Version July 2025
Dosage guidance:
Safety: Prior to treatment initiation, assess left ventricular ejection fraction (LVEF) (via echocardiogram) and conduct a comprehensive ophthalmic exam.
Clinical considerations: Mirdametinib may be associated with a moderate or high emetic potential; antiemetics may be recommended to prevent nausea and vomiting.
Neurofibromatosis type 1: Note: Continue until disease progression or unacceptable toxicity.
Children ≥2 years and Adolescents:
BSA-directed dosing: Oral: 2 mg/m2 twice daily (~12 hours apart) on days 1 to 21 of a 28-day cycle; maximum dose: 4 mg/dose.
BSA-banded dosing (fixed dose): Oral: Administer dose twice daily (~12 hours apart) on days 1 to 21 of a 28-day treatment cycle.
|
BSAa |
Recommended mirdametinib dose |
|---|---|
|
a Dosing for patients with BSA <0.4 mg/m2 has not been established. | |
|
0.4 to 0.69 m2 |
1 mg twice daily |
|
0.7 to 1.04 m2 |
2 mg twice daily |
|
1.05 to 1.49 m2 |
3 mg twice daily |
|
≥1.5 m2 |
4 mg twice daily |
Dosing adjustment for toxicity:
Children ≥2 years and Adolescents: Oral: Administer dose on days 1 to 21 of a 28-day treatment cycle; twice-daily regimens should have doses administered ~12 hours apart.
|
BSA |
Mirdametinib dosage reductiona |
|---|---|
|
a Permanently discontinue if unable to tolerate mirdametinib after one dose reduction. | |
|
0.4 to 0.69 m2 |
1 mg once daily |
|
0.7 to 1.04 m2 |
2 mg in the morning and 1 mg in the evening |
|
1.05 to 1.49 m2 |
2 mg twice daily |
|
≥1.5 m2 |
3 mg twice daily |
|
Adverse reaction |
Description/severity |
Mirdametinib dosage modification |
|---|---|---|
|
Cardiovascular toxicity: Left ventricular dysfunction |
Asymptomatic, absolute decrease in LVEF ≥10% from baseline and is < LLN |
Withhold mirdametinib until ≤ grade 1. Then resume mirdametinib at a reduced dose. |
|
Any absolute decrease in LVEF ≥20% from baseline |
Permanently discontinue mirdametinib. | |
|
Dermatologic toxicity |
First sign of dermatologic toxicity |
Initiate supportive care. |
|
Intolerable grade 2 or grade 3 |
Withhold mirdametinib until ≤ grade 1. Then resume mirdametinib at a reduced dose. | |
|
Grade 3 or 4 dermatitis acneiform or non-acneiform rash |
Withhold mirdametinib until ≤ grade 1. Then resume mirdametinib at a reduced dose. | |
|
Ocular toxicity |
New or worsening visual changes |
Evaluate with a comprehensive ophthalmic examination. |
|
Grade ≤2 |
Continue mirdametinib at the current dose. Consider ophthalmologic examinations every 2 to 4 weeks until resolution to ≤ grade 1 or baseline. | |
|
Grade ≥3 |
Withhold mirdametinib until ≤ grade 1 or baseline. • If recovery in ≤14 days: Resume mirdametinib at a reduced dose. • If recovery in >14 days: Consider permanent mirdametinib discontinuation. | |
|
Symptomatic retinal pigment epithelium detachment |
Withhold mirdametinib until ≤ grade 1 or baseline. Then resume at the same dose. | |
|
Retinal vein occlusion |
Permanently discontinue mirdametinib. | |
|
Other adverse reactions |
Intolerable grade 2 or grade 3 |
Withhold mirdametinib until ≤ grade 1. Then resume mirdametinib at a reduced dose. |
|
Grade 4 |
Consider permanent mirdametinib discontinuation. |
Children ≥2 years and Adolescents: Oral:
CrCl ≥30 mL/minute: No dosage adjustment necessary.
CrCl <30 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
End-stage kidney disease: There are no dosage adjustments provided in the manufacturer's labeling (effect on mirdametinib pharmacokinetics is unknown).
Children ≥2 years and Adolescents: Oral:
Mild (total bilirubin ≤ ULN and AST > ULN, or total bilirubin 1 to 1.5 times ULN) hepatic impairment: No dosage adjustment necessary.
