Trametinib
BRAF and MEK inhibitors
BRAF and MEK inhibitorsHigh alert
An error with this medicine can cause serious harm: double checks and protocols are used.Pregnancy: avoid
Avoid in pregnancy. Can harm the fetus: a pregnancy test is done before starting, effective contraception is used during treatment and for a time afterwards (by women and by men…
The first MEK inhibitor: an oral drug, usually with dabrafenib, for BRAF V600 melanoma, lung and thyroid cancer. Watch heart, eyes and skin.
Also called: trametinib dimethyl sulfoxide
Quick facts
- Group
- BRAF and MEK inhibitors
- Target
- MEK1 and MEK2 (MAP2K1/2) kinases
- Used for
- BRAF V600E/K melanoma
- Key effects
- Rash · Diarrhoea · Fatigue
- Monitor
- Heart function · Blood pressure
- ATC
- L01EE01
No doses: the clinician sets them by the current guideline.
Mechanism of action
The figure shows trametinib in the allosteric pocket of rabbit MEK1 bound to human KSR2; the pocket matches human MEK1.
Trametinib binds reversibly to an allosteric pocket next to the ATP site of MEK1 and MEK2, the kinases just downstream of BRAF. MEK can no longer activate ERK, so the MAPK growth signal stops even when BRAF is mutated. Used with dabrafenib it delays resistance; unlike BRAF inhibitors, it does not cause cutaneous squamous cell carcinoma.
- Binds an allosteric pocket of MEK1 and MEK2
- MEK cannot activate ERK: the MAPK signal stops
- With dabrafenib: two-step block, delayed resistance
Indications
- BRAF V600E/K melanoma: alone or with dabrafenib when unresectable or metastatic, and with dabrafenib after surgery when lymph nodes are involved. Melanoma →
- BRAF V600E metastatic non-small cell lung cancer, with dabrafenib. Lung cancer →
- BRAF V600E anaplastic thyroid cancer, with dabrafenib. Follicular, oncocytic (Hürthle cell) and anaplastic thyroid carcinoma →
- BRAF V600E low-grade glioma in children, with dabrafenib. Childhood brain tumours (medulloblastoma, pilocytic astrocytoma, craniopharyngioma) →
Adverse effects
Common
- Rash, acne-like dermatitis, dry and itchy skin
- Diarrhoea
- Fatigue, swelling and lymphoedema
- Nausea, headache, nail-fold infection
Contraindications
- Little benefit after a BRAF inhibitor has failed
Key interactions
- Dabrafenib
- Intended partner; fever and chills are typical of the pair.
- Anticoagulants and antiplatelet drugs
- Add to its bleeding risk.
What is monitored
- Heart function (ejection fraction) before and during treatment
- Blood pressure
- Eye examination if vision changes
- Skin examinations before, during and for months after treatment
Administration and safety
- Oral tablets once daily on an empty stomach, away from meals, swallowed whole.
- Stored in the refrigerator, in the original bottle with its desiccant, protected from light and moisture.
Pregnancy and breastfeeding
Avoid in pregnancy. Can harm the fetus: a pregnancy test is done before starting, effective contraception is used during treatment and for a time afterwards (by women and by men with partners who could conceive), and breastfeeding is avoided.
Nursing care
- Check blood pressure; teach to report breathlessness, swelling or palpitations.
- Teach to report blurred vision, halos or vision loss at once.
- Teach skin care for rash and to report bleeding, black stools or coughing blood.
- Confirm a negative pregnancy test before the first dose and teach contraception during treatment and afterwards.
Pharmacokinetics
- Absorption
- Oral, once daily, on an empty stomach; a high-calorie meal reduces absorption.
- Metabolism
- Not a CYP substrate.
- Half-life
- Long: about 4 to 5 days.
Test yourself
Think of the answer, then tap the question to see it.
How does trametinib bind MEK?
Reversibly, in an allosteric pocket next to the ATP site of MEK1 and MEK2.
Which BRAF-inhibitor toxicity does trametinib not cause?
Cutaneous squamous cell carcinoma.
Which heart test is followed on trametinib?
The left ventricular ejection fraction (echocardiogram), because it can cause cardiomyopathy.
Connections
← Back to the class: BRAF and MEK inhibitors
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: Trametinib: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2023); Trametinib Dimethyl Sulfoxide - NCI (National Cancer Institute, 2024); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).
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Representative model, for educational purposes only.