Version July 2025
Dosage guidance:
Safety: Consider the benefit versus risks of withholding pirtobrutinib for 3 to 7 days prior to and after surgery (depending upon the type of surgery and risk of bleeding).
Clinical considerations: Consider prophylaxis (including vaccinations and antimicrobial prophylaxis) in patients who are at increased risk for infections, including opportunistic infections.
Chronic lymphocytic leukemia/small lymphocytic lymphoma, relapsed or refractory: Oral: 200 mg once daily; continue until disease progression or unacceptable toxicity (Ref).
Mantle cell lymphoma, relapsed or refractory: Oral: 200 mg once daily; continue until disease progression or unacceptable toxicity (Ref).
Missed dose: If a dose is missed by more than 12 hours, do not make up the dose; administer the dose on the next day as scheduled.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
eGFR ≥30 mL/minute: No dosage adjustment necessary.
eGFR 15 to 29 mL/minute: Reduce the dose from 200 mg once daily to 100 mg once daily. If the current dose is 100 mg once daily, reduce the dose to 50 mg once daily. If the current dose is 50 mg once daily, discontinue pirtobrutinib.
eGFR <15 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling; the effect on pirtobrutinib pharmacokinetics is unknown.
Hemodialysis: There are no dosage adjustments provided in the manufacturer's labeling; the effect on pirtobrutinib pharmacokinetics is unknown.
Hepatic impairment prior to treatment: No dosage adjustment necessary.
Hepatic impairment during treatment: Drug-induced liver injury: Withhold pirtobrutinib if suspected; discontinue pirtobrutinib upon confirmation.
|
Adverse reaction |
Occurrence |
Pirtobrutinib dosage modification |
|---|---|---|
|
a Dosage modification is not recommended for asymptomatic lymphocytosis. | ||
|
b Asymptomatic lipase increase may not necessarily require dosage modification. | ||
|
c Evaluate benefits versus risks before resuming pirtobrutinib at the same dose following grade 4 nonhematologic toxicity. | ||
|
Hematologic toxicitya: ANC 500 to <1,000/mm3 with fever and/or infection ANC <500/mm3 lasting ≥7 days Platelets 25,000 to <50,000/mm3 with bleeding Platelets <25,000/mm3 |
First occurrence |
Interrupt pirtobrutinib until recovery to grade 1 or baseline; then restart at the original dose (usual initial dose is 200 mg once daily). |
|
Second occurrence |
Interrupt pirtobrutinib until recovery to grade 1 or baseline; then restart at 100 mg once daily. | |
|
Third occurrence |
Interrupt pirtobrutinib until recovery to grade 1 or baseline; then restart at 50 mg once daily. | |
|
Fourth occurrence |
Discontinue pirtobrutinib. | |
|
Nonhematologic toxicity, grade 3 or higherb, c |
First occurrence |
Interrupt pirtobrutinib until recovery to grade 1 or baseline; then restart at the original dose (usual initial dose is 200 mg once daily)c. |
|
Second occurrence |
Interrupt pirtobrutinib until recovery to grade 1 or baseline; then restart at 100 mg once dailyc. | |
|
Third occurrence |
Interrupt pirtobrutinib until recovery to grade 1 or baseline; then restart at 50 mg once dailyc. | |
|
Fourth occurrence |
Discontinue pirtobrutinib. | |
|
Atrial fibrillation or atrial flutter |
Manage appropriately; reduce dose, temporarily withhold, or permanently discontinue pirtobrutinib based on the severity. | |
|
Bleeding |
Reduce dose, temporarily withhold, or permanently discontinue pirtobrutinib based on the severity. | |
|
Infections |
Evaluate promptly and manage appropriately as clinically indicated; reduce dose, temporarily withhold, or permanently discontinue pirtobrutinib based on the severity. | |
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Reported adverse reactions are for adults.
