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Talazoparib

Medically reviewed by Drugs.com. Last updated on April 30, 2020.

Pronunciation

(tal a ZOE pa rib)

Index Terms

  • BMN 673
  • BMN-673
  • Talazoparib Tosylate

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule, Oral, as tosylate:

Talzenna: 0.25 mg, 1 mg

Brand Names: U.S.

  • Talzenna

Pharmacologic Category

  • Antineoplastic Agent, PARP Inhibitor

Pharmacology

Talazoparib is a poly (ADP-ribose) polymerase (PARP) enzyme inhibitor, including PARP1 and PARP2. PARP enzymes are involved in DNA transcription, cell cycle regulation, and DNA repair. Talazoparib is a potent PARP inhibitor, with both strong catalytic inhibition and a PARP-trapping potential that is significantly greater than other PARP inhibitors (Litton 2018). Catalytic inhibition causes cell death due to accumulation of irreparable DNA damage; talazoparib also traps PARP-DNA complexes, which may be more effective in cell death than enzymatic inhibition alone (Litton 2018).

Distribution

Vd: 420 L

Metabolism

Minimal hepatic metabolism; metabolic pathways include mono-oxidation, dehydrogenation, cysteine conjugation of mono-desfluoro-talazoparib, and glucuronide conjugation

Excretion

Urine: ~69% (54.6% as unchanged drug); Feces: ~20% (13.6% as unchanged drug)

Time to Peak

1 to 2 hours

Half-Life Elimination

90 (±58) hours

Protein Binding

74%

Special Populations: Renal Function Impairment

Steady-state exposure (AUC0-24) and peak concentration (Cmax) increased by 12%, 43%, and 163% and 11%, 32%, and 89% in patients with mild (eGFR 60 to 89 mL/minute/1.73 m2), moderate (eGFR 30 to 59 mL/minute/1.73 m2), and severe (eGFR 15 to 29 mL/minute/1.73 m2) renal impairment, respectively, compared to patients with normal renal function.

Use: Labeled Indications

Breast cancer, locally advanced or metastatic (BRCA-mutated, HER2-negative): Treatment of deleterious or suspected deleterious germline breast cancer susceptibility gene (BRCA)-mutated (gBRCAm) human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer in adults (as detected by an approved test).

Contraindications

There are no contraindications listed in the manufacturer's labeling.

Dosing: Adult

Note: Administer only to patients with germline BRCA mutation (as detected by an approved test).

Breast cancer, locally advanced or metastatic, BRCA-mutated, HER2-negative: Oral: 1 mg once daily until disease progression or unacceptable toxicity (Litton 2018)

Missed doses: If a dose is missed or vomited, an additional dose should not be administered; administer the next dose at the usual scheduled time.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Adjustment for Toxicity

Consider therapy interruption with or without dose reduction for adverse reactions, depending on the severity and clinical presentation. Talazoparib should be discontinued if more than 3 dose reductions are necessary.

Recommended talazoparib dose reductions for toxicity:

Initial/usual starting dose: 1 mg once daily

First dose reduction: 0.75 mg once daily

Second dose reduction: 0.5 mg once daily

Third dose reduction: 0.25 mg once daily

Hematologic toxicity:

Hemoglobin <8 g/dL: Withhold talazoparib until hemoglobin is ≥9 g/dL, then resume therapy at a reduced dose.

Neutrophils <1,000/mm3: Withhold talazoparib until neutrophils are ≥1,500/mm3, then resume therapy at a reduced dose.

Platelets <50,000/mm3: Withhold talazoparib until platelets are ≥75,000/mm3, then resume therapy at a reduced dose.

MDS/AML (confirmed): Discontinue therapy

Nonhematologic toxicity: Grade 3 or 4 toxicity: Withhold talazoparib until toxicity is ≤ grade 1, then consider resuming therapy at a reduced dose or discontinuing talazoparib (depending on the severity of the toxicity).

Administration

Oral: Administer with or without food. Swallow capsules whole; do not open or dissolve capsule.

Storage

Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F).

Drug Interactions

5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Monitor therapy

Amiodarone: May increase the serum concentration of Talazoparib. Management: If concurrent use cannot be avoided, reduce talazoparib dose to 0.75 mg once daily. When amiodarone is discontinued, increase the talazoparib dose to the dose used before initiation of amiodarone after 3 to 5 times the half-life of amiodarone. Consider therapy modification

AtorvaSTATin: May increase the serum concentration of Talazoparib. Monitor therapy

BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

BCRP/ABCG2 Inhibitors: May increase the serum concentration of Talazoparib. Monitor therapy

Carvedilol: May increase the serum concentration of Talazoparib. Management: If concurrent use cannot be avoided, reduce talazoparib dose to 0.75 mg once daily. When carvedilol is discontinued, increase the talazoparib dose to the dose used before initiation of carvedilol after 3 to 5 times the half-life of carvedilol. Consider therapy modification

Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Monitor therapy

Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Avoid combination

Clarithromycin: May increase the serum concentration of Talazoparib. Management: If concurrent use cannot be avoided, reduce talazoparib dose to 0.75 mg once daily. When clarithromycin is discontinued, increase the talazoparib dose to the dose used before initiation of clarithromycin after 3 to 5 times the half-life of clarithromycin. Consider therapy modification

CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Monitor therapy

Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Consider therapy modification

DilTIAZem: May increase the serum concentration of Talazoparib. Monitor therapy

Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Avoid combination

Erdafitinib: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates (High risk with Inhibitors). Monitor therapy

Felodipine: May increase the serum concentration of Talazoparib. Monitor therapy

FluvoxaMINE: Talazoparib may increase the serum concentration of FluvoxaMINE. Monitor therapy

