Spexotras 0.05 mg/ml powder for oral solution

Package leaflet: Information for the patient

Introduction

Package leaflet: information for the patient

Spexotras 0.05 mg/ml powder for oral solution

trametinib

Read the entire 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 questions, consult the doctor, pharmacist, or nurse.
• This medicine has been prescribed for your child only, and you should not give it to other people, even if they have the same symptoms as your child, as it may harm them.
• If your child experiences any adverse effects, consult the doctor, pharmacist, or nurse, even if they are adverse effects not listed in this leaflet. See section 4.
• The information in this leaflet is intended for you or your child, but throughout the leaflet, it will refer only to "your child".

Contents of the leaflet

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

1. What Spexotras is and what it is 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 tumour called glioma.

Spexotras may be used in patients with:

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

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

In combination with dabrafenib, Spexotras targets these faulty proteins and slows down or stops tumour progression. Also read the package leaflet for dabrafenib dispersible tablets.

2. What you need to know before starting Spexotras

Do not give Spexotras

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

Warnings and precautions

Talk to the doctor before starting Spexotras. The doctor needs to know if your child:

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

Before your child starts taking Spexotras, during and after treatment, the doctor will carry out checks to prevent complications.

Skin examination

Treatment may cause skin cancer. In general, these skin changes remain localized and can be removed by surgery, and treatment can continue without interruption. The doctor may examine 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. Tell the doctor as soon as possible if you notice any changes in your child's skin, such as a new wart, a sore on the skin, or a red bump that bleeds or does not heal, or a change in the size or color of a mole.

Tumour lysis syndrome

If your child experiences the following symptoms, tell the doctor immediately, as this may be a potentially life-threatening condition: nausea, difficulty breathing, irregular heartbeat, muscle cramps, seizures, cloudy urine, reduced urine output, 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 (tumour lysis syndrome or TLS), which may lead to changes in kidney function (see also section 4).

Children under 1 year 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.

Patients over 18 years of age

Information on treatment in patients over 18 years of age with glioma is limited, so the doctor must evaluate whether treatment should continue into adulthood.

Other medicines and Spexotras

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

Pregnancy, breastfeeding and fertility

Pregnancy

• If your daughter is pregnant or you think she might be pregnant, consult the doctor or nurse before using this medicine. Spexotras could harm the unborn baby.
• If your daughter becomes pregnant while taking this medicine, consult the doctor immediately.

Breastfeeding

It is unknown whether Spexotras passes into breast milk. If your daughter is breastfeeding or planning to breastfeed, she must inform the doctor. You, your daughter, and the doctor will decide whether to take Spexotras or breastfeed.

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 the doctor about options to improve the chances that your child may have children in the future.

Contraception

• If your daughter could become pregnant, she must use a reliable method of birth control (contraception) while taking Spexotras and for at least 16 weeks after stopping it.
• Hormonal contraceptive methods (such as the pill, injections, or patches) may be less effective while taking Spexotras in combination with dabrafenib dispersible tablets. Therefore, while taking this combination of medicines, she needs to use another effective method of contraception to prevent pregnancy. Consult the doctor or nurse.

Driving and using machines

Spexotras may cause side effects that could affect your child's ability to drive, ride a bicycle/motorcycle, use machinery, or participate in other activities requiring alertness. If your child has vision problems or feels tired, weak, or lacks energy, they should avoid such activities.

A description of the side effects can be found in section 4. For more information, read all of this leaflet.

If you are unsure, speak with the doctor, pharmacist, or nurse. Your child's ability to perform such activities may also be affected by their 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 (a main component of table/cooking salt) in each ml of Spexotras oral solution. This corresponds to 4% of the maximum daily recommended sodium intake for an adult at the maximum daily dose of trametinib.

Spexotras contains potassium

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

3. How to give Spexotras

Follow exactly the instructions given by the doctor, pharmacist, or nurse on how to administer this medicine to your child. If in doubt, consult again with the doctor, pharmacist, or nurse.

How much to give

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

The doctor will decide whether your child needs to take a lower dose depending on any side effects they may experience.

How to give it

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

• Give Spexotras once daily. Giving Spexotras at the same time every day will help you remember when to administer the medicine. Administer Spexotras either with the morning dose or with the evening dose of dabrafenib dispersible tablets. Doses of dabrafenib should be given approximately 12 hours apart.
• Give Spexotras on an empty stomach, at least 1 hour before or 2 hours after a meal, meaning:
  • after taking Spexotras, your child should wait at least 1 hour before eating.
  • after eating, your child should wait at least 2 hours before taking Spexotras.
  • if necessary, breastfeeding and/or formula feeding may be given on demand.

If you give more Spexotras than you should

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

If you forget to give Spexotras

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

If 12 hours or more have passed 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 regular 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 stop treatment with Spexotras

Give Spexotras for as long as the doctor has instructed. Do not stop treatment unless told to do so by the doctor.

