Talzenna

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Talzenna

Classes

Small Molecule Antineoplastic Poly (ADP-ribose) Polymerase (PARP) Inhibitors

Administration

Emetic Risk
Minimal/Low
Administer prn antiemetics as necessary.

Oral Administration Oral Solid Formulations

Swallow the capsules whole; do not open or dissolve.
Talazoparib may be taken with or without food.
If a patient vomits or misses a dose, an additional dose should not be taken. The patient should take the next dose at the regularly scheduled time.

Adverse Reactions
Severe

anemia / Delayed / 39.0-45.0
neutropenia / Delayed / 18.0-21.0
thrombocytopenia / Delayed / 8.0-15.0
fatigue / Early / 3.0-4.0
nausea / Early / 0.3-2.0
vomiting / Early / 0-2.0
headache / Early / 0-2.0
dizziness / Early / 0-1.5
anorexia / Delayed / 0.3-1.0
diarrhea / Early / 0-1.0
new primary malignancy / Delayed / 0.4-0.4
leukemia / Delayed / Incidence not known
bone fractures / Delayed / Incidence not known
thromboembolism / Delayed / Incidence not known

Moderate

stomatitis / Delayed / 2.0-8.0
bone marrow suppression / Delayed / Incidence not known
lymphopenia / Delayed / Incidence not known
elevated hepatic enzymes / Delayed / Incidence not known
hyperbilirubinemia / Delayed / Incidence not known
hyperglycemia / Delayed / Incidence not known
hypocalcemia / Delayed / Incidence not known
hypokalemia / Delayed / Incidence not known
hypomagnesemia / Delayed / Incidence not known
hyponatremia / Delayed / Incidence not known
hypophosphatemia / Delayed / Incidence not known

Mild

alopecia / Delayed / 7.0-25.0
abdominal pain / Early / 9.0-19.0
dysgeusia / Early / 10.0-10.0
dyspepsia / Early / 4.0-10.0
anosmia / Delayed / Incidence not known
vertigo / Early / Incidence not known
asthenia / Delayed / Incidence not known

Common Brand Names

Talzenna

Dea Class

Rx

Description

PARP inhibitor
Used for BRCA-mutated HER2-negative locally advanced or metastatic breast cancer and HRR-mutated metastatic castration-resistant prostate cancer
Monitor complete blood counts; an interruption of therapy or dose reduction may be necessary for myelosuppression

Dosage And Indications
For the treatment of breast cancer. For the treatment of deleterious or suspected deleterious germline BRCA-mutated (gBRCAm), HER2-negative locally advanced or metastatic breast cancer.
NOTE: Select patients based on the presence of deleterious or suspected deleterious BRCA-mutations. Information on FDA-approved tests for the detection of BRCA-mutations is available at www.fda.gov/companiondiagnostics.
Oral dosage Adults

1 mg orally once daily until disease progression or unacceptable toxicity. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Treatment with talazoparib (n = 287) significantly improved progression-free survival (PFS) (8.6 months vs. 5.6 months) compared with provider's choice of chemotherapy (i.e., capecitabine, eribulin, gemcitabine, or vinorelbine; n = 144) in patients with gBRCAm HER2-negative locally advanced or metastatic breast cancer who had received no more than 3 prior cytotoxic chemotherapy regimens in an open-label clinical trial (EMBRACA); median overall survival was similar between groups (19.3 months vs. 19.5 months). Patients were required to have received prior treatment with an anthracycline and/or taxane (unless contraindicated) in the neoadjuvant, adjuvant, or metastatic setting; patients with prior platinum-based therapy must have had no evidence of disease progression during platinum therapy. Approximately 56% of patients had hormone receptor (HR)-positive disease; 44% had triple-negative disease. In patients with measurable disease as determined by investigator, the objective response rate was 50.2% in talazoparib-treated patients compared with 18.4% of patients in the chemotherapy arm. The median duration of response was 6.4 months versus 3.9 months, respectively.[63651]

For the treatment of prostate cancer. For the treatment of homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer (mCRPC), in combination with enzalutamide.
NOTE: Select patients based on the presence of HRR gene mutations (ATM, ATR, BRCA1, BRCA2, CDK12, CHEK2, FANCA, MLH1, MRE11A, NBN, PALB2, or RAD51C). An FDA-approved test for the detection of HRR gene mutations for use with talazoparib is not currently available.
Oral dosage Adults

