Pirtobrutinib
JAYPIRCA
Pronunciation: pir-toe-BROO-ti-nib (jay-PEER-ka)
“Jay (ap)Pears to brutally nibble”
What it isNoncovalent BTK inhibitor; CLL/SLL (untreated without 17p deletion, or after a covalent BTK inhibitor) and relapsed mantle-cell lymphoma.
Why this oneBecause it does not depend on the C481 cysteine, it keeps working after the C481S mutation that defeats ibrutinib, acalabrutinib and zanubrutinib.
What limits itSerious infection, bleeding, cytopenias, atrial arrhythmia, and second malignancies require surveillance.
Pirtobrutinib prescription history
Animated chart of estimated U.S. prescriptions per year, Tyrosine kinase inhibitors (2001–2026). Pirtobrutinib enters in 2023 (estimated).
FDA-approved for
- relapsed/refractory mantle cell lymphoma
- relapsed/refractory chronic lymphocytic leukemia
- untreated CLL/SLL without 17p deletion (2026)
Principal riskInfections, hemorrhage and cytopenias
Classes and tags
Clinical profile
Legacy pregnancy categoryN/A (post-2015 labeling)
Defining liabilitySerious infections, bleeding and cytopenias
FDA label
Read the full label on DailyMed ↗
NO BOXED WARNINGS
| FDA dosing | Population | Start | Target | Max |
|---|---|---|---|---|
| Mantle cell lymphoma, previously treated (prior BTK inhibitor) | adults | 200 mg QD | 200 mg QD until progression or unacceptable toxicity | 200 mg QD |
| CLL/SLL, previously treated | adults | 200 mg QD | 200 mg QD until progression or unacceptable toxicity | 200 mg QD |
Renal Severe (eGFR 15–29): reduce 200→100 mg QD (otherwise reduce by 50 mg; discontinue if on 50 mg). Mild–moderate (eGFR 30–89): no adjustment
Hepatic No adjustment needed
Instructions
- Swallow whole with water; do not cut, crush, or chew
- With or without food; take at the same time daily
- Missed dose >12 h: skip — take next dose as scheduled
- Toxicity (Grade ≥3 non-heme, defined cytopenias): interrupt until recovery to Grade 1/baseline, restart 200→100→50 mg QD by occurrence; discontinue on 4th occurrence
- If strong CYP3A inhibitor unavoidable: reduce dose by 50 mg (interrupt if on 50 mg); if moderate CYP3A inducer unavoidable: increase 200→300 mg (or +50 mg if on 50/100 mg)
Available strengths
- tab 50, 100 mg
Cautions
- Fatal/serious infections incl. opportunistic (Grade ≥3 in 25%, most commonly pneumonia); consider vaccination/antimicrobial prophylaxis
- Hemorrhage incl. fatal; consider withholding 3–7 days pre/post surgery
- Cytopenias (Grade 3/4 neutropenia 27%) — monitor CBC regularly
- Cardiac arrhythmias: atrial fibrillation/flutter (3.4%)
- Second primary malignancies (9%) — advise sun protection
- Hepatotoxicity incl. drug-induced liver injury — monitor bilirubin/transaminases; discontinue on confirmed DILI
- Embryo-fetal toxicity — effective contraception during and 1 week after
Adverse reactions
- Fatigue (31%)
- Decreased neutrophils (54%), hemoglobin (43%), leukocytes (32%), platelets (31%), lymphocytes (31%), calcium (30%)
- Musculoskeletal pain, diarrhea, edema, dyspnea, pneumonia, bruising (MCL ≥15%)
Pregnancy Can cause fetal harm (animal data at ~3x human exposure); verify pregnancy status before starting; advise of fetal risk
Lactation Do not breastfeed during treatment and for 1 week after last dose
Cost
| Strength | #/mo | generic $/mo | CostPlus | |
|---|---|---|---|---|
| 50 mg | tab | 30 qd | not offered | |
| 100 mg | tab | 30 qd | not offered |
Open Pirtobrutinib in the interactive console ↗
Self-check
- Pirtobrutinib: Which resistance mutation can it overcome?
C481S. - Pirtobrutinib: Does it bind BTK covalently?
No; noncovalently.