Patient Information Leaflet

Sandimmun Neoral 25 mg Soft Capsules

ciclosporina

Read this leaflet carefully before you start taking this medicine because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you are unsure about anything, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to others even if they have similar symptoms, as it may harm them.
• If you experience any side effects, consult your doctor or pharmacist, even if they are not listed in this leaflet. See section 4.

1.What Sandimmun Neoral is and what it is used for

2.What you need to know before you start taking Sandimmun Neoral

3.How to take Sandimmun Neoral

4.Possible side effects

5.Storage of Sandimmun Neoral

6.Contents of the pack and additional information

What is Sandimmun Neoral

Your medicine is called Sandimmun Neoral. It contains the active ingredient ciclosporina. It belongs to a group of medicines known as immunosuppressants. These medicines are used to reduce the body's immune reactions.

What is Sandimmun Neoral used for and how it works

• If you have undergone an organ transplant, bone marrow transplant, and stem cell transplant,Sandimmun Neoral's function is to control the body's immune system. Sandimmun Neoral prevents the rejection of transplanted organs by slowing the development of certain cells that would normally attack the transplanted tissue.
• If you have an autoimmune disease,in which the body's immune response attacks the body's own cells, Sandimmun Neoral slows down this immune reaction. These diseases include eye problems that can affect vision (endogenous uveitis, including Behçet's uveitis), severe cases of certain skin diseases (atopic dermatitis, or eczema, and psoriasis), severe rheumatoid arthritis, and a kidney disease called nephrotic syndrome.

If you are taking Sandimmun Neoral after a transplant, it can only be prescribed by a doctor experienced in transplants and/or autoimmune diseases.

The recommendations in this leaflet may vary depending on whether you are taking the medicine for a transplant or for an autoimmune disease.

Follow all the instructions given by your doctor carefully. They may be different from the general information contained in this leaflet.

Do not takeSandimmun Neoral:

-if you are allergic to ciclosporin or any of the other ingredients of this medicine(including those listed in section6).

-with medicines that containHypericum perforatum(St. John's Wort).

-with medicines that containdabigatrán etexilato(used to prevent blood clots after an operation)or bosentán and aliskirén(used to lower high blood pressure).

If this applies to you, do not take Sandimmun Neoral andinform your doctor. If you are unsure, consult your doctor before taking Sandimmun Neoral.

Warnings and precautions

Inform your doctor immediately before and during treatment with Sandimmun Neoral:

• if you experience any signs of infection, such as fever or sore throat.Sandimmun Neoral suppresses the immune system and may also affect your body's ability to fight infections.
• if you have liver problems.
• if you have kidney problems. Your doctor will perform regular blood tests and may change your dose as needed.
• if you have high blood pressure. Your doctor will monitor your blood pressure regularly and may prescribe a medicine to lower your blood pressure if necessary.
• if you have low levels of magnesium in your body. Your doctor may prescribe magnesium supplements, especially after your operation if you have had a transplant.
• if you have high levels of potassium in your blood.
• if you suffer from gout.
• if you need to receive a vaccine.

If you experience any of the above situations before or during treatment with Sandimmun Neoral, inform your doctor immediately.

Sun protection and sunlight

Sandimmun Neoral suppresses your immune system. This may increase the risk of developing cancer, particularly skin cancer and lymphatic system cancer. Therefore, you should limit your exposure to the sun and UV rays as follows:

• Wear protective clothing.
• Apply sunscreen with a high protection factor frequently.

Consult your doctor before taking Sandimmun Neoral:

• if you have or have had problems related to alcohol.
• if you suffer from epilepsy.
• if you have any liver problems.
• if you are pregnant.
• if you are breastfeeding.
• if this medicine is prescribed to a child.

If any of these situations apply to you (or you are unsure), inform your doctor before taking Sandimmun Neoral. This is because this medicine contains alcohol (see section , “Sandimmun Neoral containsethanol”, later).

Monitoring during treatment with Sandimmun Neoral

Your doctor will monitor:

• thelevels of ciclosporin in your blood, especially if you have had a transplant,
• yourblood pressurebefore starting treatment and regularly during treatment,
• how yourliver and kidneys are functioning,
• yourlipid levels in your blood(fats).

If you have any questions about how Sandimmun Neoral works or why you have been prescribed this medicine, consult your doctor.

