Sandimmun Neoral: detailed information

Patient Information Leaflet

Sandimmun Neoral 10 mg soft capsules, 25 mg soft capsules, 50 mg soft capsules, 100 mg soft capsules

ciclosporin
Please read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

Keep this leaflet. You may need to read it again.
If you have any questions, ask your doctor or pharmacist.
This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it may be harmful.
If you experience any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist. See section 4.

Contents of this leaflet:

What Sandimmun Neoral is and what it is used for
What you need to know before taking Sandimmun Neoral
How to take Sandimmun Neoral
Possible side effects
How to store Sandimmun Neoral
Contents of the pack and other information

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

What Sandimmun Neoral is
The name of this medicine is Sandimmun Neoral. It contains the active substance ciclosporin. Ciclosporin
belongs to a group of medicines known as immunosuppressive agents. These medicines
are used to reduce the body's immune responses.
What Sandimmun Neoral is used for and how Sandimmun Neoral works

If you have received an organ, bone marrow, or stem cell transplant, the function of Sandimmun Neoral is to suppress your body's immune system. Sandimmun Neoral prevents rejection of the transplanted organ by blocking the development of certain cells that would normally attack the transplanted tissue.
If you suffer from an autoimmune disease, in which your body's immune response attacks its own cells, Sandimmun Neoral blocks this immune reaction. These diseases include sight-threatening eye disorders (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 known as nephrotic syndrome.

2. What you need to know before taking Sandimmun Neoral

If you are taking Sandimmun Neoral following a transplant, the medicine will be prescribed to you only by a physician experienced in transplantation and/or autoimmune diseases.
The warning reported in this patient information leaflet may vary depending on whether you are taking the medicine for a transplant or for an autoimmune disease.
Carefully follow all instructions provided by your doctor. These may differ from the general information contained in this leaflet.

Do not take Sandimmun Neoral:

if you are allergic to ciclosporin or to any of the other ingredients of this medicine (listed in section 6).
with products containing Hypericum perforatum (St. John’s wort).
with medicines containing dabigatran etexilate (used to prevent blood clots after surgery), or bosentan and aliskiren (used to reduce high blood pressure).

Do not take Sandimmun Neoral and inform your doctor if any of the above conditions apply to you.
If you are unsure, ask your doctor before taking Sandimmun Neoral.

Warnings and precautions
Before and during treatment with Sandimmun Neoral, inform your doctor immediately:

if you have 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 regularly perform blood tests and, if necessary, may adjust your dose.
if you develop high blood pressure. Your doctor will monitor your blood pressure regularly and, if needed, may prescribe a medicine to lower it.
if you have low levels of magnesium in your body. Your doctor may prescribe magnesium supplements, especially shortly after transplantation.
if you have high levels of potassium in your blood.
if you have gout.
if you require vaccination. If any of the above conditions apply to you, before or during treatment with Sandimmun Neoral, inform your doctor immediately.

Sun exposure and sun protection
Sandimmun Neoral suppresses the immune system. This increases the risk of developing cancer, particularly of the skin and lymphatic system. You should limit exposure to sunlight and UV light:

by wearing appropriate protective clothing.
by frequently applying sunscreen with a high protection factor.

Inform your doctor before taking Sandimmun Neoral:

if you have or have had alcohol-related problems.
if you have epilepsy.
if you have any liver problems.
if you are pregnant.
if you are breastfeeding.
if this medicine is to be prescribed for a child. If you have any of the above conditions (or are unsure), inform your doctor before taking Sandimmun Neoral. This is because this medicine contains alcohol (see section below “Sandimmun Neoral contains ethanol”).

Monitoring during treatment with Sandimmun Neoral
Your doctor will monitor:

ciclosporin blood levels, especially if you have undergone a transplant,
blood pressure before starting treatment and regularly during treatment,
liver and kidney function,
blood lipids (fats). If you have any questions about how Sandimmun Neoral works or why this medicine has been prescribed for you, ask your doctor.

