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  • CLASSES

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

    DEA CLASS

    Rx

    DESCRIPTION

    PARP inhibitor
    Used for deleterious or suspected deleterious germline BRCA-mutated HER2-negative locally advanced or metastatic breast cancer
    Monitor complete blood counts; an interruption of therapy or dose reduction may be necessary for myelosuppression

    COMMON BRAND NAMES

    Talzenna

    HOW SUPPLIED

    Talazoparib/TALZENNA Oral Cap: 0.25mg, 1mg

    DOSAGE & INDICATIONS

    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 http://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) 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). 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]

    MAXIMUM DOSAGE

    Adults

    1 mg PO once daily.

    Geriatric

    1 mg PO once daily.

    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.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Mild hepatic impairment (total bilirubin less than or equal to the upper limit of normal (ULN) and AST greater than ULN; OR total bilirubin 1.1 to 1.5 times ULN and any AST): No dose adjustment is necessary.
    Moderate to severe hepatic impairment (total bilirubin 1.6 times ULN or higher and any AST): Talazoparib has not been studied in this population.

    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 is 0.75 mg PO once daily.
    Severe renal impairment (CrCL 15 to 29 mL/min): The recommended dose of talazoparib is 0.5 mg PO once daily.
    Hemodialysis: Talazoparib has not been studied in this population.[63651]

    ADMINISTRATION

    Oral Administration
    Oral Solid Formulations

    Swallow the capsules or tablets 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.

    STORAGE

    Talzenna:
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    Anemia, bone marrow suppression, leukemia, leukopenia, myelodysplastic syndrome (MDS), neutropenia, new primary malignancy, thrombocytopenia

    Bone marrow suppression consisting of anemia, leukopenia/neutropenia, and/or thrombocytopenia has been reported in patients treated with talazoparib. Monitor complete blood counts at baseline and monthly thereafter; an interruption of therapy or dose reduction may be necessary for patients with hematologic toxicity. Do not start talazoparib until patients have adequately recovered from hematologic toxicity caused by previous therapy. New primary malignancy, specifically myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) have been reported in 2 patients in clinical trials (n = 584); both patients had received previous chemotherapy with platinum agents and/or other DNA damaging agents including radiotherapy. If hematologic toxicity persists beyond 4 weeks, refer the patient to a hematologist for further investigations, including bone marrow analysis and blood sample for cytogenetics. Discontinue talazoparib if MDS/AML is confirmed.

    Pregnancy

    Pregnancy should be avoided by females of reproductive potential during talazoparib treatment and for at least 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 dose 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.

    Contraception requirements, infertility, male-mediated teratogenicity, pregnancy testing, reproductive risk

    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 at least 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 at least 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]

    Breast-feeding

    Due to the potential for serious adverse reactions in nursing infants from talazoparib, advise women to discontinue breast-feeding during treatment and for at least 1 month after the final dose. It is not known whether talazoparib is present in human milk, although many drugs are excreted in human milk.

    ADVERSE REACTIONS

    Severe

    anemia / Delayed / 39.0-39.0
    neutropenia / Delayed / 21.0-21.0
    thrombocytopenia / Delayed / 15.0-15.0
    fatigue / Early / 3.0-3.0
    vomiting / Early / 2.0-2.0
    headache / Early / 2.0-2.0
    elevated hepatic enzymes / Delayed / 1.0-2.0
    hyperglycemia / Delayed / 2.0-2.0
    anorexia / Delayed / 0-1.0
    nausea / Early / 0-1.0
    diarrhea / Early / 1.0-1.0
    hypocalcemia / Delayed / 1.0-1.0
    new primary malignancy / Delayed / 0.3-0.3
    leukemia / Delayed / Incidence not known

    Moderate

    leukopenia / Delayed / 17.0-17.0
    stomatitis / Delayed / 8.0-8.0
    lymphopenia / Delayed / 7.0-7.0
    bone marrow suppression / Delayed / Incidence not known

    Mild

    alopecia / Delayed / 25.0-25.0
    abdominal pain / Early / 19.0-19.0
    dizziness / Early / 17.0-17.0
    dysgeusia / Early / 10.0-10.0
    dyspepsia / Early / 10.0-10.0
    asthenia / Delayed / Incidence not known

