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Trametinib Dimethyl Sulfoxide (Monograph)

Brand name: Mekinist
Drug class: Antineoplastic Agents

Medically reviewed by Drugs.com on Jul 10, 2024. Written by ASHP.

Introduction

Antineoplastic agent; an inhibitor of mitogen-activated extracellular signal-regulated kinase (MEK) 1 and MEK2 in cells with b-Raf serine-threonine kinase (BRAF) V600E or V600K mutations.

Uses for Trametinib Dimethyl Sulfoxide

Melanoma

In combination with dabrafenib as adjuvant therapy following complete resection of melanoma with BRAF V600E or V600K mutation and nodal involvement.

Alone or in combination with dabrafenib for treatment of unresectable or metastatic melanoma in selected patients with BRAF V600E or V600K mutation (designated an orphan drug by FDA as monotherapy or when used in combination for this use).

FDA-approved in vitro diagnostic test (e.g., THxID BRAF kit) required to confirm presence of BRAF V600E or V600K mutation prior to initiation of monotherapy or combination therapy.

Not recommended for use as a single agent in patients with melanoma who have experienced disease progression following treatment with a BRAF inhibitor.

NSCLC

Used in combination with dabrafenib for treatment of metastatic non-small cell lung cancer (NSCLC) in patients with BRAF V600E mutation (designated an orphan drug by FDA when used in combination for this use).

FDA-approved diagnostic test (e.g., THxID BRAF kit) required to confirm presence of BRAF V600E mutation prior to initiation of therapy.

Anaplastic Thyroid Cancer

Used in combination with dabrafenib for treatment of locally advanced or metastatic anaplastic thyroid cancer in patients with BRAF V600E mutation when no satisfactory locoregional treatment options are available (designated an orphan drug by FDA when used in combination for this use).

Testing required to confirm presence of BRAF V600E mutation prior to initiation of therapy; no FDA-approved diagnostic test currently available for detection of BRAF V600E in anaplastic thyroid cancer.

BRAF V600E-mutant Solid Tumors

Used in combination with dabrafenib for treatment of adult and pediatric patients ≥1 year of age with unresectable or metastatic solid tumors (excluding colorectal cancer) with BRAF V600E mutation who have progressed following prior treatment and have no satisfactory alternative treatment. Designated an orphan drug by FDA when used in combination for malignant glioma.

Accelerated approval for this indication is based on response rate and duration of response. Continued approval may be contingent upon verification and description of clinical benefit in confirmatory studies.

Testing required to confirm presence of BRAF V600E mutation prior to initiation of therapy; no FDA-approved diagnostic test currently available for detection of BRAF V600E in solid tumors other than melanoma and NSCLC.

Not indicated for BRAF-mutant colorectal cancer because of intrinsic resistance to BRAFinhibition.

Low-Grade Glioma

Used in combination with dabrafenib for treatment of low-grade glioma withBRAF V600E mutation in pediatric patients ≥1 year of age who require systemic therapy (designated an orphan drug by FDA when used in combination for this use).

Testing required to confirm presence of BRAF V600E mutation prior to initiation of therapy; no FDA-approved diagnostic test currently available for detection of BRAF V600E in solid tumors other than melanoma and NSCLC.

Trametinib Dimethyl Sulfoxide Dosage and Administration

General

Pretreatment Screening

Patient Monitoring

Premedication and Prophylaxis

Other General Considerations

Administration

Oral Administration

Administer orally once daily, approximately every 24 hours, at least 1 hour before or 2 hours after a meal.

If dose is missed by ≤12 hours, take missed dose immediately.

If dose is vomited, do not take additional dose and take next dose at the regularly scheduled time.

Tablets

Do not crush or break.

Oral Solution

For administration by caregiver.

Reconstitute prior to use by tapping bottle to loosen the powder, then adding 90 mL of distilled or purified water. Shake for up to 5 minutes until powder is dissolved and solution is clear.

