dabrafenib mesilate: clinical use

Prescribing considerations

• Confirm the appropriate BRAF V600 mutation using a validated test before initiation.
• Treatment should be initiated and supervised by a clinician experienced in systemic anti-cancer therapy.
• Finlee is intended for use with trametinib oral solution for licensed paediatric glioma indications; consult both product SmPCs.
• Review CYP2C8/CYP3A4 inhibitors and inducers, sensitive enzyme substrates, anticoagulants and hormonal contraceptives.
• Establish a fever-management plan and assess febrile patients for infection, dehydration, hypotension and renal impairment.
• Use caution in severe renal impairment and moderate or severe hepatic impairment because clinical data are limited.
• Consider risks in people with prior or concurrent RAS-associated malignancy and around radiotherapy.

Contraindications and cautions

• Hypersensitivity to dabrafenib or any formulation excipient.

Monitoring

• BRAF mutation status before treatment.
• Skin examination before and regularly during treatment, with continued surveillance after stopping.
• Temperature and symptoms of infection, dehydration or hypotension.
• Renal function, including serum creatinine.
• Liver function, particularly during early combination treatment.
• Blood pressure and blood glucose as clinically indicated.
• New visual symptoms, eye pain or photophobia.
• Cardiac function and respiratory symptoms when used with trametinib, following the trametinib SmPC.
• Unexplained abdominal pain, bleeding, thromboembolic symptoms and signs of new malignancy.

Clinical pharmacology

Dabrafenib inhibits RAF kinases carrying activating BRAF codon-600 mutations and suppresses downstream ERK signalling. It is metabolised mainly through CYP2C8 and CYP3A4 and induces several CYP enzymes and transporters, accounting for its broad interaction potential.

Formulation and product differences

• Tafinlar hard capsules support the selected adult melanoma and non-small cell lung cancer indications.
• Finlee dispersible tablets support the selected paediatric glioma indications and are prepared as an oral suspension; administration through a compatible feeding tube is possible.
• Capsules must be swallowed whole, whereas dispersible tablets are mixed with still water using the supplied cup.
• Finlee must not replace another dabrafenib formulation because bioequivalence has not been demonstrated.
• Finlee contains a small amount of benzyl alcohol and should remain in its original moisture-protective packaging.

Capsule

Route: Oral

Strengths: 50 mg, 75 mg

Dispersible tablet

Route: Oral

Strengths: 10 mg