Entrectinib

What it is and how it works

Entrectinib inhibits the tropomyosin receptor kinases TRKA, TRKB and TRKC, ROS1 and ALK. In tumours driven by NTRK gene fusions or ROS1 rearrangements it blocks downstream signalling, inhibiting cell proliferation and inducing apoptosis; it penetrates the central nervous system.

Indications

Solid tumours with an NTRK gene fusion that are locally advanced or metastatic and lack satisfactory alternatives; ROS1-positive advanced non-small cell lung cancer not previously treated with ROS1 inhibitors.

Dosage and administration (summary)

Adults: 600 mg orally once daily, with or without food, until disease progression or unacceptable toxicity; dose reductions are made for adverse reactions, and the dose is reduced with moderate or strong CYP3A4 inhibitors.

Contraindications

Hypersensitivity to entrectinib or to any excipient.

Warnings and precautions

Can cause congestive heart failure, QT prolongation, cognitive disorders, dizziness, mood disorders, hyperuricaemia, skeletal fractures and hepatotoxicity; monitor ECG, electrolytes, liver function and uric acid. Avoid strong and moderate CYP3A inducers and grapefruit. Patients should not drive if they experience cognitive or neurological adverse effects.

Pregnancy

May cause fetal harm; avoid in pregnancy and use effective contraception during treatment and for a period afterwards as specified in the product information.

Storage and supply

Store below 30 °C in the original container, protected from moisture.

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