SPEXOTRAS 0.05 mg/mL ORAL SOLUTION POWDER

Introduction

Package Leaflet: Information for the Patient

Spexotras 0.05mg/ml powder for oral solution

trametinib

Read all of this leaflet carefully before your child starts taking this medicine, because it contains important information.

• Keep this leaflet, as you may need to read it again.
• If you have any further questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for your child only. Do not give it to others, as it may harm them, even if they have the same symptoms as your child.
• If your child experiences side effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this leaflet. See section 4.
• The information in this leaflet is for you or your child, but the leaflet will only say "your child".

Contents of the Package Leaflet

1. What is Spexotras and what is it used for
2. What you need to know before giving Spexotras
3. How to give Spexotras
4. Possible side effects
5. Storage of Spexotras
6. Contents of the pack and further information

1. What is Spexotras and what is it used for

Spexotras is a medicine that contains the active substance trametinib.

It is used in combination with another medicine (dabrafenib dispersible tablets) in children from 1 year of age to treat a type of brain tumor called glioma.

Spexotras may be used in patients with:

• low-grade glioma
• high-grade glioma when the patient has received at least one treatment with radiation and/or chemotherapy.

Spexotras, in combination with dabrafenib dispersible tablets, is used to treat patients whose brain tumor has a specific mutation (change) in a gene called BRAF. This mutation causes the body to produce defective proteins that, in turn, can cause the development of the tumor. The doctor will assess this mutation before starting treatment.

In combination with dabrafenib, Spexotras targets these defective proteins and slows down or stops the development of the tumor. Also, read the package leaflet of dabrafenib dispersible tablets.

2. What you need to know before giving Spexotras

Do not give Spexotras

• if your child is allergicto trametinib or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

Consult your doctor before starting to give Spexotras. The doctor needs to know if your child:

• has heart problemssuch as heart failure or problems with the way the heart beats.
• has or has ever had lung or breathing problems, such as difficulty breathing often accompanied by dry cough, shortness of breath, and fatigue.
• has eye problems, such as blockage of the veins that supply the eye (retinal vein occlusion) or swelling of the eye that may be due to fluid loss (chorioretinopathy).
• has or has had liver problems.
• has or has ever had kidney problems
• has or has had gastrointestinal problemssuch as diverticulitis (inflamed bags in the colon) or metastases in the gastrointestinal tract.

Before your child starts taking Spexotras, during, and after treatment, the doctor will perform checks to avoid complications.

Skin examination

Treatment may cause skin cancer. In general, these skin changes remain local and can be removed by surgery, and treatment can continue without interruption. The doctor may review your child's skin before and regularly during treatment.

Check your child's skin monthly during treatment and for 6 months after stopping this medicine and report to the doctoras soon as possible if you notice any changes in your child's skin such as a new wart, skin sore, or a reddish lump that bleeds or does not heal, or a change in the size or color of a mole.

Tumor lysis syndrome

If your child experiences the following symptoms, report to the doctor immediately, as it may be a potentially life-threatening condition: nausea, difficulty breathing, irregular heartbeats, muscle cramps, seizures, cloudy urine, decreased urine production, and fatigue. These may be caused by a group of metabolic complications that can occur during cancer treatment and are caused by the breakdown products of dying cancer cells (tumor lysis syndrome or TLS) and can cause changes in kidney function (see also section 4).

Childrenunder 1year of age

Spexotras in combination with dabrafenib dispersible tablets has not been evaluated in children under 1 year of age. Therefore, Spexotras is not recommended in this age group.

Patient over 18years of age

Information on treatment in patients over 18 years of age with glioma is limited, so the doctor must assess the continuation of treatment until adulthood.

Other medicines andSpexotras

Before starting treatment, tell your doctor, pharmacist, or nurse if your child is taking, has recently taken, or might take any other medicines, including medicines used to thin the blood or any other medicine obtained without a prescription.

