Note: Administer only to patients with germline BRCA mutation (as detected by an approved test).
Breast cancer, locally advanced or metastatic, BRCA-mutated, HER2-negative: Oral: 1 mg once daily until disease progression or unacceptable toxicity (Litton 2018).
Missed doses: If a dose is missed or vomited, an additional dose should not be administered; administer the next dose at the usual scheduled time.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
CrCl ≥60 mL/minute: No dosage adjustment necessary.
CrCl 30 to 59 mL/minute: Reduce dose to 0.75 mg once daily.
CrCl 15 to 29 mL/minute: Reduce dose to 0.5 mg once daily.
CrCl <15 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Hemodialysis: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Mild, moderate, or severe impairment: No dosage adjustment is necessary.
Refer to adult dosing.
Consider therapy interruption with or without dose reduction for adverse reactions, depending on the severity and clinical presentation. Talazoparib should be discontinued if more than 3 dose reductions are necessary.
Recommended talazoparib dose reductions for toxicity:
Initial/usual 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
Hematologic toxicity:
Hemoglobin <8 g/dL: Withhold talazoparib until hemoglobin is ≥9 g/dL, then resume therapy at a reduced dose.
Neutrophils <1,000/mm3: Withhold talazoparib until neutrophils are ≥1,500/mm3, then resume therapy at a reduced dose.
Platelets <50,000/mm3: Withhold talazoparib until platelets are ≥75,000/mm3, then resume therapy at a reduced dose.
MDS/AML (confirmed): Discontinue therapy
Nonhematologic toxicity: Grade 3 or 4 toxicity: Withhold talazoparib until toxicity is ≤ grade 1, then consider resuming therapy at a reduced dose or discontinuing talazoparib (depending on the severity of the toxicity).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral, as tosylate:
Talzenna: 0.25 mg, 0.5 mg, 0.75 mg, 1 mg
No
Oral: Administer with or without food. Swallow capsules whole; do not open or dissolve capsule.
This medication is not on the NIOSH (2016) list; however, it may meet the criteria for a hazardous drug. Talazoparib may cause carcinogenicity, reproductive toxicity, teratogenicity, and genotoxicity.
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).
Note: Facilities may perform risk assessment of some hazardous drugs to determine if appropriate for alternative handling and containment strategies (USP-NF 2020). Refer to institution-specific handling policies/procedures.
Breast cancer, locally advanced or metastatic (BRCA-mutated, HER2-negative): Treatment of 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 in adults (as detected by an approved test).
Talazoparib may be confused with niraparib, olaparib, rucaparib, tepotninb, tucatinib
This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its lists of drug classes which have a heightened risk of causing significant patient harm when used in error.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%
Central nervous system: Fatigue (62%), headache (33%), dizziness (17%)
Dermatologic: Alopecia (25%)
Endocrine & metabolic: Increased serum glucose (54%), decreased serum calcium (28%)
Gastrointestinal: Nausea (49%), vomiting (25%), diarrhea (22%), decreased appetite (21%), abdominal pain (19%)
Hematologic & oncologic: Decreased hemoglobin (90%; grade 3: 39%), anemia (53%; grade 3: 38%; grade 4: 1%), neutropenia (35%; grade 3: 18%; grade 4: 3%), thrombocytopenia (27%; grade 3: 11%; grade 4: 4%), leukopenia (17%)
Hepatic: Increased serum aspartate aminotransferase (37%), increased serum alkaline phosphatase (36%), increased serum alanine aminotransferase (33%)
1% to 10%:
Gastrointestinal: Dysgeusia (10%), dyspepsia (10%), stomatitis (8%)
Hematologic & oncologic: Lymphocytopenia (7%)
Frequency not defined: Hematologic & oncologic: Bone marrow depression
<1%, postmarketing, and/or case reports: Acute myelocytic leukemia, myelodysplastic syndrome
There are no contraindications listed in the manufacturer's labeling.
