Drug information of talazoparib
Talazoparib is used to treat HER2-negative breast cancer that has spread to other parts of the body.
Mechanism of effect
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. 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 .
Talazoparib prevents PARP-mediated repair of DNA damage in cancer cells, allowing accumulation of damage and PARP-DNA complexes.
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
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.
Half-life: 90 hr
Clearance: 6.45 L/hr
Excretion: Urine (~68.7% [54.6% unchanged]), feces (19.7% [13.6% unchanged])
Drug indicationsHER2-negative metastatic breast cancer.
Breast cancer, locally advanced or metastatic (BRCA-mutated, HER2-negative)
1 mg PO qDay with or without food
Continue until disease progression or unacceptable toxicity occurs
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
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).
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.
- Mild (CrCl 60-89 mL/min): No dosage adjustment required
- Moderate (CrCl 30-59 mL/min): Reduce dose to 0.75 mg qDay
- Severe (CrCl 15-29 mL/min): Reduce dose to 0.5 mg qDay
Side effectsanemia , Diarrhea , Headache , nausea , abdominal pain , vomiting , vertigo , thrombocytopenia , neutropenia , lymphopenia , leukopenia , Hypocalcemia , Acute Myeloid Leukemia , tiredness
Decreased hemoglobin -Decreased leukocytes -Decreased lymphocytes -Decreased neutrophils -Fatigue -Decreased platelets -Increased glucose -Anemia -Nausea -Increased AST -Increased alkaline phosphatase -Neutropenia -Increased ALT -Headache -Decreased calcium - Vomiting -Alopecia -Diarrhea -Decreased appetite -Abdominal pain -Dizziness - Dysgeusia -Dyspepsia -Stomatitis -Lymphopenia -Bone marrow depression-Acute myelocytic leukemia, myelodysplastic syndrome
InteractionsAmiodarone , Erythromycin , Itraconazole , Imatinib , Propafenone , Pantoprazole , lasmiditan , vemurafenib , stiripentol , tucatinib , Darolutamide , Istradefylline , Siponimod , Eliglustat , Gefitinib , neratinib , Acalabrutinib , cobicistat , Fostamatinib , Ibrutinib , elagolix , Flibanserin , Mefloquine , Ivacaftor , Regorafenib , Ponatinib , Dabrafenib , Eltrombopag , ombitasvir , vandetanib , Eluxadoline , Lopinavir , Osimertinib , Quinine , Grapefruit , safinamide , Lomitapide , dronedarone , ritonavir , dasabuvir , Carvedilol , Ketoconazole , Clarithromycin , ledipasvir and sofosbuvir , Ranolazine , Quinidine , Posaconazole , Dipyridamole , Sunitinib , Cyclosporine , Lapatinib , Verapamil , Meningococcal conjugate vaccine , rolapitant , Fidaxomicin
-Myelosuppression (eg, anemia, leukopenia/neutropenia, and/or thrombocytopenia) reported;
-Based on its mechanism of action and findings from animal data, fetal harm may occur when administered to a pregnant woman.
- Myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) reported; If MDS/AML is confirmed, discontinue treatment.
-Coadministration with P-gp inhibitors (ie, amiodarone, carvedilol, clarithromycin, itraconazole, verapamil) may increase talazoparib exposure.
-Coadministration with BCRP inhibitors may increase talazoparib exposure.
-Nausea and vomiting (usually mild to moderate) may commonly occur; diarrhea may also occur.
- Talazoparib exposure is increased in patients with renal impairment. Dosage adjustment is recommended in patients with moderate to severe impairment
Points of recommendation
-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
-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 a dose is missed or vomited, an additional dose should not be administered; administer the next dose at the usual scheduled time
-Administer orally with or without food
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.
Advise females of reproductive potential to use effective contraception during treatment and for ≥7 months following the last dose.
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.
Based on animal studies, impaired fertility in males of reproductive potential may occur.
Breast feeding warning
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.
Ask a Pharmacist