>10%:
Cardiovascular: Edema (18% to 21%), hypertension (12%)
Dermatologic: Skin rash (14% to 19%)
Endocrine & metabolic: Decreased serum calcium (19% to 40%), decreased serum potassium (13%), decreased serum sodium (13% to 30%), increased serum potassium (11%)
Gastrointestinal: Abdominal pain (11% to 25%), constipation (13% to 14%), decreased appetite (12%), diarrhea (19% to 26%), increased serum lipase (12% to 21%), nausea (11% to 21%), stomatitis (12%; grades 3/4: <1%)
Hematologic & oncologic: Bruise (16% to 36%), decreased hemoglobin (42% to 48%; grades 3/4: 9% to 19%), decreased neutrophils (36% to 63%; grades 3/4: 10% to 45%), decreased platelet count (30% to 39%; grades 3/4: 7% to 15%), hemorrhage (11% to 22%; grades 3/4: 3%; including gastrointestinal hemorrhage, intracranial hemorrhage, major hemorrhage, life-threatening), lymphocytopenia (23% to 32%; grades 3/4: 6% to 15%), lymphocytosis (34% to 64%), second primary malignant neoplasm (13%; including malignant melanoma, malignant solid tumor [breast carcinoma, genitourinary neoplasm], non-melanoma skin carcinoma, non-skin carcinoma)
Hepatic: Increased serum alanine aminotransferase (11% to 23%), increased serum alkaline phosphatase (11% to 21%), increased serum aspartate aminotransferase (17% to 23%)
Nervous system: Dizziness (10% to 15%), falling (14%), fatigue (29% to 36%), headache (20%), insomnia (14%), neurologic signs and symptoms (12%; including confusion, encephalopathy, memory impairment, mental status changes), peripheral neuropathy (14% to 16%; grades 3/4: ≤4%)
Neuromuscular & skeletal: Arthralgia (≤19%), arthritis (≤19%), musculoskeletal pain (27% to 32%)
Renal: Increased serum creatinine (23% to 30%), kidney impairment (12%; including acute kidney injury, kidney failure)
Respiratory: Cough (14% to 33%), dyspnea (17% to 22%), pneumonia (16% to 27%), respiratory tract infection (11%; including lower respiratory tract infection [<10%], upper respiratory tract infection [10% to 13%])
Miscellaneous: Fever (13% to 20%)
1% to 10%:
Cardiovascular: Supraventricular tachycardia (10%; including atrial fibrillation, sinus tachycardia)
Genitourinary: Urinary tract infection
Hematologic & oncologic: Febrile neutropenia (7%), tumor lysis syndrome
Infection: Herpes virus infection, sepsis (2% to 7%)
Ophthalmic: Visual disturbance
Respiratory: Pleural effusion (2%)
Frequency not defined:
Cardiovascular: Atrial flutter
Hepatic: Hepatotoxicity
Infection: Infection (including bacterial infection, fungal infection, opportunistic infection [including pneumonia due to Pneumocystis jirovecii], serious infection, viral infection)
There are no contraindications listed in the manufacturer's labeling.
Concerns related to adverse effects:
• Cardiovascular effects: Atrial fibrillation and atrial flutter have been reported in a small percentage of patients who received pirtobrutinib; grade 3 or 4 atrial fibrillation or flutter have been observed (rarely). Cases of supraventricular tachycardia and cardiac arrest have occurred. Patients with cardiac risk factors (eg, hypertension or previous arrhythmias) may be at increased risk for atrial fibrillation/flutter. Signs and symptoms of arrhythmias include palpitations, dizziness, syncope, and dyspnea.
• Cytopenias: Grade 3 or 4 cytopenias, including neutropenia, anemia, and thrombocytopenia have occurred with pirtobrutinib; grade 4 neutropenia and thrombocytopenia have been observed.
• Hemorrhage: Fatal and serious hemorrhage has occurred with pirtobrutinib. Major hemorrhage (defined as ≥ grade 3 bleeding or any CNS bleeding) occurred in a small percentage of patients (including GI hemorrhage); fatal hemorrhage occurred rarely. Bleeding of any grade, excluding bruising and petechiae, has occurred. Major hemorrhage has occurred, both with and without concurrent antithrombotic agents (consider risks versus benefits of concurrent antithrombotic agents with pirtobrutinib).
• Hepatotoxicity: Hepatotoxicity, including severe, life-threatening, and potentially fatal drug-induced liver injury, has occurred with pirtobrutinib.
