Trametinib is a selective mitogen activated protein kinase (MEK1/MEK2) inhibitor that inhibits tumor cell proliferation and survival by blocking the activity of MEK protein in the RAS/RAF/MEK/ERK signaling pathway.

1、 Drug name

1. Common name: Trametinib

2. Product Name: Mekinist ®

2、 Indications

1. This product is a kinase inhibitor suitable for treating patients with BRAFV600E or V600K mutations confirmed by FDA approved testing methods:

Monotherapy for unresectable or metastatic melanoma treated with BRAF inhibitors.

2. Combination therapy with Dabrafenib:

Non resectable or metastatic melanoma.

Adjuvant treatment for melanoma with complete resection and lymph node involvement.

Metastatic non-small cell lung cancer.

3. Usage restriction: Not applicable for the treatment of colorectal cancer, as it is known to have inherent resistance to BRAF inhibition.

3、 Specifications

Tablets: 2 milligrams.

4、 Main components

Active ingredient: Trimetanib.

5、 Usage and dosage

1. Adult patients: The recommended dosage is 2 milligrams, taken orally once daily.

2. Pediatric patients (based on weight): weight 26 to 37 kilograms: 1 milligrams per day; 38 to 50 kilograms: 1.5 milligrams per day; 51 kilograms and above: 2 milligrams per day.

3. Usage: Take the medication at the same time every day, with an interval of about 24 hours between two doses. It should be taken on an empty stomach at least 1 hour before or 2 hours after meals. Tablets should be swallowed whole and should not be crushed or broken apart. Oral solutions should be administered by caregivers and training should be received before use.

4. Omission treatment: If the medication is missed, it should be taken as soon as possible. If the next scheduled administration time is less than 12 hours away, skip this dose and take the next dose at the original scheduled time.

5. Vomiting treatment: If vomiting occurs after taking medication, there is no need to take additional doses, and the next dose should be taken according to the original plan.

6、 Dose adjustment

1. Dose adjustment is required for adverse reactions. Adjustment can be divided into dose suspension, dose reduction, or permanent discontinuation.

2. Dose reduction: Both tablets and oral solutions provide specific reduction plans, usually allowing up to two reductions. If the dosage is still intolerable, the medication will be permanently discontinued.

3. Dose adjustment for specific adverse reactions (requiring suspension or permanent discontinuation):

Bleeding (Level 3 pause, Level 4 permanent discontinuation of medication).

Venous thromboembolism (non complex events suspended for up to 3 weeks, permanent discontinuation of medication for life-threatening pulmonary embolism).

Cardiomyopathy (asymptomatic left ventricular ejection fraction decreased by ≥ 10% and below the lower limit of normal, suspended for up to 4 weeks; symptomatic or decreased by>20%, permanently discontinued).

Eye toxicity (permanent discontinuation of medication for retinal vein occlusion; suspension of retinal pigment epithelium detachment for up to 3 weeks).

Interstitial lung disease/pneumonia (permanent discontinuation of medication for treatment related patients).

Severe fever response (paused when body temperature ≥ 100.4 ° F); When there is high fever or complications, permanent discontinuation of medication may be considered.

Severe skin toxicity (permanent discontinuation of medication for severe skin adverse reactions; temporary suspension of up to 3 weeks for intolerant grade 2 or 3-4 rashes).

Other adverse reactions (intolerable grade 2 or any grade 3 pause; first grade 4 event pause or permanent discontinuation; recurrent grade 4 event permanent discontinuation).

7、 Medication precautions

1. New malignant tumors: When used in combination with dalafenib, skin and non skin new malignant tumors may occur. Skin assessment and monitoring of signs of malignant tumors should be conducted before treatment, every 2 months during treatment, and 6 months after discontinuation of medication.

2. Bleeding: Severe bleeding events (including intracranial and gastrointestinal bleeding) may occur, and bleeding signs need to be monitored.

3. Colitis and gastrointestinal perforation: may occur and require close monitoring.

4. Cardiomyopathy: Left ventricular ejection fraction should be evaluated by echocardiography or multi gated acquisition scans before treatment, 1 month after starting treatment, and every 2 to 3 months thereafter.

5. Eye toxicity: Ophthalmic evaluation is required when visual impairment occurs. Retinal vein occlusion requires permanent discontinuation of medication.

6. Interstitial lung disease/pneumonia: If new or progressive lung symptoms occur, medication should be temporarily suspended, and those diagnosed as treatment related should permanently discontinue medication.

7. Severe fever reaction: It is common when used in combination with dalafenib and needs to be monitored and managed.

8. Severe skin toxicity: Monitor skin reactions and secondary infections.

9. Hyperglycemia: It is necessary to monitor the blood sugar of patients with diabetes or hyperglycemia.

10. Embryo fetal toxicity: may cause harm to the fetus. Women with fertility need to take effective contraceptive measures during treatment and for 4 months after the last dose. Male patients need to use condoms during the same period.

11. Risks of combination therapy: When used in combination with dalafenib, it is necessary to refer to the prescription information of dalafenib to understand the related risks.

8、 Medication for special populations

1. Pregnant women: May cause harm to the fetus, inform pregnant women of the risks.

2. Breastfeeding women: It is not recommended to breastfeed during the treatment period and within 4 months after the last dose.

3. Women and men with fertility: May impair fertility. Pregnancy testing is required and effective contraceptive measures should be used.

4. Pediatric patients: Combination therapy with dalafenib is used for specific indications in children aged 1 year and older. The safety and efficacy of monotherapy in children have not yet been established.

5. Elderly individuals: In some studies, an increased incidence of peripheral edema and anorexia has been observed in elderly patients.

6. Liver injury patients: Mild liver injury does not require dose adjustment. The recommended dosage for patients with moderate to severe liver injury has not yet been established, and the risk benefit balance should be considered before administration.

9、 Adverse reactions

1. The most common adverse reactions (≥ 20%):

Single drug: rash, diarrhea, lymphedema.

Combination of Darafenib: Depending on the indications, it mainly includes fever, fatigue, nausea, vomiting, diarrhea, rash, chills, headache, hypertension, peripheral edema, bleeding, cough, difficulty breathing, dry skin, decreased appetite, joint pain, muscle pain, etc.

2. Serious adverse reactions: including newly diagnosed malignant tumors, bleeding, colitis and gastrointestinal perforation, venous thromboembolism, cardiomyopathy, ocular toxicity, interstitial lung disease/pneumonia, severe fever reactions, severe skin toxicity, hyperglycemia, etc.

10、 Contraindications

None.

11、 Drug interactions

Qumeitinib is a CYP2C8 inhibitor and has no clinically relevant inhibitory effect on major CYP enzymes. It is a substrate for P-glycoprotein and bile salt efflux pumps.

12、 Storage method

Tablets: Refrigerate at 2 ° C to 8 ° C (36 ° F to 46 ° F). Keep dry and away from light. Place in the original bottle, do not remove the desiccant, do not place in the medicine box.

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