LuciPirto Pirtobrutinib Tablets

[Drug Name]

Generic Name: Pirtobrutinib Tablets

English Name: Pirtobrutinib Tablets

Brand Names: Jiepali, Jaypirca, LuciPirto

Development Code: LOXO-305

Specification: 50 mg/tablet; 30 tablets/box

Approval Number (Lao National Drug Administration): 06 L1110/24

Manufacturer: Lucius Pharmaceuticals Co., Ltd. (Laos)

[Composition]

Active Ingredient: Pirtobrutinib

Chemical Name: 5-amino-3-{4-[(5-fluoro-2-methoxybenzoylamino)methyl]phenyl}-1-[(2S)-1,1,1-trifluoropropan-2-yl]-1H-pyrazole-4-carboxamide

Molecular Formula: C₂₂H₂₁F₄N₅O₃

Molecular Weight: 479.44

Excipients: Hydroxypropyl methylcellulose acetate succinate, microcrystalline cellulose, lactose monohydrate, croscarmellose sodium, silicon dioxide, magnesium stearate, film coating premix (hydroxypropyl methylcellulose, titanium dioxide, triacetin, FD&C Blue No. 2 Aluminum Lake)

[Description]

This product is a film-coated tablet; when the coating is removed, it appears white or off-white.

[Indications]

Approved Indications in China

1. Mantle Cell Lymphoma (MCL): As monotherapy, indicated for adult patients with relapsed or refractory Mantle Cell Lymphoma (MCL) who have previously received at least two lines of systemic therapy (including a Bruton's tyrosine kinase [BTK] inhibitor).

2. Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL): As monotherapy, indicated for adult patients with relapsed or refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) who have previously received at least one line of systemic therapy (including a BTK inhibitor) (Added in 2026). **Approved Indications (Outside China)**

Adult patients with relapsed or refractory CLL/SLL who have previously received treatment with a covalent BTK inhibitor.

Adult patients with relapsed or refractory MCL who have previously received at least two lines of systemic therapy (including a BTK inhibitor).

**[Pharmacology and Toxicology]**

**Pharmacological Action**

Pirtobrutinib is the world's first highly selective, non-covalent (reversible) BTK inhibitor.

**Mechanism of Action:** It acts independently of the C481 site on the BTK protein, binding to BTK in a non-covalent, reversible manner to inhibit the B-cell receptor signaling pathway and block the proliferation and survival of tumor B cells.

**Resistance Advantage:** It can overcome resistance to covalent BTK inhibitors—such as ibrutinib and zanubrutinib—that is caused by the C481S mutation.

**Selectivity:** It selectively inhibits BTK with high specificity, exhibiting low affinity for other kinases and resulting in minimal off-target effects.

**Toxicology Studies**

**Genotoxicity:** Negative results were observed in the in vitro bacterial reverse mutation assay, the in vitro human lymphocyte chromosomal aberration assay, and the in vivo mouse bone marrow micronucleus assay.

**Reproductive Toxicity:** No teratogenic effects were observed in studies conducted on rats and rabbits; no significant effects on male or female fertility were noted.

**Carcinogenicity:** Long-term carcinogenicity studies have not yet been conducted.

**[Pharmacokinetics]**

**Absorption:** Rapidly absorbed following oral administration; time to maximum concentration (Tmax) is approximately 2–4 hours, and absolute bioavailability is approximately 55%.

**Distribution:** Plasma protein binding is approximately 97%, and the steady-state volume of distribution is approximately 150 L.

**Metabolism:** Primarily metabolized by the hepatic enzyme CYP3A4, with minor contributions from CYP2C8 and CYP2C19.

**Excretion:** The elimination half-life (t½) is approximately 16–19 hours; approximately 60% is excreted via feces, and 30% via urine.

**Special Populations:** No dose adjustment is required for patients with mild hepatic or renal impairment; dose reduction is required for patients with moderate to severe hepatic impairment or severe renal impairment. [Dosage and Administration]

Recommended Dosage

Standard Dose: 200 mg orally once daily, continued until disease progression or the occurrence of intolerable toxicity.

Administration: May be taken with or without food; swallow the tablet whole; do not chew, crush, or split the tablet.

