Selumetinib

Selumetinib is a prescription medication used for the treatment of neurofibromatosis type 1 in patients aged 2 years and older who have symptomatic, inoperable plexiform neurofibromas.

• Selumetinib is available under the following different brand names: Koselugo

Common side effects of Selumetinib include:

• vomiting
• rash
• abdominal pain
• diarrhea
• nausea
• dry skin
• fatigue
• musculoskeletal pain
• fever
• acne
• inflammation of the mouth and lips
• headache
• nail infection
• itching

Serious side effects of Selumetinib include:

• visual impairment
• dry mouth
• facial edema
• increased weight
• dyspnea
• hypertension

Rare side effects of Selumetinib include:

• none 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, light-headedness, or passing out

This is not a complete list of side effects and other serious side effects or health problems that may occur as a result of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Pediatric dosage

Capsule

• 10 mg
• 25 mg

Neurofibromatosis type 1

Pediatric dosage

• Children younger than 2 years or having body surface area (BSA) less than 0.55 m2: Safety and efficacy not established
• Children aged 2 years and older
  • BSA of 0.55 m2 and more: 25 mg/m2 orally twice a day (every 12 hour)
  • Recommended dosage based on BSA
    • 0.55-0.69 m2: 20 mg orally every morning and 10 mg orally every evening
    • 0.7-0.89 m2: 20 mg orally twice a day
    • 0.9-1.09 m2: 25 mg orally twice a day
    • 1.1-1.29 m2: 30 mg orally twice a day
    • 1.3-1.49 m2: 35 mg orally twice a day
    • 1.5-1.69 m2: 40 mg orally twice a day
    • 1.7-1.89 m2: 45 mg orally twice a day
    • 1.9 m2 and more: 50 mg orally twice a day

Dosage Considerations – Should be Given as Follows:

• See "Dosages"

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, healthcare provider, or pharmacist first.

• Selumetinib has severe interactions with no other drugs.
• Selumetinib has serious interactions with at least 95 drugs.
• Selumetinib has moderate interactions with the following drugs:
  • abciximab
  • anagrelide
  • aspirin
  • berotralstat
  • cangrelor
  • cilostazol
  • clopidogrel
  • dipyridamole
  • encorafenib
  • eptifibatide
  • fostemsavir
  • oteseconazole
  • ponesimod
  • prasugrel
  • ticagrelor
  • ticlopidine
  • tirofiban
  • vitamin E
  • vorapaxar
• Selumetinib has minor interactions with no other drugs.

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, or if you have health questions, concerns.

Contraindications

• None

Effects of drug abuse

• None

Short-Term Effects

• See "What Are Side Effects Associated with Using Selumetinib?"

Long-Term Effects

• See "What Are Side Effects Associated with Using Selumetinib?"

Cautions

• Rash occurred; other skin toxicities, including severe palmoplantar erythrodysesthesia syndrome, occurred; monitor for severe rashes
• Increased creatine phosphokinase (CPK) occurred; rhabdomyolysis occurred in an unapproved adult population who received selumetinib; obtain serum CPK before initiating, periodically during treatment, and as clinically indicated
• May cause fetal harm when administered to a pregnant woman based on animal studies and mechanism of action
• Gastrointestinal toxicity
  • Diarrhea occurred
  • Serious gastrointestinal toxicities (eg, perforation, colitis, ileus, intestinal obstruction) occurred in an unapproved population of adult patients
  • Colitis occurred in an unapproved population of pediatric patients
  • Advise to start an antidiarrheal agent (eg, loperamide) immediately after the first episode of unformed, loose stool and to increase fluid intake during diarrhea episodes
• Ocular toxicity
  • Blurred vision, photophobia, cataracts, and ocular hypertension occurred
  • Serious ocular toxicities, including retinal vein occlusion and retinal pigment epithelial detachment (RPED), occurred in an unapproved population of adult patients with multiple tumor types
  • RPED occurred in the pediatric population during treatment and resulted in permanent discontinuation
  • Conduct comprehensive ophthalmic assessments before initiating treatment, at regular intervals during treatment, and for new or worsening visual changes
• Cardiomyopathy
  • Cardiomyopathy (decrease in left ventricular ejection fraction [LVEF] of 10% and below the baseline) occurred; all patients with decreased LVEF were asymptomatic and identified during routine echocardiography
  • Safety has not been established in patients with a history of impaired LVEF or a baseline ejection fraction below the institutional lower limit of normal
  • Assess ejection fraction by echocardiogram before initiating treatment, every 3 months during the first year of treatment, every 6 months thereafter, and as clinically indicated
  • If the dose is withheld, obtain an echocardiogram or a cardiac MRI every 3-6 weeks, then every 2-3 months or as directed by the cardiologist once resolved
• Drug interaction overview
• Selumetinib is a substrate of CYP3A4, BCRP, and P-gp transporters
• Antiplatelet antagonists or vitamin K antagonists
• Capsules contain vitamin E, and daily intake of vitamin E that exceeds the recommended or safe limits may increase the risk for bleeding
• An increased risk for bleeding in patients may occur when coadministered with vitamin K antagonists or antiplatelet antagonists
• Supplemental vitamin E is not recommended if daily vitamin E intake will exceed the recommended or safe limits
• Monitor for bleeding and international normalized ratio
• Strong and moderate CYP3A4 inhibitors
  • Coadministration with a strong or moderate CYP3A4 inhibitor or fluconazole may increase selumetinib plasma concentration
  • Avoid coadministration
• Strong or moderate CYP3A4 inducers
  • Coadministration with a strong or moderate CYP3A4 inducer decreased selumetinib plasma concentrations
  • Avoid coadministration

Pregnancy and Lactation

• Based on findings from animal studies and its mechanism of action, fetal harm may occur when administered to a pregnant woman
• No data available on use in pregnant women to evaluate drug-associated risk
• Verify pregnancy status before initiating treatment
• Contraception
  • Females of reproductive potential or males with females of reproductive potential: Use effective contraception during treatment and for 1 week after the last dose
• Lactation
  • There are no data on the presence of selumetinib or its active metabolite in human milk or their effects on breastfed child or milk production
  • Selumetinib and its active metabolite were present in the milk of lactating mice
  • Advise women not to breastfeed during treatment and for 1 week after the last dose