Drug Detail:Talzenna (Talazoparib)
Generic Name: TALAZOPARIB TOSYLATE 0.25mg
Dosage Form: capsule
Drug Class: PARP inhibitors
Patient Selection
Information on the FDA-approved tests for the detection of genetic mutations is available at http://www.fda.gov/companiondiagnostics.
gBRCAm HER2-negative Locally Advanced or Metastatic Breast Cancer
Select patients for the treatment of advanced breast cancer with TALZENNA based on the presence of germline BRCA mutations [see Indications and Usage (1.1), Clinical Studies (14.1)].
HRR Gene-mutated Metastatic Castration-Resistant Prostate Cancer
Select patients for the treatment of HRR gene-mutated mCRPC with TALZENNA based on the presence of HRR gene mutations (ATM, ATR, BRCA1, BRCA2, CDK12, CHEK2, FANCA, MLH1, MRE11A, NBN, PALB2, or RAD51C) [see Indications and Usage (1.2), Clinical Studies (14.2)].
An FDA-approved test for the detection of HRR gene mutations for use with TALZENNA is not currently available.
Recommended Dosage for gBRCAm HER2-negative Locally Advanced or Metastatic Breast Cancer
The recommended dosage of TALZENNA is 1 mg taken orally once daily, until disease progression or unacceptable toxicity.
Recommended Dosage for HRR Gene-mutated mCRPC
The recommended dosage of TALZENNA is 0.5 mg taken orally once daily in combination with enzalutamide until disease progression or unacceptable toxicity.
Refer to the enzalutamide prescribing information for recommended enzalutamide dosing information.
Patients receiving TALZENNA and enzalutamide should also receive a gonadotropin-releasing hormone (GnRH) analog concurrently or should have had bilateral orchiectomy.
Administration
Take TALZENNA with or without food.
Swallow TALZENNA capsules whole. Do not open or dissolve.
If a patient vomits or misses a dose of TALZENNA, instruct them to take the next prescribed dose at the usual time.
Dosage Modifications for Adverse Reactions
To manage adverse reactions, consider interruption of treatment with or without dose reduction based on severity and clinical presentation. Recommended dose reductions are indicated in Table 1 and Table 2. Treatment with TALZENNA should be discontinued if more than three dose reductions are required.
gBRCAm HER2-negative Locally Advanced or Metastatic Breast Cancer
|
Dose Reductions |
Dose Level |
|
Recommended starting dose |
1 mg once daily |
|
First dose reduction |
0.75 mg once daily |
|
Second dose reduction |
0.5 mg once daily |
|
Third dose reduction |
0.25 mg once daily |
HRR Gene-mutated mCRPC
|
Dose Reductions |
Dose Level |
|
Recommended starting dose |
0.5 mg once daily |
|
First dose reduction |
0.35 mg once daily |
|
Second dose reduction |
0.25 mg once daily |
|
Third dose reduction |
0.1 mg once daily |
Refer to the enzalutamide prescribing information for dose modifications for adverse reactions associated with enzalutamide.
gBRCAm HER2-negative Locally Advanced or Metastatic Breast Cancer and HRR Gene-mutated mCRPC
Monitor complete blood counts monthly and as clinically indicated [see Warnings and Precautions (5.2)].
|
Adverse Reactions |
Withhold TALZENNA Until Levels Resolve To |
Resume TALZENNA |
|
Hemoglobin <8 g/dL |
≥9 g/dL |
Resume TALZENNA at a reduced dose |
|
Platelet count <50,000/μL |
≥75,000/μL |
|
|
Neutrophil count <1,000/μL |
≥1500/µL |
|
|
Non-hematologic Grade 3 or Grade 4 |
≤Grade 1 |
Consider resuming TALZENNA at a reduced dose or discontinue |
Recommended Dosage in Patients with Renal Impairment
gBRCAm HER2-negative Locally Advanced or Metastatic Breast Cancer
The recommended dosage of TALZENNA for patients with moderate renal impairment (CLcr 30 - 59 mL/min) is 0.75 mg taken orally once daily [see Use in Specific Populations (8.7)].
The recommended dosage of TALZENNA for patients with severe renal impairment (CLcr 15 - 29 mL/min) is 0.5 mg taken orally once daily [see Use in Specific Populations (8.7)].
HRR Gene-mutated mCRPC
The recommended dosage of TALZENNA for patients with moderate renal impairment (CLcr 30 - 59 mL/min) is 0.35 mg taken orally once daily in combination with enzalutamide [see Use in Specific Populations (8.7)].
The recommended dosage of TALZENNA for patients with severe renal impairment (CLcr 15 - 29 mL/min) is 0.25 mg taken orally once daily in combination with enzalutamide [see Use in Specific Populations (8.7)].
Dosage Modifications for P-glycoprotein Inhibitors
gBRCAm HER2-negative Locally Advanced or Metastatic Breast Cancer
Avoid coadministration of TALZENNA with the following P-glycoprotein (P-gp) inhibitors: itraconazole, amiodarone, carvedilol, clarithromycin, itraconazole, and verapamil. If coadministration of TALZENNA with these P-gp inhibitors cannot be avoided, reduce the dose of TALZENNA to 0.75 mg taken orally once daily. When the P-gp inhibitor is discontinued, increase the dose of TALZENNA (after 3 – 5 half-lives of the P-gp inhibitor) to the dose of TALZENNA that was used before starting the P-gp inhibitor [see Drug Interactions (7.1)].
Monitor for increased adverse reactions and modify the dosage as recommended for adverse reactions when TALZENNA is coadministered with other P-gp inhibitors [see Dosage and Administration (2.5)].