Additionally, if you are taking Sandimmun Neoralfor a disease other than a transplant(intermediate or posterior uveitis and Behçet's uveitis, atopic dermatitis, severe rheumatoid arthritis or nephrotic syndrome), do not take Sandimmun Neoral:

• if you have kidney problems (except for nephrotic syndrome).
• if you have an infection that is not controlled with medication.
• if you have any type of cancer.
• if you have high blood pressure (hypertension) that is not controlled with medicines. If you develop high blood pressure during treatment and it cannot be controlled, your doctor must stop treatment with Sandimmun Neoral.

If any of these situations apply to you, do not take Sandimmun Neoral. If you are unsure, consult your doctor or pharmacist before taking Sandimmun Neoral.

If you are being treated for Behçet's uveitis, your doctor will monitor you closely, especially if you experience neurological symptoms (for example: frequent forgetfulness, changes in personality observed over time, psychiatric or mood disorders, burning sensation in the limbs, decreased sensitivity in the limbs, tingling sensation in the limbs, weakness in the limbs, motor disorders, headache with or without nausea and vomiting, eye disorders that include limited eye movement).

Your doctor will monitor you closely if you are an elderly person and are being treated for psoriasis or atopic dermatitis. If you have been prescribed Sandimmun Neoral to treat your psoriasis or atopic dermatitis, you should not be exposed to UVB or photochemotherapy during treatment.

Children and adolescents

Sandimmun Neoral should not be administered to children for indications other than a transplant, except for the treatment of nephrotic syndrome.

Older adults (65 years of age and older)

There is limited experience with Sandimmun Neoral in older adults. Your doctor should monitor how your kidneys are functioning.If you are over 65 years old and have psoriasis or atopic dermatitis, you should only be treated with Sandimmun Neoral if your condition is particularly severe.

Other medicines and Sandimmun Neoral

Inform your doctor or pharmacist if you are taking, have taken recently, or may need to take any other medicine.

Particularly inform your doctor or pharmacist if you are taking any of the following medicines before or during treatment with Sandimmun Neoral:

• Medicines that can affect your potassium levels. These include medicines that contain potassium, potassium supplements, potassium-sparing diuretics, and some medicines that lower your blood pressure.
• Metotrexato.It is used to treat tumors, severe psoriasis, and severe rheumatoid arthritis.

• Medicines that can increase or decrease the levels of ciclosporin (the active ingredient in Sandimmun Neoral) in your blood. Your doctor may check the level of ciclosporin in your blood when you start or stop taking other medicines.

• Medicines that can increase the level of ciclosporin in your blood include: antibiotics (such as erythromycin or azithromycin), antifungals (voriconazole, itraconazole), medicines used for heart problems or high blood pressure (diltiazem, nicardipine, verapamil, amiodarone), metoclopramide (used to prevent vomiting), oral contraceptives, danazol (used to treat menstrual disorders), medicines used to treat gout (allopurinol), bile acid and derivatives (used to treat gallstones), protease inhibitors used to treat HIV, imatinib (used to treat leukemia or tumors), colchicine, telaprevir (used to treat hepatitis C),cannabidiol (its use includes, among others, the treatment of epilepsy).
• Medicines that can decrease the level of ciclosporin in your blood include: barbiturates (used to help you sleep), certain anticonvulsants (such as carbamazepine or phenytoin), octreotide (used to treat acromegaly or neuroendocrine tumors in the intestine), medicines used to treat tuberculosis, orlistat (used to help you lose weight), medicines containing St. John's Wort, ticlopidine (used after a stroke), certain medicines that lower blood pressure (bosentan), and terbinafine (an antifungal medicine, used to treat infections of the toes and fingernails).

• Medicines that can affect your kidneys. These include: antibiotics (gentamicin, tobramycin, ciprofloxacin), antifungals that contain amphotericin B, medicines used to treat urinary tract infections that contain trimethoprim, medicines used to treat cancer that contain melphalan, medicines used to reduce the amount of acid in your stomach (H2 receptor antagonists), tacrolimus, analgesics (non-steroidal anti-inflammatory drugs such as diclofenac), acidophilic medicines (used to reduce the amount of fat in your blood).
• Nifedipino.It is used to treat high blood pressure and chest pain. You may experience inflamed gums that may grow over your teeth if you take nifedipine during your treatment with ciclosporin.
• Digoxina (used to treat heart problems), medicines that reduce cholesterol (HMG-CoA reductase inhibitors also called statins), prednisolona, etopósido (used to treat cancer), repaglinida (an oral antidiabetic medicine), immunosuppressants (everolimús, sirolimús), ambrisentán and specific cancer medicines called anthracyclines (such as doxorrubicina).
• Micofenolato de sodio or micofenolato de mofetilo (an immunosuppressant) and eltrombopag (used to treat bleeding disorders).

