Talzenna (Talazoparib) is indicated for the treatment of adult patients with locally advanced or metastatic breast cancer who are human epidermal growth factor receptor 2 (HER2)-negative and positive for germline breast cancer susceptibility gene (BRCA)-mutations (gBRCAm). The EMBRACA study was conducted to evaluate the safety of Talazoparib as monotherapy in gBRCAm patients with HER2-negative metastatic or locally advanced breast cancer who had previously received no more than 3 lines of chemotherapy.

Talzenna (Talazoparib) dose in Adults

Note: It should only be administered to patients with a germline BRCA mutation.

Talzenna (Talazoparib) dose in the treatment of locally advanced or metastatic breast cancer who are HER2-negative and BRCA mutation-positive:

• 1 mg once a day until the disease progresses or toxicity develops.
• In case of a missed dose or if the patient vomits after the intake of the drug, administration of an additional dose is not recommended. The next dose should be administered at the scheduled time.

• Dosage adjustment for concomitant therapy:

  • P-GP inhibitors:

    • The dose should be reduced to 0.75 mg once a day when co-administered with drugs like amiodarone, clarithromycin, carvedilol, itraconazole, and verapamil).
    • The dose should be increased after 3 - 5 half-lives of the P-GP inhibitors have elapsed (after the drug is discontinued).

Dose modification according to the severity of adverse effects:

Treatment of Talzenna (Talazoparib) overdose:

Specific treatment is not available if an overdose occurs. However, supportive treatment along with gastric decontamination via a gastric lavage should be performed.

Note: Talazoparib should be discontinued if three or more dose reductions are required.

Talzenna (Talazoparib) dose in Childrens

It has not been studied in pediatric population

Talzenna (Talazoparib) pregnancy Risk Category: X

• Talzenna (Talazoparib), used in pregnancy, has been associated with adverse fetal outcomes in animal studies.
• Pregnancy testing is required before you can start the treatment.
• Effective contraception should be used by females with reproductive potential for at least seven years after the last drug dose.
• Effective contraception should be used for at least four months by males who have a female partner with reproductive potential, or pregnant women.
• It can impair male fertility.

Use of Talazoparib while breastfeeding

• Because of the possible adverse effects associated with talzenna use, breastfeeding should be avoided for at least one year.

Talzenna dose in kidney disease:

• CrCl of 60 - 89 mL/minute:

  • Adjustment in the dose is not necessary

• CrCl 30 - 59 mL/minute:

  • Reduce the dose to 0.75 mg once a day.

• CrCl of less than 30 mL/minute:

  • The drug has not been studied in patients with a CrCl of less than 30 ml/min.
  • The manufacturer has not recommended any adjustments in the dose.

• Hemodialysis:

  • The drug has not been studied in patients on hemodialysis.
  • The manufacturer has not recommended any adjustments in the dose in these patients.

Talzenna dose in liver disease:

• Dosage adjustment is not necessary in patients with mild impairment i.e.:

  • A total bilirubin equals or less than the ULN (upper limits of normal) and AST greater than the upper limits of normal or
  • Total bilirubin more than 1 - 1.5 times the upper limits of normal and any AST.

• The manufacturer has not recommended any adjustment in the dose in patients with moderate hepatic impairment and severe hepatic impairment:

  • Moderate hepatic impairment includes total bilirubin of more than 1.5 - 3 times the ULN and any AST
  • Severe hepatic impairment includes total bilirubin more than 3 times the ULN and any AST.

