TALZENNA

Clinical safety rating: caution

Comprehensive clinical and safety monograph for TALZENNA (TALZENNA).

How it works

Talazoparib is a poly (ADP-ribose) polymerase (PARP) inhibitor, including PARP1 and PARP2, which plays a role in DNA repair. It traps PARP on single-strand breaks, leading to replication fork collapse, double-strand breaks, and cell death in tumors with homologous recombination repair deficiencies, such as BRCA mutations.

What the body does with it

Metabolism	Primarily metabolized by CYP3A4 and CYP2C8, with some contribution from CYP1A2, CYP2C19, CYP2D6, and CYP3A5; also undergoes amide hydrolysis.
Excretion	Talazoparib is eliminated primarily via biliary/fecal excretion (68.7%) and renal excretion (19.1%). Approximately 11% is excreted unchanged in feces and <1% unchanged in urine.
Half-life	Terminal elimination half-life is approximately 90 hours (range 74-109 hours). The long half-life supports once-daily dosing and allows for sustained poly(ADP-ribose) polymerase (PARP) inhibition.
Protein binding	Talazoparib is 74% bound to human plasma proteins. Binding is primarily to albumin (moderate binding).
Volume of Distribution	Apparent volume of distribution (Vd/F) is approximately 420 L (6 L/kg for a 70 kg patient), indicating extensive tissue distribution and binding to PARP enzymes in target tissues.
Bioavailability	Oral bioavailability is approximately 38% (range 28-48%). Food does not significantly affect absorption; talazoparib can be taken with or without food.
Onset of Action	Oral administration: Clinical effects (PARP inhibition) are observed within hours of first dose; maximal pharmacodynamic effect on PARP activity is achieved by day 8 of once-daily dosing.
Duration of Action	The pharmacodynamic effect (PARP inhibition) persists for up to 24 hours post-dose, consistent with once-daily dosing. Antitumor activity requires continuous daily dosing.

Classification & Brands

Dosing & administration

800 mg orally once daily with or without food.

Dosage form	CAPSULE
Renal impairment	No dose adjustment required for mild to moderate renal impairment (ClCr 30-89 mL/min). For severe renal impairment (ClCr <30 mL/min), reduce dose to 400 mg orally once daily. End-stage renal disease (ESRD) not studied.
Liver impairment	Mild hepatic impairment (Child-Pugh A): no adjustment. Moderate hepatic impairment (Child-Pugh B): reduce dose to 400 mg orally once daily. Severe hepatic impairment (Child-Pugh C): not recommended.
Pediatric use	Safety and efficacy not established in pediatric patients.
Geriatric use	No specific dose adjustment recommended; monitor for toxicity in patients ≥65 years due to potential decreased renal function.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for TALZENNA (TALZENNA).

Breastfeeding	No data available on presence in human milk, effects on breastfed infant, or milk production. M/P ratio unknown. Due to potential for serious adverse reactions, breastfeeding is not recommended during therapy and for at least 1 month after last dose.
Teratogenic Risk	Based on its mechanism of action as a PARP inhibitor and animal studies, talazoparib may cause fetal harm. There are no adequate human studies. First trimester: High risk of embryotoxicity and teratogenicity; avoid use. Second/third trimesters: Potential for fetal growth restriction and adverse effects on fetal DNA repair; use only if maternal benefit outweighs risk.

Warnings & precautions

■ FDA Black Box Warning

None

Side Effect Profile

Serious Effects

Absolute Contraindications

["None known based on manufacturer labeling"]

Clinical Precautions

Precautions

["Myelodysplastic syndrome/Acute myeloid leukemia (MDS/AML) reported in patients receiving PARP inhibitors","Bone marrow suppression: Monitor complete blood counts regularly","Embryo-fetal toxicity: Can cause fetal harm; advise females of reproductive potential to use effective contraception","Potential for severe myelosuppression: Dose interruption, reduction, or discontinuation may be required"]

Clinical Tips & Counseling

Drug interactions

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TALZENNA

Clinical safety rating: caution

Comprehensive clinical and safety monograph for TALZENNA (TALZENNA).

How it works

What the body does with it

Metabolism	Primarily metabolized by CYP3A4 and CYP2C8, with some contribution from CYP1A2, CYP2C19, CYP2D6, and CYP3A5; also undergoes amide hydrolysis.
Excretion	Talazoparib is eliminated primarily via biliary/fecal excretion (68.7%) and renal excretion (19.1%). Approximately 11% is excreted unchanged in feces and <1% unchanged in urine.
Half-life	Terminal elimination half-life is approximately 90 hours (range 74-109 hours). The long half-life supports once-daily dosing and allows for sustained poly(ADP-ribose) polymerase (PARP) inhibition.
Protein binding	Talazoparib is 74% bound to human plasma proteins. Binding is primarily to albumin (moderate binding).
Volume of Distribution	Apparent volume of distribution (Vd/F) is approximately 420 L (6 L/kg for a 70 kg patient), indicating extensive tissue distribution and binding to PARP enzymes in target tissues.
Bioavailability	Oral bioavailability is approximately 38% (range 28-48%). Food does not significantly affect absorption; talazoparib can be taken with or without food.
Onset of Action	Oral administration: Clinical effects (PARP inhibition) are observed within hours of first dose; maximal pharmacodynamic effect on PARP activity is achieved by day 8 of once-daily dosing.
Duration of Action	The pharmacodynamic effect (PARP inhibition) persists for up to 24 hours post-dose, consistent with once-daily dosing. Antitumor activity requires continuous daily dosing.

Classification & Brands

Dosing & administration

800 mg orally once daily with or without food.

Dosage form	CAPSULE
Renal impairment	No dose adjustment required for mild to moderate renal impairment (ClCr 30-89 mL/min). For severe renal impairment (ClCr <30 mL/min), reduce dose to 400 mg orally once daily. End-stage renal disease (ESRD) not studied.
Liver impairment	Mild hepatic impairment (Child-Pugh A): no adjustment. Moderate hepatic impairment (Child-Pugh B): reduce dose to 400 mg orally once daily. Severe hepatic impairment (Child-Pugh C): not recommended.
Pediatric use	Safety and efficacy not established in pediatric patients.
Geriatric use	No specific dose adjustment recommended; monitor for toxicity in patients ≥65 years due to potential decreased renal function.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for TALZENNA (TALZENNA).

Breastfeeding	No data available on presence in human milk, effects on breastfed infant, or milk production. M/P ratio unknown. Due to potential for serious adverse reactions, breastfeeding is not recommended during therapy and for at least 1 month after last dose.
Teratogenic Risk	Based on its mechanism of action as a PARP inhibitor and animal studies, talazoparib may cause fetal harm. There are no adequate human studies. First trimester: High risk of embryotoxicity and teratogenicity; avoid use. Second/third trimesters: Potential for fetal growth restriction and adverse effects on fetal DNA repair; use only if maternal benefit outweighs risk.

Warnings & precautions

■ FDA Black Box Warning

None

Side Effect Profile

Serious Effects

Absolute Contraindications

["None known based on manufacturer labeling"]

Clinical Precautions

Precautions

Clinical Tips & Counseling

Drug interactions

Loading safety data…