Additionally, if you are taking Sandimmun Neoral for a condition other than transplantation (intermediate uveitis, 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 therapy.
if you have any type of cancer.
if you have uncontrolled high blood pressure (hypertension) despite treatment. If high blood pressure develops during treatment and cannot be controlled, Sandimmun Neoral must be discontinued by your doctor. Do not take Sandimmun Neoral if any of the above conditions apply to you. If you are unsure, inform your doctor or pharmacist before taking Sandimmun Neoral.

If you are being treated for Behçet’s uveitis, your doctor will pay particular attention to whether you develop neurological symptoms (for example: increased forgetfulness, personality changes observed over time, psychiatric or mood disorders, burning sensation in limbs, reduced limb sensitivity, tingling in limbs, limb weakness, walking difficulties, headache with or without nausea and vomiting, vision disturbances including limited eye movement).
If you are elderly and being treated for psoriasis or atopic dermatitis, your doctor will monitor you closely. If Sandimmun Neoral has been prescribed for the treatment of psoriasis or atopic dermatitis, you must not be exposed to UVB radiation or phototherapy during treatment.

Children and adolescents
Sandimmun Neoral must not be administered to children for conditions other than transplantation, except for the treatment of nephrotic syndrome.

Elderly (65 years of age and older)
Experience with Sandimmun Neoral in elderly patients is limited. Your doctor must monitor proper kidney function. If you are over 65 years old and suffer from psoriasis or atopic dermatitis, treatment with Sandimmun Neoral should only be initiated if the condition is particularly severe.

Other medicines and Sandimmun Neoral
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
In particular, inform your doctor or pharmacist if you are taking any of the following medicines before or during treatment with Sandimmun Neoral:

Medicines that may affect potassium levels. These include medicines containing potassium, potassium supplements, diuretic tablets known as potassium-sparing diuretics, and certain medicines that lower blood pressure.
Methotrexate. This medicine is used to treat cancer, severe psoriasis, and severe rheumatoid arthritis.
Medicines that may increase or decrease ciclosporin (the active substance in Sandimmun Neoral) blood levels. Your doctor may monitor your ciclosporin blood levels when starting or stopping other medicines.
Medicines that may increase ciclosporin blood levels 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 for nausea), oral contraceptives, danazol (used to treat menstrual disorders), medicines used to treat gout (allopurinol), cholic 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 (used, among other things, to treat seizures).
Medicines that may decrease ciclosporin blood levels include: barbiturates (used to promote sleep), certain anticonvulsants (such as carbamazepine or phenytoin), octreotide (used to treat acromegaly or neuroendocrine tumors of the intestine), antibacterial medicines used to treat tuberculosis, orlistat (used to promote weight loss), herbal medicines containing St. John’s wort, ticlopidine (used after stroke), certain medicines that lower blood pressure (bosentan), and terbinafine (an antifungal medicine used to treat foot and nail infections).
Medicines that may affect the kidneys. These include: antibacterial medicines (gentamicin, tobramycin, ciprofloxacin), antifungal medicines containing amphotericin B, medicines used for urinary tract infections containing trimethoprim, cancer medicines containing melphalan, medicines used to reduce stomach acid (acid secretion inhibitors of the H-\receptor antagonist type), tacrolimus, painkillers (non-steroidal anti-inflammatory drugs such as diclofenac), fibric acid derivatives (used to reduce blood fat levels).
Nifedipine. This is used to treat high blood pressure and heart pain. If you are taking nifedipine during ciclosporin treatment, you may develop swollen, thickened gums around your teeth.
Digoxin (used to treat heart problems), cholesterol-lowering medicines (HMG-CoA reductase inhibitors, also known as statins), prednisolone, etoposide (used to treat cancer), repaglinide (an antidiabetic medicine), immunosuppressants (everolimus, sirolimus), ambrisentan, and specific anticancer medicines called anthracyclines (e.g. doxorubicin).
Mycophenolate sodium or mycophenolate mofetil (an immunosuppressant) and eltrombopag (used to treat clotting disorders). If you experience any of the above conditions (or are unsure), inform your doctor or pharmacist before taking Sandimmun Neoral.

