talazoparib (Rx)

Brand and Other Names:Talzenna
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

capsule

  • 0.25mg
  • 1mg

Breast Cancer

Indicated for adults with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm) HER2-negative locally advanced or metastatic breast cancer

1 mg PO qDay with or without food

Continue until disease progression or unacceptable toxicity occurs

Dosage Modifications

Consider treatment interruption or dosage reduction in the event of adverse reactions

0.25-mg capsule available for dose reduction

Dose reduction levels for adverse reactions

  • First dose reduction: 0.75 mg (three 0.25-mg capsules) qDay
  • Second dose reduction: 0.5 mg (two 0.25-mg capsules) qDay
  • Third dose reduction: 0.25 mg (one 0.25-mg capsule) qDay
  • Discontinue treatment if >3 dose reductions are required

Hemoglobin <8 g/dL

  • Withhold until levels resolve to hemoglobin ≥9 g/dL
  • Resume treatment at reduced dose

Platelet count <50,000/mcL

  • Withhold until levels resolve to platelet count ≥75,000/mcL
  • Resume treatment at reduced dose

Neutrophil count <1000/mcL

  • Withhold until levels resolve to neutrophil count ≥1500/mcL
  • Resume treatment at reduced dose

Nonhematologic Grade ≥3

  • Withhold until resolve to Grade ≤1
  • Consider resuming at a reduced dose or discontinue

Coadministration with P-glycoprotein (P-gp) inhibitors

  • P-gp inhibitors (ie, amiodarone, carvedilol, clarithromycin, itraconazole, verapamil): Avoid use; if coadministration cannot be avoided, reduce talazoparib dose to 0.75 mg qDay
  • Once these P-gp inhibitors are discontinued, increase dose (after 3-5 half-lives of the inhibitor) to dose used prior to initiating the P-gp inhibitor
  • Other P-gp inhibitors that were not specifically studied in preclinical trials may also increase talazoparib systemic exposure; if coadministered, cautiously monitor

Renal impairment

  • Mild (CrCl 60-89 mL/min): No dosage adjustment
  • Moderate (CrCl 30-59 mL/min): Reduce dose to 0.75 mg qDay
  • Severe (CrCl <30 mL/min) or patients requiring hemodialysis: Not studied

Hepatic impairment

  • Mild (total bilirubin ≤1x ULN and any AST > ULN OR total bilirubin >1-1.5x ULN and any AST): No dosage adjustment
  • Moderate-to-severe (total bilirubin >1.5x ULN AND any AST): Not studied

Dosing Considerations

Select patients for therapy based on presence of germline BRCA mutations

Information on FDA-approved test for the detection of BRCA mutations is available at http://www.fda.gov/companiondiagnostics

<18 years: Safety and efficacy not established

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Interactions

Interaction Checker

and talazoparib

No Results

     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

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            Adverse Effects

            Adverse effects include all grades unless otherwise stated

            >10%

            Decreased hemoglobin (90%)

            Decreased leukocytes (84%)

            Decreased lymphocytes (76%)

            Decreased neutrophils (68%)

            Fatigue (62%)

            Decreased platelets (55%)

            Increased glucose (54%)

            Anemia (53%)

            Nausea (49%)

            Increased AST (37%)

            Increased alkaline phosphatase (36%)

            Neutropenia (35%)

            Increased ALT (33%)

            Headache (33%)

            Decreased calcium (28%)

            Thrombocytopenia (27%)

            Vomiting (25%)

            Alopecia (25%)

            Diarrhea (22%)

            Decreased appetite (21%)

            Abdominal pain (19%)

            Dizziness (17%)

            Leukopenia (17%)

            Grade 3

            • Decreased hemoglobin (39%)
            • Anemia (38%)
            • Neutropenia (18%)
            • Decreased neutrophils (17%)
            • Decreased lymphocytes (17%)
            • Decreased leukocytes (14%)
            • Thrombocytopenia (11%)
            • Decreased platelets (11%)

            1-10%

            Dysgeusia (10%)

            Dyspepsia (10%)

            Stomatitis (8%)

            Lymphopenia (7%)

            Grade 3

            • Decreased platelets (4%)
            • Decreased neutrophils (3%)
            • Fatigue (3%)
            • Increased glucose (2%)
            • Increased alkaline phosphate (2%)
            • Vomiting (2%)
            • Headache (2%)
            • Increased AST/ALT (1-2%)
            • Decreased calcium (1%)

            Grade 4

            • Thrombocytopenia (4%)
            • Neutropenia (3%)
            • Anemia (1%)

