Selumetinib Dosage

Medically reviewed by Drugs.com. Last updated on Apr 29, 2024.

Applies to the following strengths: 10 mg; 25 mg

Usual Pediatric Dose for:

Fibromatosis

Additional dosage information:

Renal Dose Adjustments
Liver Dose Adjustments
Dose Adjustments
Precautions
Dialysis
Other Comments

Usual Pediatric Dose for Fibromatosis

Recommended dosage in pediatric patients ages 2 to 18 years old: 25 mg/m2 orally twice a day (approximately every 12 hours) until disease progression or unacceptable toxicity.

Recommended dosage to achieve 25 mg/m2 twice a day based on body surface area (BSA):

BSA less than 0.55 mg/m2: No dose recommendation.
BSA 0.55 to 0.69 m2: 20 mg orally in the morning and 10 mg in the evening
BSA 0.7 to 0.89 m2: 20 mg orally twice a day
BSA 0.9 to 1.09 m2: 25 mg orally twice a day
BSA 1.1 to 1.29 m2: 30 mg orally twice a day
BSA 1.3 to 1.49 m2: 35 mg orally twice a day
BSA 1.5 to 1.69 m2: 40 mg orally twice a day
BSA 1.7 to 1.89 m2: 45 mg orally twice a day
BSA 1.9 mg/m2 or greater: 50 mg orally twice a day

Comments:

Do not administer to patients who are unable to swallow.

Use: For the treatment of pediatric patients 2 years of age and older with neurofibromatosis type 1 (NF1) who have symptomatic, inoperable plexiform neurofibromas (PN).

Renal Dose Adjustments

No adjustment recommended.

Liver Dose Adjustments

MILD HEPATIC DYSFUNCTION (Child-Pugh A): No dose adjustment recommended.

MODERATE HEPATIC DYSFUNCTION (Child-Pugh B): Reduce starting dosage to 20 mg/m2 twice a day.
Recommended dosage to achieve 20 mg/m2 twice a day based on body surface area (BSA):

BSA 0.55 to 0.69 m2: 10 mg orally twice a day
BSA 0.7 to 0.89 m2: 20 mg orally in the morning and 10 mg in the evening
BSA 0.9 to 1.09 m2: 20 mg orally twice a day
BSA 1.1 to 1.29 m2: 25 mg orally twice a day
BSA 1.3 to 1.49 m2: 30 mg orally in the morning and 25 mg in the evening
BSA 1.5 to 1.69 m2: 35 mg orally in the morning and 30 mg in the evening
BSA 1.7 to 1.89 m2: 35 mg orally twice a day
BSA 1.9 m2 or greater: 40 mg orally twice a day

SEVERE HEPATIC DYSFUNCTION (Child-Pugh C): Recommended dosage is unknown or not established.

Dose Adjustments

RECOMMENDED DOSE REDUCTIONS FOR ADVERSE REACTIONS:
General: If patient is unable to tolerate therapy after 2 dose reductions, therapy should be permanently discontinued.
Dose reduction recommendations based on body surface area (BSA):
BSA 0.55 to 0.69 m2:

First dose reduction: 10 mg orally twice a day
Second dose reduction: 10 mg orally once a day

BSA 0.7 to 0.89 m2:

First dose reduction: 20 mg orally in the morning and 10 mg in the evening
Second dose reduction: 10 mg orally twice a day

BSA 0.9 to 1.09 m2:

First dose reduction: 25 mg orally in the morning and 10 mg in the evening
Second dose reduction: 10 mg orally twice a day

BSA 1.1 to 1.29 m2:

First dose reduction: 25 mg orally in the morning and 20 mg in the evening
Second dose reduction: 20 mg orally in the morning and 10 mg in the evening

BSA 1.3 to 1.49 m2:

First dose reduction: 25 mg orally twice a day
Second dose reduction: 25 mg orally in the morning and 10 mg in the evening

BSA 1.5 to 1.69 m2:

First dose reduction: 30 mg orally twice a day
Second dose reduction: 25 mg orally in the morning and 20 mg in the evening

BSA 1.7 to 1.89 m2:

First dose reduction: 35 mg orally in the morning and 30 mg in the evening
Second dose reduction: 25 mg orally in the morning and 20 mg in the evening

BSA 1.9 m2 or greater:

First dose reduction: 35 mg orally twice a day
Second dose reduction: 25 mg orally twice a day

RECOMMENDED DOSE MODIFICATIONS FOR ADVERSE REACTIONS:
Cardiomyopathy:

Asymptomatic decrease in left ventricular ejection fraction (LVEF) of 10% or greater from baseline and less than lower level of normal: Withhold therapy until resolution; resume at reduced dose.
Symptomatic decreased LVEF: Permanently discontinue therapy.
Grade 3 or 4 decreased LVEF: Permanently discontinue therapy.

Ocular Toxicity:

Retinal pigment epithelial detachment (RPED): Withhold therapy until resolution; resume at reduced dose.
Retinal vein occlusion (RVO): Permanently discontinue therapy.

Gastrointestinal Toxicity:

Grade 3 diarrhea: Withhold until improved to Grade 0 or 1, then resume at same dose. Permanently discontinue if no improvement within 3 days.
Grade 4 diarrhea: Permanently discontinue therapy.
Grade 3 or 4 colitis: Permanently discontinue therapy.