If any of these situations apply to you (or you are unsure), inform your doctor or pharmacist before taking Sandimmun Neoral.

Taking Sandimmun Neoral with food and drinks

Do not take Sandimmun Neoral with grapefruit or grapefruit juice. This is because it may affect the functioning of Sandimmun Neoral.

Pregnancy and breastfeeding

Consult your doctor or pharmacist before taking this medicine.

• Inform your doctor if you are pregnant or intend to become pregnant.The experience with Sandimmun Neoral in pregnant women is limited. In general, Sandimmun Neoral should not be administered during pregnancy. If you need to take this medicine, your doctor will discuss the potential benefits and risks of taking it during pregnancy.
• Inform your doctor if you are breastfeeding.Breastfeeding is not recommended during treatment with Sandimmun Neoral. This is because ciclosporin, the active ingredient, passes into breast milk and may affect your baby.

Hepatitis C

Inform your doctor if you have hepatitis C. Your liver function may change with hepatitis C treatment, which may affect ciclosporin levels in your blood. Your doctor may need to closely monitor ciclosporin levels in your blood and adjust your dose after starting hepatitis C treatment.

Driving and operating machinery

You may feel drowsy, disoriented, or have blurred vision after taking Sandimmun Neoral. Be careful when driving or operating machinery until you know how it affects you.

Sandimmun Neoral containsethanol

Sandimmun Neoral contains 25 mg of alcohol (ethanol) per 25 mg Sandimmun Neoral capsule, which corresponds to 11.8% v/v. A dose of 500 mg of Sandimmun Neoral contains 500 mg of ethanol, equivalent to about 13ml of beer or 5ml of wine. The small amount of alcohol in this medicine will have no perceptible effect.

Sandimmun Neoral contains ricin oil

Sandimmun Neoral may cause stomach discomfort and diarrhea because it contains ricin oil.

Sandimmun Neoral contains propylene glycol

This medicine contains 46.42 mg of propylene glycol in each 25 mg capsule.

If the baby is under 4 weeks old, consult your doctor or pharmacist, especially if the baby has been given other medicines that contain propylene glycol or alcohol.

Sandimmun Neoral contains sodium

This medicine contains less than 23 mg of sodium (1 mmol) per 25 mg capsule; it is essentially “sodium-free”.

Follow exactly the administration instructions of this medication as indicated by your doctor. In case of doubt, consult your doctor again.

Do not take more than the recommended dose.

Your doctor will carefully adjust the dose of this medication to your individual needs. Taking too much of this medication can affect your kidneys. You will have regular blood tests and hospital visits, especially after the transplant. This will allow you to consult with your doctor about your treatment and any problems you may have.

How much Sandimmun Neoral should you take

Your doctor will tell you the correct dose of Sandimmun Neoral for you. This depends on your body weight and the reason you are taking this medication. Your doctor will also inform you how often you should take your medication.

• For adults:

Organ, bone marrow, and stem cell transplant

• The usual total daily dose is between 2 mg and 15 mg per kilogram of body weight. This is divided into two doses.
• Higher doses are usually used before and just after your transplant. Lower doses are used once your transplanted organ or bone marrow is stabilized.
• Your doctor will adjust the dose to one that is ideal for you. To do this, your doctor may need to do some blood tests.

Endogenous uveitis

• The usual total daily dose is between 5 mg and 7 mg per kilogram of body weight. This is divided into two doses.

Nephrotic syndrome

• The usual total daily dose for adults is 5 mg per kilogram of body weight. This is divided into two doses. In patients with renal impairment, the first daily dose should not exceed 2.5 mg per kilogram of body weight.

Severe rheumatoid arthritis

• The usual total daily dose is between 3 mg and 5 mg per kilogram of body weight. This is divided into two doses.

Psoriasis and atopic dermatitis

• The usual total daily dose is between 2.5 mg and 5 mg per kilogram of body weight. This is divided into two doses.

• For children:

Nephrotic syndrome

• The usual total daily dose for children is 6 mg per kilogram of body weight. This is divided into two doses. In patients with renal impairment, the first daily dose should not exceed 2.5 mg per kilogram of body weight.

Follow exactly the instructions of your doctor and never change the dose yourself, even if you feel well.

