BALVERSA 4 mg FILM-COATED TABLETS

2. What you need to know before you take Balversa

Do not take Balversa

• if you are allergic to erdafitinib or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

Tell your doctor before starting Balversa if:

• you have high levels of phosphate in your blood
• you have eye or vision problems
• you are pregnant
• you are a woman who can become pregnant

Eye problems

Balversa increases the risk of a condition called central serous retinopathy (CSR; a disease where fluid builds up and separates the macula, the central part of the retina at the back of the eye, causing blurred and distorted vision). The risk of CSR is higher in people 65 years and older.

• Before starting treatment with Balversa, you will have a thorough eye exam, including tests to check your vision, retina, and eye structure.
• Your doctor will closely monitor your eyes with monthly eye exams during the first 4 months of treatment and every 3 months thereafter.
• If you experience any abnormal vision symptoms, your doctor will do an urgent eye exam.
• Tell your doctor right away if you have any symptoms of CSR, such as blurred vision or reduced peripheral vision, a dark spot in central vision, distorted central vision where lines appear curved or bent, objects appear smaller or farther away than they are, colors appear faded, floaters or spots that move through your field of vision, flashes of light, or a feeling of looking through a curtain. See also section 4, under “Most important side effects”.
• If you experience CSR during treatment with Balversa, your doctor may need to temporarily stop your treatment. Your treatment will be permanently stopped if the symptoms do not resolve within 4 weeks or are very severe.

While taking Balversa, you should regularly use eye drops or gels to prevent and treat dry eyes.

High levels of phosphate in the blood (hyperphosphatemia)

Balversa may cause high levels of phosphate in the blood. This is a known side effect of Balversa that usually occurs in the first few weeks after starting treatment. This can lead to a buildup of minerals such as calcium in soft tissues, cutaneous calcinosis (a buildup of calcium in the skin, causing hard nodules and lumps), and non-uremic calcinosis (a rare skin disease that causes painful skin ulcers due to a buildup of calcium in blood vessels).

• Your doctor will monitor your phosphate levels in your blood during treatment. You may be advised to limit your intake of phosphate-rich foods and avoid taking other medicines that may increase phosphate levels.
• Vitamin D supplements are not recommended during treatment with Balversa, as they may also contribute to increased phosphate and calcium levels.
• If your phosphate levels in your blood are too high, your doctor may suggest taking a medicine to help control them.
• If you have high phosphate levels in your blood, your doctor may need to adjust your dose of Balversa or stop treatment with Balversa.
• Tell your healthcare provider right away if you experience any of the following symptoms, which may be signs of hyperphosphatemia:

• painful skin lesions
• muscle cramps
• numbness, or
• tingling around the mouth.

Skin disorders

While taking Balversa, you may experience itching, dryness, or redness of the skin, swelling, peeling, or pain to the touch, especially on the hands or feet (palmar-plantar erythrodysesthesia). You should monitor your skin and avoid unnecessary exposure to sunlight, excessive use of soap, and excessive bathing. You should use moisturizing products regularly and avoid perfumed products.

Photosensitivity

While taking Balversa, you may become more sensitive to sunlight. This can cause skin damage. You should be careful and take precautions when outdoors in the sun. Precautions may include wearing clothing that covers your skin and using sunscreens to protect yourself from harmful sun rays.

Nail disorders

While taking Balversa, you may experience separation of the nails from the nail bed, infection of the skin around the nails, or changes in nail color. You should monitor your nails for signs of infection and practice preventive nail care, such as maintaining good hygiene and using over-the-counter nail hardeners.

Mucosal disorders

While taking Balversa, you may experience dryness or sores in the mouth. You should practice good oral hygiene and avoid spicy or acidic foods while taking Balversa.

Children and adolescents

This medicine should not be used in children and adolescents as there is no experience with the use of Balversa in this age group.

Other medicines and Balversa

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines. Taking Balversa with other medicines may affect how Balversa works and may cause side effects.

The following medicines may reduce the effectiveness of Balversa by reducing the amount of Balversa in your blood:

• carbamazepine (used to treat epilepsy)
• rifampicin (used to treat tuberculosis)
• phenytoin (used to treat epilepsy)
• St. John's Wort (used to treat depression)

The following medicines may increase the risk of side effects of Balversa by increasing the amount of Balversa in your blood:

• fluconazole (used to treat fungal infections)
• itraconazole (used to treat fungal infections)
• ketoconazole (used to treat fungal infections)
• posaconazole (used to treat fungal infections)
• voriconazole (used to treat fungal infections)
• miconazole (used to treat fungal infections)
• ceritinib (used to treat lung cancer)
• clarithromycin (used to treat infections)
• telithromycin (used to treat infections)
• elvitegravir (used to treat HIV)
• ritonavir (used to treat HIV)
• paritaprevir (used to treat hepatitis)
• saquinavir (used to treat HIV)
• nefazodone (used to treat depression)
• nelfinavir (used to treat HIV)
• tipranavir (used to treat HIV)
• lopinavir (used to treat HIV)
• amiodarone (used to treat arrhythmias)
• piperine (used as a supplement)

Balversa may increase the risk of side effects of other medicines by increasing the amount of these medicines in your blood. These include:

• midazolam (used to treat seizures)
• hormonal contraceptives
• colchicine (used to treat gout)
• digoxin (used to treat certain arrhythmias or heart failure)
• dabigatran (used as an anticoagulant)
• apixaban (used as an anticoagulant)

Taking Balversa with food

Do not take Balversa with grapefruit or Seville oranges, which includes eating them, drinking their juice, or taking a supplement that may contain them. This is because they may increase the amount of Balversa in your blood.

