Selumetinib

Selumetinib (Koselugo) is used to treat neurofibromatosis type 1 (NF1) in adults and children 1 year and older with plexiform neurofibromas that cause symptoms and cannot be completely removed by surgery. It is taken twice a day.

Selumetinib gained FDA approval on April 10, 2020. There is no generic selumetinib; it is only available under the brand name Koselugo.

Take or give selumetinib (Koselugo) exactly as your healthcare provider tells you to.

• Do not change your dose or stop taking selumetinib unless your healthcare provider tells you to.
• Your healthcare provider will decide on the right dose of selumetinib based on your or your child’s weight or size (body surface area).
• Take or give selumetinib 2 times a day, about 12 hours apart.

Selumetinib (Koselugo) comes in capsules and oral granules.

• If your healthcare provider prescribes selumetinib capsules: Take selumetinib capsules with or without food. Swallow selumetinib capsules whole. Do not open, chew, or crush the capsules. Tell your healthcare provider if you or your child has trouble swallowing capsules.
• If your healthcare provider prescribes selumetinib oral granules: See the Instructions for Use for the instructions on how to prepare and take or give selumetinib oral granules. Prepare selumetinib oral granules by carefully opening the capsule and sprinkling all of the oral granules on a small amount (about 1 to 3 teaspoons) of smooth yogurt, or fruit puree containing the following fruits: apple, banana, pear, or strawberry. Take or give the selumetinib oral granules and food mixture within 30 minutes of preparing the dose. If the prepared dose of selumetinib oral granules and food mixture is not taken or given within 30 minutes, do not take or give the prepared dose. Throw away the mixture and prepare a new dose. If part of a dose is taken or given within 30 minutes of preparing, throw away the remainder of the mixture and do not prepare a new dose. Take or give the full dose within 30 minutes next time. The selumetinib (Koselugo) oral granules should flow freely. Do not use if the oral granules are clumped or stuck inside the capsule shell. Contact your pharmacy if this happens. Throw away the empty capsule shells after use. Do not swallow, chew, or dissolve the capsule shells of selumetinib oral granules. Do not chew or crush the selumetinib oral granules. Do not add oral granules to liquids. Do not mix selumetinib oral granules in grapefruit or any juice, fruit puree, or jam containing Seville oranges.

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

• have heart problems.
• have eye problems.
• have liver problems.
• are pregnant or plan to become pregnant,
• are breastfeeding or plan to breastfeed.

It is not known if selumetinib is safe and effective in children under 1 year of age.

Pregnancy

Selumetinib can harm an unborn baby. Your healthcare provider should check to see if you are pregnant before you begin treatment with selumetinib. Females who can become pregnant should use effective birth control (contraception) during treatment with selumetinib and for 1 week after their last dose.

Males with female partners who can become pregnant should use effective birth control (contraception) during treatment with selumetinib and for 1 week after their last dose.

Tell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment with this treatment.

Breastfeeding

It is not known if selumetinib passes into your breast milk. Do not breastfeed during treatment with selumetinib and for 1 week after your last dose. Talk to your healthcare provider about the best way to feed your baby during this time.

Common Side Effects

The most common side effects of selumetinib in children are:

• Vomiting
• Diarrhea
• Increased levels of an enzyme called creatine phosphokinase (CPK) in your blood
• Dry skin
• Redness around the fingernails
• Nausea
• Skin bumps that look like acne
• Fever.

The most common side effects of selumetinib in adults are:

• Rash
• Diarrhea
• Skin bumps that look like acne (dermatitis acneiform).

Serious side effects and warnings

Selumetinib may cause the following serious side effects.

Heart problems

Selumetinib 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 selumetinib 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

Selumetinib can cause eye problems that can lead to blindness, including retinal vein occlusion (RVO) and retinal pigment epithelial detachment (RPED). Your healthcare provider will check your vision before and during treatment with selumetinib. 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.

Stomach, Intestine, and Mouth (Gastrointestinal) Problems

Selumetinib can cause diarrhea, vomiting, nausea, and mouth sores. Diarrhea can be severe with selumetinib. Tell your healthcare provider right away the first time that you get diarrhea during treatment. Your healthcare provider may give you medicine to help control your diarrhea and may tell you to drink more fluids.

Skin Problems

Selumetinib can cause severe skin rashes. Tell your healthcare provider if you get any of the following signs of skin problems:

• A rash that covers a large area of your body
• Flat skin rash
• Raised bumps on your skin
• Skin bumps that look like acne
• Blisters
• Peeling skin
• Itchy rash
• Hair thinning or hair loss (alopecia).

Increased Level of an Enzyme Called Creatine Phosphokinase (CPK) in Your Blood and Muscle Problems

Selumetinib can cause severe muscle problems. Treatment with selumetinib may increase the level of an enzyme in your blood called creatine phosphokinase (CPK), which may be a sign of muscle damage. Increased levels of CPK in the blood are common during treatment with selumetinib and can also be severe. Your healthcare provider should do a blood test to check your blood levels of CPK before and during treatment with selumetinib. Tell your healthcare provider right away if you get any of the following signs or symptoms:

• Muscle aches or pain
• Dark reddish urine
• Muscle spasms and weakness.

Notes:

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

These are not all of the possible side effects of selumetinib. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Selumetinib works by blocking proteins called MEK1/2, part of a cellular signaling chain (the RAS-RAF-MEK-ERK pathway), which is often overactive in cancers. This pathway helps tumors to grow.