    DRUG INTERACTIONS

    Acalabrutinib: (Major) Avoid coadministration of acalabrutinib with talazoparib due to increased talazoparib exposure. If concomitant use is unavoidable, monitor for an increase in talazoparib-related adverse reactions. Talazoparib is a BCRP substrate and acalabrutinib is a BCRP inhibitor. The effect of concomitant administration of BCRP inhibitors on the pharmacokinetics of talazoparib has not been studied; however, BCRP inhibitors may increase talazoparib exposure.
    Amiodarone: (Major) Avoid coadministration of amiodarone with talazoparib 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. Talazoparib is a P-glycoprotein (P-gp) substrate and amiodarone is a P-gp inhibitor. In clinical trials, coadministration with P-gp inhibitors, including amiodarone, increased talazoparib exposure by approximately 45% and increased the rate of talazoparib dose reduction.
    Amlodipine; Atorvastatin: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with atorvastatin is necessary. In clinical trials, coadministration with atorvastatin increased talazoparib exposure by approximately 8%.
    Amoxicillin; Clarithromycin; Lansoprazole: (Major) Avoid coadministration of clarithromycin with talazoparib 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. Talazoparib is a P-glycoprotein (P-gp) substrate and clarithromycin is a P-gp inhibitor. In clinical trials, coadministration with P-gp inhibitors, including clarithromycin, increased talazoparib exposure by approximately 45% and increased the rate of talazoparib dose reduction.
    Amoxicillin; Clarithromycin; Omeprazole: (Major) Avoid coadministration of clarithromycin with talazoparib 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. Talazoparib is a P-glycoprotein (P-gp) substrate and clarithromycin is a P-gp inhibitor. In clinical trials, coadministration with P-gp inhibitors, including clarithromycin, increased talazoparib exposure by approximately 45% and increased the rate of talazoparib dose reduction.
    Atazanavir; Cobicistat: (Major) Avoid coadministration of cobicistat with talazoparib due to increased talazoparib exposure. If concomitant use is unavoidable, monitor for an increase in talazoparib-related adverse reactions. Talazoparib is a BCRP and P-glycoprotein (P-gp) substrate; cobicistat is a BCRP and P-gp inhibitor. Coadministration with other P-gp inhibitors increased talazoparib exposure by 8% to 45%. The effect of concomitant administration of BCRP inhibitors on the pharmacokinetics of talazoparib has not been studied; however, BCRP inhibitors may increase talazoparib exposure.
    Atorvastatin: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with atorvastatin is necessary. In clinical trials, coadministration with atorvastatin increased talazoparib exposure by approximately 8%.
    Atorvastatin; Ezetimibe: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with atorvastatin is necessary. In clinical trials, coadministration with atorvastatin increased talazoparib exposure by approximately 8%.
    Azithromycin: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with azithromycin is necessary. In clinical trials, coadministration with azithromycin increased talazoparib exposure by approximately 8%.
    Brigatinib: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with brigatinib is necessary. Talazoparib is a BCRP and P-glycoprotein (P-gp) substrate. Brigatinib inhibits both P-gp and BCRP in vitro and may have the potential to increase concentrations of substrates of these transporters. Coadministration with other P-gp inhibitors increased talazoparib exposure by 8% to 45%. The effect of concomitant administration of BCRP inhibitors on the pharmacokinetics of talazoparib has not been studied; however, BCRP inhibitors may increase talazoparib exposure.
    Cabozantinib: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with cabozantinib is necessary. Talazoparib is a P-glycoprotein (P-gp) substrate and cabozantinib is a P-gp inhibitor. Coadministration with other P-gp inhibitors increased talazoparib exposure by 8% to 45%.
    Capmatinib: (Major) Avoid coadministration of capmatinib with talazoparib if possible due to increased talazoparib exposure. If concomitant use is unavoidable, monitor for an increase in talazoparib-related adverse reactions. Talazoparib is a P-glycoprotein (P-gp) and BCRP substrate. Capmatinib is a P-gp and BCRP inhibitor. The effect of concomitant administration of BCRP inhibitors on the pharmacokinetics of talazoparib has not been studied; however, BCRP inhibitors may increase talazoparib exposure. Coadministration with other P-gp inhibitors increased talazoparib exposure by 8% to 45%.
    Carvedilol: (Major) Avoid coadministration of carvedilol with talazoparib 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. Talazoparib is a P-glycoprotein (P-gp) substrate and carvedilol is a P-gp inhibitor. In clinical trials, coadministration with P-gp inhibitors, including carvedilol, increased talazoparib exposure by approximately 45% and increased the rate of talazoparib dose reduction.
    Clarithromycin: (Major) Avoid coadministration of clarithromycin with talazoparib 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. Talazoparib is a P-glycoprotein (P-gp) substrate and clarithromycin is a P-gp inhibitor. In clinical trials, coadministration with P-gp inhibitors, including clarithromycin, increased talazoparib exposure by approximately 45% and increased the rate of talazoparib dose reduction.
    Cobicistat: (Major) Avoid coadministration of cobicistat with talazoparib due to increased talazoparib exposure. If concomitant use is unavoidable, monitor for an increase in talazoparib-related adverse reactions. Talazoparib is a BCRP and P-glycoprotein (P-gp) substrate; cobicistat is a BCRP and P-gp inhibitor. Coadministration with other P-gp inhibitors increased talazoparib exposure by 8% to 45%. The effect of concomitant administration of BCRP inhibitors on the pharmacokinetics of talazoparib has not been studied; however, BCRP inhibitors may increase talazoparib exposure.