0.5 mg PO once daily, in combination with enzalutamide 160 mg PO once daily. Continue until disease progression or unacceptable toxicity. Patients should concurrently receive treatment with a gonadotropin-releasing hormone (GnRH) analog or have had a bilateral orchiectomy. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. At an interim analysis of a multicenter, randomized, double-blind, phase 3 clinical trial (TALAPRO-2), first-line treatment of asymptomatic or mildly symptomatic HRR gene-mutated mCRPC with talazoparib plus enzalutamide significantly improved median radiographic progression-free survival (rPFS) compared with placebo plus enzalutamide in men receiving ongoing androgen deprivation therapy (not established vs. 13.8 months); these results were consistent in patients regardless of whether patients received prior abiraterone (9%) or docetaxel (29%) in the castration-sensitive setting. Overall survival data were not yet mature at the time of the interim analysis. In an exploratory subgroup analysis, median rPFS was significantly improved in the talazoparib arm in patients with BRCA-mutated mCRPC (not established vs. 11 months); the improvement in rPFS did not reach statistical significance in patients with non-BRCA HRR-mutated mCRPC (24.7 months vs. 16.7 months).

Dosing Considerations
Hepatic Impairment

No dose adjustment is necessary in patients with mild, moderate, or severe hepatic impairment.

Renal Impairment

Mild renal impairment (CrCL 60 to 89 mL/min): No dose adjustment is necessary.
Moderate renal impairment (CrCL 30 to 59 mL/min): The recommended dose of talazoparib for breast cancer patients is 0.75 mg PO once daily. The recommended dose of talazoparib for prostate cancer patients is 0.35 mg PO once daily.
Severe renal impairment (CrCL 15 to 29 mL/min): The recommended dose of talazoparib for breast cancer patients is 0.5 mg PO once daily. The recommended dose of talazoparib for prostate cancer patients is 0.25 mg PO once daily.
Hemodialysis: Talazoparib has not been studied in this population.[63651]