• Infection: Fatal and serious infections (including bacterial, viral, or fungal infections) as well as opportunistic infections have occurred in patients treated with pirtobrutinib; grade 3 or higher infections have been reported (eg, pneumonia, sepsis, neutropenic fever). Opportunistic infections occurring after pirtobrutinib treatment have included Pneumocystis jirovecii pneumonia and fungal infection.
• Secondary malignancy: Second primary malignancies, including nonskin carcinomas, have developed in patients treated with pirtobrutinib monotherapy. The most frequent malignancy was nonmelanoma skin cancer; other second primary malignancies observed were solid tumors (including genitourinary and breast cancers) and melanoma. Advise patients to use sun protection.
Special populations:
• Older adults: Patients ≥65 years of age experienced higher rates of ≥ grade 3 and serious adverse reactions (compared to patients <65 years of age).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Jaypirca: 50 mg, 100 mg [contains fd&c blue #2 (indigotine,indigo carmine)]
No
Tablets (Jaypirca Oral)
50 mg (per each): $307.23
100 mg (per each): $460.85
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Pirtobrutinib is available through specialty pharmacies/distributors and various specialty institutions/accounts. Examples from the manufacturer may be found at https://www.jaypirca.com/hcp/savings-support#access-resources.
Oral: Administer with or without food at approximately the same time each day. Swallow tablets whole; do not cut, crush, or chew.
Chronic lymphocytic leukemia/small lymphocytic lymphoma, relapsed or refractory: Treatment of chronic lymphocytic leukemia or small lymphocytic lymphoma after at least 2 lines of systemic therapy, including a Bruton tyrosine kinase (BTK) inhibitor and a BCL-2 inhibitor, in adults.
Mantle cell lymphoma, relapsed or refractory: Treatment of relapsed or refractory mantle cell lymphoma (MCL) after at least 2 lines of systemic therapy, including a BTK inhibitor, in adults.
Jaypirca may be confused with Jakafi.
Pirtobrutinib may be confused with acalabrutinib, ibrutinib, pexidartinib, zanubrutinib.
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes (chemotherapeutic agent, parenteral and oral) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Acute Care, Community/Ambulatory Care, and Long-Term Care Settings).
Substrate of BCRP, CYP3A4 (Major), P-glycoprotein (Minor), UGT1A8, UGT1A9; Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits BCRP, CYP2C19 (Weak), CYP2C8 (Moderate), CYP3A4 (Weak), P-glycoprotein;
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
5-Aminosalicylic Acid Derivatives: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
Abrocitinib: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
Afatinib: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Afatinib. Management: If combined, administer the P-gp inhibitor simultaneously with, or after, the dose of afatinib. Monitor closely for signs and symptoms of afatinib toxicity and if the combination is not tolerated, reduce the afatinib dose by 10 mg. Risk D: Consider Therapy Modification
Agents with Antiplatelet Effects: Pirtobrutinib may increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Aliskiren: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Aliskiren. Risk C: Monitor
Alpelisib: BCRP/ABCG2 Inhibitors may increase serum concentration of Alpelisib. Management: Avoid coadministration of BCRP/ABCG2 inhibitors and alpelisib due to the potential for increased alpelisib concentrations and toxicities. If coadministration cannot be avoided, closely monitor for increased alpelisib adverse reactions. Risk D: Consider Therapy Modification
ALPRAZolam: CYP3A4 Inhibitors (Weak) may increase serum concentration of ALPRAZolam. Risk C: Monitor
Amodiaquine: CYP2C8 Inhibitors (Moderate) may increase serum concentration of Amodiaquine. Risk X: Avoid
Anticoagulants: Pirtobrutinib may increase anticoagulant effects of Anticoagulants. Risk C: Monitor
Antithymocyte Globulin (Equine): Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of immunosuppressive therapy is reduced. Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor
Antithyroid Agents: Myelosuppressive Agents may increase neutropenic effects of Antithyroid Agents. Risk C: Monitor
Baricitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Baricitinib. Risk X: Avoid
BCG Products: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of BCG Products. Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Beta-Acetyldigoxin: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Beta-Acetyldigoxin. Risk C: Monitor
Bilastine: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Bilastine. Risk X: Avoid
Brincidofovir: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Brincidofovir. Risk C: Monitor
Brivudine: May increase adverse/toxic effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
