Talazoparib

Oral
Germline BRCA-mutated human epidermal growth factor receptor 2 negative locally advanced carcinoma of breast, Germline BRCA-mutated human epidermal growth factor receptor 2 negative metastatic carcinoma of breast

Patients taking P-glycoprotein (P-gp) inhibitors (e.g. itraconazole, amiodarone, carvedilol, verapamil, clarithromycin): Reduce dose to 0.75 mg once daily. After discontinuation of the P-gp inhibitor, increase the dose after 3-5 half-lives of the P-gp inhibitor to the dose used before the initiation of the P-gp inhibitor.

CrCl (mL/min)	Dosage
15-29	Decrease dose to 0.5 mg once daily.
30-59	Decrease dose to 0.75 mg once daily.

May be taken with or without food. Swallow whole, do not open/dissolve.

Pregnancy and lactation.

Concomitant use with P-gp inhibitors. Moderate to severe renal impairment.

Significant: Bone marrow suppression (e.g. anaemia, leucopenia/neutropenia, thrombocytopenia), myelodysplastic syndrome/acute myeloid leukaemia.
Blood and lymphatic system disorders: Lymphopenia.
Gastrointestinal disorders: Nausea, vomiting, diarrhoea, abdominal pain, dysgeusia, stomatitis, dyspepsia.
General disorders and administration site conditions: Fatigue.
Metabolism and nutrition disorders: Decreased appetite.
Nervous system disorders: Dizziness, headache.
Skin and subcutaneous tissue disorders: Alopecia.

PO: Z (Animal studies showed embryo-foetal harm and death. Avoid during pregnancy.)

This drug may cause fatigue or dizziness, if affected, do not drive or operate machinery. Women of childbearing potential must use proven birth control methods during and for at least 7 months after treatment. Consider using other reliable contraceptive methods recommended by the doctor as hormonal contraceptives are not recommended for breast cancer patients. Male patients with partners of reproductive potential should use effective contraceptive methods during treatment and for at least 4 months after treatment.

Confirm germline BRCA-mutation before initiation of treatment. Screen for pregnancy prior to treatment initiation. Monitor CBC (at baseline, monthly, and as necessary), renal function tests. Monitor for signs and symptoms of myeloid leukaemia/myelodysplastic syndrome.

Increased exposure with certain P-gp inhibitors (e.g. itraconazole, amiodarone, carvedilol, verapamil, clarithromycin).

Description:
Mechanism of Action: Talazoparib, an antineoplastic agent, is an inhibitor of poly (ADP-ribose) polymerase (PARP) enzymes, including PARP1 and PARP2. PARP enzymes are vital for DNA transcription, cell cycle regulation, and DNA repair. Talazoparib exhibits its effect by catalytic inhibition, thereby causing cell death due to the accumulation of irreversible DNA damage. It also traps PARP-DNA complexes, which may be more efficacious in cell death than enzymatic inhibition only.
Pharmacokinetics:
Absorption: Time to peak plasma concentration: 1-2 hours.
Distribution: Volume of distribution: 420 L. Plasma protein binding: Approx 74%.
Metabolism: Metabolised in the liver (minimal) via mono-oxidation, dehydrogenation, cysteine conjugation of mono-desluoro-talazoparib, and glucuronide conjugation.
Excretion: Via urine (approx 69%; 54.6% as unchanged drug); faeces (approx 20%; 13.6% as unchanged drug). Elimination half-life: 90 (±58) hours.

Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 135565082, Talazoparib. https://pubchem.ncbi.nlm.nih.gov/compound/Talazoparib. Accessed Nov. 24, 2022.

Store between 15-30°C. This is a cytotoxic drug. Follow applicable procedures for receiving, handling, administration, and disposal.

Targeted Cancer Therapy

L01XK04 - talazoparib ; Belongs to the class of poly (ADP-ribose) polymerase (PARP) inhibitors. Used in the treatment of cancer.

Anon. Talazoparib. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 06/10/2022.

Buckingham R (ed). Talazoparib. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 06/10/2022.

Joint Formulary Committee. Talazoparib. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 06/10/2022.

Talzenna 0.25 mg and 1 mg Hard Capsules (Pfizer [Malaysia] Sdn. Bhd.). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 06/10/2022.

Talzenna 1 mg Hard Capsules (Pfizer Limited). MHRA. https://products.mhra.gov.uk. Accessed 06/10/2022.

Talzenna Capsule (Pfizer Laboratories Div Pfizer Inc). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 06/10/2022.