Source: European Medicines Agency (EU) Revision Year: 2019 Publisher: Pfizer Europe MA EEIG, Boulevard de la Plaine 17, 1050, Bruxelles, Belgium
Talzenna is indicated as monotherapy for the treatment of adult patients with germline BRCA1/2-mutations, who have HER2-negative locally advanced or metastatic breast cancer. Patients should have been previously treated with an anthracycline and/or a taxane in the (neo)adjuvant, locally advanced or metastatic setting unless patients were not suitable for these treatments (see section 5.1). Patients with hormone receptor (HR)-positive breast cancer should have been treated with a prior endocrine-based therapy, or be considered unsuitable for endocrine-based therapy.
Treatment with Talzenna should be initiated and supervised by a physician experienced in the use of anticancer medicinal products.
Patients should be selected for the treatment of breast cancer with Talzenna based on the presence of deleterious or suspected deleterious germline BRCA mutations determined by an experienced laboratory using a validated test method.
Genetic counselling for patients with BRCA mutations should be performed according to local regulations, as applicable.
The recommended dose is 1 mg talazoparib once daily. Patients should be treated until disease progression or unacceptable toxicity occurs.
If the patient vomits or misses a dose, an additional dose should not be taken. The next prescribed dose should be taken at the usual time.
To manage adverse drug reactions, interruption of treatment or dose reduction based on severity and clinical presentation should be considered (Table 2). Recommended dose reductions are indicated in Table 1.
Table 1. Dose adjustments for toxicities:
| Dose level | |
|---|---|
| Recommended starting dose | 1 mg (one 1 mg capsule) once daily |
| First dose reduction | 0.75 mg (three 0.25 mg capsules) once daily |
| Second dose reduction | 0.5 mg (two 0.25 mg capsules) once daily |
| Third dose reduction | 0.25 mg (one 0.25 mg capsule) once daily |
Complete blood count should be obtained prior to starting Talzenna therapy and monitored monthly and as clinically indicated (see Table 2 and section 4.4).
Table 2. Dose modification and management:
| Withhold Talzenna until levels resolve to | Resume Talzenna | |
|---|---|---|
| Haemoglobin <8 g/dl | ≥9 g/dl | Resume Talzenna at next lower dose |
| Platelet count <50,000/μl | ≥75,000/μl | |
| Neutrophil count <1,000/μl | ≥1,500/µl | |
| Non-haematologic adverse reaction Grade 3 or Grade 4 | ≤ Grade 1 | Consider resuming Talzenna at next lower dose or discontinue |
Strong inhibitors of P-gp may lead to increased talazoparib exposure. Concomitant use of strong P-gp inhibitors during treatment with talazoparib should be avoided. Co-administration should only be considered after careful evaluation of the potential benefits and risks. If co-administration with a strong P-gp inhibitor is unavoidable, the Talzenna dose should be reduced to 0.75 mg once daily. When the strong P-gp inhibitor is discontinued, the Talzenna dose should be increased (after 3‐5 half-lives of the P-gp inhibitor) to the dose used prior to the initiation of the strong P-gp inhibitor (see section 4.5).
No dose adjustment is required for patients with mild hepatic impairment (total bilirubin ≤1 × upper limit of normal [ULN] and aspartate aminotransferase (AST) > ULN, or total bilirubin >1.0 to 1.5 × ULN and any AST). Talzenna has not been studied in patients with moderate (total bilirubin >1.5 to 3.0 × ULN and any AST) or severe hepatic impairment (total bilirubin >3.0 × ULN and any AST) (see section 5.2). Talzenna may only be used in patients with moderate or severe hepatic impairment if the benefit outweighs the potential risk, and the patient should be carefully monitored for hepatic function and adverse events.
No dose adjustment is required for patients with mild renal impairment (60 mL/min≤ creatinine clearance [CrCl] <90 mL/min). For patients with moderate renal impairment (30 mL/min≤ CrCl <60 mL/min), the recommended starting dose of Talzenna is 0.75 mg once daily. Talzenna has not been studied in patients with severe renal impairment (CrCl <30 mL/min) or patients requiring haemodialysis. Talzenna is not recommended for use in patients with severe renal impairment or requiring haemodialysis (see section 5.2). Talzenna may only be used in patients with severe renal impairment if the benefit outweighs the potential risk, and the patient should be carefully monitored for renal function and adverse events (see section 5.2).
No dose adjustment is necessary in elderly (≥65 years of age) patients (see section 5.2).
The safety and efficacy of Talzenna in children and adolescents < 18 years of age have not been established. No data are available.
Talzenna is for oral use. To avoid contact with the capsule content, the capsules should be swallowed whole, and must not be opened or dissolved. They can be taken with or without food (see section 5.2).
There is limited experience of overdose with talazoparib. No adverse reactions were reported in one patient who accidentally self-administered thirty 1-mg capsules of talazoparib on Day 1 and was immediately treated with gastric decontamination. Symptoms of overdose are not established. In the event of overdose, treatment with talazoparib should be stopped, and physicians should consider gastric decontamination, follow general supportive measures and treat symptomatically.
Shelf life: 2 years.
This medicinal product does not require any special storage conditions.
Talzenna 0.25 mg hard capsules:
High-density polyethylene (HDPE) bottle and polypropylene (PP) closure with heat induction seal liner. Pack size: cartons of 30 capsules in a HDPE bottle.
Polyvinyl chloride/polyvinylidene chloride (PVC/PVdC) perforated unit dose blister with an aluminum peel off foil lidding. Pack sizes: cartons of 30 × 1 capsules, or 60 × 1 capsules, or 90 × 1 capsules in unit dose blisters.
Talzenna 1 mg hard capsules:
High-density polyethylene (HDPE) bottle and polypropylene (PP) closure with heat induction seal liner. Pack size: cartons of 30 capsules in a HDPE bottle.
Polyvinyl chloride/polyvinylidene chloride (PVC/PVdC) perforated unit dose blister with an aluminum peel off foil lidding. Pack size: cartons of 30 × 1 capsules in unit dose blisters.
Not all pack sizes may be marketed.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
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