Sandimmun Neoral with food and drinks
Do not take Sandimmun Neoral with grapefruit or grapefruit juice. These may affect the action of Sandimmun Neoral.

Pregnancy and breastfeeding
Ask your doctor or pharmacist for advice before taking this medicine.

Inform your doctor if you are pregnant or planning to become pregnant. Experience with Sandimmun Neoral during pregnancy is limited. In general, Sandimmun Neoral should not be taken during pregnancy. If treatment with this medicine is necessary, your doctor will discuss the benefits and potential 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. This may affect the infant.

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

Driving and using machines
You may feel drowsy, disoriented, or experience blurred vision after taking Sandimmun. Exercise caution when driving or operating machinery while taking Sandimmun until you know how it affects you.

Sandimmun Neoral contains ethanol
Sandimmun Neoral contains 10, 25, 50, and 100 mg of alcohol (ethanol) in each 10, 25, 50, and 100 mg capsule of Sandimmun Neoral, respectively, equivalent to 11.8% v/v. A 500 mg dose of Sandimmun Neoral contains 500 mg of ethanol, equivalent to approximately 13 ml of beer or 5 ml of wine.
The small amount of alcohol in this medicine will not produce significant effects.

Sandimmun Neoral contains castor oil
Sandimmun Neoral contains castor oil, which may cause stomach discomfort and diarrhoea.

Sandimmun Neoral contains propylene glycol
This medicine contains 20.84 mg of propylene glycol per 10 mg capsule.
This medicine contains 46.42 mg of propylene glycol per 25 mg capsule.
This medicine contains 90.36 mg of propylene glycol per 50 mg capsule.
This medicine contains 148.31 mg of propylene glycol per 100 mg capsule.
If the child is less than 4 weeks old, speak with your doctor or pharmacist before administering this medicine, especially if the child is taking other medicines containing propylene glycol or alcohol.

Sandimmun Neoral contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per 10, 25, 50, and 100 mg capsule, i.e., essentially “sodium-free”.

3. How to take Sandimmun Neoral

Take this medicine exactly as directed by your doctor. If you have any doubts, consult your doctor.
Do not take more than the recommended dose.
Your doctor will carefully adjust the dose of this medicine to suit your individual needs.
Taking too much medicine may affect kidney function. You will have regular blood tests and hospital visits, especially after a transplant. This will give you the opportunity to discuss your treatment and any problems you may be experiencing with your doctor.

How much Sandimmun Neoral to take

Your doctor will determine the correct dose of Sandimmun Neoral for you. The dose depends on your body weight and the reason why you are taking the medicine. Your doctor will also tell you how often to take the medicine.

In adults: Organ, bone marrow or stem cell transplant
The total daily dose is usually between 2 mg and 15 mg per kilogram of body weight. It should be divided into two doses.
Higher doses are usually used before and immediately after transplantation. Lower doses are used once the transplanted organ or bone marrow has stabilised.
Your doctor will adjust the dose to the appropriate level for you. To do this, your doctor may need to perform some blood tests. Endogenous uveitis
The total daily dose is usually between 5 mg and 7 mg per kilogram of body weight. It should be divided into two doses. Nephrotic syndrome
For adults, the total daily dose is usually 5 mg per kilogram of body weight. It should be divided into two doses. In patients with kidney problems, the initial daily dose should not exceed 2.5 mg per kilogram of body weight. Severe rheumatoid arthritis
The total daily dose is usually between 3 mg per kilogram of body weight and 5 mg per kilogram of body weight. It should be divided into two doses. Psoriasis and atopic dermatitis
The total daily dose is usually between 2.5 mg per kilogram of body weight and 5 mg per kilogram of body weight. It should be divided into two doses.
In children: Nephrotic syndrome
For children, the total daily dose is usually 6 mg per kilogram of body weight. It should be divided into two doses. In patients with kidney problems, the initial daily dose should not exceed 2.5 mg per kilogram of body weight. Follow your doctor's instructions exactly and never change the dose on your own, even if you feel well.