Pregnancy,breast-feeding, and fertility

Pregnancy

• If your daughter is pregnant or thinks she may be pregnant, consult your doctor or nurse before using this medicine. Spexotras may harm the fetus.
• If your daughter becomes pregnant while taking this medicine, consult your doctor immediately.

Breast-feeding

It is not known if Spexotras can pass into breast milk. If your daughter is breast-feeding or plans to breast-feed, she must tell her doctor. You, your daughter, and the doctor will decide whether to take Spexotras or breast-feed.

Fertility

Spexotras may affect fertility in both males and females.

Taking Spexotras with dabrafenib dispersible tablets: Dabrafenib may reduce sperm count and may not return to normal levels until after stopping treatment with dabrafenib.

Before starting treatment with dabrafenib dispersible tablets, talk to your doctor about options to improve the chances of your child having children in the future.

Contraception

• If your daughter can become pregnant, she must use a reliable method of birth control (contraceptive) while taking Spexotras and for at least 16 weeks after stopping it.
• Hormonal birth control methods (such as the pill, injections, or patches) may not be as effective when taking Spexotras in combination with dabrafenib dispersible tablets. Therefore, while taking this combination of medicines, your daughter needs to use another effective birth control method to avoid becoming pregnant. Consult your doctor or nurse.

Driving and using machines

Spexotras may cause side effects that can affect your child's ability to drive, ride a bike/motorcycle, use machines, or participate in other activities that require being alert. If your child has vision problems or feels dizzy or weak, or feels a lack of energy, they should avoid such activities.

The description of side effects can be found in section 4. For more information, read the entire package leaflet.

If you are unsure, talk to your doctor, pharmacist, or nurse. Your child's ability to perform these activities may also be affected by their own illness, symptoms, or treatment.

Spexotras contains a cyclodextrin

This medicine contains 100 mg of a cyclodextrin in each ml of Spexotras oral solution.

Spexotras contains methyl parahydroxybenzoate

It may cause allergic reactions (possibly delayed).

Spexotras contains sodium

This medicine contains 1.98 mg of sodium (main component of table/cooking salt) in each ml of Spexotras oral solution. This is equivalent to 4% of the maximum recommended daily intake of sodium for an adult at the maximum daily dose of trametinib.

Spexotras contains potassium

This medicine contains potassium, less than 1 mmol (39 mg) per maximum daily dose; this is, essentially "potassium-free".

3. How to give Spexotras

Follow exactly the administration instructions of this medicine to your child as indicated by the doctor, pharmacist, or nurse. In case of doubt, consult the doctor, pharmacist, or nurse again.

How much to give

The doctor will decide the correct dose of Spexotras based on your child's body weight.

The doctor will decide if your child needs to take a lower dose according to the side effects they have.

How to give it

Read the instructions for use at the end of this leaflet for more information on how to give the oral solution. Your pharmacist will prepare the oral solution for you.

• Give Spexotras once a day. Giving Spexotras at the same time every day will help you remember when to give the medicine. Give Spexotras eitherwith the morning orevening dose of dabrafenib dispersible tablets. The doses of dabrafenib should be given with a difference of about 12 hours.
• Give Spexotras on an empty stomach, at least 1 hour before or 2 hours after a meal, which means:
• • after taking Spexotras, your child must wait at least 1hourbefore eating.
  • after eating, your child must wait at least 2hoursbefore taking Spexotras.
  • if necessary, breast milk and/or formula can be given on demand.

If you give moreSpexotrasthan you should

If you give too much Spexotras, contact your doctor, pharmacist, or nurse immediately. If possible, show them the Spexotras packaging with the package leaflet.

If you forget to give Spexotras

If it has been less than 12 hours since the missed dose, give it as soon as you remember.

If it has been 12 hours or more since the missed dose, do not make up for the missed dose. Give the next dose at the usual time and then continue giving Spexotras at the usual time.

Do not give a double dose to make up for missed doses.

If your child vomits after taking Spexotras

If your child vomits after taking Spexotras, do not give another dose until the next scheduled dose.

