Pirtobrutinib is a novel kinase inhibitor that received its first approval in the United States in 2023. As a highly selective BTK inhibitor, it has demonstrated favorable efficacy in the treatment of relapsed or refractory mantle cell lymphoma (MCL) and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).

Dosage and Administration of Pirtobrutinib

Standard Dosing Regimen

The recommended dosage of pirtobrutinib is 200 mg taken orally once daily, which can be administered with or without food.

Treatment should continue until disease progression or the occurrence of unacceptable toxicity.

Specific Administration Details

The drug should be swallowed whole with water, and must not be split, crushed, or chewed.

It is recommended that patients take the medication at the same time each day.

If a missed dose is noticed more than 12 hours after the scheduled time, the missed dose should not be made up. The next dose should be taken as scheduled at the next regular time.

Dose Adjustments for Pirtobrutinib

Dose Adjustments for Adverse Reactions

First occurrence: In cases of grade ≥3 non-hematologic toxicity, neutropenia with fever and/or infection, etc., discontinue the drug temporarily until symptoms resolve to grade 1 or baseline, then resume treatment at the original dose (200 mg once daily).

Second occurrence: Discontinue the drug temporarily until recovery, then resume at a reduced dose of 100 mg once daily.

Third occurrence: Discontinue the drug temporarily until recovery, then resume at a further reduced dose of 50 mg once daily.

Fourth occurrence: Discontinue the drug permanently.

Management of Specific Adverse Reactions

Infection management: For grade ≥3 infections, discontinue the drug temporarily. Monitor for signs of infection regularly and evaluate treatment promptly.

Bleeding events: In case of severe bleeding, reduce the dose, temporarily discontinue, or permanently discontinue the drug based on the severity of bleeding.

Cardiac events: For arrhythmias, monitor symptoms closely and adjust the dose according to the severity.

Use of Pirtobrutinib in Special Populations

Patients with Renal Impairment

Mild to moderate renal impairment (eGFR 30–89 mL/min): No dose adjustment is required.

Severe renal impairment (eGFR 15–29 mL/min): Reduce the dose from 200 mg once daily to 100 mg once daily. If the current dose is 50 mg once daily, discontinue the drug.

Reproductive-Age Populations

Female patients: Effective contraceptive measures should be used during treatment and for 1 week after the last dose. Pregnancy status should be verified before initiating treatment.

Pregnant women: Based on animal study results, pirtobrutinib may cause fetal harm and is contraindicated in pregnant women.

Lactating women: Breastfeeding should be discontinued during treatment and for 1 week after the last dose.