Switching from Sandimmun to Sandimmun Neoral

You may previously have taken another medicine called Sandimmun soft gelatin capsules or Sandimmun oral solution. Your doctor may decide to switch you to this medicine, Sandimmun Neoral oral solution.

All these medicines contain ciclosporin as the active ingredient.
Compared to Sandimmun, Sandimmun Neoral is an improved formulation of ciclosporin. With Sandimmun Neoral, ciclosporin is better absorbed into the blood, and its absorption is less likely to be affected by food intake. This means that blood levels of ciclosporin will be more consistent with Sandimmun Neoral than with Sandimmun. If your doctor switches your medicine from Sandimmun to Sandimmun Neoral:
Do not go back to taking Sandimmun unless your doctor tells you to.
After switching from Sandimmun to Sandimmun Neoral, your doctor will monitor you more closely for a short period. This is due to changes in how ciclosporin is absorbed into the blood. Your doctor will ensure that you are taking the correct dose for your individual needs.
You may experience some side effects. If this happens, contact your doctor or pharmacist. It may be necessary to reduce the dose. Never reduce the dose on your own unless your doctor tells you to.

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

After switching from one oral ciclosporin formulation to another:

Your doctor will monitor you more closely for a short period.
You may experience some side effects. If this happens, contact your doctor or pharmacist. It may be necessary to adjust the dose. Never change the dose on your own unless your doctor tells you to.

When to take Sandimmun Neoral

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

How to take Sandimmun Neoral

Daily doses must always be taken as two divided doses.
Remove the capsules from the blister pack. Swallow the capsules whole with water.

How long to take Sandimmun Neoral

Your doctor will tell you how long you should take Sandimmun Neoral. This depends on whether you are taking the medicine after a transplant or for the treatment of a severe skin condition, rheumatoid arthritis, uveitis or nephrotic syndrome. For severe skin rash, treatment duration is usually 8 weeks.
Continue taking Sandimmun Neoral for as long as your doctor tells you to.
If you have any questions about how long to take Sandimmun Neoral, speak to your doctor or pharmacist.

If you take more Sandimmun Neoral than you should

If you have accidentally taken too much medicine, inform your doctor immediately or go to the nearest hospital emergency department. You may require medical treatment.

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 almost time for your next dose, skip the missed dose and continue with your regular schedule.
Do not take a double dose to make up for a forgotten dose.

If you stop taking Sandimmun Neoral

Do not stop taking Sandimmun Neoral unless your doctor tells you to.
Continue taking Sandimmun Neoral even if you feel well. Stopping treatment with Sandimmun Neoral may increase the risk of rejection of your transplanted organ.
If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody will get them.
Some side effects can be serious
Tell your doctor immediately if you experience any of the following serious side effects:

Like other medicines that affect the immune system, ciclosporin may affect the body's ability to fight infections and may cause tumours or other types of cancer, particularly of the skin. Signs of infection may include fever or sore throat.
Vision changes, loss of coordination, clumsiness, memory loss, difficulty speaking or understanding what others are saying, and muscle weakness. These may be signs of a brain infection called progressive multifocal leukoencephalopathy.
Brain problems with symptoms such as seizures, confusion, feeling disoriented, reduced alertness, personality changes, feeling agitated, insomnia, vision changes, blindness, coma, paralysis of part or all of the body, neck stiffness, loss of coordination with or without unusual speech or eye movements.
Swelling at the back of the eye. This may be associated with blurred vision. It may also affect vision due to increased pressure inside the head (benign intracranial hypertension).
Liver problems and liver damage, with or without yellowing of the skin and eyes, nausea, loss of appetite, and dark urine.
Kidney problems which may greatly reduce the amount of urine produced.
Low levels of red blood cells or platelets. Signs include paleness, feeling tired, difficulty breathing, dark urine (this is a sign of red blood cell breakdown), unexplained bruising or bleeding, feeling confused, feeling disoriented, reduced attention, and kidney problems.