Dose Adjustments

Dose Adjustments for Adverse Reactions

Grade 3 Non-hematologic Toxicity: Suspend treatment; once resolved to Grade ≤1, resume at a reduced dose of 100 mg once daily. If Grade ≥3 toxicity recurs, permanently discontinue the drug.

Grade 4 Hematologic Toxicity: Suspend treatment; once resolved to Grade ≤2, resume at a reduced dose of 100 mg once daily. If Grade 4 toxicity recurs, permanently discontinue the drug.

Infection: Suspend treatment for Grade ≥3 infections; resume at the original dose once the infection is controlled.

Dosage for Specific Populations

Moderate to Severe Hepatic Impairment: Recommended dose is 100 mg once daily.

Severe Renal Impairment (eGFR < 30 mL/min): Recommended dose is 100 mg once daily.

Dose Adjustments for Drug Interactions

Strong CYP3A Inhibitors (e.g., ketoconazole, itraconazole): Avoid concomitant use; if concomitant use cannot be avoided, reduce the dose to 100 mg once daily.

Strong CYP3A Inducers (e.g., rifampin, phenytoin): Avoid concomitant use.

Moderate CYP3A Inhibitors: No dose adjustment is required; monitor closely for adverse reactions.

[Adverse Reactions]

Most Common Adverse Reactions (≥15%)

Fatigue, musculoskeletal pain, diarrhea, edema, dyspnea, pneumonia, bruising.

Common Laboratory Abnormalities (≥10%)

Grade 3/4: Neutropenia, thrombocytopenia, lymphopenia, anemia.

Grade 1/2: Elevated ALT/AST, elevated bilirubin, elevated blood creatinine.

Serious Adverse Reactions (<5%)

Infections: Pneumonia, sepsis, herpes zoster.

Hemorrhage: Intracranial hemorrhage, gastrointestinal hemorrhage (incidence is lower than with covalent BTK inhibitors).

Cardiac Toxicity: Atrial fibrillation, palpitations (low incidence).

Hepatic Impairment: Drug-induced liver injury (rare; liver function monitoring is required). [Contraindications]

Contraindicated in patients with hypersensitivity to pirtobrutinib or to any of the excipients contained in this product.

[Precautions]

1. Risk of Infection

Screen for Hepatitis B/C and Tuberculosis prior to treatment; monitor for fever and signs/symptoms of infection during treatment. Discontinue treatment for Grade ≥3 infections.

2. Risk of Bleeding

Serious bleeding events are uncommon; avoid concomitant use with anticoagulants or antiplatelet agents. If concomitant use is necessary, monitor closely for signs of bleeding.

3. Hepatotoxicity

Monitor liver function prior to treatment, every 2 weeks during the first 3 months of treatment, and monthly thereafter. Discontinue treatment if ALT/AST levels exceed 5 times the Upper Limit of Normal (ULN); resume treatment at a reduced dose once levels return to baseline or Grade 1.

4. Embryo-Fetal Toxicity

May cause fetal harm; women of reproductive potential must use effective contraception during treatment and for 1 week after discontinuing the drug.

5. Lactose Intolerance

Contains lactose monohydrate; contraindicated in patients with galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption.

[Drug Interactions]

Strong CYP3A Inhibitors: Significantly increase pirtobrutinib plasma concentrations; avoid concomitant use.

Strong CYP3A Inducers: Significantly decrease pirtobrutinib plasma concentrations; avoid concomitant use.

Proton Pump Inhibitors (PPIs): No clinically significant interaction observed; may be used concomitantly.

Warfarin/Heparin: Increase the risk of bleeding; avoid concomitant use.

[Use in Specific Populations]

Pregnancy: Contraindicated in pregnant women.

Lactation: Discontinue breastfeeding during treatment and for 1 week after discontinuing the drug.

Pediatric Use: Safety and efficacy in patients <18 years of age have not been established; use is not recommended.

Geriatric Use: No dose adjustment is required for patients ≥65 years of age; monitor closely for tolerability.

Hepatic Impairment: Reduce dose in patients with moderate to severe hepatic impairment; no dose adjustment is required for mild hepatic impairment.

Renal Impairment: Reduce dose in patients with severe renal impairment; no dose adjustment is required for mild to moderate renal impairment.

[Storage]

Keep tightly closed. Store at 20°C to 25°C; excursions permitted between 15°C and 30°C.