Itraconazole: May increase the serum concentration of Talazoparib. Management: If concurrent use cannot be avoided, reduce talazoparib dose to 0.75 mg once daily. When itraconazole is discontinued, increase the talazoparib dose to the dose used before initiation of itraconazole after 3 to 5 times the half-life of itraconazole. Consider therapy modification

Lasmiditan: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates (High risk with Inhibitors). Avoid combination

Lumacaftor and Ivacaftor: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates (High risk with Inhibitors or Inducers). Lumacaftor and Ivacaftor may decrease the serum concentration of P-glycoprotein/ABCB1 Substrates (High risk with Inhibitors or Inducers). Monitor therapy

P-glycoprotein/ABCB1 Inhibitors: May increase the serum concentration of Talazoparib. Monitor therapy

Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Monitor therapy

Verapamil: May increase the serum concentration of Talazoparib. Management: If concurrent use cannot be avoided, reduce talazoparib dose to 0.75 mg once daily. When verapamil is discontinued, increase the talazoparib dose to the dose used before initiation of verapamil after 3 to 5 times the half-life of verapamil. Consider therapy modification

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

>10%

Central nervous system: Fatigue (62%), headache (33%), dizziness (17%)

Dermatologic: Alopecia (25%)

Endocrine & metabolic: Increased serum glucose (54%), decreased serum calcium (28%)

Gastrointestinal: Nausea (49%), vomiting (25%), diarrhea (22%), decreased appetite (21%), abdominal pain (19%)

Hematologic & oncologic: Decreased hemoglobin (90%; grade 3: 39%), anemia (53%; grade 3: 38%; grade 4: 1%), neutropenia (35%; grade 3: 18%; grade 4: 3%), thrombocytopenia (27%; grade 3: 11%; grade 4: 4%), leukopenia (17%)

Hepatic: Increased serum aspartate aminotransferase (37%), increased serum alkaline phosphatase (36%), increased serum alanine aminotransferase (33%)

1% to 10%:

Gastrointestinal: Dysgeusia (10%), dyspepsia (10%), stomatitis (8%)

Hematologic & oncologic: Lymphocytopenia (7%)

Frequency not defined: Hematologic & oncologic: Bone marrow depression

<1%, postmarketing, and/or case reports: Acute myelocytic leukemia, myelodysplastic syndrome

Warnings/Precautions

Concerns related to adverse effects:

• Bone marrow suppression: Anemia, leukopenia/neutropenia, and/or thrombocytopenia have been reported, including ≥ grade 3 events. Monitor complete blood counts at baseline and monthly thereafter (and as clinically indicated); do not initiate talazoparib until any hematologic toxicity caused by previous chemotherapy has adequately recovered. If prolonged hematologic toxicity occurs during therapy, interrupt treatment and monitor blood counts weekly until recovered; if counts do not recover to ≤ grade 1 after 4 weeks, further evaluation (including bone marrow and cytogenetic analyses) is necessary.

• GI toxicity: Nausea and vomiting (usually mild to moderate) may commonly occur; diarrhea may also occur.

• Secondary malignancy: Myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) have been reported (rarely) in clinical trials (for various solid tumors). The duration of talazoparib therapy prior to development of the secondary cancers ranged from 4 months to 2 years; patients had received prior chemotherapy with platinum agents and/or other DNA-damaging medications, including radiation. If prolonged hematologic toxicity occurs during talazoparib therapy and blood counts do not recover to ≤ grade 1 after 4 weeks, further evaluation (including bone marrow and cytogenetic analyses) is necessary. If MDS/AML is confirmed, discontinue therapy.

Disease-related concerns:

• Renal impairment: Talazoparib exposure is increased in patients with renal impairment. Dosage adjustment is recommended in patients with moderate to severe impairment.

Dosage form specific issues:

• Propylene glycol: Some dosage forms may contain propylene glycol; large amounts are potentially toxic and have been associated with hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP 1997; Zar 2007).

Other warnings/precautions:

• BRCA-mutation status: Select patients for the treatment of HER2-negative locally advanced or metastatic breast cancer based on the presence of deleterious or suspected deleterious BRCA-mutations. Information on approved tests for the detection of BRCA-mutations may be found at http://www.fda.gov/companiondiagnostics.

Monitoring Parameters

BRCA-mutation status; complete blood count at baseline and monthly thereafter, or as clinically indicated (weekly until recovery for prolonged hematologic toxicity), renal function, pregnancy test (prior to treatment initiation in females of reproductive potential); monitor for signs/symptoms of acute myeloid leukemia/myelodysplastic syndrome (AML/MDS). Monitor adherence.

Reproductive Considerations

Pregnancy testing is recommended prior to therapy in females of reproductive potential. Females of reproductive potential should use effective contraception during therapy and for at least 7 months after the last talazoparib dose. Males with female partners of reproductive potential or female partners who are pregnant should also use effective contraception during therapy and for at least 4 months after the last talazoparib dose.

Pregnancy Considerations

Based on the mechanism of action and information from animal reproduction studies, talazoparib may cause fetal harm if administered during pregnancy.

Patient Education

What is this drug used for?

• It is used to treat breast cancer.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Hair loss

• Headache

• Abdominal pain

• Dizziness

• Change in taste

• Mouth irritation

• Mouth sores

• Diarrhea

• Vomiting

• Nausea

• Lack of appetite

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Infection

• Bleeding like vomiting blood or vomit that looks like coffee grounds; coughing up blood; blood in the urine; black, red, or tarry stools; bleeding from the gums; abnormal vaginal bleeding; bruises without a reason or that get bigger; or any severe or persistent bleeding

• Severe loss of strength and energy

• Weight loss

• Shortness of breath

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Frequently asked questions

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.