LuciTala Talazoparib capsules

[Drug Name]

Generic Name: Talazoparib Capsules

English Name: Talazoparib capsules

Brand Names: Talzenna, LuciTala

Dosage Form: Capsules

Specifications: 0.1 mg × 30 capsules/box; 0.25 mg × 60 capsules/box

Active Ingredient: Talazoparib Tosylate

Drug Class: Poly(ADP-ribose) polymerase (PARP) inhibitor

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

Drug Approval Number: 12 L 1421/25 / 12 L 1420/25

[Description]

White, opaque hard capsules containing a white to off-white powder.

[Pharmacological Class]

Poly(ADP-ribose) polymerase (PARP) inhibitor; classified as a third-generation, highly selective PARP inhibitor possessing potent PARP-trapping capability.

[Indications]

Breast Cancer: Indicated for the treatment of adult patients with locally advanced or metastatic breast cancer who are HER2-negative and harbor deleterious or suspected deleterious germline *BRCA1/2* mutations (g*BRCA*m).

Prostate Cancer: Indicated for use in combination with enzalutamide for the treatment of adult patients with metastatic castration-resistant prostate cancer (mCRPC) who harbor homologous recombination repair gene mutations (HRRm).

Patients with a history of prior chemotherapy (e.g., anthracyclines, taxanes) are preferred; however, patients who have not received prior chemotherapy may also be considered.

Note: Not indicated for patients with *BRCA* wild-type or somatic mutations (s*BRCA*m), unless within the context of a clinical trial.

[Dosage and Administration]

Standard Dosage:

Recommended Dose: 1 mg (four 0.25 mg capsules) once daily, taken orally.

May be taken with or without food. Capsules should be swallowed whole; do not chew, crush, or open the capsules. Dosage Adjustment (Due to Adverse Reactions):

Adverse Reactions: In the event of adverse reactions, consider treatment interruption or dose reduction (e.g., by using the 0.25 mg capsule).

Renal Impairment:

Mild (CrCl 60–89 mL/min): No dosage adjustment required.

Moderate (CrCl 30–59 mL/min): Reduce dose to 0.75 mg once daily.

Severe (CrCl <30 mL/min) or requiring hemodialysis: Not studied; use with caution.

Hepatic Impairment:

Mild (Total bilirubin ≤1 × ULN and AST > ULN, or total bilirubin >1–1.5 × ULN and AST normal): No dosage adjustment required.

Moderate to Severe (Total bilirubin >1.5 × ULN and AST abnormal): Not studied; use with caution.

P-glycoprotein (P-gp) Inhibitors: Avoid concomitant use with amiodarone, carvedilol, clarithromycin, itraconazole, verapamil, etc. If concomitant use is unavoidable, reduce the dose to 0.75 mg once daily; resume the original dose 3–5 half-lives after discontinuing the P-gp inhibitor.

[Contraindications]

Patients with hypersensitivity to talazoparib or any of its excipients;

Pregnant women (highly teratogenic);

Severe hepatic impairment (Child-Pugh Class C);

Concomitant use with strong CYP3A4 inducers (e.g., rifampin, carbamazepine, phenytoin), due to significant reduction in plasma drug concentrations.

[Boxed Warning] (FDA/NMPA Critical Warning)

1. Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML):

Incidence is approximately 1.5%; may be fatal. If diagnosed, the drug must be permanently discontinued.

2. Embryo-Fetal Toxicity:

May cause fetal malformations or death. Women of reproductive potential must use effective contraception during treatment and for 7 months after discontinuing the drug. 【Adverse Reactions】

Common Adverse Reactions (Incidence ≥10%):

Hematologic System: Decreased hemoglobin (90%), decreased white blood cells (84%), decreased lymphocytes (76%), decreased neutrophils (68%), decreased platelets (55%).

Systemic Symptoms: Fatigue (62%).

Other: Myelodysplastic Syndrome (MDS) / Acute Myeloid Leukemia (AML) (potential risk).

【Precautions】

1. BRCA Testing:

An NMPA-approved companion diagnostic assay (e.g., BRACAnalysis CDx) must be used to confirm the presence of a germline *BRCA* mutation (g*BRCA*m).

2. Hematologic Monitoring:

Perform a complete blood count (CBC) prior to initiating treatment and monthly thereafter; monitoring every 2 weeks is recommended during the first 2 months of treatment.

3. Drug Interactions:

Avoid concomitant use with strong CYP3A4 inducers.

Concomitant use with P-gp inhibitors (e.g., verapamil) may increase drug concentrations; use with caution.

4. Effects on Fertility:

May cause male infertility; sperm banking prior to treatment is recommended.

5. Lactation:

Breastfeeding is contraindicated during treatment and for 1 month following the last dose.

【Use in Specific Populations】

Pregnant Women: Pregnancy Category X (Contraindicated); animal studies have demonstrated teratogenicity.

Lactating Women: Avoid breastfeeding for 1 month following the last dose.

Pediatric Patients (<18 years): Safety has not been established; use is not recommended.

Geriatric Patients (≥65 years): No initial dose adjustment is required; however, these patients may be at increased risk for anemia and require closer monitoring.

Hepatic Impairment:

Mild (Child-Pugh Class A): No dose adjustment required.

Moderate (Child-Pugh Class B): Reduce initial dose to 0.75 mg once daily (qd).

Severe (Child-Pugh Class C): Contraindicated.

Renal Impairment:

Mild to Moderate (CrCl ≥30 mL/min): No dose adjustment required.

Severe (CrCl <30 mL/min) or End-Stage Renal Disease (on dialysis): Initial dose is 0.75 mg once daily (qd). [Pharmacology and Toxicology]

Mechanism of Action:

Inhibits PARP1/2 enzyme activity, thereby blocking single-strand DNA repair;

Exhibits potent "PARP trapping" (trapping of PARP-DNA complexes), leading to replication fork collapse and double-strand breaks;

In BRCA-deficient cells, the absence of homologous recombination repair (HRR) results in synthetic lethality.

Selectivity: Demonstrates 100-fold greater cytotoxicity against BRCA-mutated tumor cells compared to olaparib (in vitro).

[Pharmacokinetics]

Absorption: Tmax is 1–4 hours; a high-fat meal does not affect exposure levels;

Distribution: Protein binding rate is approximately 71%; widely distributed throughout tissues;

Metabolism: Primarily oxidized via CYP3A4; secondarily metabolized via UGT1A9/1A1;

Half-life: Approximately 56 hours;

Excretion: Feces (64%), Urine (17%).

[Storage]

Store in a tightly sealed container at temperatures below 25°C; keep in the original packaging to protect from moisture.

Important Note:

Talazoparib is the first PARP inhibitor to demonstrate significant superiority over chemotherapy (e.g., capecitabine, eribulin) in a Phase III clinical trial (the EMBRACA study), achieving a median PFS of 8.6 months versus 5.6 months.

It is mandatory to confirm that the patient is positive for a germline BRCA mutation (gBRCAm) and to ensure they undergo standardized clinical management, including continuous monitoring for hematologic toxicity and the risk of MDS/AML throughout the course of treatment.