Celiprolol: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Celiprolol. Risk C: Monitor
Chikungunya Vaccine (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Chikungunya Vaccine (Live). Risk X: Avoid
Chloramphenicol (Ophthalmic): May increase adverse/toxic effects of Myelosuppressive Agents. Risk C: Monitor
Chloramphenicol (Systemic): Myelosuppressive Agents may increase myelosuppressive effects of Chloramphenicol (Systemic). Risk X: Avoid
Cladribine: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Cladribine. Risk X: Avoid
CloBAZam: CYP2C19 Inhibitors (Weak) may increase serum concentration of CloBAZam. CYP2C19 Inhibitors (Weak) may increase active metabolite exposure of CloBAZam. Risk C: Monitor
Clofazimine: May increase serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor
CloZAPine: Myelosuppressive Agents may increase adverse/toxic effects of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor
Coccidioides immitis Skin Test: Coadministration of Immunosuppressants (Miscellaneous Oncologic Agents) and Coccidioides immitis Skin Test may alter diagnostic results. Management: Consider discontinuing these oncologic agents several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider Therapy Modification
Colchicine: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Colchicine. Colchicine distribution into certain tissues (e.g., brain) may also be increased. Management: This combination is often contraindicated, but combined use may be permitted with dose adjustment and monitoring. Recommendations vary based on brand, indication, use of CYP3A4 inhibitors, and hepatic/renal function. See interaction monograph for details. Risk D: Consider Therapy Modification
COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor
COVID-19 Vaccine (mRNA): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of COVID-19 Vaccine (mRNA). Management: Give a 3-dose primary series for all patients aged 6 months and older taking immunosuppressive medications or therapies. Booster doses are recommended for certain age groups. See CDC guidance for details. Risk D: Consider Therapy Modification
COVID-19 Vaccine (Subunit): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of COVID-19 Vaccine (Subunit). Risk C: Monitor
CycloSPORINE (Systemic): CYP3A4 Inhibitors (Weak) may increase serum concentration of CycloSPORINE (Systemic). Risk C: Monitor
CycloSPORINE (Systemic): P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of CycloSPORINE (Systemic). Risk C: Monitor
CYP3A4 Inducers (Moderate): May decrease serum concentration of Pirtobrutinib. Management: Avoid concomitant use if possible. If combined, if the current pirtobrutinib dose is 200 mg once daily, increase to 300 mg once daily. If current pirtobrutinib dose is 50 mg or 100 mg once daily, increase the dose by 50 mg. Risk D: Consider Therapy Modification
CYP3A4 Inducers (Strong): May decrease serum concentration of Pirtobrutinib. Risk X: Avoid
CYP3A4 Inhibitors (Moderate): May increase serum concentration of Pirtobrutinib. Risk C: Monitor
CYP3A4 Inhibitors (Strong): May increase serum concentration of Pirtobrutinib. Management: Avoid concomitant use when possible. If combined, reduce the pirtobrutinib dose by 50 mg. If current dose is 50 mg, interrupt pirtobrutinib treatment during strong CYP3A4 inhibitor use. Risk D: Consider Therapy Modification
Dabigatran Etexilate: P-glycoprotein/ABCB1 Inhibitors may increase active metabolite exposure of Dabigatran Etexilate. Risk C: Monitor
Daprodustat: CYP2C8 Inhibitors (Moderate) may increase serum concentration of Daprodustat. Management: Reduce the daprodustat starting dose by half if combined with moderate CYP2C8 inhibitors, unless the dose is 1 mg, then no dose adjustment is required. Monitor hemoglobin and adjust daprodustat dose when starting or stopping moderate CYP2C8 inhibitors. Risk D: Consider Therapy Modification
Dasabuvir: CYP2C8 Inhibitors (Moderate) may increase serum concentration of Dasabuvir. Risk C: Monitor
Deferiprone: Myelosuppressive Agents may increase neutropenic effects of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider Therapy Modification
Dengue Tetravalent Vaccine (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Dengue Tetravalent Vaccine (Live). Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Denosumab: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and immunosuppressants. If combined, monitor patients for signs/symptoms of serious infections. Risk D: Consider Therapy Modification
Desloratadine: CYP2C8 Inhibitors (Moderate) may increase serum concentration of Desloratadine. Risk C: Monitor
Deucravacitinib: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
Digitoxin: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Digitoxin. Risk C: Monitor