Moderate (total bilirubin >1.5 to 3 times ULN and any AST) or severe (total bilirubin >3 times ULN and any AST) hepatic impairment: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
(For additional information see "Mirdametinib: Drug information")
Dosage guidance:
Safety: Prior to treatment initiation, assess left ventricular ejection fraction (via echocardiogram) and conduct a comprehensive ophthalmic exam.
Dosage forms considerations: Mirdametinib is available in 2 dosage forms: Capsules for oral administration and tablets for oral suspension.
Clinical considerations: Mirdametinib may be associated with a moderate or high emetic potential; antiemetics may be recommended to prevent nausea and vomiting.
Neurofibromatosis type 1: Oral: 2 mg/m2 (maximum dose: 4 mg) twice daily (approximately every 12 hours) on days 1 to 21 of a 28-day treatment cycle; continue until disease progression or unacceptable toxicity (Ref).
|
Recommended Mirdametinib Dose Based on BSA | |
|---|---|
|
BSA |
Recommended Oral Mirdametinib Dose (for Capsules or for Tablets for Oral Suspension) |
|
≥1.5 m2 |
4 mg twice daily on days 1 to 21 of a 28-day treatment cycle |
|
1.05 to 1.49 m2 |
3 mg twice daily on days 1 to 21 of a 28-day treatment cycle |
|
0.7 to 1.04 m2 |
2 mg twice daily on days 1 to 21 of a 28-day treatment cycle |
Missed dose: If a dose is missed, do not administer an additional dose; administer the next dose at its scheduled time. If vomiting occurs after a dose is administered, do not administer an additional dose; administer the next dose at its scheduled time.
Kidney impairment prior to treatment initiation:
CrCl 30 to 89 mL/minute: No dosage adjustment necessary.
CrCl <30 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
End-stage kidney disease: There are no dosage adjustments provided in the manufacturer's labeling (effect on mirdametinib pharmacokinetics is unknown).
Hepatic impairment prior to treatment initiation:
Mild (total bilirubin ≤ ULN and AST > ULN, or total bilirubin 1 to 1.5 times ULN) hepatic impairment: No dosage adjustment necessary.
Moderate (total bilirubin >1.5 to 3 times ULN and any AST) or severe (total bilirubin >3 times ULN and any AST) hepatic impairment: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in children, adolescents, and adults unless otherwise indicated.
>10%:
Cardiovascular: Left ventricular dysfunction (children, adolescents: 27%; adults: 16%)
Dermatologic: Alopecia (<20%), hair discoloration (<20%), paronychia (children, adolescents: 32%; adults: 2%), skin rash (children, adolescents: 73%; adults: 90%; including acneiform eruption, eczema, erythematous rash, exfoliation of skin, exfoliative dermatitis, maculopapular rash, palmar-plantar erythrodysesthesia, papule of skin, pruritic rash, pustular rash)
Endocrine & metabolic: Decreased serum bicarbonate (children, adolescents: 21%; adults: 11%), decreased serum calcium (20% to 23%), decreased serum glucose (children, adolescents: 36%; adults: 5%), hypercholesterolemia (16% to 23%), increased serum triglycerides (children, adolescents: 45%; adults: 29%)
Gastrointestinal: Abdominal pain (children, adolescents: 39%; adults: 24%), constipation (<20%), diarrhea (55% to 59%), nausea (children, adolescents: 27%; adults: 52%), stomatitis (children, adolescents: 20%; adults: 5%), vomiting (38% to 39%)
Hematologic & oncologic: Decreased hemoglobin (21% to 29%), decreased neutrophils (children, adolescents: 31%; adults: 7%), leukopenia (children, adolescents: 40%; adults: 7%), lymphocytopenia (children, adolescents: 2%; adults: 16%), lymphocytosis (children, adolescents: 27%; adults: 7%)
Hepatic: Increased serum alanine aminotransferase (children, adolescents: 21%; adults: 9%), increased serum alkaline phosphatase (children, adolescents: 29%; adults: 13%), increased serum aspartate aminotransferase (9% to 18%)
Nervous system: Fatigue (children, adolescents: 29%; adults: 13%), headache (children, adolescents: 34%; adults: 14%), peripheral neuropathy (children, adolescents: 4%; adults: 21%)
Neuromuscular & skeletal: Increased creatine phosphokinase in blood specimen (55% to 59%), musculoskeletal pain (41%)
Ophthalmic: Ocular toxicity (19% to 28%; including blurred vision [adults: 9%], retinal pigment epithelium detachment [<20%], retinal vein occlusion [adults: 3%])
Renal: Increased serum creatinine (children, adolescents: 30%; adults: 13%)
Respiratory: Cough (children, adolescents: 21%; adults: 9%), upper respiratory tract infection (children, adolescents: 23%)
Miscellaneous: Fever (children, adolescents: 20%; adults: 7%)
Frequency not defined (any population):
Cardiovascular: Hypertension, peripheral edema
Dermatologic: Squamous cell carcinoma of skin, urticaria, xeroderma
Endocrine & metabolic: Dehydration
Gastrointestinal: Ischemic colitis, viral gastrointestinal infection
Genitourinary: Urinary tract infection
Nervous system: Cerebrovascular accident, dizziness, falling, seizure
Neuromuscular & skeletal: Femoral neck fracture
Ophthalmic: Diplopia
Renal: Acute kidney injury, nephrolithiasis
Respiratory: Chronic obstructive pulmonary disease, wheezing
There are no contraindications listed in the manufacturer's labeling.