If you have any further 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 everyone 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 vomit that looks like “coffee grounds”, passing red stools or black, tar-like 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 rash occurring at the same time. These may be signs of a condition in which the immune system produces too many infection-fighting cells, which can cause various symptoms (hemophagocytic lymphohistiocytosis).
• Nausea, difficulty breathing, irregular heartbeat, muscle cramps, seizures, cloudy urine, reduced urine output, and fatigue. These may be signs of a condition caused by the rapid breakdown of cancer cells, which in some people can be fatal (tumour lysis syndrome or TLS).
• Reddish spots on the trunk, circular or target-like, with or without central blisters, skin peeling, mouth, throat, nose, genital or eye ulcers. These may be signs of serious skin rashes, which can be life-threatening and may be preceded by fever and flu-like symptoms (Stevens-Johnson syndrome), widespread rash, fever, and enlarged lymph nodes (DRESS).

Other side effects

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

• Headache

• Dizziness

• Cough

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

• Skin problems such as rash, acne-like rash, dry or itchy skin, redness of the skin

• Wart-like growths (cutaneous papilloma)

• Skin infection under the nails

• Pain in arms, legs or joints

• Lack of energy or feeling weak or tired

• Weight gain

• Upper respiratory tract infections 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 (anaemia)

Common (may affect up to 1 in 10 people)

• Frequent urination with pain or burning sensation (urinary tract infection)
• Skin effects including skin infection (cellulitis), inflammation of hair follicles on the skin, inflamed and peeling skin (generalised exfoliative dermatitis), thickening of the outer layer of skin (hyperkeratosis)
• Decreased appetite
• Low blood pressure (hypotension)
• High blood pressure (hypertension)
• Shortness of breath
• Mouth ulcers or pain, inflammation of the mucosa
• Inflammation of the fatty layer 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)
• Chest discomfort, fatigue, dizziness, palpitations (reduced ejection fraction)
• Localised swelling of tissues (oedema)
• 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 levels of sodium or phosphate in the blood
• Decreased platelet count in the blood (cells that help blood to clot)
• Increased sensitivity of the skin to sunlight

Uncommon (may affect up to 1 in 100 people)

• Nerve problems that may cause pain, loss of sensation or tingling in the hands and feet and/or muscle weakness (peripheral neuropathy)
• Inflammation of the intestines (colitis)
• Cracked skin
• Night sweats
• Excessive sweating
• Raised, painful, red to dark purple skin spots or sores appearing mainly on arms, legs, face and neck, with fever (signs of acute febrile neutrophilic dermatosis)

In addition to the side effects listed above, the following side effects have so far only been reported in adult patients, although they could also occur in children:

• Nerve problems that may cause pain, loss of sensation or tingling in the hands and feet and/or muscle weakness (peripheral neuropathy)
• Dry mouth
• Kidney failure
• Benign skin tumour (acrochordon)
• Inflammatory disease mainly affecting the skin, lungs, eyes, and lymph nodes (sarcoidosis)
• Inflammation of the kidneys
• Hole (perforation) in the stomach or intestines
• Inflammation of the heart muscle which may cause difficulty breathing, fever, palpitations, and chest pain
• Localised skin reactions at tattoo sites

Reporting of side effects

If your child experiences any side effects, talk to your doctor, pharmacist, or nurse, even if it is a possible side effect 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 stated on the label of the vial and on the outer packaging, after EXP. The expiry date refers to the last day of the month indicated.

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 and packaging that you no longer need. This will help protect the environment.

6. Contents of the container and additional information

Composition of Spexotras

• 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 components are: sodium sulfobutyletherbeta-cyclodextrin (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), methylparaben (E 218) (see section 2), and strawberry flavouring.

Appearance of the product and contents of the container

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

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

Marketing Authorization Holder

Novartis Europharm Limited
Vista Building
Elm Park, Merrion Road
Dublin 4
Ireland

Manufacturer

Novartis Pharmaceuticals S.R.L.
Str. Livezeni nr.7A
540472 Targu Mures
Romania

Novartis Farmacéutica S.A.
Gran Via de les Corts Catalanes 764
08013 Barcelona
Spain

Novartis Pharma GmbH
Sophie-Germain-Strasse 10
90443 Nuremberg
Germany

For further information about this medicinal product, please contact the local representative of the Marketing Authorization Holder:

Date of the most recent review of this leaflet:

Other sources of information

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

This information is intended for the pharmacist only:

Instructions for reconstitution (for the pharmacist only):

1. Wash and dry 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. Alternatively, gently shake.

Note: It is possible that white floating particles inherent to the product may be visible in the final reconstituted solution.

1. Separate the bottle adapter from the oral syringe. Remove the cap from the bottle and insert the bottle adapter into the neck of the bottle. Press firmly until the bottle adapter is fully inserted. The bottle adapter must be flush with the neck of the bottle.
2. Record the preparation date on the carton. The solution expires 35 days after preparation.
3. Inform the recipient about 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. Always follow exactly the instructions for administering Spexotras given by the healthcare professional or pharmacist.

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