Once reconstituted, solution yields a concentration of 0.05 mg/mL of trametinib.

May administer from oral dosing syringe or feeding tube.

Dosage

Available as trametinib dimethyl sulfoxide; dosage expressed in terms of trametinib.

Pediatric Patients

BRAF V600E-mutant Solid Tumors
Oral

Recommended dosage of trametinib oral solution and tablets (in combination with dabrafenib) in pediatric patients ≥1 year of age is based on body weight (see Table 1 and Table 2). Recommended tablet dosage not established for patients weighing <26 kg. Continue therapy until disease progression or unacceptable toxicity occurs.

BRAF V600E-mutant Low-Grade Glioma
Oral

Recommended dosage of trametinib oral solution and tablets (in combination with dabrafenib) in pediatric patients ≥1 year of age is based on body weight see Table 1 and Table 2). Recommended tablet dosage not established for patients weighing <26 kg. Continue therapy until disease progression or unacceptable toxicity occurs.

Concentration of trametinib oral solution: 0.05 mg/mL.

Table 1. Dosing of Trametinib Oral Solution in Pediatric Patients ≥1 Year of Age1

Body Weight

Recommended Oral Dosage

8 kg

0.3 mg (6 mL) once daily

9 kg

0.35 mg (7 mL) once daily

10 kg

0.35 mg (7 mL) once daily

11 kg

0.4 mg (8 mL) once daily

12—13 kg

0.45 mg (9 mL) once daily

14—17 kg

0.55 mg (11 mL) once daily

18—21 kg

0.7 mg (14 mL) once daily

22—25 kg

0.85 mg (17 mL) once daily

26—29 kg

0.9 mg (18 mL) once daily

30—33 kg

1 mg (20 mL) once daily

34—37 kg

1.15 mg (23 mL) once daily

38—41 kg

1.25 mg (25 mL) once daily

42—45 kg

1.4 mg (28 mL) once daily

46—50 kg

1.6 mg (32 mL) once daily

≥51 kg

2 mg (40 mL) once daily

Table 2. Dosing of Trametinib Tablets in Pediatric Patients ≥1 Year of Age1

Body Weight

Recommended Oral Dosage

26—37 kg

1 mg (two 0.5-mg tablets) once daily

38—50 kg

1.5 mg (three 0.5-mg tablets) once daily

≥51 kg

2 mg once daily

Adults

Melanoma
Adjuvant Therapy for Melanoma
Oral

2 mg once daily (use in combination with dabrafenib). Continue therapy for up to 1 year or until disease progression or unacceptable toxicity occurs.

Monotherapy for Unresectable or Metastatic Melanoma
Oral

2 mg once daily. Continue therapy until disease progression or unacceptable toxicity occurs.

Combination Therapy for Unresectable or Metastatic Melanoma
Oral

2 mg once daily (use in combination with dabrafenib). Continue therapy until disease progression or unacceptable toxicity occurs.

NSCLC
Oral

2 mg once daily (use in combination with dabrafenib). Continue therapy until disease progression or unacceptable toxicity occurs.

Anaplastic Thyroid Cancer
Oral

2 mg once daily (use in combination with dabrafenib). Continue therapy until disease progression or unacceptable toxicity occurs.

BRAF V600E-mutant Solid Tumors
Oral

2 mg once daily (use in combination with dabrafenib). Continue therapy until disease progression or unacceptable toxicity occurs.

Dosage Modification for Toxicity

Dosage may be reduced or therapy temporarily interrupted in patients who develop adverse effects (Tables 3 and 4). Up to 2 dosage reductions for toxicity may be made. Permanently discontinue trametinib if unable to tolerate a maximum of 2 dosage reductions. When used in combination with dabrafenib, dosage modification of dabrafenib for toxicity also may be required.

Permanently discontinue trametinib if unable to tolerate maximum of 2 dosage reductions.