In mice genetically engineered to develop neurofibromas similar to those in people with NF1 (neurofibromatosis type 1), selumetinib stopped the pathway's signals and reduced the number, size, and growth of these benign tumors. This suggests it could work similarly in humans with NF1.

Selumetinib (Koselugo) belongs to the drug class called kinase inhibitors.

Adult and Pediatric Dose of Selumetinib Capsules for NF1

• 25 mg/m² orally twice daily
• Take with or without food.
• Swallow whole. Do NOT open, chew, or crush.

Adult and Pediatric Dose of Selumetinib Oral Granules for NF1

• Equivalent to 25 mg/m² orally twice daily.
• Sprinkle onto or mix with soft food.

Note: The healthcare team will determine the exact amount of granules needed.

Adult and Pediatric Dose of Selumetinib Oral Granules for NF1 (Hepatic Impairment)

• Moderate (Child-Pugh B): 20 mg/m² twice daily
• Severe (Child-Pugh C): Dosage not established

Adult and Pediatric Dose of Selumetinib Oral Granules for NF1 (Strong or Moderate CYP3A4 inhibitors or fluconazole)

• Reduce the dose as per the Prescribing Information instructions.

Avoid St John’s wort, grapefruit or grapefruit juice, and Seville orange during treatment with selumetinib.

If you or your child misses a dose of selumetinib capsules or selumetinib oral granules, take or give the dose as soon as you remember, unless the next dose is due within 6 hours.

• If your scheduled dose is due within 6 hours, skip the dose and take or give the next dose at the regular time. Do not take two doses at one time.

If you or your child vomits after taking a dose of selumetinib capsules or selumetinib oral granules, do not take an additional dose. Take the next dose at the regular scheduled time.

If you or your child takes too much selumetinib, call your healthcare provider, seek emergency medical attention, or call the Poison Help line at 1-800-222-1222.

In the SPRINT clinical trial (NCT01362803), 66% (33/50) of children and tweens taking selumetinib saw their plexiform shrink by at least 20%. Results were seen as early as 3.3 months into treatment. 64% maintained that response for 3+ years.

In the KOMET clinical trial (NCT04924608), 20% of adults saw their plexiform shrink by at least 20% with selumetinib compared with 5% taking placebo. 86% sustained response for 6+ months with safety consistent with pediatric data.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Especially tell your healthcare provider if you are taking:

• Aspirin
• Blood thinners, or other medicines to treat blood clots
• Supplements containing Vitamin E.

Selumetinib contains vitamin E, which may increase your risk of bleeding.

This is not a complete list of interactions. See the Koselugo (selumetinib) Prescribing Information for more information.

Store capsules and granules at room temperature between 68°F and 77°F (20°C and 25°C) away from moisture and heat. Do not store selumetinib oral granules above 86°F (30°C).

• If the temperature is above 86°F (30°C), store selumetinib oral granules in the refrigerator between 36°F to 46°F (2°C to 8°C).
• Selumetinib oral granules may clump together or stick to the capsule shell if the medicine gets too hot, and you may not get your full dose.
• Keep Selumetinib oral granules cold in a cooler bag with a cold pack if you need to take them anywhere.

The bottle of selumetinib capsules and granules contains a desiccant packet to reduce moisture. Do not throw away the desiccant packet. Keep the capsules and granules in their original bottle. Keep the bottle tightly closed.

Keep out of the reach of children.

Selumetinib is only available as Koselugo capsules and granules.

Active ingredient: selumetinib.

Capsule inactive ingredients:

• The 10 mg and 25 mg capsules contain: vitamin E polyethylene glycol succinate.
• Capsule shell (10 mg): carnauba wax, carrageenan, hypromellose, potassium chloride, purifiedwater, and titanium dioxide.
• Capsule printing ink (10 mg): ammonium hydroxide, iron oxide black, propylene glycol, and shellac.
• Capsule shell (25 mg): carnauba wax and/or corn starch, carrageenan, FD&C blue 2, ferric oxideyellow, hypromellose, potassium chloride, purified water, and titanium dioxide.
• Capsule printing ink (25 mg): carnauba wax, FD&C Blue 2 aluminum lake, ferric oxide red, ferric oxide yellow, glyceryl monooleate, and shellac.

Oral granules inactive ingredients:

• The 5 mg and 7.5 mg uncoated cores contain: glyceryl dibehenate and stearoyl polyoxylglycerides.
• The 5 mg and 7.5 mg granule coatings contain: acetone, hypromellose acetate succinate, and stearic acid.
• The 5 mg shell contains: ferric oxide yellow, hypromellose, and titanium dioxide.
• The 5 mg printing ink contains: butyl alcohol, dehydrated alcohol, ferric oxide black, isopropyl alcohol,potassium hydroxide, propylene glycol, purified water, shellac, and strong ammonia solution.
• The 7.5 mg shell contains: ferric oxide red, hypromellose, and titanium dioxide.
• The 7.5 mg printing ink contains: butyl alcohol, dehydrated alcohol, ferric oxide black, isopropyl alcohol, potassium hydroxide, propylene glycol, purified water, shellac, and strong ammonia solution.

Company

Selumetinib is distributed by AstraZeneca Pharmaceuticals LP, Wilmington, DE 19850.