Conversion from Sandimmun to Sandimmun Neoral

You may have already been taking another medication called Sandimmun soft gelatin capsules or Sandimmun oral solution. Your doctor may decide to switch you to Sandimmun Neoral oral solution.

• All these medications contain cyclosporine as the active ingredient.
• Sandimmun Neoral is a different and improved formulation of cyclosporine compared to Sandimmun. Cyclosporine is better absorbed into the blood with Sandimmun Neoral and is less likely to be affected by food intake. This means that cyclosporine levels in the blood remain more constant with Sandimmun Neoral than with Sandimmun.

If your doctor switches you from Sandimmun to Sandimmun Neoral:

• Do not take Sandimmun again unless your doctor tells you to.
• After the conversion from Sandimmun to Sandimmun Neoral, your doctor will monitor you more closely for a short period of time. This is because of the change in how cyclosporine is absorbed into the blood. Your doctor will ensure that you take the correct dose according to your individual needs.
• You may experience some side effects. If this happens, inform your doctor or pharmacist. You may need to reduce your dose. Never reduce your dose yourself, unless your doctor tells you to.

If your doctor switches you from one oral cyclosporine formulation to another

After you switch from one oral cyclosporine formulation to another:

• Your doctor will monitor you more closely for a short period of time.
• You may experience some side effects. If this happens, inform your doctor or pharmacist. You may need to modify your dose. Never modify your dose yourself, unless your doctor tells you to.

When to take Sandimmun Neoral

Take Sandimmun Neoralat the same time every day. This is very important if you have had a transplant.

How to take Sandimmun Neoral

Your daily dose should always be divided into 2doses.

Remove the capsules from the blister. Swallow the capsules whole with a glass of water.

How long to take Sandimmun Neoral

Your doctor will tell you how long you need to take Sandimmun Neoral. This depends on whether you are taking it after a transplant or for the treatment of severe skin diseases, rheumatoid arthritis, uveitis, or nephrotic syndrome. In the case of severe skin eruption, treatment usually lasts 8weeks.

Continue taking Sandimmun Neoral for as long as your doctor tells you to.

If you have any doubts about how long you should take Sandimmun Neoral, consult your doctor or pharmacist.

If you take too much Sandimmun Neoral

If you accidentally take an excessive dose of the medication, inform your doctor immediately, or go to the nearest hospital emergency room. You may need medical attention.

You can also call the Toxicology Information Service at phone 91 562 04 20, indicating the medication and the amount taken.

If you forget to take Sandimmun Neoral

• If you forget to take a dose, take it as soon as you remember. However, if it is close to the next dose, skip the missed dose. Then continue as usual.
• Do not take a double dose to make up for the missed doses.

If you interrupt treatment with Sandimmun Neoral

Do not interrupt treatment with Sandimmun Neoral unless your doctor tells you to.

Continue taking Sandimmun Neoral even if you feel well.The interruption of treatment with Sandimmun Neoral may increase the risk of rejection of your transplanted organ.

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

Like all medicines, this medicine may cause side effects, although not everyone will experience them.

Some side effects can be serious

Inform your doctor immediatelyif you notice any of the following serious side effects:

• Like other medicines that act on the immune system, ciclosporin may affect your body's ability to fight certain infections and may cause tumors or other malignant diseases, especially of the skin. Signs of infection could be fever or sore throat.
• Visual disturbances, lack of coordination, clumsiness, memory loss, difficulty speaking or understanding what others say, and muscle weakness. These could be signs of a brain infection called progressive multifocal leukoencephalopathy.
• Brain problems with signs such as seizures, confusion, disorientation, decreased sensitivity, changes in personality, agitation, insomnia, visual disturbances, blindness, coma, paralysis of part or all of the body, torticollis, lack of coordination with or without abnormal speech or eye movement.
• Inflammation in the back of the eye that may be associated with blurry vision. It may also affect your vision due to an increase in pressure within the head (benign intracranial hypertension).
• Liver damage and alteration with or without yellow discoloration of the eyes or skin, nausea, vision loss, and dark urine.
• Kidney problems, which may significantly reduce the amount of urine you produce.
• Decrease in the number of red or white blood cells. These signs include pale skin, fatigue, shortness of breath, dark urine (sign of red blood cell rupture), unexplained bleeding or bruising, confusion, disorientation, lack of attention, and kidney problems.

Other side effects include:

Very common:may affect more than 1 in 10people

• Kidney problems.
• High blood pressure.
• Headache.
• Uncontrollable body agitation.
• Excessive facial and body hair growth.
• Increased blood lipids.

