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Precautions of Trametinib

1.New Primary Malignancies  

Cutaneous Malignancies

Perform dermatologic evaluations prior to initiation of Trametinib when used with dabrafenib, every 2 months  while on therapy, and for up to 6 months following discontinuation of the combination.

Non-Cutaneous Malignancies

Based on its mechanism of action, dabrafenib may promote growth and development of malignancies with  activation of RAS through mutation or other mechanisms; refer to the prescribing information for dabrafenib.

Monitor patients receiving Trametinib and dabrafenib closely for signs or symptoms of non-cutaneous  malignancies. No dose modification is required for Trametinib in patients who develop non-cutaneous  malignancies.

2.Hemorrhage

Permanently discontinue Trametinib for all Grade 4 hemorrhagic events and for any Grade 3 hemorrhagic events that do not improve. Withhold Trametinib for Grade 3 hemorrhagic events; if improved, resume Trametinib at the next lower dose level.

3.Colitis and Gastrointestinal Perforation

Monitor patients closely for colitis and gastrointestinal perforations.

4.Venous Thromboembolic Events

Advise patients to immediately seek medical care if they develop symptoms of DVT or PE, such as shortness of breath, chest pain, or arm or leg swelling. Permanently discontinue Trametinib for life-threatening PE.  Withhold Trametinib for uncomplicated DVT and PE for up to 3 weeks; if improved, Trametinib may be  resumed at a lower dose level.

5.Cardiomyopathy

Cardiomyopathy, including cardiac failure, can occur with Trametinib.

Assess LVEF by echocardiogram or multigated acquisition (MUGA) scan before initiation of Trametinib as a  single agent or with dabrafenib, one month after initiation, and then at 2- to 3-month intervals while on  treatment. For an asymptomatic absolute decrease in LVEF of 10% or greater from baseline that is below the  LLN, withhold Trametinib for up to 4 weeks. If improved to normal LVEF value, resume Trametinib at a lower dose. If no improvement to normal LVEF value within 4 weeks, permanently discontinue Trametinib.  For symptomatic cardiomyopathy or an absolute decrease in LVEF of greater than 20% from baseline that is  below LLN, permanently discontinue Trametinib.

from FDA，2024.03