Trametinib

Trametinib is a prescription medication used to treat melanoma, non-small cell lung cancer, and thyroid cancer. 

• Trametinib is available under various brand names: Mekinist

Common side effects of Trametinib include:

• nausea,
• vomiting,
• diarrhea,
• loss of appetite,
• fever,
• chills,
• tiredness,
• headache,
• bleeding,
• increased blood pressure,
• muscle or joint pain,
• cough,
• shortness of breath,
• swelling in the arms, face, and legs,
• rash, and
• dry skin

Serious side effects of Trametinib include:

• hives,
• difficulty breathing,
• swelling of the face, lips, tongue, or throat,
• cough,
• shortness of breath,
• fever,
• chills,
• lightheadedness,
• little or no urination,
• severe headache,
• blurred vision,
• dizziness,
• nausea,
• stomach pain,
• severe diarrhea,
• increased thirst or urination,
• eye pain or swelling,
• vision changes,
• seeing halos around lights,
• seeing color “dots” in the vision,
• severe skin rash,
• skin pain or swelling,
• redness and peeling skin on the hands or feet,
• weakness,
• headache,
• bloody or tarry stools,
• coughing up blood,
• vomit that looks like coffee grounds,
• chest pain,
• sudden cough,
• pain or swelling in an arm or leg,
• pale skin,
• cold feeling in an arm or leg,
• pounding heartbeats, and
• swelling in the feet or ankles

Rare side effects of Trametinib include:

• none

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors;
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult and pediatric dosage

Tablet

• 0.5 mg
• 2 mg

Melanoma

Adult dosage

• BRAF V600E or V600K mutation-positive unresectable or metastatic melanoma
• 2 mg orally every day
• May also be used in combination with dabrafenib 150 mg orally twice daily
• Adjuvant treatment of BRAF V600E or V600K mutation-positive melanoma
• 2 mg orally once daily plus dabrafenib 150 mg orally twice daily

Non-Small Cell Lung Cancer

Adult dosage

• 2 mg orally once daily plus dabrafenib 150 mg orally twice daily

Thyroid Cancer

Adult dosage

• 2 mg orally once daily plus dabrafenib 150 mg orally twice daily
• BRAF V600E Mutation-Positive Unresectable or Metastatic Solid Tumors

Adult dosage

• 2 mg orally once daily plus dabrafenib 150 mg orally twice daily

Pediatric dosage

• Aged below 6 years OR weighing below 26 kg: Safety and efficacy not established
• Aged above 6 years and weighing above 26 kg
  • 26-37 kg: Trametinib 1 mg orally once daily with dabrafenib 75 mg orally twice daily with
  • 38-50 kg: Trametinib 1.5 mg once daily with dabrafenib 100 mg orally twice daily
  • Above 51 kg: Trametinib 2 mg once daily with dabrafenib 150 mg orally twice daily
• Continue until disease progression or unacceptable toxicity

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Trametinib has no noted severe interactions with any other drugs.
• Trametinib has no noted serious interactions with any other drugs.
• Trametinib has no noted moderate interactions with any other drugs.
• Trametinib has no noted minor interactions with any other drugs.

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all your products. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, or if you have health questions or concerns.

Contraindications

• None

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Trametinib?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Trametinib?”