Digoxin: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Digoxin. Management: Measure digoxin serum concentrations before initiating treatment with these P-glycoprotein (P-gp) inhibitors. Reduce digoxin concentrations by either reducing the digoxin dose by 15% to 30% or by modifying the dosing frequency. Risk D: Consider Therapy Modification
Dofetilide: CYP3A4 Inhibitors (Weak) may increase serum concentration of Dofetilide. Risk C: Monitor
DOXOrubicin (Conventional): P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of DOXOrubicin (Conventional). Risk X: Avoid
DOXOrubicin (Liposomal): P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of DOXOrubicin (Liposomal). Risk C: Monitor
Edoxaban: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Edoxaban. Risk C: Monitor
Ensartinib: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Ensartinib. Risk X: Avoid
Etoposide Phosphate: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Etoposide Phosphate. Risk C: Monitor
Etoposide: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Etoposide. Risk C: Monitor
Etrasimod: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
Everolimus: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Everolimus. Risk C: Monitor
Filgotinib: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
Finerenone: CYP3A4 Inhibitors (Weak) may increase serum concentration of Finerenone. Risk C: Monitor
Flibanserin: CYP3A4 Inhibitors (Weak) may increase serum concentration of Flibanserin. Risk C: Monitor
Fusidic Acid (Systemic): May increase serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Consider avoiding this combination if possible. If required, monitor patients closely for increased adverse effects of the CYP3A4 substrate. Risk D: Consider Therapy Modification
Glecaprevir and Pibrentasvir: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Glecaprevir and Pibrentasvir. Risk C: Monitor
Grapefruit Juice: May increase serum concentration of Pirtobrutinib. Risk C: Monitor
Inebilizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Inebilizumab. Risk C: Monitor
Influenza Virus Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating immunosuppressants if possible. If vaccination occurs less than 2 weeks prior to or during therapy, revaccinate at least 3 months after therapy discontinued if immune competence restored. Risk D: Consider Therapy Modification
Ixabepilone: CYP3A4 Inhibitors (Weak) may increase serum concentration of Ixabepilone. Risk C: Monitor
Lapatinib: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Lapatinib. Risk C: Monitor
Larotrectinib: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Larotrectinib. Risk C: Monitor
Lefamulin: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Lefamulin. Management: Avoid concomitant use of lefamulin tablets with P-glycoprotein/ABCB1 inhibitors. If concomitant use is required, monitor for lefamulin adverse effects. Risk D: Consider Therapy Modification
Leflunomide: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents. Risk D: Consider Therapy Modification
Lemborexant: CYP3A4 Inhibitors (Weak) may increase serum concentration of Lemborexant. Management: The maximum recommended dosage of lemborexant is 5 mg, no more than once per night, when coadministered with weak CYP3A4 inhibitors. Risk D: Consider Therapy Modification
Linezolid: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
Lomitapide: CYP3A4 Inhibitors (Weak) may increase serum concentration of Lomitapide. Management: Patients on lomitapide 5 mg/day may continue that dose. Patients taking lomitapide 10 mg/day or more should decrease the lomitapide dose by half. The lomitapide dose may then be titrated up to a max adult dose of 30 mg/day. Risk D: Consider Therapy Modification
Mavacamten: CYP2C19 Inhibitors (Weak) may increase serum concentration of Mavacamten. Management: Start mavacamten at 5 mg/day if stable on a weak CYP2C19 inhibitor, and reduce the mavacamten dose by one dose level if initiating a weak CYP2C19 inhibitor. Avoid initiating weak CYP2C19 inhibitors in patients on mavacamten 2.5 mg/day. Risk D: Consider Therapy Modification
Mavorixafor: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Mavorixafor. Risk C: Monitor
Midazolam: CYP3A4 Inhibitors (Weak) may increase serum concentration of Midazolam. Risk C: Monitor
Morphine (Systemic): P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Morphine (Systemic). Risk C: Monitor
Mumps- Rubella- or Varicella-Containing Live Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Mumps- Rubella- or Varicella-Containing Live Vaccines. Mumps- Rubella- or Varicella-Containing Live Vaccines may increase adverse/toxic effects of Immunosuppressants (Miscellaneous Oncologic Agents). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Nadofaragene Firadenovec: Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid
Nadolol: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Nadolol. Risk C: Monitor
Naldemedine: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Naldemedine. Risk C: Monitor