If any of them severely affect you,inform your doctor.

Common:may affect up to 1 in 10people

• Seizures (convulsions).
• Liver problems.
• Increased blood sugar.
• Fatigue.
• Loss of appetite.
• Nausea (sensation of dizziness), vomiting, abdominal discomfort, diarrhea.
• Excessive hair growth
• Acne, hot flashes.
• Fever.
• Decrease in the number of white blood cells.
• Sensation of numbness or tingling.
• Muscle pain, muscle spasms.
• Stomach ulcer.
• Excessive gum tissue growth that may cover your teeth.
• Excess uric acid or potassium in the blood, decreaseof magnesium levels in the blood.

If any of them severely affect you,inform your doctor.

Rare:may affect up to 1 in 100people

• Symptoms of brain alterations including sudden attacks, mental confusion, insomnia, disorientation, visual disturbances, unconsciousness, sensation of weakness in the limbs, movement deterioration.
• Skin rash.
• Generalized inflammation.
• Weight gain.
• Decrease in the number of red and white blood cells in the blood that may increase the risk of bleeding.

If any of them severely affect you,inform your doctor.

Very rare:may affect up to 1 in 10,000people

• Inflammation in the back of the eye that may be associated with increased pressure within the head and vision deterioration.

If this affects you severely,inform your doctor.

Frequency not known:Cannot be estimated from available data.

• Severe liver problems with and without yellow discoloration of the eyes or skin, nausea (sensation of dizziness), loss of appetite, dark urine, facial, foot, hand, and/or body swelling.
• Bleeding under the skin or purple-colored skin spots, unexplained sudden bleeding.
• Migraine or severe headache, often with dizziness or sensation of the same (nausea, vomiting) and light sensitivity.
• Pain in the legs and feet.
• Hearing loss.

If any of them severely affect you,inform your doctor.

If you experience side effects, consult your doctor or pharmacist, even if it is about side effects that do not appear in this prospectus.

Other side effects in children and adolescents

No additional side effects are expected in children and adolescents compared to adults.

Reporting of side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is about possible side effects that do not appear in this prospectus.You can also report them directly tothrough the Spanish System for Pharmacovigilance of Medicines for Human Use (www.notificaRAM.es).By reporting side effects, you can contribute to providing more information on the safety of this medicine.

• Keep this medication out of the sight and reach of children.
• Do not use this medication after the expiration date that appears on the packaging.
• Do not store the capsules in a warm place.Do not store at a temperature above 25°C.
• Store in the original packaging to protect it from moisture.
• Store the capsules in the blister. Only remove them when you are ready to take your medication.
• When the blister is opened, a characteristic smell may be perceived, which is completely normal and does not mean the capsule is in a bad state.
• Medications should not be thrown down the drain or in the trash. Dispose of the packaging and unused medications at the SIGRE collection point at the pharmacy. If in doubt, ask your pharmacist how to dispose of unused packaging and medications. By doing so, you will help protect the environment.

Composition of Sandimmun Neoral

• The active ingredient is cyclosporin.Cada cápsula contiene 25 mg de ciclosporina.
• The other components are:
• • Content of the capsule: alpha-tocopherol, anhydrous ethanol, propylene glycol, mono-di-triglycerides of corn oil, macrogolglycerol hydroxystearate/hydrogenated ricin oil polioxylo.
  • Capsule coating: iron oxide black (E172), titanium dioxide (E171), 85% glycerol, propylene glycol, gelatin.
  • Printing: carmine acid (E 120),aluminum chloride hexahydrate, sodium hydroxide, propylene glycol, hypromellose/hydroxypropylmethylcellulose 2910, isopropanol/isopropyl alcohol.

Appearance of Sandimmun Neoral and packaging contents

Sandimmun Neoral 25 mg soft capsules are oval-shaped, blue-gray in color, with the imprint “NVR 25mg” in red.

They are available in packaging of5, 20, 30, 50, 60 and 90soft capsules.

Only some packaging sizes may be commercially available.

Marketing authorization holder and manufacturer responsible

Marketing authorization holder

Novartis Farmacéutica, S.A.

Gran Via de les Corts Catalanes, 764

08013 – Barcelona (Spain)

Phone: +34 93 306 42 00

Manufacturer responsible

This medicine is authorized in the member states of the European Economic Area and in the United Kingdom (Northern Ireland) with the following names:

Last review date of this leaflet: 05/2023

Other sources of information

The detailed information on this medicine is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)http://www.aemps.gob.es/