Table 3. Trametinib Tablet Dosage Modifications for Toxicity1

Recommended Dosage

1 mg orally once daily

1.5 mg orally once daily

2 mg orally once daily

First dose reduction

0.5 mg (one 0.5-mg tablet) orally once daily

1 mg (two 0.5-mg tablets) orally once daily

1.5 mg (three 0.5-mg tablets) orally once daily

Second dose reduction

N/A

0.5 mg (one 0.5-mg tablet) orally once daily

1 mg (two 0.5-mg tablets) orally once daily

Concentration of trametinib oral solution: 0.05 mg/mL.

Permanently discontinue trametinib if unable to tolerate a maximum of 2 dosage reductions.

Table 4. Trametinib Oral Solution Dosage Modifications for Toxicity1

Body Weight and Recommended Dosage

First Dose Reduction

Second Dose Reduction

8kg

0.3 mg (6 mL) once daily

5 mL once daily

3 mL once daily

9 kg

0.35 mg (7 mL) once daily

5 mL once daily

4 mL once daily

10 kg

0.35 mg (7 mL) once daily

5 mL once daily

4 mLonce daily

11 kg

0.4 mg (8 mL) once daily

6 mL once daily

4 mL once daily

12—13 kg

0.45 mg (9 mL) once daily

7 mL once daily

5 mL once daily

14—17 kg

0.55 mg (11 mL) once daily

8 mL once daily

6 mL once daily

18—21 kg

0.7 mg (14 mL) once daily

11 mL once daily

7 mL once daily

22—25 kg

0.85 mg (17 mL) once daily

13 mL once daily

9 mL once daily

26—29 kg

0.9 mg (18 mL) once daily

14 mL once daily

9 mL once daily

30—33 kg

1 mg (20 mL) once daily

15 mL once daily

10 mL once daily

34—37 kg

1.15 mg (23 mL) once daily

17 mL once daily

12 mL once daily

38—41 kg

1.25 mg (25 mL) once daily

19 mL once daily

13 mL once daily

42—45 kg

1.4 mg (28 mL) once daily

21 mL once daily

14 mL once daily

46—50 kg

1.6 mg (32 mL) once daily

24 mL once daily

16 mL once daily

≥51 kg

2 mg (40 mL) once daily

30 mL once daily

20 mL once daily

Dosage Modification for New Primary Cutaneous Malignancies

If new cutaneous malignancies occur, dosage modification of trametinib not necessary.

Dosage Modification for New Primary Noncutaneous Malignancies

If new noncutaneous malignancies occur in patients receiving trametinib/dabrafenib combination therapy, dosage modification of trametinib not necessary.

Dosage Modification for Febrile Drug Reactions

Fever (temperature of 38–40°C) or any initial symptom of fever recurrence: Interrupt trametinib therapy until the adverse reaction resolves. Once fever resolves, may resume trametinib at same or reduced dosage.

Fever >40°C or fever with complications (e.g., rigors, hypotension, dehydration, renal failure): Interrupt trametinib therapy until fever resolves for ≥24 hours; may resume trametinib at same or reduced dosage or permanently discontinue.

Dosage Modification for Dermatologic Effects

Intolerable grade 2 skin toxicity: Interrupt trametinib for up to 3 weeks. If improvement noted within 3 weeks, resume drug at reduced dosage. Permanently discontinue therapy in those with skin toxicity not improving within 3 weeks of treatment interruption.

Grade 3 or 4 skin toxicity: Interrupt therapy for up to 3 weeks. If improvement observed within 3 weeks, resume drug at reduced dosage. Permanently discontinue therapy in those with intolerable skin toxicity not improving within 3 weeks of treatment interruption.

Severe cutaneous adverse reactions (SCARs): Permanently discontinue trametinib.

Dosage Modification for Cardiac Effects

Asymptomatic decrease in left ventricular ejection fraction (LVEF) from baseline of ≥10% and to a level below institution-specific lower limit of normal: Interrupt trametinib for up to 4 weeks. If LVEF improves to normal values within 4 weeks, resume drug at reduced dosage. Permanently discontinue therapy in those with decreased LVEF not improving within 4 weeks of treatment interruption.