Other side effects include:
Very common: May affect more than 1 in 10 people.

Kidney problems.
High blood pressure.
Headache.
Uncontrollable body tremors.
Excessive growth of body and facial hair.
High levels of lipids in the blood. If any of these effects become severe, tell your doctor.

Common: May affect up to 1 in 10 people.

Seizures (fits).
Liver problems.
High blood sugar levels.
Tiredness.
Loss of appetite.
Nausea (feeling unwell), vomiting, abdominal discomfort/pain, diarrhoea.
Excessive hair growth.
Acne, hot flushes.
Fever.
Low levels of white blood cells in the blood.
Tingling or numbness sensations.
Muscle pain, muscle spasms.
Stomach ulcer.
Overgrowth of the gums and covering of the teeth.
High levels of uric acid or potassium in the blood, low levels of magnesium in the blood. If any of these effects become severe, tell your doctor.

Uncommon: May affect up to 1 in 100 people.

Symptoms of brain disorders including sudden seizures, mental confusion, insomnia, disorientation, vision disturbances, loss of consciousness, feeling of weakness in limbs, reduced movement.
Skin rash.
Generalised swelling.
Weight gain.
Low levels of red blood cells, low levels of platelets in the blood which may increase the risk of bleeding. If any of these effects become severe, tell your doctor.

Rare: May affect up to 1 in 1,000 people.

Nerve problems with numbness or tingling in the fingers and toes.
Inflammation of the pancreas with severe pain in the upper stomach.
Muscle weakness, loss of muscle strength, pain in the leg or hand muscles or in any part of the body.
Destruction of red blood cells, leading to kidney problems with symptoms such as swelling of the face, stomach, hands and/or feet, reduced urine volume, difficulty breathing, chest pain, seizures, loss of consciousness.
Changes in menstrual cycle, breast enlargement in men. If any of these effects become severe, tell your doctor.

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

Swelling at the back of the eye which may be associated with increased pressure inside the head and visual disturbances. If this effect becomes severe, tell your doctor.

Not known: Frequency cannot be estimated from the available data.

Severe liver problems with or without yellowing of the skin or eyes, nausea (feeling unwell), loss of appetite, dark urine, swelling of the face, feet, hands and/or whole body.
Bleeding under the skin or purple spots, sudden bleeding without apparent cause.
Migraine or severe headache, often with nausea, vomiting and sensitivity to light.
Pain in legs and feet.
Hearing impairment. If any of these effects become severe, tell your doctor.

If you get any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist.
Additional 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 get any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at www.agenziafarmaco.gov.it/content/come-segnalare-una-sospetta-reazione-avversa. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Sandimmun Neoral

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton.
Do not store the capsules in a warm place. Do not store above 25°C.
Store in the original packaging to protect the medicine from moisture.
Leave the capsules in the blister. Only remove the capsules from the blister when it is time to take the medicine.
Upon opening the blister, a characteristic odour may be noticed. This is normal and does not affect the use of the medicine.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Sandimmun Neoral contains