Drug Interactions

Abrocitinib: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with abrocitinib is necessary. Talazoparib is a P-gp substrate and abrocitinib is a P-gp inhibitor.
Acalabrutinib: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if concomitant use of acalabrutinib is necessary. Concomitant use may increase talazoparib exposure. Talazoparib is a BCRP substrate and acalabrutinib is a BCRP inhibitor.
Adagrasib: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with adagrasib is necessary. Talazoparib is a P-gp substrate and adagrasib is a P-gp inhibitor.
Amiodarone: (Major) Avoid coadministration of amiodarone with talazoparib when used for the treatment of breast cancer due to increased talazoparib exposure. If concomitant use is unavoidable, reduce the dose of talazoparib to 0.75 mg PO once daily. If amiodarone is discontinued, wait at least 3 to 5 half-lives of amiodarone before increasing the dose of talazoparib to the prior dose used before amiodarone therapy. A talazoparib dose reduction is not necessary for patients with prostate cancer; monitor for an increase in talazoparib-related adverse reactions. Talazoparib is a P-gp substrate and amiodarone is a P-gp inhibitor. In clinical trials, coadministration with amiodarone increased talazoparib exposure by 45%.
Amoxicillin; Clarithromycin; Omeprazole: (Major) Avoid coadministration of clarithromycin with talazoparib when used for the treatment of breast cancer due to increased talazoparib exposure. If concomitant use is unavoidable, reduce the dose of talazoparib to 0.75 mg PO once daily. If clarithromycin is discontinued, wait at least 3 to 5 half-lives of clarithromycin before increasing the dose of talazoparib to the prior dose used before clarithromycin therapy. A talazoparib dose reduction is not necessary for patients with prostate cancer; monitor for an increase in talazoparib-related adverse reactions. Talazoparib is a P-gp substrate and clarithromycin is a P-gp inhibitor. In clinical trials, coadministration with clarithromycin increased talazoparib exposure by 45%.
Asciminib: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with asciminib is necessary. Talazoparib is a P-gp substrate and asciminib is a P-gp inhibitor.
Atazanavir; Cobicistat: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if concomitant use of cobicistat is necessary. Concomitant use may increase talazoparib exposure. Talazoparib is a P-gp and BCRP substrate; cobicistat is a P-gp and BCRP inhibitor.
Berotralstat: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with berotralstat is necessary. Talazoparib is a P-gp substrate and berotralstat is a P-gp inhibitor.
Brigatinib: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if concomitant use of brigatinib is necessary. Concomitant use may increase talazoparib exposure. Talazoparib is a P-gp and BCRP substrate; brigatinib is a P-gp and BCRP inhibitor.
Cabozantinib: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with cabozantinib is necessary. Talazoparib is a P-gp substrate and cabozantinib is a P-gp inhibitor.
Cannabidiol: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with cannabidiol is necessary. Talazoparib is a P-gp substrate and cannabidiol is a P-gp inhibitor.
Capmatinib: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if concomitant use of capmatinib is necessary. Concomitant use may increase talazoparib exposure. Talazoparib is a P-gp and BCRP substrate; capmatinib is a P-gp and BCRP inhibitor.
Carvedilol: (Major) Avoid coadministration of carvedilol with talazoparib when used for the treatment of breast cancer due to increased talazoparib exposure. If concomitant use is unavoidable, reduce the dose of talazoparib to 0.75 mg PO once daily. If carvedilol is discontinued, wait at least 3 to 5 half-lives of carvedilol before increasing the dose of talazoparib to the prior dose used before carvedilol therapy. A talazoparib dose reduction is not necessary for patients with prostate cancer; monitor for an increase in talazoparib-related adverse reactions. Talazoparib is a P-gp substrate and carvedilol is a P-gp inhibitor. In clinical trials, coadministration with carvedilol increased talazoparib exposure by 45%.
Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine.
Clarithromycin: (Major) Avoid coadministration of clarithromycin with talazoparib when used for the treatment of breast cancer due to increased talazoparib exposure. If concomitant use is unavoidable, reduce the dose of talazoparib to 0.75 mg PO once daily. If clarithromycin is discontinued, wait at least 3 to 5 half-lives of clarithromycin before increasing the dose of talazoparib to the prior dose used before clarithromycin therapy. A talazoparib dose reduction is not necessary for patients with prostate cancer; monitor for an increase in talazoparib-related adverse reactions. Talazoparib is a P-gp substrate and clarithromycin is a P-gp inhibitor. In clinical trials, coadministration with clarithromycin increased talazoparib exposure by 45%.
Cobicistat: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if concomitant use of cobicistat is necessary. Concomitant use may increase talazoparib exposure. Talazoparib is a P-gp and BCRP substrate; cobicistat is a P-gp and BCRP inhibitor.
Conivaptan: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with conivaptan is necessary. Talazoparib is a P-gp substrate and conivaptan is a P-gp inhibitor.
Cyclosporine: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if concomitant use of cyclosporine is necessary. Concomitant use may increase talazoparib exposure. Talazoparib is a P-gp and BCRP substrate; cyclosporine is a P-gp and BCRP inhibitor.