Symptomatic cardiomyopathy or an absolute decrease in LVEF from baseline >20% and to a level below institution-specific lower limit of normal: Permanently discontinue trametinib.

Dosage Modification for Hemorrhage

Grade 3 hemorrhagic events: Withhold trametinib therapy. If improvement observed, resume therapy at reduced dosage. If no improvement observed, permanently discontinue the drug.

Grade 4 hemorrhagic events: Permanently discontinue trametinib.

Dosage Modification for Venous Thromboembolism

Uncomplicated DVT or PE: Interrupt trametinib for up to 3 weeks. If improvement to grade 0 or 1 observed within 3 weeks, resume therapy at lower dosage. If no improvement observed within 3 weeks, permanently discontinue trametinib.

Life-threatening PE: Permanently discontinue trametinib.

Dosage Modification for Ocular Effects

Retinal pigment epithelial detachments: Interrupt trametinib for up to 3 weeks. If such retinal detachments improve within 3 weeks, resume drug at the same or a reduced dosage. Permanently discontinue therapy or resume therapy at a reduced dosage in those with retinal pigment epithelial detachments not improving within 3 weeks.

Retinal vein occlusion: Permanently discontinue trametinib.

Uveitis with trametinib/dabrafenib combination therapy: Dosage modification of trametinib not necessary.

Dosage Modification for Pulmonary Effects

Treatment-related interstitial lung disease or pneumonitis: Permanently discontinue trametinib.

Dosage Modification for Other Toxicity

Intolerable grade 2 or any grade 3 adverse reaction: Interrupt treatment. If adverse reaction improves to grade 0 or 1, resume drug at reduced dosage. If adverse reaction does not improve to grade 0 or 1, permanently discontinue trametinib.

Grade 4 adverse reaction (first occurrence): Interrupt treatment until adverse reaction improves to grade 0 or 1, then resume therapy at reduced dosage. If the grade 4 adverse reaction does not improve to grade 0 or 1, permanently discontinue trametinib.

Grade 4 adverse reaction (recurrent): Permanently discontinue trametinib.

Special Populations

Hepatic Impairment

Mild hepatic impairment: No dosage adjustment required.

Moderate (bilirubin concentration >1.5–3 times the ULN and any AST concentration) or severe (bilirubin concentration 3–10 times the ULN and any AST concentration) hepatic impairment: Appropriate dosage not established. Consider the potential risks and benefits of the drug when initiating trametinib therapy or determining the appropriate dosage.

Renal Impairment

Estimated glomerular filtration rate (GFR) 15–89 mL/minute per 1.73 m2: No dosage adjustment required.

Geriatric Patients

No specific dosage recommendations in patients ≥65 years of age.

Cautions for Trametinib Dimethyl Sulfoxide

Contraindications

Warnings/Precautions

Combination Therapy

When combination therapy with trametinib includes use of dabrafenib, cautions, precautions, and contraindications of dabrafenib also must be considered.

New Primary Malignancies

New primary cutaneous and noncutaneous malignancies are a known class effect of BRAF inhibitors (i.e., dabrafenib, encorafenib, vemurafenib). Cutaneous squamous cell carcinoma, keratoacanthomas, new primary melanoma, basal cell carcinoma, and noncutaneous malignancies reported in patients receiving trametinib in combination with dabrafenib.

Perform dermatologic evaluations for new cutaneous malignancies prior to initiation of and every 2 months during therapy with trametinib and dabrafenib, then for up to 6 months following discontinuance of combination therapy. In addition, monitor patients closely for signs or symptoms of new noncutaneous malignancies.

Hemorrhage

Hemorrhage (sometimes fatal), including intracranial or GI hemorrhage, has occurred during trametinib/dabrafenib combination therapy.