Concerns related to adverse effects:
• Bone marrow suppression: Anemia, leukopenia/neutropenia, and/or thrombocytopenia have been reported, including ≥ grade 3 events. Monitor complete blood counts at baseline and monthly thereafter (and as clinically indicated); do not initiate talazoparib until any hematologic toxicity caused by previous chemotherapy has adequately recovered. If prolonged hematologic toxicity occurs during therapy, interrupt treatment and monitor blood counts weekly until recovered; if counts do not recover to ≤ grade 1 after 4 weeks, further evaluation (including bone marrow and cytogenetic analyses) is necessary.
• Secondary malignancy: Myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) have been reported (rarely) in clinical trials (for various solid tumors). The duration of talazoparib therapy prior to development of the secondary cancers ranged from 4 months to 5 years; patients had received prior chemotherapy with platinum agents and/or other DNA-damaging medications, including radiation. If prolonged hematologic toxicity occurs during talazoparib therapy and blood counts do not recover to ≤ grade 1 after 4 weeks, further evaluation (including bone marrow and cytogenetic analyses) is necessary. If MDS/AML is confirmed, discontinue therapy.
Disease-related concerns:
• Renal impairment: Talazoparib exposure is increased in patients with renal impairment. Dosage adjustment is recommended in patients with moderate to severe impairment.
Dosage form specific issues:
• Propylene glycol: Some dosage forms may contain propylene glycol; large amounts are potentially toxic and have been associated with hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP 1997; Zar 2007).
Other warnings/precautions:
• BRCA-mutation status: Select patients for the treatment of HER2-negative locally advanced or metastatic breast cancer based on the presence of deleterious or suspected deleterious BRCA-mutations. Information on approved tests for the detection of BRCA-mutations may be found at http://www.fda.gov/companiondiagnostics.
Substrate of BCRP/ABCG2, P-glycoprotein/ABCB1 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Amiodarone: May increase the serum concentration of Talazoparib. Management: If concurrent use cannot be avoided, reduce talazoparib dose to 0.75 mg once daily. When amiodarone is discontinued, increase the talazoparib dose to the dose used before initiation of amiodarone after 3 to 5 times the half-life of amiodarone. Risk D: Consider therapy modification
Atorvastatin: May increase the serum concentration of Talazoparib. Risk C: Monitor therapy
BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
BCRP/ABCG2 Inhibitors: May increase the serum concentration of Talazoparib. Risk C: Monitor therapy
Carvedilol: May increase the serum concentration of Talazoparib. Management: If concurrent use cannot be avoided, reduce talazoparib dose to 0.75 mg once daily. When carvedilol is discontinued, increase the talazoparib dose to the dose used before initiation of carvedilol after 3 to 5 times the half-life of carvedilol. Risk D: Consider therapy modification
Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy
Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk X: Avoid combination
Clarithromycin: May increase the serum concentration of Talazoparib. Management: If concurrent use cannot be avoided, reduce talazoparib dose to 0.75 mg once daily. When clarithromycin is discontinued, increase the talazoparib dose to the dose used before initiation of clarithromycin after 3 to 5 times the half-life of clarithromycin. Risk D: Consider therapy modification
CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor therapy
Darolutamide: May increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider therapy modification
DilTIAZem: May increase the serum concentration of Talazoparib. Risk C: Monitor therapy
Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X: Avoid combination
Eltrombopag: May increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Encorafenib: May increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Felodipine: May increase the serum concentration of Talazoparib. Risk C: Monitor therapy
Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. Risk X: Avoid combination
FluvoxaMINE: Talazoparib may increase the serum concentration of FluvoxaMINE. Risk C: Monitor therapy
Futibatinib: May increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Gilteritinib: May increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Itraconazole: May increase the serum concentration of Talazoparib. Management: If concurrent use cannot be avoided, reduce talazoparib dose to 0.75 mg once daily. When itraconazole is discontinued, increase the talazoparib dose to the dose used before initiation of itraconazole after 3 to 5 times the half-life of itraconazole. Risk D: Consider therapy modification
