Gomekli (mirdametinib)

The recommended dose reductions for adverse reactions are provided in Table 2.

Table 2: Recommended Mirdametinib Dose Reductions for Adverse Reactions

Body Surface Area (m2) Reduced Dosage 0.4 to 0.69 1 mg once daily 0.7 to 1.04 2 mg in the morning and 1 mg in the evening 1.05 to 1.49 2 mg in the morning and 2 mg in the evening >=1.5 3 mg in the morning and 3 mg in the evening

Permanently discontinue mirdametinib in patients unable to tolerate the drug after one dose reduction.

The recommended dosage modifications for adverse reactions are provided in Table 3.

Table 3: Recommended Dosage Modifications and Management of Adverse Reactions for Mirdametinib

Adverse Reaction Severity Dosage Modification Ocular Toxicity Grade <=2 Continue mirdametinib at current dose level. Consider ophthalmologic examinations every 2 to 4 weeks until resolution to Grade <=1 or baseline. Ocular Toxicity Grade >=3 Withhold mirdametinib until <=Grade 1 or baseline. If recovery occurs in <=14 days, resume mirdametinib at the next lower dose. If recovery occurs in >14 days, consider permanent discontinuation of mirdametinib. Ocular Toxicity Symptomatic Retinal Withhold mirdametinib Pigment Epithelium until Grade <=1 or Detachment (RPED) baseline. Resume mirdametinib at the same dose. Ocular Toxicity Retinal Vein Occlusion Permanently discontinue (RVO) mirdametinib. Left Ventricular Asymptomatic, absolute Withhold mirdametinib Dysfunction decrease in left until Grade <=1. Resume ventricular ejection mirdametinib at reduced fraction (LVEF) >=10% dose. from baseline and < the lower limit of normal Left Ventricular Any absolute decrease in Permanently discontinue Dysfunction LVEF >=20% from baseline mirdametinib. Dermatologic Adverse Intolerable Grade 2 or Withhold mirdametinib Reactions Grade 3 until Grade <=1. Resume mirdametinib at reduced dose. Dermatologic Adverse Grade 3 or 4 Dermatitis Withhold mirdametinib Reactions until Grade <=1. Dermatologic Adverse Acneiform or Resume mirdametinib at Reactions Non-Acneiform Rash reduced dose. Other Adverse Reactions Intolerable Grade 2 or Withhold mirdametinib Grade 3 until Grade <=1. Resume mirdametinib at reduced dose. Other Adverse Reactions Grade 4 Consider permanent discontinuation of mirdametinib.

Administer mirdametinib orally twice daily with or without food. Mirdametinib is commercially available as capsules and tablets for oral suspension.

No dosing information is available for this tab.

No formal drug interaction studies have been performed to date with mirdametinib. The effect of concomitant use of strong cytochrome P-450 (CYP) 3A4 inducers that also co-induce uridine diphosphate glucuronosyltransferases (UGTs), P-glycoprotein (P-gp), and carboxylesterase (CES) enzymes on mirdametinib pharmacokinetics is unknown.

Mirdametinib does not inhibit CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, or CYP3A4. Mirdametinib does not induce CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, or CYP3A4. Mirdametinib has no detectable or limited (<50%) inhibition of UGT1A1, UGT1A3, UGT1A4, UGT1A6, UGT1A9, UGT2B7, and UGT2B15. Mirdametinib does not inhibit breast cancer resistance protein (BCRP), P-gp, organic anion transporting polypeptide 1B1 (OATP1B1), OATP1B3, organic cation transporter 2 (OCT2), OAT1, OAT3, multidrug and toxin extrusion 1 (MATE1), or MATE2K transporters. Mirdametinib is a substrate of BCRP and P-gp transporters.

There are no contraindication interactions for this drug.

There are no severe interactions for this drug.

There are no moderate interactions for this drug.

*None.

• Lactation

• Chronic heart failure
• Pregnancy

There are no moderate contraindications for this drug.

The most common adverse reactions (>25%) in adults were rash, diarrhea, nausea, musculoskeletal pain, vomiting, and fatigue. The most common Grade 3 or 4 laboratory abnormality (>2%) in adults was increased creatine phosphokinase.

The most common adverse reactions (>25%) in pediatric patients were rash, diarrhea, musculoskeletal pain, abdominal pain, vomiting, headache, paronychia, left ventricular dysfunction, and nausea. The most common Grade 3 or 4 laboratory abnormalities (>2%) in pediatric patients were decreased neutrophil count and increased creatine phosphokinase.

More Frequent

• Left ventricular failure

More Frequent

• Acute abdominal pain
• Diarrhea
• Fatigue
• Headache disorder
• Increased creatine kinase level
• Musculoskeletal pain
• Nausea
• Neutropenic disorder
• Paronychia
• Skin rash
• Vomiting

Less Frequent

• Abnormal hepatic function tests
• Acneiform eruption
• Alopecia
• Anemia
• Blurred vision
• Constipation
• Eczema
• Fever
• Hair discoloration
• Hypercholesterolemia
• Hypertriglyceridemia
• Hypocalcemia
• Hypoglycemic disorder
• Increased alkaline phosphatase
• Kidney stone
• Leukopenia
• Maculopapular rash
• Peripheral neuropathy
• Retinal pigment epithelial detachment
• Stomatitis
• Upper respiratory infection

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Safety and effectiveness of mirdametinib have been established in pediatric patients 2 years of age and older with neurofibromatosis type 1 (NF1) with symptomatic plexiform neurofibromas (PN) based on the results of the ReNeu study, a single-arm trial conducted in 58 pediatric patients >=2 years of age. The ReNeu study demonstrated improvement in overall response rate per REiNS criteria and duration of response.

Safety and effectiveness of mirdametinib have not been established in pediatric patients younger than 2 years of age.

Mirdametinib can cause fetal harm or loss of pregnancy when administered to a pregnant woman. In embryo-fetal development studies, oral administration of mirdametinib to pregnant rats and rabbits during the period of organogenesis caused embryo-fetal mortality, structural abnormalities and growth alterations. Advise pregnant women of the potential risk to a fetus.

There are no data on the presence of mirdametinib or its metabolites in human milk or their effects on a breastfed child or milk production. Because of the potential for adverse reactions in breastfed children, advise women not to breastfeed during treatment with mirdametinib and for 1 week after the last dose.

The manufacturer makes no specific dosage recommendations for geriatric patients.

Of the 133 patients with NF1-PN who received mirdametinib in clinical studies, 2 (1.5%) were 65 years of age and older and no patients were 75 years of age and older. Clinical studies of mirdametinib did not include sufficient numbers of patients 65 years of age and older to determine whether they respond differently than younger adult patients.