If hemorrhagic events occur, dosage modification and/or treatment discontinuance may be necessary. For grade 3 hemorrhagic events, interrupt trametinib therapy. If improvement observed, trametinib may be resumed at a reduced dosage. If no improvement observed, permanently discontinue trametinib. For grade 4 hemorrhagic events, permanently discontinue trametinib.

Colitis and GI Perforation

Colitis and GI perforation, sometimes fatal, has occurred with monotherapy and trametinib/dabrafenib combination therapy.

Monitor patients closely for manifestations of colitis and GI perforation.

Venous Thromboembolic Events

Venous thromboembolism (VTE) has occurred during trametinib/dabrafenib combination therapy.

Advise patients to immediately seek medical care if they develop symptoms of DVT or PE (e.g., shortness of breath, chest pain, arm or leg swelling). Dosage modification or treatment discontinuance may be necessary if DVT or PE occurs.

Cardiomyopathy

Cardiomyopathy, including cardiac failure, reported with monotherapy and trametinib/dabrafenib combination therapy.

Assess LVEF by echocardiogram or multigated radionuclide angiography (MUGA) prior to initiation and after 1 month of therapy, then every 2–3 months during therapy.

If cardiomyopathy occurs, treatment interruption, dosage reduction, or drug discontinuance is warranted.

Ocular Toxicities

Retinal pigment epithelial detachments and retinal vein occlusion reported with trametinib therapy. Retinal vein occlusion may lead to macular edema, decreased visual function, neovascularization, and glaucoma.

Perform ophthalmologic evaluation periodically and as clinically indicated during therapy. In patients reporting vision loss or visual disturbances, perform ophthalmologic evaluations within 24 hours.

If retinal pigment epithelial detachment is diagnosed, withhold trametinib. If resolution is confirmed within 3 weeks, resume trametinib at the same or a reduced dosage. If no improvement observed within 3 weeks, permanently discontinue or resume therapy at a reduced dosage.

Permanently discontinue trametinib in patients with confirmed retinal vein occlusion.

If uveitis occurs in patients receiving combination therapy with trametinib and dabrafenib, no dosage modification of trametinib required.

Interstitial Lung Disease/Pneumonitis

Interstitial lung disease or pneumonitis reported with monotherapy or trametinib/dabrafenib combination therapy.

In patients with new or progressive pulmonary manifestations (e.g., cough, dyspnea, hypoxia, pleural effusion, infiltrates), interrupt trametinib treatment pending results of clinical investigation.

Permanently discontinue trametinib in patients diagnosed with treatment-related interstitial lung disease or pneumonitis.

Serious Febrile Reactions

Serious febrile drug reactions (including fever accompanied by hypotension, rigors/chills, dehydration, or renal failure) reported during trametinib/dabrafenib combination therapy.

If patient’s temperature ≥100.4°F (38.0°C), interrupt trametinib (and dabrafenib, if used in combination); evaluate for signs and symptoms of infection and monitor renal function (e.g., serum creatinine) during and following severe pyrexia. May resume trametinib (and dabrafenib, if used in combination) ≥24 hours after recovery at same or reduced dosage.

Use prophylactic antipyretics when resuming trametinib following serious febrile reactions or fever associated with complications. Use corticosteroids (e.g., prednisone 10 mg daily) for at least 5 days for second or subsequent occurrences of prolonged fever (lasting >3 days) or fever associated with complications (e.g., dehydration, hypotension, renal failure, severe chills/rigors) without evidence of an active infection.

Serious Skin Toxicities

Severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome and drug reaction with eosinophilia and systemic symptoms, reported in postmarketing surveillance during therapy with trametinib in combination with dabrafenib.

Monitor for new or worsening serious skin toxicities. If dermatologic toxicity occurs, dosage modification or treatment discontinuance may be necessary. Permanently discontinue trametinib if SCARs occur.

Hyperglycemia

Hyperglycemia reported in patients receiving trametinib/dabrafenib combination therapy.