            <1%

            Decreased appetite, Grade 3

            Nausea, Grade 3

            Decreased lymphocytes, Grade 4

            Decreased leukocytes, Grade 4

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            Warnings

            Contraindications

            None

            Cautions

            Myelosuppression (eg, anemia, leukopenia/neutropenia, and/or thrombocytopenia) reported; monitor CBC count for cytopenia at baseline and monthly thereafter; do not start until patients have adequately recovered from hematological toxicity caused by previous therapy

            Based on its mechanism of action and findings from animal data, fetal harm may occur when administered to a pregnant woman (see Pregnancy)

            Myelodysplastic syndrome/acute myeloid leukemia

            • Myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) reported; MDS/AML reported (0.3%) in solid tumor in clinical studies; duration of treatment in these patients prior to developing MDS/AML was 4 months and 24 months, respectively
            • Do not start until patients have adequately recovered from hematological toxicity caused by previous chemotherapy
            • For prolonged hematological toxicities, interrupt and monitor blood cell counts weekly until recovery; if levels do not recover after 4 weeks, refer patient to a hematologist for further investigations
            • If MDS/AML is confirmed, discontinue treatment

            Drug interactions overview

            • P-gp and BCRP transporters substrate
            • Effect of P-gp inhibitors
              • Coadministration with P-gp inhibitors may increase talazoparib exposure
              • In clinical studies, coadministration with P-gp inhibitors (ie, amiodarone, carvedilol, clarithromycin, itraconazole, verapamil) resulted in an ~45% increase in talazoparib exposure and an increase in the rate of talazoparib dose reduction
              • When coadministering with P-gp inhibitors not listed above, monitor for potential increased adverse reactions
            • Effect of BCRP inhibitors
              • Coadministration with BCRP inhibitors may increase talazoparib exposure
              • If coadministration cannot be avoided, monitor potential increased adverse reactions when coadministering
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            Pregnancy

            Pregnancy

            Based on findings from animal studies and its mechanism of action, embryo-fetal harm may occur when administered to a pregnant woman

            No data available on use in pregnant women to inform a drug-associated risk

            Recommend a pregnancy test for females of reproductive potential prior to initiating treatment

            Animal data

            • In an animal reproduction study, administration of talazoparib to pregnant rats during organogenesis caused fetal malformations and structural skeletal variations and embryo-fetal death at maternal exposures that were 0.24 times the AUC in patients receiving the recommended dose of 1 mg qDay

            Contraception

            • Females: Advise females of reproductive potential to use effective contraception during treatment and for ≥7 months following the last dose
            • Males: Based on genotoxicity and animal reproduction studies, advise males with female partners of reproductive potential and pregnant partners to use effective contraception during treatment and for ≥4 months following the last dose

            Infertility

            • Based on animal studies, impaired fertility in males of reproductive potential may occur

            Lactation

            There are no data on the presence of talazoparib in human milk, the drug effects on milk production, or on the breastfed child

            Because of the potential for serious adverse reactions in a breastfed child, advise lactating women not to breastfeed during treatment and for ≥1 month after the final dose

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.

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            Pharmacology

            Mechanism of Action

            Poly ADP ribose polymerase (PARP) inhibitor; PARP enzymes are involved in normal cellular homeostasis, such as DNA transcription, cell cycle regulation, and DNA repair

            Absorption

            Peak plasma concentration, steady-state: 16.4 ng/mL

            Peak plasma time: 1-2 hr

            AUC, steady-state: 208 ng·hr/mL

            Steady-state reached within 2-3 weeks

            Food effect

            • Following a single oral 0.5-mg dose with high-fat, high-calorie food (~800-1000 calories with 150, 250, and 500-600 calories from protein, carbohydrate, and fat, respectively), mean peak plasma concentration of talazoparib was decreased by 46%, the median peak plasma time was delayed from 1-4 hr, and AUC was not affected

            Distribution

            Vd: 420 L

            Protein bound: 74%

            Metabolism

            Undergoes minimal hepatic metabolism

            Identified metabolic pathways of talazoparib in humans include mono-oxidation, dehydrogenation, cysteine conjugation of mono-desfluoro-talazoparib, and glucuronide conjugation

            Elimination

            Half-life: 90 hr

            Clearance: 6.45 L/hr

            Excretion: Urine (~68.7% [54.6% unchanged]), feces (19.7% [13.6% unchanged])

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            Administration

            Oral Administration

            Administer orally with or without food

            Swallow hard capsules whole; do not open or dissolve

            If patient vomits or misses a dose, do not take an additional dose; take next dose at usual time

            Storage

            Capsules: Store at 20-25°C (68-77°F); excursions permitted between 15-30°C (59-86°F)

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            Formulary

            FormularyPatient Discounts

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            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
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            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
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            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.