The active substance is ciclosporin. Each capsule contains 10 mg of ciclosporin.
The other components are:
o Capsule contents: alpha-tocopherol, absolute ethanol, propylene glycol, mono-di-glycerides of maize oil, macrogol glycerol hydroxystearate/hydrogenated polyoxyl castor oil.
o Capsule shell: titanium dioxide (E 171), glycerol 85%, propylene glycol, gelatin.
o Printing ink: carmine acid (E 120), aluminium chloride hexahydrate, sodium hydroxide, propylene glycol, hypromellose/hydroxypropylmethylcellulose 2910, isopropanol/isopropyl alcohol.
The active substance is ciclosporin. Each capsule contains 25 mg of ciclosporin.
The other components are:
o Capsule contents: alpha-tocopherol, absolute ethanol, propylene glycol, mono-di-glycerides of maize oil, macrogol glycerol hydroxystearate/hydrogenated polyoxyl castor oil.
o Capsule shell: black iron oxide (E172), titanium dioxide (E171), glycerol 85%, propylene glycol, gelatin.
o Printing ink: carmine acid (E 120), aluminium chloride hexahydrate, sodium hydroxide, propylene glycol, hypromellose/hydroxypropylmethylcellulose 2910, isopropanol/isopropyl alcohol.
The active substance is ciclosporin. Each capsule contains 50 mg of ciclosporin.
The other components are:
o Capsule contents: alpha-tocopherol, absolute ethanol, propylene glycol, mono-di-glycerides of maize oil, macrogol glycerol hydroxystearate/hydrogenated polyoxyl castor oil.
o Capsule shell: titanium dioxide (E 171), glycerol 85%, propylene glycol, gelatin.
o Printing ink: carmine acid (E 120), aluminium chloride hexahydrate, sodium hydroxide, propylene glycol, hypromellose/hydroxypropylmethylcellulose 2910, isopropanol/isopropyl alcohol.
The active substance is ciclosporin. Each capsule contains 100 mg of ciclosporin.
The other components are:
o Capsule contents: alpha-tocopherol, absolute ethanol, propylene glycol, mono-di-glycerides of maize oil, macrogol glycerol hydroxystearate/hydrogenated polyoxyl castor oil.
o Capsule shell: black iron oxide (E172), titanium dioxide (E171), glycerol 85%, propylene glycol, gelatin.
o Printing ink: carmine acid (E 120), aluminium chloride hexahydrate, sodium hydroxide, propylene glycol, hypromellose/hydroxypropylmethylcellulose 2910, isopropanol/isopropyl alcohol.

Description of the appearance of Sandimmun Neoral and contents of the pack
The 10 mg soft capsules of Sandimmun Neoral are oval-shaped, yellow-white in colour, with "NVR 10" printed in red.
The 25 mg soft capsules of Sandimmun Neoral are oval-shaped, blue-grey in colour, with "NVR 25mg" printed in red.
The 50 mg soft capsules of Sandimmun Neoral are elongated, yellow-white in colour, with "NVR 50mg" printed in red.
The 100 mg soft capsules of Sandimmun Neoral are elongated, blue-grey in colour, with "NVR 100mg" printed in red.
Sandimmun Neoral 10 mg, 25 mg, 50 mg and 100 mg soft capsules
Packs of 5, 20, 30, 50, 60 and 90 soft capsules
Packs of 100 and 250 soft capsules
Packs of 100 (5 x 20), 250 (5 x 50), 300 (5 x 60) and 500 (10 x 50) soft capsules
Not all pack sizes may be marketed.

Marketing Authorization Holder
Novartis Farma S.p.A.
Viale Luigi Sturzo, 43
20154 Milano MI
Italy

Manufacturer
Novartis Farma S.p.A.
Via Provinciale Schito 131
80058 Torre Annunziata NA
Italy
Lek Pharmaceuticals d.d.
Trimlini 2D
9220 Lendava
Slovenia
Novartis Farma S.p.A.
Viale Luigi Sturzo, 43
20154 Milano MI
Italy
Novartis Farmaceutica S.A.
Gran Vía de les Corts Catalanes, 764
08013 Barcelona
Spain

This medicinal product is authorized in the Member States of the European Economic Area and in the United Kingdom (Northern Ireland) under the following names:

Name	European Economic Area Member States
Sandimmun Neoral	Austria, Bulgaria, Cyprus, Czech Republic, Denmark, Estonia, Greece, Spain, Finland, Croatia, Hungary, Iceland, Italy, Lithuania, Latvia, Malta, Norway, Poland, Portugal, Romania, Sweden, Slovakia, Slovenia
Neoral	Ireland, Netherlands, United Kingdom (Northern Ireland)
Néoral	France
Neoral - Sandimmun	Belgium, Luxembourg
Immunosporin
Sandimmun Optoral	Germany

Other sources of information
More detailed information on this medicinal product is available on the website of the Italian Medicines Agency (http://www.aifa.gov.it/)
Patient Information Leaflet

Sandimmun Neoral 100 mg/ml oral solution

ciclosporin
Please read this leaflet carefully before taking this medicine as it contains
important information for you.

Keep this leaflet. You may need to read it again.
If you have any questions, consult your doctor or pharmacist.
This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it may be harmful.
If you experience any side effect, including those not listed in this leaflet, consult your doctor or pharmacist. See section 4.

Contents of this leaflet:

What Sandimmun Neoral is and what it is used for
What you need to know before taking Sandimmun Neoral
How to take Sandimmun Neoral
Possible side effects
How to store Sandimmun Neoral
Contents of the pack and other information

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

What Sandimmun Neoral is
The name of the medicine is Sandimmun Neoral. It contains the active substance ciclosporin. Ciclosporin
belongs to a group of medicines known as immunosuppressive agents. These medicines
are used to reduce the body's immune responses.
What Sandimmun Neoral is used for and how Sandimmun Neoral works

If you have had an organ transplant, a bone marrow transplant, or a stem cell transplant, the function of Sandimmun Neoral is to suppress your body's immune system. Sandimmun Neoral prevents rejection of the transplanted organ by blocking the development of certain cells that would normally attack the transplanted tissue.
If you suffer from an autoimmune disease, in which your body's immune response attacks its own cells, Sandimmun Neoral suppresses the immune reaction. These diseases include sight-threatening eye disorders (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 known as nephrotic syndrome.

2. What you should know before taking Sandimmun Neoral

If you are taking Sandimmun Neoral following a transplant, the medicine will be prescribed to you only by a physician experienced in transplantation and/or autoimmune diseases.
The warnings provided in this leaflet may vary depending on whether you are taking the medicine for a transplant or for an autoimmune disease.
Carefully follow all instructions given by your doctor. These may differ from the general information contained in this leaflet.

Do not take Sandimmun Neoral:

if you are allergic to ciclosporin or to any of the other ingredients of this medicine (listed in section 6).
with products containing Hypericum perforatum (St. John’s wort).
with medicines containing dabigatran etexilate (used to prevent blood clots after surgery), or bosentan and aliskiren (used to reduce high blood pressure).

Do not take Sandimmun Neoral and inform your doctor if any of the above conditions apply to you.
If you are unsure, ask your doctor before taking Sandimmun Neoral.

Warnings and precautions
Before and during treatment with Sandimmun Neoral, inform your doctor immediately if:

you have any signs of infection, such as fever or sore throat. Sandimmun Neoral suppresses the immune system and may impair your body’s ability to fight infections.
you have liver problems.
you have kidney problems. Your doctor will regularly perform blood tests and, if necessary, may adjust your dose.
you develop high blood pressure. Your doctor will monitor your blood pressure regularly and, if needed, may prescribe medication to lower it.
you have low magnesium levels in your body. Your doctor may prescribe magnesium supplements, especially shortly after transplantation.
you have high potassium levels in your blood.
you have gout.
you require vaccination. If any of the above conditions apply to you, before or during treatment with Sandimmun Neoral, inform your doctor immediately.

by wearing appropriate protective clothing,
by frequently applying sunscreen with a high sun protection factor.