Monitor serum glucose concentrations prior to initiation of therapy and as clinically appropriate in patients with preexisting diabetes mellitus or hyperglycemia.

Hemophagocytic Lymphohistiocytosis

Hemophagocytic lymphohistiocytosis (HLH) reported in postmarketing reports from patients receiving trametinib/dabrafenib combination therapy.

Interrupt treatment if HLH suspected. If HLH confirmed, discontinue treatment and initiate appropriate management of HLH.

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm; embryotoxic and abortifacient in animals.

Verify pregnancy status in females of reproductive potential prior to initiating trametinib.

Advise female patients of childbearing potential to use effective contraception during, and for 4 months following, treatment.

If used during pregnancy, apprise of potential fetal hazard.

Specific Populations

Pregnancy

May cause fetal harm; verify pregnancy status in females of reproductive potential prior to initiation.

Lactation

Not known whether distributed into human milk. Effects on breast-fed infants and milk production also unknown. Discontinue breast-feeding during therapy and for 4 months after the last dose.

Females and Males of Reproductive Potential

May reduce female fertility.

Verify pregnancy status in females of reproductive potential prior to initiating trametinib.

Advise females of reproductive potential to use effective contraception during and for 4 months following treatment.

Advise males with female partners of reproductive potential to use condoms during trametinib therapy and for at least 4 months after the last dose.

Pediatric Use

Safety and efficacy of trametinib in combination with dabrafenib not established in pediatric patients <1 year of age, or when trametinib used as monotherapy in pediatric patients.

Geriatric Use

Monotherapy: Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.

Combination therapy: No overall differences in efficacy of trametinib/dabrafenib combination therapy relative to younger adults with melanoma; some adverse effects (i.e., peripheral edema, anorexia) occurred more frequently in geriatric patients with metastatic melanoma. Insufficient experience with trametinib/dabrafenib combination therapy in patients ≥65 years of age with NSCLC to determine whether geriatric patients respond differently than younger adults. Insufficient experience in younger adults with anaplastic thyroid cancer to determine whether geriatric patients respond differently than younger adults.

Hepatic Impairment

Mild hepatic impairment did not substantially affect systemic exposure of trametinib.

Appropriate dosage not established in patients with moderate to severe hepatic impairment. Moderate or severe hepatic impairment did not substantially increase systemic exposure compared with patients with normal hepatic function.

Renal Impairment

Estimated GFR 15–89 mL/minute per 1.73 m2 did not substantially affect systemic exposure of trametinib.

Common Adverse Effects

The most common adverse reactions (≥20%) in adults receiving trametinib monotherapy for unresectable or metastatic melanoma are rash, diarrhea, and lymphedema.

The most common adverse reactions (≥20%) in adults receiving trametinib in combination with dabrafenib for adjuvant treatment of melanoma include pyrexia, fatigue, nausea, headache, rash, chills, diarrhea, vomiting, arthralgia, and myalgia.

The most common adverse reactions (≥20%) in adults receiving trametinib in combination with dabrafenib for unresectable or metastatic melanoma include pyrexia, nausea, rash, chills, diarrhea, vomiting, hypertension, and peripheral edema.

The most common adverse reactions (≥20%) in adults receiving trametinib in combination with dabrafenib for metastatic NSCLC include pyrexia, fatigue, nausea, vomiting, diarrhea, dry skin, decreased appetite, edema, rash, chills, hemorrhage, cough, and dyspnea.

The most common adverse reactions (≥20%) in adults receiving trametinib in combination with dabrafenib for other solid tumors include pyrexia, fatigue, nausea, rash, chills, headache, hemorrhage, cough, vomiting, constipation, diarrhea, myalgia, arthralgia, and edema.

The most common adverse reactions (≥20%) in pediatric patients receiving trametinib in combination with dabrafenib for solid tumors include pyrexia, rash, vomiting, fatigue, dry skin, cough, diarrhea, dermatitis acneiform, headache, abdominal pain, nausea, hemorrhage, constipation, and paronychia.