Cautions

• See Dosage Modifications
• New primary malignancies, cutaneous and noncutaneous, can occur when trametinib is used in combination with dabrafenib, and with dabrafenib as a single agent
• Hemorrhage, including major hemorrhages, can occur when used in combination with dabrafenib
• Venous thromboembolism can occur when used in combination with dabrafenib
• Interstitial lung disease reported; withhold dose for patients with symptoms (eg, cough, dyspnea, hypoxia, pleural effusion, or infiltrates); permanently discontinue therapy for treatment-related ILD or pneumonitis
• Colitis and gastrointestinal perforation can occur; monitor patients closely for colitis and gastrointestinal perforations
• May cause fetal harm when administered to a pregnant woman (see Pregnancy)
• Febrile reactions
  • Serious febrile reactions and fever of any severity accompanied by hypotension, rigors or chills, dehydration, or renal failure, can occur when trametinib is used in combination with dabrafenib and with dabrafenib as a single agent; upon resolution, resume at the same or lower dose
  • Withhold trametinib when used as monotherapy, and with dabrafenib when used in combination, if the patient’s temperature is greater than or equal to 100.4°F
  • In case of recurrence, therapy can be interrupted at the first symptom of pyrexia; fever may be complicated by hypotension, rigors or chills, dehydration, or renal failure; evaluate for signs and symptoms of an infection; monitor serum creatinine and other evidence of renal function during and following severe pyrexia
  • Administer antipyretics as secondary prophylaxis when resuming therapy if the patient had a prior episode of severe febrile reaction or fever associated with complications
  • Administer corticosteroids (e.g., prednisone 10 mg daily) for at least 5 days for a second or subsequent pyrexia if the temperature does not return to baseline within 3 days of onset of pyrexia, or for pyrexia associated with complications, such as dehydration, hypotension renal failure, or severe chills/rigors, and there is no evidence of active infection
• Hyperglycemia
  • Coadministration with dabrafenib: Hyperglycemia can occur when trametinib is used in combination with dabrafenib and with dabrafenib as a single agent
  • Monitor serum glucose levels upon initiation and as clinically appropriate when administered with dabrafenib in patients with pre-existing diabetes or hyperglycemia
  • Initiate or optimize anti-hyperglycemic medications as clinically indicated
• Cardiomyopathy
  • Risk of cardiomyopathy when used as a single agent or with dabrafenib; reassess LVEF after 1 month of treatment and then ~every 2-3 months thereafter
  • For an asymptomatic absolute decrease in LVEF of 10% or greater from baseline that is below the LLN, withhold the drug for up to 4 weeks; if improved to normal LVEF value, resume at a lower dose; if no improvement to normal LVEF value within 4 weeks, permanently discontinue
• Ocular toxicities
  • Risk (rare) for retinal pigment epithelial detachment (RPED); monitor for visual disturbances
  • Withhold therapy if RPED diagnosed; if the resolution of RPED is documented on repeat ophthalmological evaluation within 3 weeks, resume treatment at same or reduced dose; if no improvement after 3 weeks, resume at reduced dose or permanently discontinue therapy
  • Retinal vein occlusion reported; urgently (within 24 hr) perform ophthalmology evaluation for patient-reported vision loss
• Skin toxicity
  • Risk of serious skin toxicity including rash, dermatitis, acneiform rash, palmar-plantar erythrodysesthesia syndrome, and erythema
  • Withhold treatment for intolerable or severe skin toxicity; resume treatment at a lower dose in patients with improvement or recovery from skin toxicity within 3 weeks
  • Permanently discontinue therapy if skin toxicity has not improved in 3 weeks

Pregnancy & Lactation

• Based on its mechanism of action and findings from animal reproduction studies, trametinib can cause fetal harm when administered to a pregnant woman
• Insufficient data are available on pregnant women exposed to trametinib to assess the risk
• Trametinib was embryotoxic and abortifacient in rabbits at doses greater than or equal to those resulting in exposures ~0.3 times the human exposure at the recommended clinical dose
• Advise patients of the potential risk to the fetus
• Contraception
  • Advise female patients of reproductive potential to use effective contraception during treatment with trametinib and for 4 months after the last dose
  • Advise female patients of reproductive potential that trametinib may impair fertility; increased follicular cysts and decreased corpora lutea were observed in female rats at dose exposures equivalent to 0.3 times the human exposure at the recommended dose
• Lactation
  • There are no data on the presence of trametinib in human milk, the effects of trametinib on the breastfed infant, or milk production
  • Advise women not to breastfeed during treatment with trametinib and for 4 months following the last dose