Daclatasvir: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if concomitant use of daclatasvir is necessary. Concomitant use may increase talazoparib exposure. Talazoparib is a P-gp and BCRP substrate; daclatasvir is a P-gp and BCRP inhibitor.
Darolutamide: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if concomitant use of darolutamide is necessary. Concomitant use may increase talazoparib exposure. Talazoparib is a BCRP substrate and darolutamide is a BCRP inhibitor.
Darunavir; Cobicistat: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if concomitant use of cobicistat is necessary. Concomitant use may increase talazoparib exposure. Talazoparib is a P-gp and BCRP substrate; cobicistat is a P-gp and BCRP inhibitor.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if concomitant use of cobicistat is necessary. Concomitant use may increase talazoparib exposure. Talazoparib is a P-gp and BCRP substrate; cobicistat is a P-gp and BCRP inhibitor.
Dextromethorphan; Quinidine: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with quinidine is necessary. Talazoparib is a P-gp substrate and quinidine is a P-gp inhibitor.
Dronedarone: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with dronedarone is necessary. Talazoparib is a P-gp substrate and dronedarone is a P-gp inhibitor.
Elacestrant: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if concomitant use of elacestrant is necessary. Concomitant use may increase talazoparib exposure. Talazoparib is a P-gp and BCRP substrate; elacestrant is a P-gp and BCRP inhibitor.
Elagolix: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with elagolix is necessary. Talazoparib is a P-gp substrate and elagolix is a P-gp inhibitor.
Elagolix; Estradiol; Norethindrone acetate: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with elagolix is necessary. Talazoparib is a P-gp substrate and elagolix is a P-gp inhibitor.
Elbasvir; Grazoprevir: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if concomitant use of elbasvir is necessary. Concomitant use may increase talazoparib exposure. Talazoparib is a BCRP substrate and elbasvir is a BCRP inhibitor. (Moderate) Monitor for an increase in talazoparib-related adverse reactions if concomitant use of grazoprevir is necessary. Concomitant use may increase talazoparib exposure. Talazoparib is a BCRP substrate and grazoprevir is a BCRP inhibitor.
Elexacaftor; tezacaftor; ivacaftor: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with ivacaftor is necessary. Talazoparib is a P-gp substrate and ivacaftor is a P-gp inhibitor.
Eliglustat: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with eliglustat is necessary. Talazoparib is a P-gp substrate and eliglustat is a P-gp inhibitor.
Eltrombopag: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if concomitant use of eltrombopag is necessary. Concomitant use may increase talazoparib exposure. Talazoparib is a BCRP substrate and eltrombopag is a BCRP inhibitor.
Eluxadoline: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if concomitant use of eluxadoline is necessary. Concomitant use may increase talazoparib exposure. Talazoparib is a BCRP substrate and eluxadoline is a BCRP inhibitor.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if concomitant use of cobicistat is necessary. Concomitant use may increase talazoparib exposure. Talazoparib is a P-gp and BCRP substrate; cobicistat is a P-gp and BCRP inhibitor.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if concomitant use of cobicistat is necessary. Concomitant use may increase talazoparib exposure. Talazoparib is a P-gp and BCRP substrate; cobicistat is a P-gp and BCRP inhibitor.
Enasidenib: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if concomitant use of enasidenib is necessary. Concomitant use may increase talazoparib exposure. Talazoparib is a P-gp and BCRP substrate; enasidenib is a P-gp and BCRP inhibitor.
Encorafenib: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if concomitant use of encorafenib is necessary. Concomitant use may increase talazoparib exposure. Talazoparib is a BCRP substrate and encorafenib is a BCRP inhibitor.
Erdafitinib: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with erdafitinib is necessary. Talazoparib is a P-gp substrate and erdafitinib is a P-gp inhibitor.
Erythromycin: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with erythromycin is necessary. Talazoparib is a P-gp substrate and erythromycin is a P-gp inhibitor.
Etravirine: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with etravirine is necessary. Talazoparib is a P-gp substrate and etravirine is a P-gp inhibitor.
Flibanserin: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with flibanserin is necessary. Talazoparib is a P-gp substrate and flibanserin is a P-gp inhibitor.
Fostamatinib: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if concomitant use of fostamatinib is necessary. Concomitant use may increase talazoparib exposure. Talazoparib is a P-gp and BCRP substrate; fostamatinib is a P-gp and BCRP inhibitor.
Fostemsavir: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if concomitant use of fostemsavir is necessary. Concomitant use may increase talazoparib exposure. Talazoparib is a BCRP substrate and fostemsavir is a BCRP inhibitor.
Futibatinib: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if concomitant use of futibatinib is necessary. Concomitant use may increase talazoparib exposure. Talazoparib is a P-gp and BCRP substrate; futibatinib is a P-gp and BCRP inhibitor.
Gilteritinib: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if concomitant use of gilteritinib is necessary. Concomitant use may increase talazoparib exposure. Talazoparib is a P-gp and BCRP substrate; gilteritinib is a P-gp and BCRP inhibitor.