    Conivaptan: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with conivaptan is necessary. Talazoparib is a P-glycoprotein (P-gp) substrate and conivaptan is a P-gp inhibitor. Coadministration with other P-gp inhibitors increased talazoparib exposure by 8% to 45%.
    Cyclosporine: (Major) Avoid coadministration of cyclosporine with talazoparib due to increased talazoparib exposure. If concomitant use is unavoidable, monitor for an increase in talazoparib-related adverse reactions. Talazoparib is a BCRP and P-glycoprotein (P-gp) substrate; cyclosporine is a BCRP and P-gp inhibitor. Coadministration with other P-gp inhibitors increased talazoparib exposure by 8% to 45%. The effect of concomitant administration of BCRP inhibitors on the pharmacokinetics of talazoparib has not been studied; however, BCRP inhibitors may increase talazoparib exposure.
    Daclatasvir: (Major) Avoid coadministration of daclatasvir with talazoparib due to increased talazoparib exposure. If concomitant use is unavoidable, monitor for an increase in talazoparib-related adverse reactions. Talazoparib is a BCRP and P-glycoprotein (P-gp) substrate; daclatasvir is a BCRP and P-gp inhibitor. Coadministration with other P-gp inhibitors increased talazoparib exposure by 8% to 45%. The effect of concomitant administration of BCRP inhibitors on the pharmacokinetics of talazoparib has not been studied; however, BCRP inhibitors may increase talazoparib exposure.
    Darolutamide: (Major) Avoid coadministration of darolutamide with talazoparib if possible due to increased talazoparib exposure. If concomitant use is unavoidable, monitor for an increase in talazoparib-related adverse reactions. Talazoparib is a BCRP substrate and darolutamide is a BCRP inhibitor. The effect of concomitant administration of BCRP inhibitors on the pharmacokinetics of talazoparib has not been studied; however, BCRP inhibitors may increase talazoparib exposure.
    Darunavir; Cobicistat: (Major) Avoid coadministration of cobicistat with talazoparib due to increased talazoparib exposure. If concomitant use is unavoidable, monitor for an increase in talazoparib-related adverse reactions. Talazoparib is a BCRP and P-glycoprotein (P-gp) substrate; cobicistat is a BCRP and P-gp inhibitor. Coadministration with other P-gp inhibitors increased talazoparib exposure by 8% to 45%. The effect of concomitant administration of BCRP inhibitors on the pharmacokinetics of talazoparib has not been studied; however, BCRP inhibitors may increase talazoparib exposure.
    Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) Avoid coadministration of cobicistat with talazoparib due to increased talazoparib exposure. If concomitant use is unavoidable, monitor for an increase in talazoparib-related adverse reactions. Talazoparib is a BCRP and P-glycoprotein (P-gp) substrate; cobicistat is a BCRP and P-gp inhibitor. Coadministration with other P-gp inhibitors increased talazoparib exposure by 8% to 45%. The effect of concomitant administration of BCRP inhibitors on the pharmacokinetics of talazoparib has not been studied; however, BCRP inhibitors may increase talazoparib exposure.
    Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Major) Avoid coadministration of dasabuvir with talazoparib due to increased talazoparib exposure. If concomitant use is unavoidable, monitor for an increase in talazoparib-related adverse reactions. Talazoparib is a BCRP substrate and dasabuvir is a BCRP inhibitor. The effect of concomitant administration of BCRP inhibitors on the pharmacokinetics of talazoparib has not been studied; however, BCRP inhibitors may increase talazoparib exposure. (Major) Avoid coadministration of paritaprevir with talazoparib due to increased talazoparib exposure. If concomitant use is unavoidable, monitor for an increase in talazoparib-related adverse reactions. Talazoparib is a BCRP substrate and paritaprevir is a BCRP inhibitor. The effect of concomitant administration of BCRP inhibitors on the pharmacokinetics of talazoparib has not been studied; however, BCRP inhibitors may increase talazoparib exposure. (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with ritonavir is necessary. Talazoparib is a P-glycoprotein (P-gp) substrate and ritonavir is a P-gp inhibitor. Coadministration with other P-gp inhibitors increased talazoparib exposure by 8% to 45%.
    Dextromethorphan; Quinidine: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with quinidine is necessary. Talazoparib is a P-glycoprotein (P-gp) substrate and quinidine is a P-gp inhibitor. Coadministration with other P-gp inhibitors increased talazoparib exposure by 8% to 45%.
    Diltiazem: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with diltiazem is necessary. In clinical trials, coadministration with diltiazem increased talazoparib exposure by approximately 8%.
    Dronedarone: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with dronedarone is necessary. Talazoparib is a P-glycoprotein (P-gp) substrate and dronedarone is a P-gp inhibitor. Coadministration with other P-gp inhibitors increased talazoparib exposure by 8% to 45%.
    Elagolix: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with elagolix is necessary. Talazoparib is a P-glycoprotein (P-gp) substrate and elagolix is a P-gp inhibitor. Coadministration with other P-gp inhibitors increased talazoparib exposure by 8% to 45%.
    Elagolix; Estradiol; Norethindrone acetate: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with elagolix is necessary. Talazoparib is a P-glycoprotein (P-gp) substrate and elagolix is a P-gp inhibitor. Coadministration with other P-gp inhibitors increased talazoparib exposure by 8% to 45%.