The most common adverse reactions (≥20%) in pediatric patients receiving trametinib in combination with dabrafenib for low-grade glioma (LGG) include pyrexia, rash, headache, vomiting, musculoskeletal pain, fatigue, diarrhea, dry skin, nausea, hemorrhage, abdominal pain, and dermatitis acneiform.

Drug Interactions

CYP2C8 inhibitor in vitro.

Substrate of P-glycoprotein (P-gp) and bile salt export pump (BSEP).

Not a substrate for CYP isoenzymes, breast cancer resistance protein (BCRP), organic anion transporter polypeptide (OATP) 1B1, OATP1B3, OATP2B1, organic cation transporter (OCT) 1, multidrug resistance-associated protein (MRP) 2, or multidrug and toxic compound extrusion 1 (MATE1).

Not an inhibitor of CYP isoenzymes 1A2, 2A6, 2B6, 2C9, 2C19, 2D6, or 3A4.

Not an inhibitor of organic anion transporter polypeptide (OATP) 1B1, OATP1B3, organic anion transporter (OAT) 1, OAT3, OCT2, P-gp, BCRP, BSEP, MRP2, or MATE1.

Drugs Metabolized by Hepatic Microsomal Enzymes

Sensitive substrates of CYP3A4: Concomitant administration of trametinib had no clinically relevant effects on AUC or peak plasma concentrations of the sensitive CYP3A4 substrate.

Specific Drugs

Drug

Interaction

Dabrafenib

No clinically relevant effects on AUC of trametinib

Trametinib Dimethyl Sulfoxide Pharmacokinetics

Absorption

Bioavailability

72% (tablets) and 81% (oral solution).

Onset

Following oral administration, peak plasma concentrations achieved 1.5 hours after dose.

Food

High-fat, high-calorie meal decreased AUC by 24% and peak plasma concentrations after administration of trametinib tablets by 70%; also delayed time to peak plasma concentrations by approximately 4 hours.

Distribution

Plasma Protein Binding

97.4%.

Elimination

Metabolism

Principally metabolized by deacetylation with or without mono-oxygenation or in combination with glucuronidation.

Elimination Route

Following oral administration of radiolabeled dose, >80% recovered in feces and <20% in urine.

Half-life

3.9–4.8 days.

Special Populations

Mild hepatic impairment (total bilirubin concentration at or below ULN with AST concentration exceeding ULN or total bilirubin concentration exceeding ULN, but not >1.5 times the ULN, with any AST concentration) has no clinically relevant effect on systemic exposure; moderate or severe hepatic impairment did not increase exposure.

Renal impairment (eGFR 15–89 mL/minute per 1.73 m2) has no clinically relevant effect on systemic exposure. Renal impairment not likely to have clinically important effect on systemic exposure; renal excretion of drug is low.

Clinically important differences in pharmacokinetics based on age (18—93 years), sex, or weight (36—170 kg) not observed. Insufficient data to determine influence of race or ethnicity on exposure.

In pediatric patients 1—17 years of age, exposures at recommended weight-adjusted dosage were within ranges observed in adults. Weight (6—156 kg) in pediatric patients has a substantial impact on oral clearance.

Stability

Storage

Oral

Tablets

2–8°C; do not freeze.

Dispense in original bottle; do not remove desiccant. Protect from moisture and light.

Do not store in pill boxes.

Oral solution

Prior to reconstitution, 2–8°C; store in original container to protect from light and moisture.

After reconstitution, <25°C; do not freeze. Discard remaining solution 35 days after reconstitution.

Actions

Advice to Patients

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Trametinib Dimethyl Sulfoxide

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

For Solution

0.05 mg/mL

Mekinist

Tablets

0.5 mg (of trametinib)

Mekinist

Novartis

2 mg (of trametinib)

Mekinist

Novartis

AHFS DI Essentials™. © Copyright 2025, Selected Revisions July 10, 2024. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

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