Glecaprevir; Pibrentasvir: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if concomitant use of glecaprevir is necessary. Concomitant use may increase talazoparib exposure. Talazoparib is a P-gp and BCRP substrate; glecaprevir is a P-gp and BCRP inhibitor. (Moderate) Monitor for an increase in talazoparib-related adverse reactions if concomitant use of pibrentasvir is necessary. Concomitant use may increase talazoparib exposure. Talazoparib is a P-gp and BCRP substrate; pibrentasvir is a P-gp and BCRP inhibitor.
Grapefruit juice: (Major) Advise patients to avoid grapefruit juice while taking talazoparib due to increased talazoparib exposure. Talazoparib is a P-gp substrate and grapefruit juice is a P-gp inhibitor.
Ibrutinib: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if concomitant use of ibrutinib is necessary. Concomitant use may increase talazoparib exposure. Talazoparib is a P-gp and BCRP substrate; ibrutinib is a P-gp and BCRP inhibitor.
Isavuconazonium: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with isavuconazonium is necessary. Talazoparib is a P-gp substrate and isavuconazonium is a P-gp inhibitor.
Istradefylline: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with istradefylline is necessary. Talazoparib is a P-gp substrate and istradefylline is a P-gp inhibitor.
Itraconazole: (Major) Avoid coadministration of itraconazole with talazoparib when used for the treatment of breast cancer due to increased talazoparib exposure. If concomitant use is unavoidable, reduce the dose of talazoparib to 0.75 mg PO once daily. If itraconazole is discontinued, wait at least 3 to 5 half-lives of itraconazole before increasing the dose of talazoparib to the prior dose used before itraconazole therapy. A talazoparib dose reduction is not necessary for patients with prostate cancer; monitor for an increase in talazoparib-related adverse reactions. Talazoparib is a P-gp substrate and itraconazole is a P-gp inhibitor. In clinical trials, coadministration with itraconazole increased talazoparib exposure by 56%.
Ivacaftor: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with ivacaftor is necessary. Talazoparib is a P-gp substrate and ivacaftor is a P-gp inhibitor.
Ketoconazole: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with ketoconazole is necessary. Talazoparib is a P-gp substrate and ketoconazole is a P-gp inhibitor.
Lansoprazole; Amoxicillin; Clarithromycin: (Major) Avoid coadministration of clarithromycin with talazoparib when used for the treatment of breast cancer due to increased talazoparib exposure. If concomitant use is unavoidable, reduce the dose of talazoparib to 0.75 mg PO once daily. If clarithromycin is discontinued, wait at least 3 to 5 half-lives of clarithromycin before increasing the dose of talazoparib to the prior dose used before clarithromycin therapy. A talazoparib dose reduction is not necessary for patients with prostate cancer; monitor for an increase in talazoparib-related adverse reactions. Talazoparib is a P-gp substrate and clarithromycin is a P-gp inhibitor. In clinical trials, coadministration with clarithromycin increased talazoparib exposure by 45%.
Lapatinib: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with lapatinib is necessary. Talazoparib is a P-gp substrate and lapatinib is a P-gp inhibitor.
Lasmiditan: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with lasmiditan is necessary. Talazoparib is a P-gp substrate and lasmiditan is a P-gp inhibitor.
Ledipasvir; Sofosbuvir: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if concomitant use of ledipasvir is necessary. Concomitant use may increase talazoparib exposure. Talazoparib is a P-gp and BCRP substrate; ledipasvir is a P-gp and BCRP inhibitor.
Leflunomide: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if concomitant use of leflunomide is necessary. Concomitant use may increase talazoparib exposure. Talazoparib is a BCRP substrate and leflunomide is a BCRP inhibitor.
Lenacapavir: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if concomitant use of lenacapavir is necessary. Concomitant use may increase talazoparib exposure. Talazoparib is a P-gp and BCRP substrate; lenacapavir is a P-gp and BCRP inhibitor.
Leniolisib: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if concomitant use of leniolisib is necessary. Concomitant use may increase talazoparib exposure. Talazoparib is a BCRP substrate and leniolisib is a BCRP inhibitor.
Levoketoconazole: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with ketoconazole is necessary. Talazoparib is a P-gp substrate and ketoconazole is a P-gp inhibitor.
Lomitapide: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with lomitapide is necessary. Talazoparib is a P-gp substrate and lomitapide is a P-gp inhibitor.
Lonafarnib: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with lonafarnib is necessary. Talazoparib is a P-gp substrate and lonafarnib is a P-gp inhibitor.
Lopinavir; Ritonavir: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with ritonavir is necessary. Talazoparib is a P-gp substrate and ritonavir is a P-gp inhibitor.
Lumacaftor; Ivacaftor: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with ivacaftor is necessary. Talazoparib is a P-gp substrate and ivacaftor is a P-gp inhibitor. (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with lumacaftor; ivacaftor is necessary. Talazoparib is a P-gp substrate and lumacaftor; ivacaftor is a P-gp inhibitor.
Lumacaftor; Ivacaftor: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with lumacaftor; ivacaftor is necessary. Talazoparib is a P-gp substrate and lumacaftor; ivacaftor is a P-gp inhibitor.
Maribavir: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if concomitant use of maribavir is necessary. Concomitant use may increase talazoparib exposure. Talazoparib is a P-gp and BCRP substrate; maribavir is a P-gp and BCRP inhibitor.