Concerns related to adverse effects:
• Cardiotoxicity: Mirdametinib may cause left ventricular dysfunction. In the overall study population, decreased left ventricular ejection fraction (LVEF) of 10% to <20% occurred in one-fifth of patients, and decreased LVEF of ≥20% occurred in a small number of patients. All cases of decreased LVEF were identified during routine echocardiography. The median time to first onset of decreased LVEF was 70 days in adults and 132 days in pediatric patients. Decreased LVEF resolved in a majority of these patients. Mirdametinib has not been studied in patients with a history of clinically significant cardiac disease or LVEF <55% prior to treatment initiation.
• Dermatologic toxicity: Mirdametinib may cause dermatologic adverse reactions, including rash. In the overall population, rash occurred in a majority of mirdametinib-treated patients, including grade 2 and 3 events. The most frequent rashes included dermatitis acneiform, generalized rash, eczema, maculopapular rash, and pustular rash.
• Ocular toxicity: Mirdametinib may cause ocular toxicity, including retinal vein occlusion, retinal pigment epithelium detachment, and blurred vision. Overall, ocular toxicity occurred in one-fourth of mirdametinib-treated patients, including grade 1, 2, and 3 events. Ocular toxicity occurred at a slightly higher incidence in adults (compared to younger patients). Blurred vision, cases of retinal vein occlusion (including a grade 3 event), and a case of retinal pigment epithelium detachment were observed in adult patients.
Dosage form specific issues:
• Propylene glycol: Some dosage forms may contain propylene glycol; large amounts are potentially toxic and have been associated hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (Ref). See manufacturer's labeling.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
Gomekli: 1 mg, 2 mg [contains fd&c blue #1 (brilliant blue)]
Tablet Soluble, Oral:
Gomekli: 1 mg [contains corn starch; grape flavor]
No
Capsules (Gomekli Oral)
1 mg (per each): $247.50
2 mg (per each): $495.00
Tablet,Dispersible (Gomekli Oral)
1 mg (per each): $247.50
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Mirdametinib is available through specialty pharmacies, specialty distributors, and various specialty institutions/accounts. Examples from the manufacturer may be found at https://www.springworkstxcares.com/resources/gomekli/Product_Fact_Sheet_and_Ordering_Guide_(GOMEKLI).pdf.
Note: Mirdametinib may be associated with a moderate or high emetic potential; antiemetics may be recommended to prevent nausea and vomiting.
Oral: Administer with or without food.
Capsules: Must be swallowed whole with water; do not open, break, or chew capsules. If more than one capsule is required for a dose, have patient swallow one capsule at a time.
Tablets for oral suspension: May be swallowed whole or may be dispersed in water and administered orally as a liquid. If swallowing whole and more than one tablet is required for a dose, have patient swallow one tablet at a time. For patients who are unable to swallow whole tablets, an oral suspension may be prepared from the tablets for oral suspension.
Preparation and administration of oral suspension (prepared from tablets): Add the required number of tablets to a dosing cup containing ~5 to 10 mL of water. Gently swirl the water and tablets until the tablets are fully dispersed (~2 to 4 minutes). Once dispersed, the oral suspension will appear white and cloudy. Administer the oral suspension immediately after preparation either using the dosing cup or an oral syringe; must be administered within 30 minutes of preparation. Following administration, rinse the container used for preparation with ~5 to 10 mL of water and administer directly from dosing cup or if oral syringe was used to administer dose, draw up water from dosing cup into the oral syringe to administer; this process ensures delivery of entire dose. Discard preparation if not administered within 30 minutes after preparation.
