Pirtobrutinib

Pirtobrutinib is mainly used to treat adult patients with recurrent or refractory mantle cell lymphoma (MCL), especially those who have received at least second-line systemic therapy (including BTK inhibitors).

pirtobrutinib is a non covalent (reversible) BTK (Bruton's tyrosine kinase) inhibitor developed by Eli Lilly and Company. It is the first and only non covalent BTK inhibitor approved by the FDA, with a unique mechanism of action and excellent therapeutic efficacy.

1.Main components

pirtobrutinib

2.Adapt to the population

Patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

3.Medication for special populations

3.1Pregnancy 

pirtobrutinib can cause fetal harm when administered to a pregnant woman. There are no available data on pirtobrutinib use in pregnant women to evaluate for a drug-associated risk.

3.2Lactation

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 pirtobrutinib and for one week after the last dose.

3.3Females and Males of Reproductive Potential

Based on findings from animal studies, pirtobrutinib can cause fetal harm when administered to a pregnant woman.

3.4Pediatric Use

Safety and effectiveness of pirtobrutinib have not been established in pediatric patients.

3.5Geriatric Use

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. 

3.6Renal Impairment

Severe renal impairment (eGFR15-29 mL/min) increases pirtobrutinib exposure. Reduce the pirtobrutinib dosage in patients with severe renal impairment. No dosage adjustment of pirtobrutinib is recommended in patients with mild (60-89 mL/min) or moderate (30-59 mL/min) renal impairment.

3.7Hepatic Impairment

No dosage adjustment of pirtobrutinib 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).

4.Drug overdose

Drug overdose is not yet clear.

5.Drug storage

Store pirtobrutinib 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). 

6.Pharmacokinetics

Pirtobrutinib exposure (AUC) and Cmax increases proportionally following single oral doses ranging from 300 mg to 800 mg (1.5 to 4 times the approved recommended dosage) and once daily doses ranging from 25 – 300 mg (0.125 to 1.5 times the recommended dosage). Steady state was achieved within 5 days of once daily dosing, and the mean (CV%) accumulation ratio was 1.63 (26.7%) based on AUC after administration of 200 mg dosages. 

from FDA，2024.06