    Elbasvir; Grazoprevir: (Major) Avoid coadministration of elbasvir with talazoparib due to increased talazoparib exposure. If concomitant use is unavoidable, monitor for an increase in talazoparib-related adverse reactions. Talazoparib is a BCRP substrate and elbasvir is a BCRP inhibitor. The effect of concomitant administration of BCRP inhibitors on the pharmacokinetics of talazoparib has not been studied; however, BCRP inhibitors may increase talazoparib exposure. (Major) Avoid coadministration of grazoprevir with talazoparib due to increased talazoparib exposure. If concomitant use is unavoidable, monitor for an increase in talazoparib-related adverse reactions. Talazoparib is a BCRP substrate and grazoprevir is a BCRP inhibitor. The effect of concomitant administration of BCRP inhibitors on the pharmacokinetics of talazoparib has not been studied; however, BCRP inhibitors may increase talazoparib exposure.
    Elexacaftor; tezacaftor; ivacaftor: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with ivacaftor is necessary. Talazoparib is a P-glycoprotein (P-gp) substrate and ivacaftor is a P-gp inhibitor. Coadministration with other P-gp inhibitors increased talazoparib exposure by 8% to 45%.
    Eliglustat: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with eliglustat is necessary. Talazoparib is a P-glycoprotein (P-gp) substrate and eliglustat is a P-gp inhibitor. Coadministration with other P-gp inhibitors increased talazoparib exposure by 8% to 45%.
    Eltrombopag: (Major) Avoid coadministration of eltrombopag with talazoparib due to increased talazoparib exposure. If concomitant use is unavoidable, monitor for an increase in talazoparib-related adverse reactions. Talazoparib is a BCRP substrate and eltrombopag is a BCRP inhibitor. The effect of concomitant administration of BCRP inhibitors on the pharmacokinetics of talazoparib has not been studied; however, BCRP inhibitors may increase talazoparib exposure.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Major) Avoid coadministration of cobicistat with talazoparib due to increased talazoparib exposure. If concomitant use is unavoidable, monitor for an increase in talazoparib-related adverse reactions. Talazoparib is a BCRP and P-glycoprotein (P-gp) substrate; cobicistat is a BCRP and P-gp inhibitor. Coadministration with other P-gp inhibitors increased talazoparib exposure by 8% to 45%. The effect of concomitant administration of BCRP inhibitors on the pharmacokinetics of talazoparib has not been studied; however, BCRP inhibitors may increase talazoparib exposure.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Avoid coadministration of cobicistat with talazoparib due to increased talazoparib exposure. If concomitant use is unavoidable, monitor for an increase in talazoparib-related adverse reactions. Talazoparib is a BCRP and P-glycoprotein (P-gp) substrate; cobicistat is a BCRP and P-gp inhibitor. Coadministration with other P-gp inhibitors increased talazoparib exposure by 8% to 45%. The effect of concomitant administration of BCRP inhibitors on the pharmacokinetics of talazoparib has not been studied; however, BCRP inhibitors may increase talazoparib exposure.
    Enalapril; Felodipine: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with felodipine is necessary. In clinical trials, coadministration with felodipine increased talazoparib exposure by approximately 8%.
    Erythromycin: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with erythromycin is necessary. Talazoparib is a P-glycoprotein (P-gp) substrate and erythromycin is a P-gp inhibitor. Coadministration with other P-gp inhibitors increased talazoparib exposure by 8% to 45%.
    Erythromycin; Sulfisoxazole: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with erythromycin is necessary. Talazoparib is a P-glycoprotein (P-gp) substrate and erythromycin is a P-gp inhibitor. Coadministration with other P-gp inhibitors increased talazoparib exposure by 8% to 45%.
    Etravirine: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with etravirine is necessary. Talazoparib is a P-glycoprotein (P-gp) substrate and etravirine is a P-gp inhibitor. Coadministration with other P-gp inhibitors increased talazoparib exposure by 8% to 45%.
    Felodipine: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with felodipine is necessary. In clinical trials, coadministration with felodipine increased talazoparib exposure by approximately 8%.
    Flibanserin: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with flibanserin is necessary. Talazoparib is a P-glycoprotein (P-gp) substrate and flibanserin is a P-gp inhibitor. Coadministration with other P-gp inhibitors increased talazoparib exposure by 8% to 45%.
    Fluvoxamine: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with fluvoxamine is necessary. In clinical trials, coadministration with fluvoxamine increased talazoparib exposure by approximately 8%.
    Fostamatinib: (Major) Avoid coadministration of fostamatinib with talazoparib due to increased talazoparib exposure. If concomitant use is unavoidable, monitor for an increase in talazoparib-related adverse reactions. Talazoparib is a BCRP and P-glycoprotein (P-gp) substrate; fostamatinib is a BCRP and P-gp inhibitor. Coadministration with other P-gp inhibitors increased talazoparib exposure by 8% to 45%. The effect of concomitant administration of BCRP inhibitors on the pharmacokinetics of talazoparib has not been studied; however, BCRP inhibitors may increase talazoparib exposure.
    Fostemsavir: (Major) Avoid concomitant use of fostemsavir with talazoparib if possible due to increased talazoparib exposure. If concomitant use is unavoidable, monitor for an increase in talazoparib-related adverse reactions. Talazoparib is a BCRP substrate and fostemsavir is a BCRP inhibitor. The effect of concomitant administration of BCRP inhibitors on the pharmacokinetics of talazoparib has not been studied; however, BCRP inhibitors may increase talazoparib exposure.
