selumetinib (Koselugo)

Brand name: Koselugo

Generic: selumetinib

Koselugo (selumetinib) is a prescription medicine that is used to treat children 2 years of age and older with neurofibromatosis type 1 (NF1) who have plexiform neurofibromas that cannot be completely removed by surgery.

It is not known if Koselugo is safe and effective in children under 2 years of age.

Koselugo may cause serious side effects, including:

• Heart problems. Koselugo can lower the amount of blood pumped by your heart which is common and can also be severe. Your healthcare provider will do tests before and during treatment with Koselugo to check how well your heart is working. Tell your healthcare provider right away if you get any of the following signs or symptoms:
  • persistent coughing or wheezing
  • shortness of breath
  • swelling of your ankles and feet
  • tiredness
  • increased heart rate
• Eye problems. Koselugo can cause eye problems that can lead to blindness. Your healthcare provider will check your vision before and during treatment with Koselugo. Tell your healthcare provider right away if you get any of the following signs or symptoms:
  • blurred vision
  • loss of vision
  • dark spots in your vision (floaters)
  • other changes to your vision
• Severe diarrhea. Diarrhea is common with Koselugo and can also be severe. Tell your healthcare provider right away the first time that you get diarrhea during treatment with Koselugo. Your healthcare provider may give you medicine to help control your diarrhea and may tell you to drink more fluids.
• Skin rash. Skin rashes are common with Koselugo and can also be severe. Tell your healthcare provider if you get any of the following signs or symptoms:
  • rash that covers a large area of your body
  • peeling skin
  • blisters
• Muscle problems (rhabdomyolysis). Muscle problems are common with Koselugo and can also be severe. Treatment with Koselugo may increase the level of enzyme in your blood called creatine phosphokinase (CPK) and may be a sign of muscle damage. Your healthcare provider should do a blood test to check your blood levels of CPK before you start taking Koselugo and during treatment. Tell your healthcare provider right away if you get any of the following signs or symptoms:
  • muscle aches or pain
  • muscle spasms and weakness
  • dark, reddish urine

Your healthcare provider may change your dose, temporarily stop, or permanently ask you to stop taking Koselugo if you have any of these side effects.

The most common side effects of Koselugo are:

• vomiting
• stomach pain
• nausea
• dry skin
• feeling of tiredness, weakness or lacking energy
• muscle and bone pain
• fever
• inflammation of the mouth
• headache
• redness around the fingernails
• itching

These are not all the possible side effects of Koselugo.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA1088.

Recommended Dosage

The recommended dosage of Koselugo is 25 mg/m² orally twice daily (approximately every 12 hours) until disease progression or unacceptable toxicity.

Take Koselugo on an empty stomach. Do not consume food 2 hours before each dose or 1 hour after each dose. The recommended dose of Koselugo based on body surface area (BSA) is shown in Table 1.

Table 1 Recommended Dosage Based on Body Surface Area

Swallow Koselugo capsules whole with water. Do not chew, dissolve or open capsule.

Do not administer to patients who are unable to swallow a whole capsule.

Do not take a missed dose of Koselugo unless it is more than 6 hours until the next scheduled dose.

If vomiting occurs after Koselugo administration, do not take an additional dose, but continue with the next scheduled dose.

Dosage Modifications For Adverse Reactions

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

Table 2 Recommended Dose Reductions for Koselugo for Adverse Reactions

Dosage modifications for adverse reactions are in Table 3.

Table 3 Recommended Dosage Modifications for Koselugo for Adverse Reactions

Dosage Modifications For Hepatic Impairment

Reduce the recommended dosage of Koselugo to 20 mg/m² orally twice daily in patients with moderate hepatic impairment (Child-Pugh B). The recommended dosage of Koselugo for use in patients with severe hepatic impairment (Child-Pugh C) has not been established [see Use In Specific Populations].

Table 4 Recommended Dosage of Koselugo for Moderate Hepatic Impairment

Dosage Modifications For Drug Interactions

Strong Or Moderate CYP3A4 Inhibitors Or Fluconazole

Avoid coadministration of strong or moderate CYP3A4 inhibitors or fluconazole with Koselugo. If coadministration with strong or moderate CYP3A4 inhibitors or fluconazole cannot be avoided, reduce the Koselugo dosage as recommended in Table 5. After discontinuation of the strong or moderate CYP3A4 inhibitor or fluconazole for 3 elimination half-lives, resume the Koselugo dose that was taken prior to initiating the inhibitor or fluconazole.

Table 5 Recommended Dosage of Koselugo for Coadministration with Strong or Moderate CYP3A4 Inhibitors or Fluconazole

How should I take Koselugo?

• Take Koselugo exactly as your healthcare provider tells you to.
• Do not change your dose or stop taking Koselugo unless your healthcare provider tells you to.
• Your healthcare provider may change your dose, temporarily stop, or permanently stop treatment with Koselugo if you have side effects.
• Your healthcare provider will decide on the right dose of Koselugo based on your weight or size (body surface area) and how many capsules of Koselugo to take.
• Koselugo should be taken around the same time each day, about 12 hours apart.
• Take Koselugo on an empty stomach. Do not eat food for 2 hours before your dose and 1 hour after your dose.
• Swallow Koselugo capsules whole with water. Do not chew, dissolve, or open the capsules.
• If you miss a dose of Koselugo, take it as soon as you remember. If it is less than 6 hours before your next scheduled dose, take your next dose at your regular time. Do not make up for the missed dose.
• If you vomit at any time after taking Koselugo, do not take an additional dose. Take your next dose at your regular time.

What should I avoid while taking Koselugo?

• Do not drink grapefruit juice, eat grapefruit or take supplements that contain grapefruit or St. John’s Wort during treatment with Koselugo.

Effect of Other Drugs on Koselugo

Before taking Koselugo, tell your healthcare provider about all of your medical conditions, including if you:

• have heart problems.
• have eye problems.
• are pregnant or plan to become pregnant. Koselugo can harm your unborn baby.
  • Your healthcare provider should check to see if you are pregnant before you begin treatment with Koselugo.
  • Females who are able to become pregnant should use effective birth control (contraception) during treatment with Koselugo and for 1 week after your last dose.
  • Males with female partners who are able to become pregnant should use effective birth control (contraception) during treatment with Koselugo and for 1 week after your last dose.
  • Tell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment with Koselugo.
• are breastfeeding or plan to breastfeed. It is not known if Koselugo passes into your breast milk.
  • Do not breastfeed during treatment with Koselugo and for 1 week after your last dose.
  • Talk to your healthcare provider about the best way to feed your baby during this time.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, or herbal supplements. Especially tell your healthcare provider if you are taking aspirin, blood thinners, or other medicines to treat blood clots. Koselugo contains vitamin E, which may increase your risk of bleeding.