosage Modifications for Adverse Reactions
Recommended dosage modifications of JAYPIRCA for adverse reactions are presented in Table 1[see Warnings and Precautions ].
Dose modification is not recommended for asymptomatic lymphocytosis. Asymptomatic lipase increase may not necessarily warrant dose modification. | ||
a Evaluate the benefit-risk before resuming treatment at the same dose for a Grade 4 non-hematological toxicity. | ||
| Adverse Reaction | Occurrences Requiring Dosage Modification | Modification (Starting Dosage: 200 mg once daily) |
| First occurrence | Interrupt JAYPIRCA until recovery to Grade 1 or baseline; restart at original dosage (200 mg once daily)a. |
| Second occurrence | Interrupt JAYPIRCA until recovery to Grade 1 or baseline; restart at 100 mg once daily. | |
| Third occurrence | Interrupt JAYPIRCA until recovery to Grade 1 or baseline; restart at 50 mg once daily. | |
| Fourth occurrence | Discontinue JAYPIRCA. | |
Dosage Modifications for Patients with Severe Renal Impairment
For patients with severe renal impairment (eGFR 15-29 mL/min), reduce the JAYPIRCA dose to 100 mg once daily if the current dose is 200 mg once daily otherwise reduce the dose by 50 mg. If the current dosage is 50 mg once daily, discontinue JAYPIRCA [see Use in Specific Populations , Clinical Pharmacology ]. No dosage adjustment of JAYPIRCA is recommended in patients with mild to moderate renal impairment (eGFR 30-89 mL/min).
Dosage Modifications for Concomitant Use with Strong CYP3A Inhibitors
Avoid concomitant use of strong CYP3A inhibitors with JAYPIRCA [see Drug Interactions , Clinical Pharmacology ]. If concomitant use of a strong CYP3A inhibitor is unavoidable, reduce the JAYPIRCA dose by 50 mg. If the current dosage is 50 mg once daily, interrupt JAYPIRCA treatment for the duration of strong CYP3A inhibitor use. After discontinuation of a strong CYP3A inhibitor for 5 half-lives, resume the JAYPIRCA dose that was taken prior to initiating the strong CYP3A inhibitor.
Dosage Modifications for Concomitant Use with CYP3A Inducers
Avoid concomitant use of strong or moderate CYP3A inducers with JAYPIRCA [see Drug Interactions , Clinical Pharmacology ]. If concomitant use with moderate CYP3A inducers is unavoidable and the current dosage of JAYPIRCA is 200 mg once daily, increase the dose to 300 mg. If the current dosage is 50 mg or 100 mg once daily, increase the dose by 50 mg.
Tablets:
Each 50 mg tablet is blue, arc-triangle shaped, film-coated, and debossed with “Lilly 50” on one side and “6902” on the other side.
Each 100 mg tablet is blue, round, film-coated, and debossed with “Lilly 100” on one side and “7026” on the other side.
Pregnancy
Risk Summary
Based on findings from animal studies, JAYPIRCA can cause fetal harm when administered to a pregnant woman. There are no available data on JAYPIRCA use in pregnant women to evaluate for a drug-associated risk. In an animal reproduction study, administration of pirtobrutinib to pregnant rats during organogenesis resulted in adverse developmental outcomes, including structural abnormalities, altered fetal growth, and embryo-fetal mortality, at maternal exposures approximately 3-times those in patients at the recommended daily dose of 200 mg (see Data). Advise pregnant women of the potential risk to a fetus.
The background risk in the U.S. general population of major birth defects is 2% to 4% and of miscarriage is 15% to 20% of clinically recognized pregnancies.
Data
Animal Data
In an embryo-fetal development study in rats, pregnant animals were administered oral doses of pirtobrutinib at up to 500 mg/kg twice daily during the period of organogenesis. Doses ≥ 375 mg/kg twice daily caused decreased fetal body weights and increased incidence of malformations and variations in the urinary tract (including absent or abnormal ureters and kidneys), reproductive tract (malpositioned ovaries and misshapen uterus), and bone (misshapen sternebrae). At 500 mg/kg twice daily, total resorption was observed. At 375 mg/kg twice daily in rats, the maternal systemic exposures (AUC) were approximately 3 times the human exposure at 200 mg once daily.
Lactation
Risk Summary
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 JAYPIRCA and for one week after the last dose.
Females and Males of Reproductive Potential
Based on findings from animal studies, JAYPIRCA can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations ].
Pregnancy Testing
Verify pregnancy status in females of reproductive potential prior to initiating JAYPIRCA.
Contraception
Females
Advise females of reproductive potential to use effective contraception during treatment with JAYPIRCA and for one week after the last dose.
Pediatric Use
Safety and effectiveness of JAYPIRCA have not been established in pediatric patients.
Geriatric Use
Of the patients with MCL who received the 200 mg dose of JAYPIRCA in BRUIN, 93 (78%) were 65 years of age and older and 39 (33%) were 75 years and older [see Clinical Studies ]. Clinical studies of JAYPIRCA did not include sufficient numbers of patients with MCL who were less than 65 years of age to determine whether older patients respond differently from younger adult patients. Of the patients with CLL/SLL who received the 200 mg once daily dose of JAYPIRCA in BRUIN, 68 (63%) were 65 years of age and older and 21 (19%) were 75 years and older [see Clinical Studies ]. No overall differences in effectiveness were observed between younger and older patients.