Naloxegol: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Naloxegol. Risk C: Monitor
Natalizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Natalizumab. Risk X: Avoid
NiMODipine: CYP3A4 Inhibitors (Weak) may increase serum concentration of NiMODipine. Risk C: Monitor
Ocrelizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ocrelizumab. Risk C: Monitor
Ofatumumab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ofatumumab. Risk C: Monitor
Olaparib: Myelosuppressive Agents may increase myelosuppressive effects of Olaparib. Risk C: Monitor
Ozanimod: CYP2C8 Inhibitors (Moderate) may increase active metabolite exposure of Ozanimod. Risk C: Monitor
PACLitaxel (Conventional): CYP2C8 Inhibitors (Moderate) may increase serum concentration of PACLitaxel (Conventional). Risk C: Monitor
PACLitaxel (Protein Bound): CYP2C8 Inhibitors (Moderate) may increase serum concentration of PACLitaxel (Protein Bound). Risk C: Monitor
PAZOPanib: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of PAZOPanib. Risk X: Avoid
Pidotimod: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Pidotimod. Risk C: Monitor
Pimecrolimus: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
Pimozide: CYP3A4 Inhibitors (Weak) may increase serum concentration of Pimozide. Risk X: Avoid
Pioglitazone: CYP2C8 Inhibitors (Moderate) may increase serum concentration of Pioglitazone. Risk C: Monitor
Pneumococcal Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Pneumococcal Vaccines. Risk C: Monitor
Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Poliovirus Vaccine (Live/Trivalent/Oral). Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Polymethylmethacrylate: Immunosuppressants (Miscellaneous Oncologic Agents) may increase hypersensitivity effects of Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider Therapy Modification
Pralsetinib: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Pralsetinib. Management: If this combo cannot be avoided, decrease pralsetinib dose from 400 mg daily to 300 mg daily; from 300 mg daily to 200 mg daily; and from 200 mg daily to 100 mg daily. Risk D: Consider Therapy Modification
Promazine: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
Rabies Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider Therapy Modification
Ranolazine: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Ranolazine. Risk C: Monitor
Relugolix, Estradiol, and Norethindrone: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Relugolix, Estradiol, and Norethindrone. Management: Avoid use of relugolix/estradiol/norethindrone with P-glycoprotein (P-gp) inhibitors. If concomitant use is unavoidable, relugolix/estradiol/norethindrone should be administered at least 6 hours before the P-gp inhibitor. Risk D: Consider Therapy Modification
Relugolix: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Relugolix. Management: Avoid coadministration of relugolix with oral P-gp inhibitors whenever possible. If combined, take relugolix at least 6 hours prior to the P-gp inhibitor and monitor patients more frequently for adverse reactions. Risk D: Consider Therapy Modification
Repaglinide: CYP2C8 Inhibitors (Moderate) may increase serum concentration of Repaglinide. Risk C: Monitor
Repotrectinib: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Repotrectinib. Risk X: Avoid
Resmetirom: CYP2C8 Inhibitors (Moderate) may increase serum concentration of Resmetirom. Management: During coadministration with moderate CYP2C8 inhibitors reduce the resmetirom dose to 80 mg daily for patients weighing 100 kg or more, or reduce the resmetirom dose to 60 mg daily for patients weighing less than 100 kg. Risk D: Consider Therapy Modification
RifAXIMin: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of RifAXIMin. Risk C: Monitor
Rimegepant: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Rimegepant. Management: Avoid administration of another dose of rimegepant within 48 hours if given concomitantly with a P-glycoprotein (P-gp) inhibitor. Risk D: Consider Therapy Modification
RisperiDONE: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of RisperiDONE. Risk C: Monitor
Ritlecitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ritlecitinib. Risk X: Avoid
RomiDEPsin: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of RomiDEPsin. Risk C: Monitor
Ropeginterferon Alfa-2b: Myelosuppressive Agents may increase myelosuppressive effects of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider Therapy Modification
Rosuvastatin: BCRP/ABCG2 Inhibitors may increase serum concentration of Rosuvastatin. Risk C: Monitor
Ruxolitinib (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ruxolitinib (Topical). Risk X: Avoid
Seladelpar: BCRP/ABCG2 Inhibitors may increase serum concentration of Seladelpar. Risk C: Monitor