Mefloquine: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with mefloquine is necessary. Talazoparib is a P-gp substrate and mefloquine is a P-gp inhibitor.
Midostaurin: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if concomitant use of midostaurin is necessary. Concomitant use may increase talazoparib exposure. Talazoparib is a BCRP substrate and midostaurin is a BCRP inhibitor.
Mitapivat: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with mitapivat is necessary. Talazoparib is a P-gp substrate and mitapivat is a P-gp inhibitor.
Nelfinavir: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with nelfinavir is necessary. Talazoparib is a P-gp substrate and nelfinavir is a P-gp inhibitor.
Neratinib: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with neratinib is necessary. Talazoparib is a P-gp substrate and neratinib is a P-gp inhibitor.
Nirmatrelvir; Ritonavir: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with ritonavir is necessary. Talazoparib is a P-gp substrate and ritonavir is a P-gp inhibitor.
Osimertinib: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if concomitant use of osimertinib is necessary. Concomitant use may increase talazoparib exposure. Talazoparib is a P-gp and BCRP substrate; osimertinib is a P-gp and BCRP inhibitor.
Oteseconazole: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if concomitant use of oteseconazole is necessary. Concomitant use may increase talazoparib exposure. Talazoparib is a BCRP substrate and oteseconazole is a BCRP inhibitor.
Pacritinib: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if concomitant use of pacritinib is necessary. Concomitant use may increase talazoparib exposure. Talazoparib is a P-gp and BCRP substrate; pacritinib is a P-gp and BCRP inhibitor.
Pirtobrutinib: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if concomitant use of pirtobrutinib is necessary. Concomitant use may increase talazoparib exposure. Talazoparib is a P-gp and BCRP substrate; pirtobrutinib is a P-gp and BCRP inhibitor.
Posaconazole: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with posaconazole is necessary. Talazoparib is a P-gp substrate and posaconazole is a P-gp inhibitor.
Pretomanid: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if concomitant use of pretomanid is necessary. Concomitant use may increase talazoparib exposure. Talazoparib is a P-gp and BCRP substrate; pretomanid is a P-gp and BCRP inhibitor.
Propafenone: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with propafenone is necessary. Talazoparib is a P-gp substrate and propafenone is a P-gp inhibitor.
Quinidine: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with quinidine is necessary. Talazoparib is a P-gp substrate and quinidine is a P-gp inhibitor.
Quinine: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with quinine is necessary. Talazoparib is a P-gp substrate and quinine is a P-gp inhibitor.
Ranolazine: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with ranolazine is necessary. Talazoparib is a P-gp substrate and ranolazine is a P-gp inhibitor.
Regorafenib: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if concomitant use of regorafenib is necessary. Concomitant use may increase talazoparib exposure. Talazoparib is a BCRP substrate and regorafenib is a BCRP inhibitor.
Ritonavir: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with ritonavir is necessary. Talazoparib is a P-gp substrate and ritonavir is a P-gp inhibitor.
Rolapitant: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if concomitant use of rolapitant is necessary. Concomitant use may increase talazoparib exposure. Talazoparib is a P-gp and BCRP substrate; rolapitant is a P-gp and BCRP inhibitor.
Safinamide: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if concomitant use of safinamide is necessary. Concomitant use may increase talazoparib exposure. Talazoparib is a BCRP substrate and safinamide is a BCRP inhibitor.
Saquinavir: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with saquinavir is necessary. Talazoparib is a P-gp substrate and saquinavir is a P-gp inhibitor.
Sarecycline: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with sarecycline is necessary. Talazoparib is a P-gp substrate and sarecycline is a P-gp inhibitor.
SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
Selpercatinib: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with selpercatinib is necessary. Talazoparib is a P-gp substrate and selpercatinib is a P-gp inhibitor.
Sodium Phenylbutyrate; Taurursodiol: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if concomitant use of taurursodiol is necessary. Concomitant use may increase talazoparib exposure. Talazoparib is a P-gp and BCRP substrate; taurursodiol is a P-gp and BCRP inhibitor.
Sofosbuvir; Velpatasvir: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if concomitant use of velpatasvir is necessary. Concomitant use may increase talazoparib exposure. Talazoparib is a P-gp and BCRP substrate; velpatasvir is a P-gp and BCRP inhibitor.
Sofosbuvir; Velpatasvir; Voxilaprevir: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if concomitant use of velpatasvir is necessary. Concomitant use may increase talazoparib exposure. Talazoparib is a P-gp and BCRP substrate; velpatasvir is a P-gp and BCRP inhibitor. (Moderate) Monitor for an increase in talazoparib-related adverse reactions if concomitant use of voxilaprevir is necessary. Concomitant use may increase talazoparib exposure. Talazoparib is a P-gp and BCRP substrate; voxilaprevir is a P-gp and BCRP inhibitor.
Sorafenib: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with sorafenib is necessary. Talazoparib is a P-gp substrate and sorafenib is a P-gp inhibitor.