In the pooled safety population in patients with hematologic malignancies, 401 (68%) were 65 years of age and older, while 154 (26%) were 75 years of age and older. Patients aged 65 years and older experienced higher rates of Grade 3 and higher adverse reactions and serious adverse reactions compared to patients who were less than 65 years of age.
Renal Impairment
Severe renal impairment (eGFR15-29 mL/min) increases pirtobrutinib exposure [see Clinical Pharmacology ]. Reduce the JAYPIRCA dosage in patients with severe renal impairment [see Dosage and Administration ]. No dosage adjustment of JAYPIRCA is recommended in patients with mild (60-89 mL/min) or moderate (30-59 mL/min) renal impairment.
Hepatic Impairment
No dosage adjustment of JAYPIRCA is recommended in patients with mild hepatic impairment (total bilirubin ≤ upper limit of normal (ULN) and aspartate aminotransferase (AST) > ULN or total bilirubin > 1 to 1.5 × ULN and any AST), moderate hepatic impairment (total bilirubin > 1.5 to 3 × ULN and any AST), or severe hepatic impairment (total bilirubin > 3 × ULN and any AST) [see Clinical Pharmacology ( 12.3)].
None.
Infections
Fatal and serious infections (including bacterial, viral, or fungal infections) and opportunistic infections have occurred in patients treated with JAYPIRCA. 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%. In patients with CLL/SLL, Grade 3 or higher infections occurred in 32% of patients, with fatal infections occurring in 8%. Opportunistic infections after treatment with JAYPIRCA have included, but are not limited to, Pneumocystis jirovecii pneumonia and fungal infection [see Adverse Reactions ].
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 JAYPIRCA [see Dosage and Administration ].
Hemorrhage
Fatal and serious hemorrhage has occurred with JAYPIRCA. Major hemorrhage (defined as Grade 3 or higher bleeding or any central nervous system bleeding) occurred in 3% of 593 patients treated with JAYPIRCA, including gastrointestinal hemorrhage; fatal hemorrhage occurred in 0.3% of patients. Bleeding of any grade, excluding bruising and petechiae, occurred in 17% of patients [see Adverse Reactions ].
Major hemorrhage occurred in 2.3% of patients taking JAYPIRCA without antithrombotic agents and 0.7% of patients taking JAYPIRCA with antithrombotic agents. Consider the risks and benefits of antithrombotic agents when co-administered with JAYPIRCA. Monitor patients for signs of bleeding. Based on severity of bleeding, reduce dose, temporarily withhold, or permanently discontinue JAYPIRCA [see Dosage and Administration ].
Consider the benefit-risk of withholding JAYPIRCA for 3 to 7 days pre- and post-surgery depending upon the type of surgery and risk of bleeding.
Cytopenias
JAYPIRCA can cause cytopenias, including neutropenia, thrombocytopenia, and anemia.
In the clinical trial, Grade 3 or 4 cytopenias, including decreased neutrophils (26%), decreased platelets (12%), and decreased hemoglobin (12%) developed in patients treated with JAYPIRCA. Grade 4 decreased neutrophils developed in 14% of patients and Grade 4 decreased platelets developed in 6% of patients [see Adverse Reactions ].
Monitor complete blood counts regularly during treatment. Based on severity, reduce dose, temporarily withhold, or permanently discontinue JAYPIRCA [see Dosage and Administration ].
Cardiac Arrhythmias
Cardiac arrhythmias, including atrial fibrillation and atrial flutter, were reported in recipients of JAYPIRCA. Atrial fibrillation or flutter were reported in 3.2% of patients, with Grade 3 or 4 atrial fibrillation or flutter reported in 1.5% of 593 patients in the clinical trial [see Adverse Reactions ]. Other serious cardiac arrhythmias such as supraventricular tachycardia and cardiac arrest occurred in 0.5% of patients. 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 JAYPIRCA [see Dosage and Administration ].
Second Primary Malignancies
Second primary malignancies, including non-skin carcinomas, developed in 9% of 593 patients treated with JAYPIRCA 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 JAYPIRCA.
Evaluate bilirubin and transaminases at baseline and throughout treatment with JAYPIRCA. For patients who develop abnormal liver tests after JAYPIRCA, monitor more frequently for liver test abnormalities and clinical signs and symptoms of hepatic toxicity. If DILI is suspected, withhold JAYPIRCA. Upon confirmation of DILI, discontinue JAYPIRCA.
Embryo-Fetal Toxicity
Based on findings in animals, JAYPIRCA can cause fetal harm when administered to a pregnant woman. In animal reproduction studies, administration of pirtobrutinib to pregnant rats during the period of organogenesis caused embryo-fetal toxicity including embryo-fetal mortality and malformations at maternal exposures (AUC) approximately 3-times the recommended dose of 200 mg once daily. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with JAYPIRCA and for one week after the last dose [see Use in Specific Populations ].