If you interrupt treatment with Spexotras

Give Spexotras for the time your doctor has indicated. Do not interrupt treatment unless your doctor tells you to.

If you have any other questions about the use of this medicine, ask your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Stop giving this medicine and seek urgent medical attention if your child has any of the following symptoms:

• coughing up blood, blood in the urine, vomiting blood, or if the vomit looks like "coffee grounds", or if they have black, tarry stools. These may be signs of bleeding.
• fever (temperature of 38°C or higher).
• chest pain or difficulty breathing, sometimes with fever or cough. These may be signs of pneumonitis or inflamed lungs (interstitial lung disease).
• blurred vision, loss of vision, or other changes in vision. These may be signs of retinal detachment.
• redness of the eyes, eye pain, increased sensitivity to light. These may be signs of uveitis.
• unexplained muscle pain, muscle cramps, or muscle weakness, dark urine. These may be signs of rhabdomyolysis.
• severe abdominal pain. This may be a sign of pancreatitis.
• fever, swollen lymph nodes, bruising, or a rash at the same time. These may be signs of a condition in which the immune system produces too many cells that fight infections, which can cause various symptoms (hemophagocytic lymphohistiocytosis).
• nausea, difficulty breathing, irregular heartbeats, muscle cramps, seizures, cloudy urine, decreased urine production, and fatigue. These may be signs of a condition resulting from the rapid breakdown of cancer cells that in some people can be life-threatening (tumor lysis syndrome or TLS).
• red patches on the trunk, circular or target-like, with or without central blisters, skin peeling, ulcers in the mouth, throat, nose, genitals, and eyes. These may be signs of severe skin reactions that can be life-threatening and may be preceded by fever and flu-like symptoms (Stevens-Johnson syndrome), widespread rash, fever, and swollen lymph nodes (DRESS).

Other possible side effects

Very common(may affect more than 1 in 10 people)

• headache
• dizziness
• cough

• diarrhea, feeling sick (nausea), being sick (vomiting), constipation, stomach pain

• skin problems such as rash, acne-like rash, dry skin or itchy skin, redness of the skin
• warty growths (cutaneous papilloma)
• infection of the skin under the nails
• pain in arms or legs or joints
• lack of energy or feeling weak or tired
• weight gain
• infections of the upper respiratory tract with symptoms such as sore throat and nasal congestion (nasopharyngitis)

• increased liver enzymes in blood tests
• low levels of white blood cells (neutropenia, leucopenia)
• low levels of red blood cells (anemia)

Common(may affect up to 1 in 10 people)

• frequent urination with pain or burning (urinary tract infection)
• skin effects including skin infection (cellulitis), inflammation of the hair follicles in the skin, inflamed and peeling skin (generalized exfoliative dermatitis), thickening of the outer layer of the skin (hyperkeratosis)
• decreased appetite
• low blood pressure (hypotension)
• high blood pressure (hypertension)
• shortness of breath
• mouth ulcers or mouth pain, inflammation of the mucous membranes
• inflammation of the fatty tissue under the skin (panniculitis)
• unusual hair loss or thinning hair
• redness, pain in hands and feet (hand-foot syndrome)
• muscle spasms
• chills
• allergic reaction (hypersensitivity)
• dehydration
• vision problems including blurred vision

• slow heart rate (bradycardia)
• fatigue, chest discomfort, feeling dizzy, palpitations (reduced ejection fraction)
• localized swelling of the tissues (edema)

• muscle pain (myalgia)
• fatigue, chills, sore throat, joint or muscle pain (flu-like illness)
• abnormal test results related to creatine phosphokinase, an enzyme found mainly in the heart, brain, and skeletal muscle
• increased blood sugar levels
• low sodium or phosphate levels in the blood
• decreased platelet count in the blood (cells that help blood clot)
• increased sensitivity of the skin to the sun

Uncommon(may affect up to 1 in 100 people)

