Trametinib

Author: Anoma Ranaweera B.V. Sc; PhD (Clinical Biochemistry, University of Liverpool, UK), 2013.

Introduction

On May 29, 2013, the U. S. Food and Drug Administration (FDA) approved trametinib (MEKINIST™ tablets, GlaxoSmithKline, LLC), as a single agent treatment for patients with non-operable or metastatic melanoma with BRAF V600E or V600K mutations as detected by an FDA-approved test, called the THxID™ – BRAF assay from bioMérieux S.A. In November 2015, the FDA approved the combination of dabrafenib and trametinib for the treatment of metastatic melanoma. Trametinib is approved by MedSafe, alone and in combination with dabrafenib, but it is not subsidised by PHARMAC in New Zealand.

BRAF mutations occur in 50% of melanomas. Trametinib targets mutant BRAF protein by inhibiting the MAPK signalling pathway, which mediates cell growth and survival.

How does trametinib work?

Which patients benefit most from trametinib?

Link to key clinical-trial evidence about trametinib.

Dosage and administration

The recommended dose of trametinib is 2 mg orally once daily, taken at least 1 hour before or at least 2 hours after a meal. A missed dose must not be taken within 12hours of the next dose.

Dose modification or partial/complete withdrawal of the drug is recommended in the case of severe skin toxicity, cardiomyopathy, ocular and pulmonary abnormalities.

What are the side effects of trametinib?

In clinical trials with trametinib, the most common side effects affecting ≥10% patients, and of any grade, were:

Serious adverse reactions (affecting ≥2%), i.e. grades 3 and 4 were:

Warnings and precautions

In clinical trials, with trametinib the following adverse reactions have also been observed.

Pregnancy

Trametinib can cause fetal harm when administered to a pregnant woman (pregnancy category D). The patient should be warned of the potential hazard to the fetus, if this drug is used during pregnancy or if the patient becomes pregnant while taking this drug. Female patients should be advised to use highly effective contraceptives during treatment with trametinib and for 4 months after treatment has stopped.

Paediatric use

To date studies evaluating trametinib in children have not been conducted.

Geriatric use

Clinical studies of trametinib did not include sufficient numbers of subjects aged 65 years and over to determine whether they respond differently from younger subjects.

Hepatic and renal impairment

No formal clinical study has been conducted to evaluate the effect of renal and hepatic impairment on the pharmacokinetics of trametinib. No dose adjustments are recommended in patients with mild renal or hepatic impairment based on population pharmacokinetic studies.

Drug interactions

No formal drug interaction studies have been conducted to evaluate human cytochrome P450 (CYP) enzyme-mediated drug interactions with trametinib.

Future directions for trametinib

New Zealand approved datasheets are the official source of information for these prescription medicines, including approved uses and risk information. Check the individual New Zealand datasheet on the Medsafe website.

Related information

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