Sotorasib: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if concomitant use of sotorasib is necessary. Concomitant use may increase talazoparib exposure. Talazoparib is a P-gp and BCRP substrate; sotorasib is a P-gp and BCRP inhibitor.
Sparsentan: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if concomitant use of sparsentan is necessary. Concomitant use may increase talazoparib exposure. Talazoparib is a P-gp and BCRP substrate; sparsentan is a P-gp and BCRP inhibitor.
Stiripentol: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if concomitant use of stiripentol is necessary. Concomitant use may increase talazoparib exposure. Talazoparib is a P-gp and BCRP substrate; stiripentol is a P-gp and BCRP inhibitor.
Sulfasalazine: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if concomitant use of sulfasalazine is necessary. Concomitant use may increase talazoparib exposure. Talazoparib is a BCRP substrate and sulfasalazine is a BCRP inhibitor.
Tacrolimus: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if concomitant use of tacrolimus is necessary. Concomitant use may increase talazoparib exposure. Talazoparib is a BCRP substrate and tacrolimus is a BCRP inhibitor.
Tafamidis: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if concomitant use of tafamidis is necessary. Concomitant use may increase talazoparib exposure. Talazoparib is a BCRP substrate and tafamidis is a BCRP inhibitor.
Tedizolid: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if concomitant use of tedizolid is necessary. Concomitant use may increase talazoparib exposure. Talazoparib is a BCRP substrate and tedizolid is a BCRP inhibitor.
Temsirolimus: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with temsirolimus is necessary. Talazoparib is a P-gp substrate and temsirolimus is a P-gp inhibitor.
Tepotinib: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with tepotinib is necessary. Talazoparib is a P-gp substrate and tepotinib is a P-gp inhibitor.
Teriflunomide: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if concomitant use of teriflunomide is necessary. Concomitant use may increase talazoparib exposure. Talazoparib is a BCRP substrate and teriflunomide is a BCRP inhibitor.
Tezacaftor; Ivacaftor: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with ivacaftor is necessary. Talazoparib is a P-gp substrate and ivacaftor is a P-gp inhibitor.
Ticagrelor: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with ticagrelor is necessary. Talazoparib is a P-gp substrate and ticagrelor is a P-gp inhibitor.
Tipranavir: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with tipranavir is necessary. Talazoparib is a P-gp substrate and tipranavir is a P-gp inhibitor.
Trandolapril; Verapamil: (Major) Avoid coadministration of verapamil with talazoparib when used for the treatment of breast cancer due to increased talazoparib exposure. If concomitant use is unavoidable, reduce the dose of talazoparib to 0.75 mg PO once daily. If verapamil is discontinued, wait at least 3 to 5 half-lives of verapamil before increasing the dose of talazoparib to the prior dose used before verapamil therapy. A talazoparib dose reduction is not necessary for patients with prostate cancer; monitor for an increase in talazoparib-related adverse reactions. Talazoparib is a P-gp substrate and verapamil is a P-gp inhibitor. In clinical trials, coadministration with verapamil increased talazoparib exposure by 45%.
Tucatinib: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with tucatinib is necessary. Talazoparib is a P-gp substrate and tucatinib is a P-gp inhibitor.
Vemurafenib: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if concomitant use of vemurafenib is necessary. Concomitant use may increase talazoparib exposure. Talazoparib is a P-gp and BCRP substrate; vemurafenib is a P-gp and BCRP inhibitor.
Venetoclax: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with venetoclax is necessary. Talazoparib is a P-gp substrate and venetoclax is a P-gp inhibitor.
Verapamil: (Major) Avoid coadministration of verapamil with talazoparib when used for the treatment of breast cancer due to increased talazoparib exposure. If concomitant use is unavoidable, reduce the dose of talazoparib to 0.75 mg PO once daily. If verapamil is discontinued, wait at least 3 to 5 half-lives of verapamil before increasing the dose of talazoparib to the prior dose used before verapamil therapy. A talazoparib dose reduction is not necessary for patients with prostate cancer; monitor for an increase in talazoparib-related adverse reactions. Talazoparib is a P-gp substrate and verapamil is a P-gp inhibitor. In clinical trials, coadministration with verapamil increased talazoparib exposure by 45%.
Voclosporin: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with voclosporin is necessary. Talazoparib is a P-gp substrate and voclosporin is a P-gp inhibitor.
Vonoprazan; Amoxicillin; Clarithromycin: (Major) Avoid coadministration of clarithromycin with talazoparib when used for the treatment of breast cancer due to increased talazoparib exposure. If concomitant use is unavoidable, reduce the dose of talazoparib to 0.75 mg PO once daily. If clarithromycin is discontinued, wait at least 3 to 5 half-lives of clarithromycin before increasing the dose of talazoparib to the prior dose used before clarithromycin therapy. A talazoparib dose reduction is not necessary for patients with prostate cancer; monitor for an increase in talazoparib-related adverse reactions. Talazoparib is a P-gp substrate and clarithromycin is a P-gp inhibitor. In clinical trials, coadministration with clarithromycin increased talazoparib exposure by 45%.
Zonisamide: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with zonisamide is necessary. Talazoparib is a P-gp substrate and zonisamide is a P-gp inhibitor.