Selexipag: CYP2C8 Inhibitors (Moderate) may increase active metabolite exposure of Selexipag. Management: Reduce the selexipag dose to once daily when combined with moderate CYP2C8 inhibitors. Revert back to twice daily selexipag dosing upon stopping the moderate CYP2C8 inhibitor. Risk D: Consider Therapy Modification
Silodosin: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Silodosin. Risk C: Monitor
Simvastatin: CYP3A4 Inhibitors (Weak) may increase serum concentration of Simvastatin. CYP3A4 Inhibitors (Weak) may increase active metabolite exposure of Simvastatin. Risk C: Monitor
Sipuleucel-T: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants prior to initiating sipuleucel-T therapy. Risk D: Consider Therapy Modification
Sirolimus (Conventional): P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Sirolimus (Conventional). Management: Avoid concurrent use of sirolimus with P-glycoprotein (P-gp) inhibitors when possible and alternative agents with lesser interaction potential with sirolimus should be considered. Monitor for increased sirolimus concentrations/toxicity if combined. Risk D: Consider Therapy Modification
Sirolimus (Protein Bound): P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Sirolimus (Protein Bound). Risk X: Avoid
Sphingosine 1-Phosphate (S1P) Receptor Modulators: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk C: Monitor
Tacrolimus (Systemic): CYP3A4 Inhibitors (Weak) may increase serum concentration of Tacrolimus (Systemic). Risk C: Monitor
Tacrolimus (Systemic): P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Tacrolimus (Systemic). Risk C: Monitor
Tacrolimus (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Tacrolimus (Topical). Risk X: Avoid
Talazoparib: BCRP/ABCG2 Inhibitors may increase serum concentration of Talazoparib. Risk C: Monitor
Talazoparib: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Talazoparib. Risk C: Monitor
Talimogene Laherparepvec: Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid
Teniposide: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Teniposide. Risk C: Monitor
Tenofovir Disoproxil Fumarate: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Tenofovir Disoproxil Fumarate. Risk C: Monitor
Tertomotide: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Tertomotide. Risk X: Avoid
Therapeutic Antiplatelets: Pirtobrutinib may increase antiplatelet effects of Therapeutic Antiplatelets. Risk C: Monitor
Tofacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Tofacitinib. Risk X: Avoid
Topotecan: BCRP/ABCG2 Inhibitors may increase serum concentration of Topotecan. Risk X: Avoid
Topotecan: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Topotecan. Risk X: Avoid
Tovorafenib: CYP2C8 Inhibitors (Moderate) may increase serum concentration of Tovorafenib. Risk X: Avoid
Treprostinil: CYP2C8 Inhibitors (Moderate) may increase serum concentration of Treprostinil. Risk C: Monitor
Triazolam: CYP3A4 Inhibitors (Weak) may increase serum concentration of Triazolam. Risk C: Monitor
Typhoid Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Typhoid Vaccine. Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Ublituximab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ublituximab. Risk C: Monitor
Ubrogepant: Pirtobrutinib may increase serum concentration of Ubrogepant. Management: Consider an alternative therapy when possible. If this combination is used, use an initial ubrogepant dose of 50 mg and second dose (at least 2 hours later if needed) of 50 mg. Risk D: Consider Therapy Modification
Upadacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Upadacitinib. Risk X: Avoid
Vaccines (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Vaccines (Live). Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Vaccines (Non-Live/Inactivated/Non-Replicating): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Vaccines (Non-Live/Inactivated/Non-Replicating). Management: Give non-live/inactivated/non-replicating vaccines at least 2 weeks prior to initiation of immunosuppressants when possible. Patients vaccinated less than 14 days before or during therapy should be revaccinated at least 3 months after therapy is complete. Risk D: Consider Therapy Modification
Venetoclax: Pirtobrutinib may increase serum concentration of Venetoclax. Risk C: Monitor
VinCRIStine: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of VinCRIStine. Risk X: Avoid
Yellow Fever Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Yellow Fever Vaccine. Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Zoster Vaccine (Live/Attenuated): Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Zoster Vaccine (Live/Attenuated). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Zoster Vaccine (Live/Attenuated). Risk X: Avoid
Verify pregnancy status prior to use in patients who could become pregnant. Patients who could become pregnant should use effective contraception during therapy and for 1 week after the last pirtobrutinib dose.
