Introduction

Talapar­ib 1 mg is a potent PARP (poly ADP‑ribose polymerase) inhibitor, designed to impair DNA repair in cancer cells bearing homologous recombination deficiencies, especially BRCA1/2 mutations. Manufactured to rigorous standards by Everest Pharmaceuticals Ltd, this oral capsule is supplied globally by Orio Pharma, supporting oncology centers and patients worldwide.

Talzap­arib exhibits strong PARP‑trapping activity, halting DNA repair and inducing cancer cell death, particularly in tumors dependent on single‑strand repair mechanisms. Its use marks a significant advancement in personalized therapy for eligible breast and prostate cancer patients.

Indications

Talazop­arib is indicated for:

1. BRCA‑mutated (gBRCAm), HER2‑negative, locally advanced or metastatic breast cancer
   
   • Administered as monotherapy in patients with deleterious germline BRCA variants.
     
2. HRR gene‑mutated metastatic castration‑resistant prostate cancer (mCRPC)
   
   • Given in combination with Enzalutamide for patients with known HRR gene alterations, including BRCA2, ATM, PALB2, RAD51 mutations.
     

These indications are backed by pivotal trials such as EMBRACA and TALAPRO-2, demonstrating improved progression‑free survival and overall response rates.

Mechanism of Action

Talazop­arib targets PARP1/2, enzymes critical for base excision repair. By inhibiting enzymatic activity and forming stable PARP–DNA complexes (PARP‑trapping), it perpetuates DNA repair breakdown. In cells deficient in homologous recombination repair mechanisms—like BRCA‑mutant tumors—this leads to accumulated genomic damage and tumor cell apoptosis. This dual mechanism ensures robust, cancer‑selective cytotoxicity.

Dosage & Administration

For gBRCAm HER2‑negative breast cancer:

• Recommended dose: 1 mg orally once daily
  
• Continue until disease progression or unacceptable toxicity
  

For HRR‑mutated mCRPC (with Enzalutamide):

• Recommended dose: 0.5 mg orally once daily alongside Enzalutamide
  
• Continue until disease progression or unacceptable toxicity
  

Administration guidelines:

• Capsules should be swallowed whole with or without food
  
• Daily dose should be taken around the same time
  
• Missed doses should not be doubled; resume next scheduled dose
  

Dose modifications:

• Offer dose interruption or reduction in case of toxicity
  
• Monitor CBC and manage hematologic side effects promptly
  

Pharmacokinetics

• Absorption: Peak plasma levels within ~1–2 hours
  
• Food effects: Can be taken with or without food
  
• Distribution: Widely distributed with low protein binding (~74%)
  
• Metabolism: Minor by CYP3A4; primary route renal
  
• Elimination: Half-life ~90 hours, allowing once-daily dosing
  

Use caution and adjust dose in moderate to severe renal impairment.

Drug Interactions

• P‑gp / BCRP inhibitors (e.g., verapamil, amiodarone): May increase Talazop­arib levels—dose reduction advised
  
• CYP3A4 inhibitors/inducers: Not clinically significant due to minimal metabolism
  
• QT‑prolonging drugs: Monitor ECG if co-administered
  
• Use with Enzalutamide: Adjust Talazoparib in prostate cancer per protocol
  

Safety Profile & Adverse Events

Hematologic:

• Anemia, neutropenia, thrombocytopenia (20–45%)
  
• Monitor CBC weekly for first 2 cycles, then monthly
  

Non‑hematologic:

• Fatigue, nausea, diarrhea, vomiting
  
• Headache, alopecia, decreased appetite
  
• Liver enzyme elevations—monitor AST/ALT
  

Rare but Serious:

• MDS/AML—discontinue if confirmed
  
• Embryo-fetal toxicity—contraindicated in pregnancy
  
• Infertility potential—advise contraception
  

Warnings & Precautions

1. Myelosuppression – Monitor for severe cytopenias; treat promptly
   
2. Secondary malignancies (MDS/AML) – discontinue upon diagnosis
   
3. Pregnancy risk – strictly contraindicated; both genders must use contraception
   
4. Infertility – counsel patients on fertility planning prior to treatment
   
5. Renal impairment – dose reduction needed; avoid in ESRD or hemodialysis
   

Use in Special Populations

• Pregnancy – Contraindicated due to teratogenic risk
  
• Lactation – Unknown excretion; avoid breastfeeding
  
• Geriatric – No dose adjustment; monitor tolerability
  
• Pediatric – Safety unestablished
  
• Hepatic impairment – Up to moderate, no adjustment; severe cases should not receive
  

Overdose Management

No specific antidote exists. Overdose may prompt severe myelosuppression, gastrointestinal toxicity, and fatigue. Discontinue and provide supportive measures. Monitor CBC, electrolytes, renal and hepatic function.

Storage & Handling

• Store at 20–25 °C, protected from moisture and heat
  
• Avoid light exposure
  
• Keep caps sealed and out of children’s reach
  
• Dispose safely following local regulations
  

Packaging

Talazop­arib 1 mg capsules come in blister packs of 28 or 56, printed clearly with drug name, strength, batch, and expiry date. Packaging meets international standards for safety and traceability.

Clinical Benefits

• Targeted efficacy in BRCA/HRR‑mutant cancers
  
• Oral administration improves patient convenience
  
• Well–characterized safety allows outpatient care
  
• Quality‑of-life improvement through reduced invasive therapy
  
• Evidence‑based: EMBRACA, TALAPRO‑1/2 demonstrate strong outcomes
  

Conclusion

Talazop­arib 1  mg Capsule is a breakthrough in personalized oncology, offering high efficacy in BRCA‑mutant breast cancer and HRR‑altered prostate cancer. With its targeted mechanism, oral convenience, and tolerable safety profile, it is an essential asset in cancer treatment protocols. Produced by Everest Pharmaceuticals Ltd and supplied by Orio Pharma, Talazop­arib ensures quality, authenticity, and global availability for institutions relying on precision oncology solutions.