Talazoparib
Talazoparib Uses, Dosage, Side Effects, Food Interaction and all others data.
Talazoparib was approved by the FDA for use in germline BRCA mutated, HER2 negative, locally advanced or metastatic breast cancer on October 16, 2018 under the trade name Talzenna . Talzenna was granted approval based on the results of the EMBRACA trial in which talazoparib resulted in a mean 8.6 months progression-free survival time versus physician's choice chemotherapy which resulted in 5.6 months progression-free survival.
Talazoparib prevents PARP-mediated repair of DNA damage in cancer cells, allowing accumulation of damage and PARP-DNA complexes . Repair related errors by error prone secondary repair pathways may also contribute to the cytotoxicity of talazoparib .
| Trade Name | Talazoparib |
| Availability | Prescription only |
| Generic | Talazoparib |
| Talazoparib Other Names | Talazoparib |
| Related Drugs | Arimidex, Ibrance, Femara, Xeloda, Herceptin, Lynparza |
| Weight | 0.25mg, 1mg |
| Type | Oral capsule |
| Formula | C19H14F2N6O |
| Weight | Average: 380.359 Monoisotopic: 380.119715421 |
| Protein binding | Talazoparib is 74% bound to plasma proteins and independent of drug concentration . |
| Groups | Approved, Investigational |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | United States |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Talazoparib is a poly-ADP ribose polymerase inhibitor used to treat HER2-, BRCA mutated locally advanced or metastatic breast cancer.
Talazoparib is indicated for the treatment of deleterious or suspected deleterious germline BRCA mutated, HER2 negative locally advanced or metastatic breast cancer in adults .
Talazoparib is also used to associated treatment for these conditions: Locally Advanced Breast Cancer (LABC), Metastatic Breast Cancer
How Talazoparib works
Talazoparib binds to and inhibits PARP1 and PARP2 at the NAD+ binding site with a Ki of 1.2 and 0.87 nM, respectively . The inhibitory effect on PAR synthesis has an EC50 of 2.51 nM.
Toxicity
Talazoparib is clastogenic due to its pharmacological mechanism . Talazoparib does not appear to be mutagenic and no data is available on carcinogenicity.
In repeat-dose toxicity studies up to 3-months duration at doses ≥0.04 mg/kg/day in rats and ≥0.01 mg/kg/day in dogs resulted in decreased organ weights, luminal cellular debris, reduced sperm, and degeneration/atrophy in the testis and epididymis . These doses were equivalent to approximately 1.0 times and 0.2 times normal human exposure. Follicular atresia of the ovary was observed in rats at doses ≥1 mg/kg/day, equivalent to 9.5 times normal human exposure. While no fertility data exists these results suggest a potential for reduced fertility due to talazoparib exposure.
Food Interaction
- Take at the same time every day.
- Take with or without food.
Talazoparib Disease Interaction
Moderate: hepatic impairment, myelosuppression, renal impairment
Volume of Distribution
Talazoparib has a mean apparent volume of distribution of 420 L .
Elimination Route
Talzenna capsules have a reach peak plasma concentration in 1-2 h . If taken with a high fat meal, Cmax decreases by 43%, Tmax increases by 1-4 h, and no change occurs in AUC.
Half Life
The mean terminal plasma half life of Talzenna capsules is 90 h with a standard deviation of 58 h .
Clearance
The mean apparent oral clearance of talazoparib is 6.45 L/h with an inter-individual variability of 31.1% . Apparent oral clearance is reduced by 14.4% in patients with mild renal impairment while mild hepatic impairment has no effect. No data is available in patients with moderate to severe renal or hepatic impairment.
Elimination Route
64.7% of talazoparib is excreted in the urine with 54.6% as unchanged drug . 19.7% is eliminated in the feces with 13.6% as unchanged drug.
Innovators Monograph
You find simplified version here Talazoparib