    Glecaprevir; Pibrentasvir: (Major) Avoid coadministration of glecaprevir with talazoparib due to increased talazoparib exposure. If concomitant use is unavoidable, monitor for an increase in talazoparib-related adverse reactions. Talazoparib is a BCRP and P-glycoprotein (P-gp) substrate; glecaprevir is a BCRP and P-gp inhibitor. Coadministration with other P-gp inhibitors increased talazoparib exposure by 8% to 45%. The effect of concomitant administration of BCRP inhibitors on the pharmacokinetics of talazoparib has not been studied; however, BCRP inhibitors may increase talazoparib exposure. (Major) Avoid coadministration of pibrentasvir with talazoparib due to increased talazoparib exposure. If concomitant use is unavoidable, monitor for an increase in talazoparib-related adverse reactions. Talazoparib is a BCRP and P-glycoprotein (P-gp) substrate; pibrentasvir is a BCRP and P-gp inhibitor. Coadministration with other P-gp inhibitors increased talazoparib exposure by 8% to 45%. The effect of concomitant administration of BCRP inhibitors on the pharmacokinetics of talazoparib has not been studied; however, BCRP inhibitors may increase talazoparib exposure.
    Grapefruit juice: (Moderate) Advise patients to avoid grapefruit juice while taking talazoparib due to increased talazoparib exposure. Talazoparib is a P-glycoprotein (P-gp) substrate and grapefruit juice is a P-gp inhibitor. Coadministration with other P-gp inhibitors increased talazoparib exposure by 8% to 45%.
    Ibrutinib: (Major) Avoid coadministration of ibrutinib with talazoparib due to increased talazoparib exposure. If concomitant use is unavoidable, monitor for an increase in talazoparib-related adverse reactions. Talazoparib is a BCRP and P-glycoprotein (P-gp) substrate; ibrutinib is a BCRP and P-gp inhibitor. Coadministration with other P-gp inhibitors increased talazoparib exposure by 8% to 45%. The effect of concomitant administration of BCRP inhibitors on the pharmacokinetics of talazoparib has not been studied; however, BCRP inhibitors may increase talazoparib exposure.
    Isavuconazonium: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with isavuconazonium is necessary. Talazoparib is a P-glycoprotein (P-gp) substrate and isavuconazonium is a P-gp inhibitor. Coadministration with other P-gp inhibitors increased talazoparib exposure by 8% to 45%.
    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. Coadministration with other P-gp inhibitors increased talazoparib exposure by 8% to 45%.
    Itraconazole: (Major) Avoid coadministration of itraconazole with talazoparib 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. Talazoparib is a P-glycoprotein (P-gp) and BCRP substrate; itraconazole is a P-gp and BCRP inhibitor. In clinical trials, coadministration with itraconazole increased talazoparib exposure by 56%. The effect of concomitant administration of BCRP inhibitors on the pharmacokinetics of talazoparib has not been studied; however, BCRP inhibition may also increase talazoparib exposure.
    Ivacaftor: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with ivacaftor is necessary. Talazoparib is a P-glycoprotein (P-gp) substrate and ivacaftor is a P-gp inhibitor. Coadministration with other P-gp inhibitors increased talazoparib exposure by 8% to 45%.
    Ketoconazole: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with ketoconazole is necessary. Talazoparib is a P-glycoprotein (P-gp) substrate and ketoconazole is a P-gp inhibitor. Coadministration with other P-gp inhibitors increased talazoparib exposure by 8% to 45%.
    Lapatinib: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with lapatinib is necessary. Talazoparib is a P-glycoprotein (P-gp) substrate and lapatinib is a P-gp inhibitor. Coadministration with other P-gp inhibitors increased talazoparib exposure by 8% to 45%.
    Ledipasvir; Sofosbuvir: (Major) Avoid coadministration of ledipasvir with talazoparib due to increased talazoparib exposure. If concomitant use is unavoidable, monitor for an increase in talazoparib-related adverse reactions. Talazoparib is a BCRP and P-glycoprotein (P-gp) substrate; ledipasvir is a BCRP and P-gp inhibitor. Coadministration with other P-gp inhibitors increased talazoparib exposure by 8% to 45%. The effect of concomitant administration of BCRP inhibitors on the pharmacokinetics of talazoparib has not been studied; however, BCRP inhibitors may increase talazoparib exposure.
    Leflunomide: (Major) Avoid coadministration of leflunomide with talazoparib due to increased talazoparib exposure. If concomitant use is unavoidable, monitor for an increase in talazoparib-related adverse reactions. Talazoparib is a BCRP substrate and leflunomide is a BCRP inhibitor. The effect of concomitant administration of BCRP inhibitors on the pharmacokinetics of talazoparib has not been studied; however, BCRP inhibitors may increase talazoparib exposure.
    Lomitapide: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with lomitapide is necessary. Talazoparib is a P-glycoprotein (P-gp) substrate and lomitapide is a P-gp inhibitor. Coadministration with other P-gp inhibitors increased talazoparib exposure by 8% to 45%.
    Lopinavir; Ritonavir: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with ritonavir is necessary. Talazoparib is a P-glycoprotein (P-gp) substrate and ritonavir is a P-gp inhibitor. Coadministration with other P-gp inhibitors increased talazoparib exposure by 8% to 45%.