Based on data from animal reproduction studies, in utero exposure to pirtobrutinib may cause fetal harm.
It is not known if pirtobrutinib is present in breast milk.
Due to the potential for serious adverse reactions in the breastfed infant, the manufacturer does not recommend breastfeeding during therapy and for 1 week after the last pirtobrutinib dose.
Monitor blood counts regularly during treatment. Monitor kidney function. Monitor bilirubin and transaminases at baseline and periodically during treatment; monitor more frequently in patients with abnormal liver tests or signs/symptoms of toxicity. Verify pregnancy status prior to treatment (in patients who could become pregnant). Monitor for signs/symptoms of infection, arrhythmia (eg, palpitations, dizziness, syncope, dyspnea), and bleeding/hemorrhage. Monitor for development of second primary malignancies. Monitor adherence.
The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
Cardiovascular monitoring: Comprehensive assessment prior to treatment including a history and physical examination, screening for cardiovascular disease risk factors such as hypertension, diabetes, dyslipidemia, obesity, and smoking (ASCO [Armenian 2017]). Assess BP at baseline and each clinical visit (as well as weekly home monitoring for initial 3 months), obtain ECG at each clinical visit, obtain a baseline echocardiography (transthoracic preferred) in high-risk patients; echocardiography is also recommended in all patients who develop atrial fibrillation (ESC [Lyon 2022]).
Pirtobrutinib is a highly selective, reversible Bruton tyrosine kinase (BTK) inhibitor (Mato 2021). BTK is a B-cell antigen receptor and cytokine receptor pathways signaling protein. BTK signaling in B-cells results in activation of pathways necessary for B-cell proliferation, trafficking, chemotaxis, and adhesion. Pirtobrutinib binds to wild type BTK as well as BTK harboring C481 mutations, which leads to inhibition of BTK kinase activity. Pirtobrutinib inhibits BTK-mediated B-cell CD69 expression and malignant B-cell proliferation. It also has demonstrated dose-dependent anti-tumor activities in BTK wild type and BTK C481S mutant animal models.
Onset: Median time to response: 1.8 months (mantle cell lymphoma [MCL]); 3.7 months (chronic lymphocytic leukemia/small lymphocytic lymphoma [CLL/SLL]).
Duration: Median duration of response: 8.3 months (MCL); 12.2 months (CLL/SLL).
Distribution: Vd: 34.1 L.
Protein binding: 96%.
Metabolism: Primarily via CYP3A4 and direct glucuronidation by UGT1A8 and UGT1A9.
Bioavailability: ~86%.
Half-life elimination: ~19 hours.
Time to peak: ~2 hours.
Excretion: Feces: 37% (18% as unchanged drug); Urine: 57% (10% as unchanged drug).
Clearance: 2.05 L/hour.
Altered kidney function: In subjects with severe impairment (eGFR 15 to 29 mL/minute), following a single 200 mg oral pirtobrutinib dose, the AUC and mean unbound AUC increased by 62% and 68%, respectively, compared to subjects with normal kidney function.
