mirdametinib

Absorption: Extent of absorption following oral administration unknown.

Distribution: Extensively distributed to tissues.

Protein Binding: >99%.

Metabolism/Excretion: Primarily metabolized by glucuronidation by UGT1A6 and UGT2B6 and by oxidation by carboxyl esterase enzymes. Primarily excreted in urine (68%), with 27% being excreted in feces, primarily as metabolites.

Half-Life: 28 hr.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	1 hr	12 hr

Contraind./Precautions ⬆ ⬇

Contraindicated in:

OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

HF;
Severe renal impairment;
Moderate or severe hepatic impairment;
Rep: Women of reproductive potential and men with female partners of reproductive potential;
Pedi: Children <2 yr (safety and effectiveness not established).

Adv. Reactions/Side Effects ⬆ ⬇

CV: HF

Derm: paronychia, rash, alopecia, hair color changes

EENT: blurred vision, retinal pigment epithelial detachment (RPED), retinal vein occlusion

Endo: hypoglycemia

F and E: hypocalcemia

GI: ↑liver enzymes, abdominal pain, diarrhea, nausea, stomatitis, vomiting, constipation

GU: ↑serum creatinine

Hemat: anemia, leukopenia, lymphocytosis, lymphopenia, neutropenia

Metab: hypercholesterolemia, hypertriglyceridemia

MS: ↑CK, pain

Neuro: fatigue, headache, peripheral neuropathy

Resp: cough, upper respiratory tract infection

Misc: fever

Interactions ⬆ ⬇

Drug-drug:

None reported.

Route/Dosage ⬆ ⬇

PO (Adults and Children Body Surface Area [BSA] ≥1.5 m²): 4 mg twice daily for the 1st 21 days of each 28-day cycle. Continue until disease progression or unacceptable toxicity.
PO (Adults and Children BSA = 1.05–1.49 m²): 3 mg twice daily for the 1st 21 days of each 28-day cycle. Continue until disease progression or unacceptable toxicity.
PO (Adults and Children BSA = 0.7–1.04 m²): 2 mg twice daily for the 1st 21 days of each 28-day cycle. Continue until disease progression or unacceptable toxicity.
PO (Adults and Children BSA = 0.4–0.69 m²): 1 mg twice daily for the 1st 21 days of each 28-day cycle. Continue until disease progression or unacceptable toxicity.

Availability ⬆ ⬇

Capsules: 1 mg; 2 mg
Tablets for oral suspension: 1 mg

Assessment ⬆ ⬇

Assess left ventricular ejection fraction (LVEF) by echocardiogram prior to initiation. Monitor LVEF every 3 mo during the 1st yr and then as clinically indicated. Left ventricular dysfunction (asymptomatic, absolute ↓ in LVEF of ≥10% from baseline and is < lower limit of normal): Hold treatment until improvement to Grade ≤1; then resume at a ↓ dose (see below); permanently discontinue mirdametinib if patient unable to tolerate after one dose ↓. Any absolute ↓ in LVEF ≥20% from baseline: Permanently discontinue mirdametinib.
Conduct comprehensive ophthalmic assessments prior to initiation and at regular intervals during treatment; evaluate any new or worsening visual changes. Monitor for ocular toxicity including retinal vein occlusion, retinal pigment epithelium detachment, and blurred vision. If Grade ≤2 ocular toxicity occurs: Continue at current dose level and consider ophthalmologic examinations every 2–4 wk until resolution to Grade ≤1. If Grade ≥3 ocular toxicity occurs: Hold treatment until improvement to Grade ≤1; if recovery occurs in ≤14 days, resume at next dose ↓ (see below); permanently discontinue mirdametinib if patient is unable to tolerate after one dose ↓; if recovery takes >14 days, consider permanently discontinuing mirdametinib. If retinal vein occlusion occurs: Permanently discontinue mirdametinib. If retinal pigment epithelium detachment occurs: Hold treatment until improvement to Grade ≤1; then resume at current dose level.
Monitor for dermatologic toxicity, including dermatitis acneiform, eczema, maculo-papular rash, pustular rash, dermatitis, erythematous rash, palmar-plantar erythrodysaesthesia syndrome, exfoliative rash, skin exfoliation, pruritic rash, papule, papular rash, and macular rash. Initiate supportive care at 1st signs of dermatologic adverse reactions. If intolerable Grade 2 or Grade 3 toxicity occurs: Hold treatment until improvement to Grade ≤1; then resume at a dose ↓ (see below); permanently discontinue mirdametinib if patient is unable to tolerate after one dose ↓. If Grade 3 or 4 dermatitis acneiform or nonacneiform rash occurs: Hold treatment until improvement to Grade ≤1; then resume at a dosage ↓ (see below); permanently discontinue mirdametinib if patient is unable to tolerate after one dose ↓.

Lab Test Considerations:

Verify negative pregnancy status prior to initiation.
May ↑ liver enzymes and serum creatinine.

Implementation ⬆ ⬇

PO: Administer without regard to food. Instruct patient to swallow one capsule or tablet at a time. DNC: Do not open, break, or chew capsules. Must be swallowed whole. If patient unable to swallow whole tablets, use tablets to prepare oral suspension with water.
To prepare oral suspension, place prescribed number of tablets in dosing cup containing 5–10 mL of water; gently swirl water and tablets until fully dispersed and white, cloudy suspension forms (takes about 2–4 min). Add an additional 5–10 mL of water to resuspend any remaining particles and administer to ensure entire dose is taken. Discard if not administered within 30 min of preparation.
Dosage Reductions for Toxicities: BSA = 0.4–0.69 m²:↓ dose to 1 mg once daily; BSA = 0.7–1.04 m²: ↓dose to 2 mg in AM and 1 mg in PM; BSA = m²1.05–1.49 m²: ↓dose to 2 mg twice daily; BSA ≥1.5 m²: ↓dose to 3 mg twice daily.

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of mirdametinib. Advise to take as directed; teach patient to either swallow tablets whole or how to disperse in water and take orally as a suspension. If a dose is missed or vomited, do not take an additional dose; take next dose at scheduled time. Advise patient to read Patient Information before starting therapy and with each Rx refill in case of changes.
Explain need for continued medical follow-up to assess effectiveness and possible side effects of medication. Periodic heart and eye exams will be needed.
Advise patient to report symptoms of ocular toxicity (blurred vision, ↓ vision, color vision changes [especially ↓ red brightness], severe eye pain, redness, light sensitivity, persistent eye irritation).
Warn patient to report symptoms and seek treatment for HF (trouble breathing, leg swelling, lung congestion, rapid weight gain).
Instruct patient to notify health care provider if any skin rash, redness, swelling, or itchiness develops, including thick calluses or blisters on the palms of the hands or soles of the feet.
Advise patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care provider before taking other medications.
Rep: May cause fetal harm. Advise women of reproductive potential to notify health care provider if pregnancy is planned or suspected or if breastfeeding. Advise women of reproductive potential to use effective contraception during treatment and for 6 wk after the last dose. Advise men with female partners of reproductive potential to use effective contraception during treatment and for 3 mo after the last dose. Advise women not to breastfeed during treatment with mirdametinib and for 1 wk after the last dose.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