trametinib dimethyl sulfoxide: clinical use

Prescribing considerations

• Confirm BRAF V600 status for adult tablet indications and BRAF V600E status for paediatric glioma using a validated test.
• Initiation and supervision require a clinician experienced in systemic anticancer treatment.
• Consult dabrafenib product information whenever combination treatment is used.
• Assess cardiac disease, bleeding risk, gastrointestinal metastases or diverticulitis, renal and hepatic impairment, previous radiotherapy and fertility intentions.
• For melanoma previously progressing on a BRAF inhibitor, recognise the limited activity of trametinib monotherapy and reduced expected combination efficacy.

Contraindications and cautions

• Hypersensitivity to trametinib or any formulation excipient.
• Use caution in impaired left-ventricular function, uncontrolled hypertension or arrhythmia, severe renal impairment, moderate-to-severe hepatic impairment, and risk factors for gastrointestinal perforation.

Monitoring

• Confirm mutation status before treatment.
• Assess LVEF before treatment, after one month and approximately every three months thereafter.
• Record baseline blood pressure and monitor during treatment.
• Monitor liver function every four weeks initially; continue as clinically indicated.
• Arrange prompt ophthalmological assessment for any new visual symptoms.
• Monitor for fever, dehydration, renal dysfunction, pulmonary symptoms, bleeding, severe skin reactions and muscle toxicity.
• With dabrafenib combination treatment, perform regular skin surveillance for new malignancies; monitor blood counts and serum creatinine as clinically appropriate.

Clinical pharmacology

Trametinib is a highly selective allosteric MEK1/MEK2 inhibitor with a long terminal half-life. It is metabolised mainly through deacetylation by hydrolytic enzymes rather than CYP metabolism, is highly protein-bound and is eliminated predominantly in faeces.

Formulation and product differences

• The tablets support the selected adult melanoma and lung-cancer indications; their paediatric efficacy and safety are not established.
• The oral solution supports the selected paediatric glioma indications and is licensed only with dabrafenib dispersible tablets.
• A pharmacist must reconstitute the oral solution; it is measured with the supplied syringe and can be administered through a nasogastric tube.
• The oral solution and tablets have different exposure profiles and should not be substituted without specialist direction.
• The oral solution contains sulfobutylbetadex sodium, methyl parahydroxybenzoate, sodium, sucralose and strawberry flavour.

Oral solution

Route: Oral

Strengths: 0.05 mg/mL