JAYPIRCA Dosage & Rx Info | Uses, Side Effects

Jaypirca Generic Name & Formulations

Legal Class

General Description

Pirtobrutinib 50mg, 100mg; tabs.

Pharmacological Class

Bruton tyrosine kinase (BTK) inhibitor.

How Supplied

Tabs 50mg—30; 100mg—60

Storage

Store Jaypirca tablets at room temperature 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F) ([see USP Controlled Room Temperature]).

Manufacturer

Eli Lilly and Company

Generic Availability

Mechanism of Action

Pirtobrutinib is a small molecule, noncovalent inhibitor of Bruton tyrosine kinase (BTK). Pirtobrutinib binds to wild type BTK and BTK harboring C481 mutations, leading to inhibition of BTK kinase activity. In nonclinical studies, pirtobrutinib inhibited BTK-mediated B-cell CD69 expression and inhibited malignant B-cell proliferation. Pirtobrutinib showed dose-dependent anti-tumor activities in BTK wild type and BTK C481S mutant mouse xenograft models.

Jaypirca Indications

Indications

In adults with relapsed or refractory mantle cell lymphoma (MCL) after at least 2 lines of systemic therapy, including a BTK inhibitor. In adults with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) after at least 2 prior lines of therapy, including a BTK inhibitor and a BCL-2 inhibitor.

Jaypirca Dosage and Administration

Adult

Swallow whole. Take at the same time each day. 200mg once daily, until disease progression or unacceptable toxicity. Severe renal impairment (eGFR 15–29mL/min): reduce to 100mg once daily if current dose is 200mg once daily, otherwise reduce dose by 50mg; if current dose is 50mg once daily, then discontinue therapy. Concomitant strong CYP3A inhibitors (if unavoidable): reduce dose by 50mg; if current dose is 50mg once daily, then interrupt therapy for the duration of strong CYP3A inhibitor use. Concomitant moderate CYP3A inducers (if unavoidable): increase to 300mg if current dose is 200mg once daily; if current dose is 50mg or 100mg daily, then increase the dose by 50mg. Dose modifications for adverse reactions: see full labeling.

Children

Not established.

Jaypirca Contraindications

Not Applicable

Jaypirca Boxed Warnings

Not Applicable

Jaypirca Warnings/Precautions

Warnings/Precautions

Risk for serious hemorrhage (monitor); consider the benefit/risk of withholding treatment for 3–7 days pre- and post-surgery. Risk for serious infections (including bacterial, viral, or fungal) and opportunistic infections. Monitor for infections, evaluate promptly, and treat appropriately; consider antimicrobial prophylaxis or vaccinations in high risk patients. Monitor for cytopenias; obtain CBCs during therapy; interrupt, reduce dose, or discontinue as warranted. Monitor for cardiac arrhythmias (esp. in those with cardiac risk factors, hypertension, previous arrhythmias); manage appropriately. Second primary malignancies (eg, non-melanoma skin cancer, solid tumors, melanoma, others); advise to use sun protection; monitor. Severe renal impairment (eGFR 15–29mL/min): reduce Jaypirca dose (see Adults). Embryo-fetal toxicity. Advise females of reproductive potential to use effective contraception during and for 1 week after the last dose. Pregnancy: exclude status prior to initiation. Nursing mothers: not recommended (during and for 1 week after the last dose).

Jaypirca Pharmacokinetics

Absorption

Absolute bioavailability (after a single oral 200mg dose): 85.5% (range: 75.9–90.9%). Median time (range) to reach peak plasma concentration (tmax): ~2 hours (0.833–4.15 hours).

Distribution

Mean apparent central volume of distribution: 32.8 L. Human protein binding: 96% (independent of concentration in vitro).

Metabolism

Primarily metabolized by CYP3A4; direct glucuronidation by UGT1A8 and UGT1A9, in vitro.

Elimination

Following a single radiolabeled dose of pirtobrutinib 200mg to healthy subjects, 37% of the dose was recovered in feces (18% unchanged) and 57% in urine (10% unchanged). Half-life: ~19 hours.

Jaypirca Interactions

Interactions

Concomitant strong CYP3A inhibitors may increase risk of pirtobrutinib toxicities (eg, itraconazole); avoid use. If concomitant strong CYP3A inhibitors is unavoidable, reduce pirtobrutinib dose (see Adults). Concomitant moderate or strong CYP3A inducers may reduce pirtobrutinib efficacy (eg, efavirenz, bosentan, rifampin); avoid use. If concomitant moderate CYP3A inducers is unavoidable, increase pirtobrutinib dose (see Adults). Concomitant sensitive P-gp, CYP2C8, BCRP, CYP2C19, or CYP3A substrates may increase risk of adverse reactions related to substrates (eg, digoxin, repaglinide, rosuvastatin, omeprazole, midazolam). Caution with antithrombotic agents; monitor for bleeding.

Jaypirca Adverse Reactions

Adverse Reactions

Fatigue, musculoskeletal pain, diarrhea, COVID-19, bruising, cough, Grade 3/4 lab abnormalities (decreased neutrophil count, decreased lymphocyte count, decreased platelet count, decreased hemoglobin).

Jaypirca Clinical Trials

Clinical Trials

Mantle Cell Lymphoma

The approval was based on data from the phase 1/2 BRUIN trial (ClinicalTrials.gov Identifier: NCT03740529), an open-label, single-arm study that included 120 patients with MCL who were previously treated with a BTK inhibitor.

Study participants received pirtobrutinib 200mg once daily until disease progression or unacceptable toxicity. The efficacy measures included overall response rate (ORR) and duration of response (DOR).

Results showed an ORR of 50% (95% CI, 41-59); 13% of patients had a complete response and 38% of patients had a partial response. The median time to response was 1.8 months (range, 0.8-4.2 months) and the median DOR was 8.3 months (95% CI, 5.7, not established). The Kaplan-Meier estimate for the DOR rate at 6 months was 65.3% (95% CI, 49.8-77.1).

Chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL)

The approval was based on data from the phase 1/2 BRUIN trial (ClinicalTrials.gov Identifier: NCT03740529), which included a subset of 108 patients with CLL/SLL who were previously treated with at least 2 prior lines of therapy, including a BTK inhibitor and a BCL-2 inhibitor.

Results showed an ORR of 72% (95% CI, 63-80) with all of the patients achieving partial response. Median DOR was 12.2 months (95% CI, 9.3-14.7) after a median follow-up of 15.7 months, based on Kaplan-Meier estimation. Median time to response was 3.7 months (range, 1.7 to 27.9 months).

Jaypirca

PAGE CONTENTS