Skin Toxicity:

Grade 3 or 4: Withhold therapy until improvement; resume at reduced dose.

Increased Creatine Phosphokinase (CPK):

Grade 4 Increased CPK: Withhold therapy until improved to Grade 0 or 1, then resume at reduced dose. Permanently discontinue therapy if no improvement within 3 weeks.
Any Increased CPK and myalgia: Withhold therapy until improved to Grade 0 or 1, then resume at reduced dose. Permanently discontinue therapy if no improvement within 3 weeks.
Rhabdomyolysis: Permanently discontinue therapy.

Other Adverse Reactions:

Grade 2 (intolerable) or Grade 3: Withhold therapy until improved to Grade 0 or 1; resume at reduced dose.
Grade 4: Withhold therapy until improved to Grade 0 or 1; resume at reduced dose. Consider discontinuation of therapy.

RECOMMENDED DOSE REDUCTIONS FOR COADMINISTRATION WITH STRONG OR MODERATE CYP450 3A4 INHIBITORS OR FLUCONAZOLE:
General Recommendations:

Avoid coadministration of strong or moderate CYP450 3A4 inhibitors or fluconazole with this drug.
If coadministration with strong or moderate CYP450 3A4 inhibitors or fluconazole cannot be avoided, reduce the dose of this drug as recommended below.
After the discontinuation of the strong or moderate CYP450 3A4 inhibitor or fluconazole for 3 elimination half-lives, resume this drug at the dose taken prior to initiating the inhibitor or fluconazole.

Dose Reduction Recommendations for Coadministration with CYP450 3A4 inhibitors or fluconazole:

If the current dosage is based on 25 mg/m2 twice a day, reduce to 20 mg/m2 twice a day.
If the current dosage is based on 20 mg/m2 twice a day, reduce to 15 mg/m2 twice a day.

Body surface area dosing recommendations to achieve 20 mg/m2 twice a day:

BSA 0.55 to 0.69 m2: 10 mg orally twice a day
BSA 0.7 to 0.89 m2: 20 mg orally in the morning and 10 mg in the evening
BSA 0.9 to 1.09 m2: 20 mg orally twice a day
BSA 1.1 to 1.29 m2: 25 mg orally twice a day
BSA 1.3 to 1.49 m2: 30 mg orally in the morning and 25 mg in the evening
BSA 1.5 to 1.69 m2: 35 mg orally in the morning and 30 mg in the evening
BSA 1.7 to 1.89 m2: 35 mg orally twice a day
BSA 1.9 m2 or greater: 40 mg orally twice a day

Body surface area dosing recommendations to achieve 15 mg/m2 twice daily:

BSA 0.55 to 0.69 m2: 10 mg orally once daily
BSA 0.7 to 0.89 m2: 10 mg orally twice a day
BSA 0.9 to 1.09 m2: 20 mg orally in the morning and 10 mg in the evening
BSA 1.1 to 1.29 m2: 25 mg orally in the morning and 10 mg in the evening
BSA 1.3 to 1.49 m2: 25 mg orally in the morning and 20 mg in the evening
BSA 1.5 to 1.69 m2: 25 mg orally twice a day
BSA 1.7 to 1.89 m2: 30 mg orally in the morning and 25 mg in the evening
BSA 1.9 m2 or greater: 30 mg orally twice a day

Precautions

CONTRAINDICATIONS: None

Safety and efficacy have not been established in patients younger than 2 years.

Consult WARNINGS section for additional precautions.

Dialysis

This drug is not dialyzable because it is highly protein bound and extensively metabolized.

Other Comments

Administration advice:

The manufacturer product information should be consulted prior to product administration.
This drug should be given on an empty stomach; food consumption should be avoided 2 hours before each dose or for 1 hour after each dose.
Capsules should be swallowed whole with water, and should not be chewed, dissolved, or opened.
Do not administer to patients who are unable to swallow a whole capsule.
Do not take a missed dose unless it is more than 6 hours until the next scheduled dose.
If vomiting occurs after administration, do not take an additional dose, but continue with the next scheduled dose.

Storage requirements:

Store at 25C (77F); excursions permitted from 15C to 30C (59F to 86F).
Dispense in original bottle and do not remove desiccant.
Protect from moisture.

Monitoring:

Cardiovascular: Assess left ventricular ejection fraction every 3 months during the first year, and then every 6 months thereafter, or as clinically indicated.
Dermatologic: Monitor for severe skin rashes.
Gastrointestinal: Monitor for diarrhea or loose stool.
General: Review patient medication list regularly for potential drug interactions.
Musculoskeletal: Assess creatine phosphokinase periodically during treatment and monitor for myalgia or muscle weakness.
Ocular: Monitor vision for new or worsening changes at regular intervals during therapy.

Patient advice:

Read the FDA-approved patient labeling (Medication Guide).
Take this drug on an empty stomach; do not eat for 2 hours before dose and for 1 hour after dose.
Use effective contraception during therapy and for 1 week after last dose.
Report symptoms associated with cardiomyopathy and reduced ejection fraction.
Inform healthcare provider of any new episodes of diarrhea or loose stool.
Report new or worsening changes in vision.
Notify healthcare provider of any changes in the skin or new rashes.
Report symptoms of muscle pain or weakness immediately to healthcare provider.
Avoid taking supplemental vitamin E