How Supplied

Talazoparib/Talzenna Oral Cap: 0.1mg, 0.25mg, 0.35mg, 0.5mg, 0.75mg, 1mg

Maximum Dosage
Adults

Breast cancer: 1 mg/day PO.
Prostate cancer: 0.5 mg/day PO.

Geriatric

Breast cancer: 1 mg/day PO.
Prostate cancer: 0.5 mg/day PO.

Adolescents

Safety and efficacy have not been established.

Children

Safety and efficacy have not been established.

Infants

Safety and efficacy have not been established.

Neonates

Safety and efficacy have not been established.

Mechanism Of Action

Talazoparib is an inhibitor of poly (ADP-ribose) polymerase (PARP) enzymes, including PARP1 and PARP2. These enzymes play a role in DNA repair. In vitro studies with cancer lines that harbored defects in DNA repair genes, including BRCA1 and BRCA2, have shown that talazoparib-induced cytotoxicity may involve inhibition of PARP enzymatic activity and increased formation of PARP-DNA complexes resulting in DNA damage, decreased cell proliferation, and apoptosis. Talazoparib anti-tumor activity was observed in human patient-derived xenograft breast cancer tumor models that expressed mutated or wild-type BRCA1 and BRCA2.

Pharmacokinetics

Talazoparib is administered orally. In vitro, it is 74% protein-bound, independent of talazoparib concentration. The mean apparent volume of distribution is 420 L. The mean terminal plasma half-life of talazoparib is 90 hours (+/- 58 hours), and the mean apparent oral clearance is 6.45 L/hour (intersubject variability, 31%). Talazoparib undergoes minimal hepatic metabolism. The identified metabolic pathways include mono-oxidation, dehydrogenation, cysteine conjugation of mono-desfluoro-talazoparib, and glucuronide conjugation. Urinary excretion is the major route of elimination, with approximately 68.7% of the total administered radioactive dose recovered in urine, 54.6% as unchanged drug; 19.7% of the total dose was recovered in the feces, with 13.6% as unchanged drug.[63651]
 
Affected drug transporters: P-gp and BCRP
Talazoparib is a P-gp and BCRP substrate. Coadministration with itraconazole (a P-gp inhibitor) increased talazoparib exposure by 56% while coadministration with the P-gp inhibitors amiodarone, carvedilol, clarithromycin, and verapamil increased talazoparib exposure by 45%; coadministration with other P-gp inhibitors did not have a clinically significant effect on the pharmacokinetics of talazoparib. Coadministration with rifampin, a P-gp inducer, increased the talazoparib Cmax by 37% with no effect on talazoparib exposure.[63651]

Oral Route

After oral administration of talazoparib 1 mg once daily, the geometric mean Cmax at steady-state 16.4 ng/mL (CV, 32%), which was reached after a median time (Tmax) of 1 to 2 hours; the geometric mean AUC at steady-state was 208 ng x hour/mL (coefficient of variation (CV), 37%). The mean trough concentration (Cmin) at steady-state after administration of talazoparib 1 mg once daily was 3.53 ng/mL (CV, 61%); the mean steady-state Cmin after administration of talazoparib 0.5 mg once daily in combination with enzalutamide ranged from 3.29 ng/mL to 3.68 ng/mL (CV, 45% to 48%). The pharmacokinetics of talazoparib were linear from 0.025 mg to 2 mg. The median accumulation ratio of talazoparib following repeated daily dosing was in the range of 2.3 to 5.2; steady-state concentrations were reached within 2 to 3 weeks when administered as a single agent and within 9 weeks when administered with enzalutamide. The exposure-response relationship and time course of pharmacodynamic response have not been fully characterized.[63651]
 
The mean Cmax of talazoparib decreased by 46% and the median Tmax was delayed from 1 to 4 hours following a single oral dose of 0.5 mg talazoparib with high-fat, high-calorie food (approximately 800 to 1,000 calories: protein, 150 calories; carbohydrate, 250 calories; fat, 500 to 600 calories); talazoparib exposure (AUC) was not affected.[63651]

Pregnancy And Lactation
Pregnancy

Pregnancy should be avoided by females of reproductive potential during talazoparib treatment and for 7 months after the last dose. Although there are no adequately controlled studies in pregnant animals or humans, talazoparib can cause fetal harm or death when administered during pregnancy based on its mechanism of action and animal studies. Women who are pregnant or who become pregnant while receiving talazoparib should be apprised of the potential hazard to the fetus. In an animal reproduction study, administration of talazoparib to pregnant rats during organogenesis at a dose of 0.24 times the AUC in humans at the recommended breast cancer dose (1 mg) caused decreased fetal body weights, an increased incidence of fetal malformations (i.e., depressed eye bulge, small eye, split sternebra, and fused cervical vertebral arch), and structural variations (i.e., misshapen or incomplete ossification of the sternebra, skull, rib, and vertebra). Exposures above this caused embryofetal deaths.

Counsel patients about the reproductive risk and contraception requirements during talazoparib treatment. Talazoparib can be teratogenic if taken by the mother during pregnancy. Females of reproductive potential should avoid pregnancy and use effective contraception during and for 7 months after treatment with talazoparib. Due to the risk of male-mediated teratogenicity, males with female partners of reproductive potential and pregnant partners should use effective contraception during and for 4 months after the last dose. Females of reproductive potential should undergo pregnancy testing prior to initiation of talazoparib. Women who become pregnant while receiving talazoparib should be apprised of the potential hazard to the fetus. Although there are no data regarding the effect of talazoparib on human fertility, male infertility has been observed in animal studies.[63651]