Tucatinib

What it is and how it works

Tucatinib is an oral, reversible and highly selective inhibitor of the HER2 (ErbB2) tyrosine kinase with minimal EGFR inhibition. It blocks HER2 and HER3 phosphorylation and downstream MAPK and AKT signalling, inhibiting proliferation of HER2-driven tumour cells, and has activity against brain metastases.

Indications

In combination with trastuzumab and capecitabine, treatment of HER2-positive locally advanced or metastatic breast cancer, including patients with brain metastases, after at least two prior anti-HER2 regimens.

Dosage and administration (summary)

Orally, 300 mg twice daily with or without food, continued until disease progression or unacceptable toxicity, with dose reductions for adverse reactions.

Contraindications

Hypersensitivity to tucatinib or excipients.

Warnings and precautions

Diarrhoea, which may be severe, and hepatotoxicity occur; monitor liver function and manage diarrhoea promptly. Tucatinib is metabolised mainly by CYP2C8: avoid strong CYP2C8 inhibitors and strong CYP3A or moderate CYP2C8 inducers; it is a strong CYP3A inhibitor and increases exposure to sensitive substrates. It may raise serum creatinine by inhibiting tubular secretion without affecting glomerular function.

Pregnancy

Can cause fetal harm; avoid in pregnancy and use effective contraception during and for at least one week after treatment.

Storage and supply

Store below 30 °C in the original bottle with desiccant, protected from moisture.

Source: reference summary prepared from the EU SmPC/EPAR, BNF and WHO Model Formulary. The approved product information in Iran governs.