    Lumacaftor; Ivacaftor: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with ivacaftor is necessary. Talazoparib is a P-glycoprotein (P-gp) substrate and ivacaftor is a P-gp inhibitor. Coadministration with other P-gp inhibitors increased talazoparib exposure by 8% to 45%. (Moderate) Monitor for an increase in talazoparib-related adverse reactions or decreased efficacy if coadministration with lumacaftor; ivacaftor is necessary. Talazoparib is a P-glycoprotein (P-gp) substrate and lumacaftor; ivacaftor has the potential to both inhibit and induce P-gp. Coadministration with other P-gp inhibitors increased talazoparib exposure 8 to 45%. The effect of P-gp inducers on talazoparib exposure has not been studied.
    Lumacaftor; Ivacaftor: (Moderate) Monitor for an increase in talazoparib-related adverse reactions or decreased efficacy if coadministration with lumacaftor; ivacaftor is necessary. Talazoparib is a P-glycoprotein (P-gp) substrate and lumacaftor; ivacaftor has the potential to both inhibit and induce P-gp. Coadministration with other P-gp inhibitors increased talazoparib exposure 8 to 45%. The effect of P-gp inducers on talazoparib exposure has not been studied.
    Mefloquine: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with mefloquine is necessary. Talazoparib is a P-glycoprotein (P-gp) substrate and mefloquine is a P-gp inhibitor. Coadministration with other P-gp inhibitors increased talazoparib exposure by 8% to 45%.
    Mifepristone: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with mifepristone is necessary. Talazoparib is a P-glycoprotein (P-gp) substrate and mifepristone is a P-gp inhibitor. Coadministration with other P-gp inhibitors increased talazoparib exposure by 8% to 45%.
    Nelfinavir: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with nelfinavir is necessary. Talazoparib is a P-glycoprotein (P-gp) substrate and nelfinavir is a P-gp inhibitor. Coadministration with other P-gp inhibitors increased talazoparib exposure by 8% to 45%.
    Neratinib: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with neratinib is necessary. Talazoparib is a P-glycoprotein (P-gp) substrate and neratinib is a P-gp inhibitor. Coadministration with other P-gp inhibitors increased talazoparib exposure by 8% to 45%.
    Ombitasvir; Paritaprevir; Ritonavir: (Major) Avoid coadministration of paritaprevir with talazoparib due to increased talazoparib exposure. If concomitant use is unavoidable, monitor for an increase in talazoparib-related adverse reactions. Talazoparib is a BCRP substrate and paritaprevir is a BCRP inhibitor. The effect of concomitant administration of BCRP inhibitors on the pharmacokinetics of talazoparib has not been studied; however, BCRP inhibitors may increase talazoparib exposure. (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with ritonavir is necessary. Talazoparib is a P-glycoprotein (P-gp) substrate and ritonavir is a P-gp inhibitor. Coadministration with other P-gp inhibitors increased talazoparib exposure by 8% to 45%.
    Osimertinib: (Major) Avoid coadministration of osimertinib with talazoparib due to increased talazoparib exposure. If concomitant use is unavoidable, monitor for an increase in talazoparib-related adverse reactions. Talazoparib is a BCRP substrate and osimertinib is a BCRP inhibitor. The effect of concomitant administration of BCRP inhibitors on the pharmacokinetics of talazoparib has not been studied; however, BCRP inhibitors may increase talazoparib exposure.
    Ponatinib: (Major) Avoid coadministration of ponatinib with talazoparib due to increased talazoparib exposure. If concomitant use is unavoidable, monitor for an increase in talazoparib-related adverse reactions. Talazoparib is a BCRP and P-glycoprotein (P-gp) substrate; ponatinib is a BCRP and P-gp inhibitor. Coadministration with other P-gp inhibitors increased talazoparib exposure by 8% to 45%. The effect of concomitant administration of BCRP inhibitors on the pharmacokinetics of talazoparib has not been studied; however, BCRP inhibitors may increase talazoparib exposure.
    Posaconazole: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with posaconazole is necessary. Talazoparib is a P-glycoprotein (P-gp) substrate and posaconazole is a P-gp inhibitor. Coadministration with other P-gp inhibitors increased talazoparib exposure by 8% to 45%.
    Propafenone: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with propafenone is necessary. Talazoparib is a P-glycoprotein (P-gp) substrate and propafenone is a P-gp inhibitor. Coadministration with other P-gp inhibitors increased talazoparib exposure by 8% to 45%.
    Quinidine: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with quinidine is necessary. Talazoparib is a P-glycoprotein (P-gp) substrate and quinidine is a P-gp inhibitor. Coadministration with other P-gp inhibitors increased talazoparib exposure by 8% to 45%.
    Quinine: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with quinine is necessary. Talazoparib is a P-glycoprotein (P-gp) substrate and quinine is a P-gp inhibitor. Coadministration with other P-gp inhibitors increased talazoparib exposure by 8% to 45%.
    Ranolazine: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with ranolazine is necessary. Talazoparib is a P-glycoprotein (P-gp) substrate and ranolazine is a P-gp inhibitor. Coadministration with other P-gp inhibitors increased talazoparib exposure by 8% to 45%.
    Regorafenib: (Major) Avoid coadministration of regorafenib with talazoparib due to increased talazoparib exposure. If concomitant use is unavoidable, monitor for an increase in talazoparib-related adverse reactions. Talazoparib is a BCRP substrate and regorafenib is a BCRP inhibitor. The effect of concomitant administration of BCRP inhibitors on the pharmacokinetics of talazoparib has not been studied; however, BCRP inhibitors may increase talazoparib exposure.
    Ritonavir: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with ritonavir is necessary. Talazoparib is a P-glycoprotein (P-gp) substrate and ritonavir is a P-gp inhibitor. Coadministration with other P-gp inhibitors increased talazoparib exposure by 8% to 45%.
