Prescription Drug Information: Talzenna

TALZENNA- talazoparib tosylate capsule
Pfizer Laboratories Div Pfizer Inc

1 INDICATIONS AND USAGE

TALZENNA is indicated for the treatment of adult patients with deleterious or suspected deleterious germline breast cancer susceptibility gene (BRCA)-mutated (gBRCAm) human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer. Select patients for therapy based on an FDA-approved companion diagnostic for TALZENNA [see Dosage and Administration (2.1)].

2 DOSAGE AND ADMINISTRATION

2.1 Patient Selection

Select patients for the treatment of advanced breast cancer with TALZENNA based on the presence of germline BRCA mutations [see Indications and Usage (1), Clinical Studies (14)]. Information on the FDA-approved test for the detection of BRCA mutations is available at http://www.fda.gov/companiondiagnostics.

2.2 Recommended Dosing

The recommended dose of TALZENNA is 1 mg taken orally once daily, with or without food.

The 0.25 mg capsule is available for dose reduction.

Patients should be treated until disease progression or unacceptable toxicity occurs.

The hard capsules should be swallowed whole and must not be opened or dissolved. If the patient vomits or misses a dose, an additional dose should not be taken. The next prescribed dose should be taken at the usual time.

2.3 Dose 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.

Table 1. Dose Reduction Levels for Adverse Reactions
Dose Level Dose
Recommended starting dose 1 mg (one 1 mg capsule) once daily
First dose reduction 0.75 mg (three 0.25 mg capsules) once daily
Second dose reduction 0.5 mg (two 0.25 mg capsules) once daily
Third dose reduction 0.25 mg (one 0.25 mg capsule) once daily

Table 2. Dose Modification and Management

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

2.4 Dose Modifications for Patients with Renal Impairment

For patients with moderate renal impairment (CLcr 30 – 59 mL/min), the recommended dose of TALZENNA is 0.75 mg once daily. For patients with severe renal impairment (CLcr 15 – 29 mL/min), the recommended dose of TALZENNA is 0.5 mg once daily [see Use in Specific Populations (8.6), Clinical Pharmacology (12.3)].

2.5 Dose Modifications for Use with P-glycoprotein (P-gp) Inhibitors

Reduce the TALZENNA dose to 0.75 mg once daily when coadministered with certain P-gp inhibitors. For additional information on interacting P-gp inhibitors, see Drug Interactions (7.1) and Clinical Pharmacology (12.3).

When the P-gp inhibitor is discontinued, increase the TALZENNA dose (after 3–5 half-lives of the P-gp inhibitor) to the dose used prior to the initiation of the P-gp inhibitor [see Drug Interactions (7.1), Clinical Pharmacology (12.3)].

3 DOSAGE FORMS AND STRENGTHS

Capsules:

  • 0.25 mg capsule with an ivory cap (printed with “Pfizer” in black) and a white body (printed with “TLZ 0.25″ in black)
  • 1 mg capsule with a light red cap (printed with “Pfizer” in black) and a white body (printed with “TLZ 1″ in black)

4 CONTRAINDICATIONS

None.

5 WARNINGS AND PRECAUTIONS

5.1 Myelodysplastic Syndrome/Acute Myeloid Leukemia

Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML) have been reported in patients who received TALZENNA. Overall, MDS/AML has been reported in 2 out of 584 (0.3%) solid tumor patients treated with TALZENNA in clinical studies. The duration of TALZENNA treatment in these two patients prior to developing MDS/AML was 4 months and 24 months, respectively. Both patients had received previous chemotherapy with platinum agents and/or other DNA damaging agents including radiotherapy.

Do not start TALZENNA until patients have adequately recovered from hematological toxicity caused by previous chemotherapy. Monitor complete blood counts for cytopenia at baseline and monthly thereafter. For prolonged hematological toxicities, interrupt TALZENNA and monitor blood counts weekly until recovery. If the levels have not recovered after 4 weeks, refer the patient to a hematologist for further investigations, including bone marrow analysis and blood sample for cytogenetics. If MDS/AML is confirmed, discontinue TALZENNA.

5.2 Myelosuppression

Myelosuppression consisting of anemia, leukopenia/neutropenia, and/or thrombocytopenia, have been reported in patients treated with TALZENNA [see Adverse Reactions (6)]. Grade ≥3 anemia, neutropenia, and thrombocytopenia were reported, respectively, in 39%, 21%, and 15% of patients receiving TALZENNA. Discontinuation due to anemia, neutropenia, and thrombocytopenia occurred, respectively, in 0.7%, 0.3%, and 0.3% of patients.

Monitor complete blood count for cytopenia at baseline and monthly thereafter. Do not start TALZENNA until patients have adequately recovered from hematological toxicity caused by previous therapy. If this occurs, dose modifications (dosing interruption with or without dose reduction) are recommended [see Dosing Modifications (2.3)].

5.3 Embryo-Fetal Toxicity

Based on its mechanism of action and findings from animal data, TALZENNA can cause fetal harm when administered to a pregnant woman. In an animal reproduction study, administration of talazoparib to pregnant rats during the period of organogenesis caused fetal malformations and structural skeletal variations, and embryo-fetal death at exposures that were 0.24 times the area under the concentration-time curve (AUC) in patients receiving the recommended human dose of 1 mg daily. Apprise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment and for at least 7 months following the last dose of TALZENNA [see Use in Specific Populations (8.1, 8.3), Clinical Pharmacology (12.1)].