Common Side Effects of Talazoparib (Talzenna) Include:

• Central Nervous System:

  • Fatigue
  • Headache
  • Dizziness

• Dermatologic:

  • Alopecia

• Endocrine & Metabolic:

  • Increased Serum Glucose
  • Decreased Serum Calcium

• Gastrointestinal:

  • Nausea
  • Vomiting
  • Diarrhea
  • Decreased Appetite
  • Abdominal Pain

• Hematologic & Oncologic:

  • Decreased Hemoglobin
  • Anemia
  • Neutropenia
  • Thrombocytopenia
  • Leukopenia

• Hepatic:

  • Increased Serum Aspartate Aminotransferase
  • Increased Serum Alkaline Phosphatase
  • Increased Serum Alanine Aminotransferase

 Talazoparib (Talzenna) side effects (Less Common):

• Gastrointestinal:

  • Dysgeusia
  • Dyspepsia
  • Stomatitis

• Hematologic & oncologic:

  • Lymphocytopenia

Rare side effects of Talzenna:

• Hematologic & oncologic:

  • Bone marrow depression

Contraindication to Talazoparib (Talzenna) Include:

It has not been mentioned by the manufacturer that there are any contraindications.

Warnings and precautions

• Suppression of bone marrow
  • It has been reported that bone marrow suppression can be caused by its use.
  • This may sometimes prove to be very serious. This can manifest as anemia or leukopenia, neutropenia or thrombocytopenia.
  • Before starting treatment, blood counts should be checked. Monthly follow-ups should also be done as indicated by the doctor.
  • If the hematological toxicity is not resolved, treatment should be stopped.
  • Patients with severe or prolonged hematological toxicity should have their blood count checked weekly until they recover. 
  • Patients with persistent cytopenia should be examined (including BMB or cytogenetic studies) after 4 weeks of treatment.
• Gastrointestinal toxicities:
  • It can cause mild to moderate dyspepsia and nausea.
• Secondary malignancy
  • Patients who have received prolonged treatment with Talazoparib or other DNA-damaging chemotherapeutics agents, such as platinum-based chemotherapeutics agents, or radiation are at increased risk for developing Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML).
  • Patients with severe or prolonged hematological toxicities should have their blood count checked weekly until they recover. 
  • Patients with persistent cytopenia should be examined (including BMB or cytogenetic studies).
  • Patients with MDS/AML should stop taking the medication.
• Renal impairment
  • Patients with impaired renal function should have their talazoparib dose adjusted to reflect the creatinine clearance.

Talazoparib: Drug Interaction

Monitor:

• BRCA-mutation status.
• Blood CBC at the start of therapy and then every month or as needed (Blood CBC should be monitored weekly in those patients who develop severe cytopenias or prolonged hematological toxicity.
• Monitor renal function tests
• A pregnancy test should be done at the start of therapy in females of reproductive potential.
• Patients should be monitored for the clinical features of acute myeloid leukemia and myelodysplastic syndrome (AML/MDS).
• Drug compliance should be monitored.

How to administer Talazoparib (Talzenna)?

• The drug may be administered with or without meals.
• The capsules should be swallowed whole (capsules should not be opened or dissolved)

Mechanism of action of Talazoparib (Talzenna):

• Talzenna (talazoparib), a powerful inhibitor of poly (ADPribose polymerase) polymerase enzyme (PARP) enzyme inhibitor (including ParP1 and PARP2), has strong PARP-trapping and catalytic inhibiting capabilities.
• PARP enzymes control DNA transcription, DNA repair and cell cycle regulation. 
• Their inhibition can lead to cell death from damaged DNA.
• In vitro studies using cancer cells with defective DNA repair genes (like BRCA-1 or BRCA-2), talazoparib-induced Cytotoxicity results in inhibition of PARP enzyme activity and an increase in the formation PARP-DNA complexes.
• The PARP DNA complexes are more toxic than enzymatic inhibition.
• This causes DNA damage, impaired cell proliferation, and apoptosis.

74% of the drug's total isProtein-bound It has minimal hepatic metabolism. 

These metabolic pathways are:Mono-oxidation, Dehydrogenation, Cystine conjugation of Mono-desfluorotalazoparib and Glucuronide Conjugation

Half-life elimination of the drug is 90 (±58) hours

The time to reach peak plasma concentration is 1 to 2 hours

Excretion is mainly via urine (about 69%) including 54.6% as unchanged drug and about 20% via fecal excretion (13.6% as unchanged drug).

Talazoparib brands (International):

• Talzenna

Talzenna (Talazoparib) Brands in Pakistan:

Talzenna (Talazoparib) is not available in Pakistan.