• irregular heartbeats (atrioventricular block)
• inflammation of the intestines (colitis)
• cracked skin
• night sweats
• excessive sweating
• purple-colored skin patches, painful, itchy, or blistering, mainly on the arms, legs, face, and neck, with fever (signs of acute febrile neutrophilic dermatosis)

In addition to the side effects described above, the following side effects have only been reported so far in adult patients, but may also occur in children:

• nervous system problems that can cause pain, loss of sensation, or tingling in the hands and feet and/or muscle weakness (peripheral neuropathy)
• dry mouth
• kidney failure
• benign skin tumor (acrocordon)
• inflammatory disease that mainly affects the skin, lungs, eyes, and lymph nodes (sarcoidosis)
• kidney inflammation
• hole (perforation) in the stomach or intestines
• inflammation of the heart muscle that can cause difficulty breathing, fever, palpitations, and chest pain

Reporting of side effects

If your child experiences any side effects, talk to your doctor, pharmacist, or nurse, even if they are not listed in this leaflet. You can also report them directly through the national reporting system listed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Spexotras

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the label of the vial and on the carton, after EXP. The expiry date refers to the last day of the month stated.

Store in the original packaging to protect from light and moisture.

Before reconstitution: Store in a refrigerator (between 2 °C and 8 °C).

After reconstitution: Store below 25 °C. Do not freeze. Discard any unused solution after 35 days following reconstitution.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the pack and further information

Composition ofSpexotras

• The active substance is trametinib. One vial contains trametinib dimethyl sulfoxide equivalent to 4.7 mg of trametinib. Each ml of reconstituted solution contains 0.05 mg of trametinib.
• The other ingredients are: sulfobutyl ether beta-cyclodextrin sodium (see section 2), sucralose (E 955), citric acid monohydrate (E 330), disodium phosphate (E 339) (see section 2), potassium sorbate (E 202) (see section 2), methyl parahydroxybenzoate (E 218) (see section 2), and strawberry flavor.

Appearance and packaging of the product

Spexotras 0.05 mg/ml powder for oral solution is a white or almost white powder.

Spexotras is supplied in a 180 ml amber glass vial with a child-resistant screw cap, containing 12 g of powder. Each carton contains one vial, a pressure adapter for the vial, and a 20 ml reusable oral syringe with graduated markings of 0.5 ml.

Marketing authorisation holder

Novartis Europharm Limited

Vista Building

Elm Park, Merrion Road

Dublin 4

Ireland

Manufacturer

Sandoz S.R.L.

Str. Livenzeni nr.7A

540472 Targu Mures

Romania

Novartis Pharma GmbH

Roonstrasse 25

90429 Nuremberg

Germany

Novartis Farmacéutica S.A.

Gran Via de les Corts Catalanes 764

08013 Barcelona

Spain

Novartis Pharma GmbH

Sophie-Germain-Strasse 10

90443 Nürnberg

Germany

You can request more information about this medicine from the local representative of the marketing authorisation holder:

Date of last revision of this prospectus:

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency website: https://www.ema.europa.eu.

This information is intended only for the pharmacist:

Reconstitution instructions (for pharmacist only):

1. Wash and dry your hands.
2. Check the expiry date of the powder in the vial.
3. Gently tap the vial to loosen the powder.
4. Remove the cap and add 90 ml of distilled or purified water to the powder in the vial.
5. Replace the cap and invert the vial repeatedly for up to 5 minutes until completely dissolved. You can also shake gently.
6. Separate the adapter from the vial and the oral syringe. Remove the cap from the vial and insert the adapter into the neck of the vial. Press firmly until the adapter is fully inserted. The adapter should be fully flush with the neck of the vial.
7. Record the preparation date on the carton. The solution expires 35 days after preparation.
8. Inform the recipient of the dose and the date the solution was prepared.

INSTRUCTIONS FOR USE

Ask your healthcare professional or pharmacist to show you how to use Spexotras correctly. Follow exactly the administration instructions of Spexotras indicated by your healthcare professional or pharmacist.

If you have any doubts about how to use Spexotras, consult your healthcare professional or pharmacist.