Based on findings from genetic toxicity and animal reproduction studies, advise male patients with female partners of reproductive potential or who are pregnant to use effective contraception during treatment and for at least 4 months following the last dose of TALZENNA [see Use in Specific Populations (8.1, 8.3), Nonclinical Toxicology (13.1)].

6 ADVERSE REACTIONS

The following clinically significant adverse reactions are described elsewhere in the labeling:

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Treatment of gBRCAm HER2-negative Locally Advanced or Metastatic Breast Cancer

EMBRACA

The safety of TALZENNA as monotherapy was evaluated in gBRCAm patients with HER2-negative locally advanced or metastatic breast cancer who had previously received no more than 3 lines of chemotherapy for the treatment of locally advanced/metastatic disease. EMBRACA was a randomized, open-label, multi-center study in which 412 patients received either TALZENNA 1 mg once daily (n=286) or a chemotherapy agent (capecitabine, eribulin, gemcitabine, or vinorelbine) of the healthcare provider’s choice (n=126) until disease progression or unacceptable toxicity. The median duration of study treatment was 6.1 months in patients who received TALZENNA and 3.9 months in patients who received chemotherapy. Dosing interruptions due to an adverse reaction of any grade occurred in 65% of patients receiving TALZENNA and 50% of those receiving chemotherapy; dose reductions due to any cause occurred in 53% of TALZENNA patients and 40% of chemotherapy patients. Permanent discontinuation due to adverse reactions occurred in 5% of TALZENNA patients and 6% chemotherapy patients.

Table 3 and Table 4 summarize the most common adverse reactions and laboratory abnormalities, respectively, in patients treated with TALZENNA or chemotherapy in the EMBRACA study.

Table 3. Adverse Reactions * (in ≥20% of Patients Receiving TALZENNA) in EMBRACA
TALZENNAN=286 (%) ChemotherapyN=126 (%)
Adverse Reactions Grades 1–4 Grade 3 Grade 4 Grades 1–4 Grade 3 Grade 4
Abbreviations: AR=adverse reaction; CTCAE=Common Terminology Criteria for Adverse Events; NCI=National Cancer Institute; N=number of patients.
*
Graded according to NCI CTCAE 4.03.
Includes anemia, hematocrit decreased, hemoglobin decreased, and red blood cell count decreased.
Includes febrile neutropenia, neutropenia and neutrophil count decreased.
§
Includes thrombocytopenia and platelet count decreased.
For TALZENNA, Grade 1 in 23%, and Grade 2 in 2%. For the chemotherapy arm, Grade 1 in 20%, and Grade 2 in 8%.
#
Includes fatigue and asthenia.
Blood and lymphatic system disorders
Anemia 53 38 1 18 4 1
Neutropenia 35 18 3 43 20 16
Thrombocytopenia § 27 11 4 7 2 0
Metabolism and nutrition disorders
Decreased appetite 21 <1 0 22 1 0
Nervous system disorders
Headache 33 2 0 22 1 0
Gastrointestinal disorders
Nausea 49 <1 0 47 2 0
Vomiting 25 2 0 23 2 0
Diarrhea 22 1 0 26 6 0
Skin and subcutaneous tissue disorders
Alopecia 25 0 0 28 0 0
General disorders and administration site conditions
Fatigue # 62 3 0 50 5 0

The following adverse reactions have been identified in <20% of the 286 patients receiving TALZENNA, and thus were not included in Table 3: abdominal pain (19%), dizziness (17%), leukopenia (17%), dysgeusia (10%), dyspepsia (10%), stomatitis (8%), and lymphopenia (7%).

Table 4 Laboratory Abnormalities Reported in ≥25% of Patients in EMBRACA
EMBRACA Study
TALZENNAN *=286 (%) ChemotherapyN *=126 (%)
Parameter Grades 1–4 Grade 3 Grade 4 Grades 1–4 Grade 3 Grade 4
Abbreviation: N=number of patients.
*
This number represents the safety population. The derived values in the table are based on the total number of evaluable patients for each laboratory parameter.
This number represents non-fasting glucose.
Decrease in hemoglobin 90 39 0 77 6 0
Decrease in leukocytes 84 14 0.3 73 22 2
Decrease in neutrophils 68 17 3 70 21 17
Decrease in lymphocytes 76 17 0.7 53 8 0.8
Decrease in platelets 55 11 4 29 2 0
Increase in glucose 54 2 0 51 2 0
Increase in aspartate aminotransferase 37 2 0 48 3 0
Increase in alkaline phosphatase 36 2 0 34 2 0
Increase in alanine aminotransferase 33 1 0 37 2 0
Decrease in calcium 28 1 0 16 0 0
Page 1 of 4 1 2 3 4

RxDrugLabels.com provides trustworthy package insert and label information about marketed prescription drugs as submitted by manufacturers to the U.S. Food and Drug Administration. Package information is not reviewed or updated separately by RxDrugLabels.com. Every individual prescription drug label and package insert entry contains a unique identifier which can be used to secure further details directly from the U.S. National Institutes of Health and/or the FDA.

Medication Sections

Medication Information by RSS

As a leading independent provider of trustworthy medication information, we source our database directly from the FDA's central repository of drug labels and package inserts under the Structured Product Labeling standard. RxDrugLabels.com provides the full prescription-only subset of the FDA's repository. Medication information provided here is not intended as a substitute for direct consultation with a qualified health professional.

Terms of Use | Copyright © 2020. All Rights Reserved.