Pregnancy, contraception, and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor beforetaking this medicine.

Information for women

• Pregnancy

• Balversa may harm your unborn baby.
• Do not take Balversa during pregnancy unless your doctor tells you to.
• Do not become pregnant during treatment with Balversa and for 1 month after the last dose of Balversa.
• Tell your doctor right away if you become pregnant.

• Pregnancy test

• Your doctor should do a pregnancy test before you start treatment with Balversa.

• Contraception

• Balversa may reduce the effectiveness of some contraceptive methods. Talk to your doctor about suitable contraceptive methods while taking Balversa. Women who can become pregnant should use highly effective contraceptive methods during treatment and for at least 1 month after treatment with Balversa.

• Breastfeeding

• Breastfeeding should be stopped during treatment with Balversa and for 1 month after the last dose of this medicine.

Information for men

Men should use effective contraception (condom) during treatment with Balversa and for 1 month after the last dose. Additionally, men should not donate or store sperm during treatment or for 1 month after the last dose.

Driving and using machines

Eye problems have been reported in patients treated with Balversa. If you have vision problems, do not drive or use tools or machines until your vision returns to normal.

Balversa contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per tablet; this is essentially “sodium-free”.

3. How to take Balversa

Take this medicine exactly as your doctor or pharmacist has told you. If you are not sure, ask your doctor or pharmacist.

How much to take

Your doctor will tell you how much to take and how often.

• The recommended starting dose of Balversa is 8 mg orally once a day.

• You may need to take one 5 mg tablet and one 3 mg tablet, or two 4 mg tablets to get this dose.

After about 2 weeks of treatment with Balversa, your doctor will do a blood test to check your phosphate levels in your blood.

• Based on the results of this blood test and whether or not you are experiencing side effects, your doctor may increase your dose to 9 mg per day.

Your doctor may also decide to reduce the dose if you experience certain side effects, such as mouth sores, redness, swelling, peeling, or pain to the touch, especially on the hands or feet, separation of the nails from the nail bed, high phosphate levels in the blood.

How to take this medicine

• Swallow the Balversa tablets whole.
• You can take this medicine with or without food.
• Try to take this medicine at the same time each day. This will help you remember to take it.
• If you vomit, do not take another tablet. Take your next dose at the usual time the next day.

If you take more Balversa than you should

If you take more Balversa than you should, call your doctor or go to the emergency room at your nearest hospital right away.

If you forget to take Balversa

• If you forget to take a dose, take it as soon as you remember that day. Take your usual dose of Balversa the next day.
• Do not take a double dose to make up for forgotten doses.

If you stop taking Balversa

Do not stop taking this medicine unless your doctor tells you to.

If you have any further questions on the use of this medicine, ask your doctor.

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people may experience them.

Most Important Adverse Effects

Inform your doctor immediately if you notice any of the following serious adverse effects:

Central Serous Retinopathy (very frequent:may affect more than 1 in 10 people)

The following symptoms may be signs of Central Serous Retinopathy:

• blurred vision or decreased peripheral vision (lateral)
• a dark spot in central vision
• distorted central vision, where lines may appear twisted or bent
• objects appear smaller or farther away than they actually are
• colors appear faded
• floaters or spots that cross your field of vision, flashes of light, or a sensation of looking through a curtain

Hyperphosphatemia (very frequent:may affect more than 1 in 10 people)

The following symptom may be a sign of hyperphosphatemia:

• high phosphate levels in the blood

Nail Disorders (very frequent:may affect more than 1 in 10 people)

The following symptoms may be signs of nail disorders:

• nails separating from the nail bed (onycholysis)
• infected skin around the nail (paronychia)
• nail malformation (nail disorder)
• change in nail color

Skin Disorders (very frequent:may affect more than 1 in 10 people)

The following symptoms may be signs of skin disorders:

• redness, swelling, scaling, or pain to the touch, especially on the hands or feet (palmar-plantar erythrodysesthesia)
• hair loss (alopecia)
• dry skin

Mucosal Disorders (very frequent:may affect more than 1 in 10 people)

The following symptoms may be signs of mucosal disorders:

• mouth sores (stomatitis)
• dry mouth

Inform your doctor immediately if you notice any of the above signs of central serous retinopathy, hyperphosphatemia, nail disorders, skin disorders, or mucosal disorders.