    Rolapitant: (Major) Avoid coadministration of rolapitant with talazoparib due to increased talazoparib exposure. If concomitant use is unavoidable, monitor for an increase in talazoparib-related adverse reactions. Talazoparib is a BCRP and P-glycoprotein (P-gp) substrate; rolapitant is a BCRP and P-gp inhibitor. Coadministration with other P-gp inhibitors increased talazoparib exposure by 8% to 45%. The effect of concomitant administration of BCRP inhibitors on the pharmacokinetics of talazoparib has not been studied; however, BCRP inhibitors may increase talazoparib exposure.
    Safinamide: (Major) Avoid coadministration of safinamide with talazoparib due to increased talazoparib exposure. If concomitant use is unavoidable, monitor for an increase in talazoparib-related adverse reactions. Talazoparib is a BCRP substrate and safinamide is a BCRP inhibitor. The effect of concomitant administration of BCRP inhibitors on the pharmacokinetics of talazoparib has not been studied; however, BCRP inhibitors may increase talazoparib exposure.
    Sapropterin: (Major) Avoid coadministration of sapropterin with talazoparib due to increased talazoparib exposure. If concomitant use is unavoidable, monitor for an increase in talazoparib-related adverse reactions. Talazoparib is a BCRP and P-glycoprotein (P-gp) substrate; sapropterin is a BCRP and P-gp inhibitor. Coadministration with other P-gp inhibitors increased talazoparib exposure by 8% to 45%. The effect of concomitant administration of BCRP inhibitors on the pharmacokinetics of talazoparib has not been studied; however, BCRP inhibitors may increase talazoparib exposure.
    Saquinavir: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with saquinavir is necessary. Talazoparib is a P-glycoprotein (P-gp) substrate and saquinavir is a P-gp inhibitor. Coadministration with other P-gp inhibitors increased talazoparib exposure by 8% to 45%.
    Sarecycline: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with sarecycline is necessary. Talazoparib is a P-glycoprotein (P-gp) substrate and sarecycline is a P-gp inhibitor. Coadministration with other P-gp inhibitors increased talazoparib exposure by 8% to 45%.
    Sirolimus: (Major) Avoid coadministration of sirolimus with talazoparib due to increased talazoparib exposure. If concomitant use is unavoidable, monitor for an increase in talazoparib-related adverse reactions. Talazoparib is a BCRP substrate and sirolimus is a BCRP inhibitor. The effect of concomitant administration of BCRP inhibitors on the pharmacokinetics of talazoparib has not been studied; however, BCRP inhibitors may increase talazoparib exposure.
    Sofosbuvir; Velpatasvir: (Major) Avoid coadministration of velpatasvir with talazoparib due to increased talazoparib exposure. If concomitant use is unavoidable, monitor for an increase in talazoparib-related adverse reactions. Talazoparib is a BCRP and P-glycoprotein (P-gp) substrate; velpatasvir is a BCRP and P-gp inhibitor. Coadministration with other P-gp inhibitors increased talazoparib exposure by 8% to 45%. The effect of concomitant administration of BCRP inhibitors on the pharmacokinetics of talazoparib has not been studied; however, BCRP inhibitors may increase talazoparib exposure.
    Sofosbuvir; Velpatasvir; Voxilaprevir: (Major) Avoid coadministration of velpatasvir with talazoparib due to increased talazoparib exposure. If concomitant use is unavoidable, monitor for an increase in talazoparib-related adverse reactions. Talazoparib is a BCRP and P-glycoprotein (P-gp) substrate; velpatasvir is a BCRP and P-gp inhibitor. Coadministration with other P-gp inhibitors increased talazoparib exposure by 8% to 45%. The effect of concomitant administration of BCRP inhibitors on the pharmacokinetics of talazoparib has not been studied; however, BCRP inhibitors may increase talazoparib exposure. (Major) Avoid coadministration of voxilaprevir with talazoparib due to increased talazoparib exposure. If concomitant use is unavoidable, monitor for an increase in talazoparib-related adverse reactions. Talazoparib is a BCRP and P-glycoprotein (P-gp) substrate; voxilaprevir is a BCRP and P-gp inhibitor. Coadministration with other P-gp inhibitors increased talazoparib exposure by 8% to 45%. The effect of concomitant administration of BCRP inhibitors on the pharmacokinetics of talazoparib has not been studied; however, BCRP inhibitors may increase talazoparib exposure.
    Sorafenib: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with sorafenib is necessary. Talazoparib is a P-glycoprotein (P-gp) substrate and sorafenib is a P-gp inhibitor. Coadministration with other P-gp inhibitors increased talazoparib exposure by 8% to 45%.
    Sulfasalazine: (Major) Avoid coadministration of sulfasalazine with talazoparib due to increased talazoparib exposure. If concomitant use is unavoidable, monitor for an increase in talazoparib-related adverse reactions. Talazoparib is a BCRP substrate and sulfasalazine is a BCRP inhibitor. The effect of concomitant administration of BCRP inhibitors on the pharmacokinetics of talazoparib has not been studied; however, BCRP inhibitors may increase talazoparib exposure.
    Tacrolimus: (Major) Avoid coadministration of tacrolimus with talazoparib due to increased talazoparib exposure. If concomitant use is unavoidable, monitor for an increase in talazoparib-related adverse reactions. Talazoparib is a BCRP substrate and tacrolimus is a BCRP inhibitor. The effect of concomitant administration of BCRP inhibitors on the pharmacokinetics of talazoparib has not been studied; however, BCRP inhibitors may increase talazoparib exposure.
    Tafamidis: (Major) Avoid coadministration of tafamidis with talazoparib if possible due to increased talazoparib exposure. If concomitant use is unavoidable, monitor for an increase in talazoparib-related adverse reactions. Talazoparib is a BCRP substrate and tafamidis is a BCRP inhibitor. The effect of concomitant administration of BCRP inhibitors on the pharmacokinetics of talazoparib has not been studied; however, BCRP inhibitors may increase talazoparib exposure.
