Trametinib
MEKINIST
What it isMEK inhibitor; BRAF V600 melanoma and other BRAF-mutant tumors, with dabrafenib.
Why this oneCombining MEK with BRAF blockade delays resistance and reduces the paradoxical skin toxicity of BRAF inhibition alone.
What limits itRash, diarrhea, reduced ejection fraction and retinal vein occlusion. Pyrexia is common with the combination.
FDA-approved for
- BRAF V600 melanoma with dabrafenib (2013)
- NSCLC, anaplastic thyroid cancer
FDA label
Read the full label on DailyMed ↗
| FDA dosing | Population | Start | Target | Max |
|---|---|---|---|---|
| BRAF V600E/K melanoma, NSCLC, ATC, solid tumors, low-grade glioma (per indication, +/- dabrafenib) | Adult | 2 mg QD | 2 mg QD | 2 mg QD |
| Same (tablets, weight-based) | Peds >=26 kg | 1 mg QD (26-37 kg); 1.5 mg QD (38-50 kg); 2 mg QD (>=51 kg) |
Renal Undefined
Hepatic No adjustment in mild impairment; not established in moderate/severe
Instructions
- Confirm BRAF V600 mutation before starting.
- Take on an empty stomach (>=1 h before or >=2 h after a meal), same time each day ~24 h apart.
- Do not crush or break tablets.
- Do not take a missed dose within 12 h of the next dose.
Cautions
- Cardiomyopathy / decreased LVEF
- Retinal vein occlusion, retinal pigment epithelial detachment
- Interstitial lung disease/pneumonitis
- Serious skin toxicity
- Hemorrhage; venous thromboembolism
- Embryo-fetal toxicity
Adverse reactions
- Rash
- Diarrhea
- Lymphedema (single agent)
- With dabrafenib: pyrexia, nausea, chills, vomiting, hypertension, peripheral edema, fatigue
Pregnancy Can cause fetal harm; advise effective contraception
Lactation Do not breastfeed during and after treatment (potential serious adverse reactions)
NO BOXED WARNINGS
Principal riskReduced ejection fraction; retinal vein occlusion
Cost, est. cash$5,000–$30,000+/month or cycle
Generic entry2034 est.
Classes and tags
Clinical profile
Legacy pregnancy categoryD
Defining liabilityMyelosuppression and agent-specific hepatic, cardiac, pulmonary, neurologic or reproductive toxicity require oncology monitoring.
Mechanism of action: Trametinib ballicule