Leflunomide: May increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Lumacaftor and Ivacaftor: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates (High risk with Inhibitors or Inducers). Lumacaftor and Ivacaftor may decrease the serum concentration of P-glycoprotein/ABCB1 Substrates (High risk with Inhibitors or Inducers). Risk C: Monitor therapy
Olaparib: Myelosuppressive Agents may enhance the myelosuppressive effect of Olaparib. Risk C: Monitor therapy
Osimertinib: May increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Oteseconazole: May increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Pacritinib: May increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk X: Avoid combination
P-glycoprotein/ABCB1 Inhibitors: May increase the serum concentration of Talazoparib. Risk C: Monitor therapy
Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Regorafenib: May increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Rolapitant: May increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Management: Monitor patients receiving rolapitant for increased exposure to and/or effects of BCRP/ABCG2 substrates. Use the lowest effective rosuvastatin dose when used in combination with rolapitant. Risk C: Monitor therapy
Ropeginterferon Alfa-2b: Myelosuppressive Agents may enhance the myelosuppressive effect of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider therapy modification
Tafamidis: May increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Taurursodiol: May increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk X: Avoid combination
Tedizolid: May increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Teriflunomide: May increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Verapamil: May increase the serum concentration of Talazoparib. Management: If concurrent use cannot be avoided, reduce talazoparib dose to 0.75 mg once daily. When verapamil is discontinued, increase the talazoparib dose to the dose used before initiation of verapamil after 3 to 5 times the half-life of verapamil. Risk D: Consider therapy modification
Voxilaprevir: May increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk X: Avoid combination
Pregnancy testing is recommended prior to therapy in females of reproductive potential. Females of reproductive potential should use effective contraception during therapy and for at least 7 months after the last talazoparib dose. Males with female partners of reproductive potential or female partners who are pregnant should also use effective contraception during therapy and for at least 4 months after the last talazoparib dose.
Based on the mechanism of action and information from animal reproduction studies, talazoparib may cause fetal harm if administered during pregnancy.
It is not known if talazoparib is present in breast milk. Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer during treatment and for at least 1 month following the last talazoparib dose.
BRCA-mutation status; complete blood count at baseline and monthly thereafter, or as clinically indicated (weekly until recovery for prolonged hematologic toxicity), renal function. Pregnancy test (prior to treatment initiation in females of reproductive potential). Monitor for signs/symptoms of acute myeloid leukemia/myelodysplastic syndrome (AML/MDS). Monitor adherence.
The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
Talazoparib is a poly (ADP-ribose) polymerase (PARP) enzyme inhibitor, including PARP1 and PARP2. PARP enzymes are involved in DNA transcription, cell cycle regulation, and DNA repair. Talazoparib is a potent PARP inhibitor, with both strong catalytic inhibition and a PARP-trapping potential that is significantly greater than other PARP inhibitors (Litton 2018). Catalytic inhibition causes cell death due to accumulation of irreparable DNA damage; talazoparib also traps PARP-DNA complexes, which may be more effective in cell death than enzymatic inhibition alone (Litton 2018).
Distribution: Vd: 420 L
Protein binding: 74%
Metabolism: Minimal hepatic metabolism; metabolic pathways include mono-oxidation, dehydrogenation, cysteine conjugation of mono-desfluoro-talazoparib, and glucuronide conjugation
Half-life elimination: 90 (±58) hours
Time to peak: 1 to 2 hours
Excretion: Urine: ~69% (54.6% as unchanged drug); Feces: ~20% (13.6% as unchanged drug)
Altered kidney function: Steady-state exposure (AUC0-24) and peak concentration (Cmax) increased by 12%, 43%, and 163% and 11%, 32%, and 89% in patients with mild (eGFR 60 to 89 mL/minute/1.73 m2), moderate (eGFR 30 to 59 mL/minute/1.73 m2), and severe (eGFR 15 to 29 mL/minute/1.73 m2) renal impairment, respectively, compared to patients with normal renal function.
Capsules (Talzenna Oral)
0.25 mg (per each): $216.42
0.5 mg (per each): $649.27
0.75 mg (per each): $649.27
1 mg (per each): $649.27
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