Your doctor may ask you to stop taking Balversa or refer you to a specialist if you experience eye or vision problems.

Other adverse effects may occur with the following frequencies:

Very frequent(may affect more than 1 in 10 people):

• diarrhea
• decreased appetite
• alteration of taste with a metallic, sour, or bitter taste of food (dysgeusia)
• weight loss
• constipation
• feeling of dizziness (nausea)
• vomiting
• stomach pain
• dry eye
• feeling of weakness and great fatigue
• low sodium levels in the blood (hyponatremia)
• elevated creatinine levels in the blood (elevated creatinine)
• elevated levels of the liver enzyme alanine aminotransferase in the blood (elevated ALT)
• elevated levels of the liver enzyme aspartate aminotransferase in the blood (elevated AST)
• low red blood cell count (anemia)
• nasal bleeding (epistaxis)

Frequent(may affect up to 1 in 10 people):

• painful nails
• formation of ridges on the nails or nail breakage
• very dry skin
• cracked, thickened, or scaly skin
• itching or itchy skin rash (eczema)
• abnormal growth or appearance of the skin
• skin rash
• dry or inflamed eyes (conjunctivitis)
• ulcers or inflammation of the front of the eye (cornea)
• cloudy vision (cataract)
• red and swollen eyelids
• excessive tearing
• high calcium levels in the blood
• low phosphate levels in the blood
• nasal dryness
• indigestion (dyspepsia)
• sudden decrease in kidney function
• high levels of parathyroid hormone (PTH) (hyperparathyroidism)
• kidney failure
• kidney problems (renal dysfunction)
• liver damage (hepatic cytolysis)
• abnormal liver function
• high bilirubin levels in the blood

Uncommon(may affect up to 1 in 100 people):

• bleeding under the nail
• discomfort or pain in the nails
• skin reaction
• thinning of the skin
• redness of the palms of the hands
• dryness of membranes (including nose, mouth, eyes, vagina)
• calcium deposits in blood vessels that can cause blood clots, skin ulcers, and serious infections

Inform your doctor if you experience any of the above adverse effects.

Reporting Adverse Effects

If you experience any type of adverse effect, consult your doctor, even if it is a possible adverse effect that is not listed in this leaflet. You can also report them directly through the national reporting system included in Appendix V. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of Balversa

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

Do not use this medicine after the expiration date that appears on the box and on the bottle after "EXP". The expiration date is the last day of the month indicated.

This medicine does not require special storage conditions.

Do not use this medicine if the packaging is damaged or shows signs of tampering.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of the packaging and any unused medicine. This will help protect the environment.

6. Package Contents and Additional Information

Composition of Balversa

• The active ingredient is erdafitinib.
• Each film-coated tablet contains 3 mg, 4 mg, or 5 mg of erdafitinib.
• The other ingredients are:

• Tablet core: Sodium croscarmellose, magnesium stearate (E572), mannitol (E421), meglumine, and microcrystalline cellulose (E460).

• Film coating (Opadry amb II): Glycerol monocaprylate type I, partially hydrolyzed polyvinyl alcohol, sodium lauryl sulfate, talc, titanium dioxide (E171), yellow iron oxide (E172), red iron oxide (E172) (only for 4 mg and 5 mg tablets), and black iron oxide (E172) (only for 5 mg tablets).

Appearance of Balversa and Package Contents

The 3 mg Balversa film-coated tablets are yellow, round, biconvex, and engraved with "3" on one side and "EF" on the other.

The 4 mg Balversa film-coated tablets are orange, round, biconvex, and engraved with "4" on one side and "EF" on the other.

The 5 mg Balversa film-coated tablets are brown, round, biconvex, and engraved with "5" on one side and "EF" on the other.

The Balversa film-coated tablets are supplied in a child-resistant bottle. Only certain package sizes may be marketed.

Bottle:

The tablets are supplied in a plastic bottle with a child-resistant closure. Each bottle may contain 28, 56, or 84 film-coated tablets. Each carton contains one bottle.

3 mg tablet:

• Each carton of 56 film-coated tablets contains a bottle with 56 tablets.
• Each carton of 84 film-coated tablets contains a bottle with 84 tablets.

4 mg tablet:

• Each carton of 28 film-coated tablets contains a bottle with 28 tablets.
• Each carton of 56 film-coated tablets contains a bottle with 56 tablets.

5 mg tablet:

• Each carton of 28 film-coated tablets contains a bottle with 28 tablets.

Marketing Authorization Holder

Janssen-Cilag International NV

Turnhoutseweg 30

B-2340 Beerse

Belgium

Manufacturer

Janssen Cilag SpA

Via C. Janssen,

Borgo San Michele

Latina 04100

Italy

You can request more information about this medicine by contacting the local representative of the marketing authorization holder:

Date of Last Revision of this Leaflet:

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