Missed dose: If a dose is missed, do not administer an additional dose; administer the next dose at its scheduled time. If vomiting occurs after a dose is administered, do not administer an additional dose; administer the next dose at its scheduled time.
Oral: Administer with or without food. Mirdametinib may be associated with a moderate or high emetic potential; antiemetics may be recommended to prevent nausea and vomiting.
Capsules: Swallow whole (with water); do not open, break or chew capsules. Do not administer to patients who are unable to swallow a whole capsule. If more than one capsule is required for a dose, swallow one capsule at a time.
Tablets for oral suspension: May be swallowed whole (with water) or may be dispersed in drinking water and administered orally as a suspension. If swallowing whole, if more than one tablet is required for a dose, have patient swallow one tablet at a time. For patients who are unable to swallow whole tablets, an oral suspension may be prepared.
Preparation and administration of oral suspension (prepared from tablets): Add the required number of tablets to a dosing cup containing ~5 to 10 mL of drinking water. Gently swirl the water and tablets until the tablets are fully dispersed and an oral suspension is obtained. This takes ~2 to 4 minutes for tablets to fully disperse. Once dispersed, the oral suspension will appear white and cloudy. Administer the oral suspension immediately after preparation either using the dosing cup or an oral syringe. After administration of the prepared suspension, add ~5 to 10 mL of drinking water to the dosing cup and gently swirl to resuspend any remaining particles. Administer the remaining “rinse” suspension to ensure the full dose is administered. Administer within 30 minutes of preparing the oral suspension; discard if not administered within 30 minutes after preparation.
Capsules, tablets for suspension: Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F). Protect from light.
Treatment of neurofibromatosis type 1 in patients with symptomatic plexiform neurofibromas not amenable to complete resection (FDA approved in ages ≥2 years and adults).
Mirdametinib may be confused with binimetinib, cobimetinib, mirikizumab, momelotinib, selumetinib, trametinib.
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes (chemotherapeutic agent, parenteral and oral) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Acute Care, Community/Ambulatory Care, and Long-Term Care Settings).
Substrate of BCRP, P-glycoprotein (Minor), UGT1A6, UGT2B7; Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential;
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program
There are no known significant interactions.
Verify pregnancy status prior to initiating treatment in patients who could become pregnant. Patients who could become pregnant should use effective contraception during therapy and for 6 weeks after the last dose of mirdametinib. Patients with partners who could become pregnant should use effective contraception during therapy and for 3 months after the last mirdametinib dose.
Based on the mechanism of action and data from animal reproduction studies, in utero exposure to mirdametinib may cause fetal harm.
The manufacturer reports a first trimester spontaneous abortion occurred in one patient 31 days after the last dose of mirdametinib during a clinical study.
Assess left ventricular ejection fraction (by echocardiogram) prior to treatment initiation and every 3 months during the first year and then as clinically indicated. Conduct a comprehensive ophthalmic assessment prior to treatment initiation and at regular intervals during treatment and with any new or worsening visual changes (eg, blurred vision). Verify pregnancy status prior to initiating treatment in patients who could become pregnant. Monitor for signs/symptoms of ocular toxicity, dermatologic toxicity, and cardiotoxicity.
The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (Ref) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow up.
Mirdametinib is a selective, potent, small molecule mitogen-activated protein kinase kinases 1 and 2 (MEK1/2) inhibitor (Ref). MEK1/2 proteins are upstream regulators of the extracellular signal-related kinase (ERK) pathway. In vitro, mirdametinib inhibited MEK1 and MEK2 kinase activity and downstream ERK phosphorylation. Mirdametinib inhibited ERK phosphorylation and reduced neurofibroma tumor volume and proliferation in a neurofibromatosis type 1 animal model.
Onset: Median time to onset of response: Adults: 7.8 months (range: 4 to 19 months).
Distribution: Vd: 255 L.
Protein binding: >99%.
Metabolism: Glucuronidation and oxidation via UGT (primarily UGT1A6 and UGT2B7) and via carboxyl esterase enzymes.
Half-life elimination: 28 hours.
Time to peak: Median: Capsule: 1.1 hours (range: 0 to 4 hours); Tablet: 0.8 hours (range: 0.4 to 3 hours).
Excretion: Urine: 68% (0.7% as unchanged drug); Feces: 27% (~8% as unchanged drug).
Clearance: 6.3 L//hour.