    Tedizolid: (Major) Avoid coadministration of tedizolid with talazoparib due to increased talazoparib exposure. If concomitant use is unavoidable, monitor for an increase in talazoparib-related adverse reactions. Talazoparib is a BCRP substrate and tedizolid is a BCRP inhibitor. The effect of concomitant administration of BCRP inhibitors on the pharmacokinetics of talazoparib has not been studied; however, BCRP inhibitors may increase talazoparib exposure.
    Telithromycin: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with telithromycin is necessary. Talazoparib is a P-glycoprotein (P-gp) substrate and telithromycin is a P-gp inhibitor. Coadministration with other P-gp inhibitors increased talazoparib exposure by 8% to 45%.
    Temsirolimus: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with temsirolimus is necessary. Talazoparib is a P-glycoprotein (P-gp) substrate and temsirolimus is a P-gp inhibitor. Coadministration with other P-gp inhibitors increased talazoparib exposure by 8% to 45%.
    Teriflunomide: (Major) Avoid coadministration of teriflunomide with talazoparib due to increased talazoparib exposure. If concomitant use is unavoidable, monitor for an increase in talazoparib-related adverse reactions. Talazoparib is a BCRP substrate and teriflunomide is a BCRP inhibitor. The effect of concomitant administration of BCRP inhibitors on the pharmacokinetics of talazoparib has not been studied; however, BCRP inhibitors may increase talazoparib exposure.
    Tezacaftor; Ivacaftor: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with ivacaftor is necessary. Talazoparib is a P-glycoprotein (P-gp) substrate and ivacaftor is a P-gp inhibitor. Coadministration with other P-gp inhibitors increased talazoparib exposure by 8% to 45%.
    Ticagrelor: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with ticagrelor is necessary. Talazoparib is a P-glycoprotein (P-gp) substrate and ticagrelor is a P-gp inhibitor. Coadministration with other P-gp inhibitors increased talazoparib exposure by 8% to 45%.
    Trandolapril; Verapamil: (Major) Avoid coadministration of verapamil with talazoparib 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. Talazoparib is a P-glycoprotein (P-gp) substrate and verapamil is a P-gp inhibitor. In clinical trials, coadministration with P-gp inhibitors, including verapamil, increased talazoparib exposure by approximately 45% and increased the rate of talazoparib dose reduction.
    Tucatinib: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with tucatinib is necessary. Talazoparib is a P-glycoprotein (P-gp) substrate and tucatinib is a P-gp inhibitor. Coadministration with other P-gp inhibitors increased talazoparib exposure by 8% to 45%.
    Vemurafenib: (Major) Avoid coadministration of vemurafenib with talazoparib due to increased talazoparib exposure. If concomitant use is unavoidable, monitor for an increase in talazoparib-related adverse reactions. Talazoparib is a BCRP and P-glycoprotein (P-gp) substrate; vemurafenib is a BCRP and P-gp inhibitor. Coadministration with other P-gp inhibitors increased talazoparib exposure by 8% to 45%. The effect of concomitant administration of BCRP inhibitors on the pharmacokinetics of talazoparib has not been studied; however, BCRP inhibitors may increase talazoparib exposure.
    Venetoclax: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with venetoclax is necessary. Talazoparib is a P-glycoprotein (P-gp) substrate and venetoclax is a P-gp inhibitor. Coadministration with other P-gp inhibitors increased talazoparib exposure by 8% to 45%.
    Verapamil: (Major) Avoid coadministration of verapamil with talazoparib 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. Talazoparib is a P-glycoprotein (P-gp) substrate and verapamil is a P-gp inhibitor. In clinical trials, coadministration with P-gp inhibitors, including verapamil, increased talazoparib exposure by approximately 45% and increased the rate of talazoparib dose reduction.
    Zonisamide: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with zonisamide is necessary. Talazoparib is a P-glycoprotein (P-gp) substrate and zonisamide is a P-gp inhibitor. Coadministration with other P-gp inhibitors increased talazoparib exposure by 8% to 45%.

    PREGNANCY AND LACTATION

    Pregnancy

    Pregnancy should be avoided by females of reproductive potential during talazoparib treatment and for at least 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 dose 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.

    Due to the potential for serious adverse reactions in nursing infants from talazoparib, advise women to discontinue breast-feeding during treatment and for at least 1 month after the final dose. It is not known whether talazoparib is present in human milk, although many drugs are excreted in human milk.

    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 in cancer patients (intersubject variability, 31.1%). Talazoparib undergoes minimal hepatic metabolism. The identified metabolic pathways in humans 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-glycoprotein (P-gp) and BCRP
    Talazoparib is a P-gp and BCRP substrate. Coadministration with certain P-gp inhibitors increased talazoparib exposure by 8% to 56% in clinical trials. Coadministration with rifampin, a P-gp inducer, increased the talazoparib Cmax by 37% with no effect on talazoparib exposure. The effect of BCRP inhibitors on the pharmacokinetics of talazoparib has also not been studied; coadministration may increase 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 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.[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]