Inform your doctor before taking Sandimmun Neoral if:

you have or have had alcohol-related problems.
you have epilepsy.
you have any liver problems.
you are pregnant.
you are breastfeeding.
this medicine is to be prescribed to a child. If you experience any of the above conditions (or are unsure), inform your doctor before taking Sandimmun Neoral. This medicine contains alcohol (see section below “Sandimmun Neoral contains ethanol”).

Monitoring during treatment with Sandimmun Neoral
Your doctor will monitor:

ciclosporin blood levels, especially if you have undergone a transplant,
blood pressure before starting treatment and regularly during treatment,
the function of your liver and kidneys,
blood lipids (fats). If you have any questions about how Sandimmun Neoral works or why it has been prescribed to you, ask your doctor.

Additionally, if you are taking Sandimmun Neoral for a condition other than transplantation (intermediate uveitis, 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 nephrotic syndrome).
if you have an infection that is not controlled by therapy.
if you have any type of cancer.
if you have uncontrolled high blood pressure (hypertension) despite treatment. If high blood pressure develops during treatment and cannot be controlled, Sandimmun Neoral must be discontinued by your doctor. Do not take Sandimmun Neoral if any of the above conditions apply to you. If you are unsure, inform your doctor or pharmacist before taking Sandimmun Neoral.

If you are being treated for Behçet’s uveitis, your doctor will closely monitor you for neurological symptoms (e.g., increasing forgetfulness, personality changes over time, psychiatric or mood disorders, burning sensations in limbs, reduced limb sensitivity, tingling in limbs, limb weakness, walking difficulties, headache with or without nausea and vomiting, visual disturbances including limited eye movement).
If you are elderly and being treated for psoriasis or atopic dermatitis, your doctor will monitor you closely. If Sandimmun Neoral has been prescribed for the treatment of psoriasis or atopic dermatitis, you must not undergo UVB radiation or phototherapy during treatment.

Children and adolescents
Sandimmun Neoral must not be administered to children for conditions other than transplantation, except for the treatment of nephrotic syndrome.

Elderly (aged 65 years and over)
Experience with Sandimmun Neoral in elderly patients is limited. Your doctor must monitor proper kidney function. If you are over 65 years of age and suffer from psoriasis or atopic dermatitis, treatment with Sandimmun Neoral should only be considered if the condition is particularly severe.

Medicines that may affect potassium levels. These include potassium-containing medicines, potassium supplements, diuretics known as potassium-sparing diuretics, and certain blood pressure-lowering medicines.
Methotrexate. This medicine is used to treat cancer, severe psoriasis, and severe rheumatoid arthritis.
Medicines that may increase or decrease ciclosporin (the active ingredient in Sandimmun Neoral) blood levels. Your doctor may monitor ciclosporin blood levels when starting or stopping other medicines.
Medicines that may increase ciclosporin blood levels 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 for nausea), oral contraceptives, danazol (used for menstrual disorders), medicines used to treat gout (allopurinol), cholic 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 (used, among other things, to treat seizures).
Medicines that may decrease ciclosporin blood levels include: barbiturates (used to induce sleep), certain anticonvulsants (such as carbamazepine or phenytoin), octreotide (used to treat acromegaly or intestinal neuroendocrine tumors), antibacterial medicines used to treat tuberculosis, orlistat (used to promote weight loss), herbal products containing St. John’s wort, ticlopidine (used after stroke), certain blood pressure-lowering medicines (bosentan), and terbinafine (an antifungal used to treat foot and nail infections).
Medicines that may affect the kidneys. These include: antibacterial medicines (gentamicin, tobramycin, ciprofloxacin), antifungal medicines containing amphotericin B, medicines used for urinary tract infections containing trimethoprim, cancer medicines containing melphalan, medicines used to reduce stomach acid (acid secretion inhibitors of the H2-receptor antagonist type), tacrolimus, painkillers (non-steroidal anti-inflammatory drugs such as diclofenac), fibric acid derivatives (used to lower blood fat levels).
Nifedipine. This is used to treat high blood pressure and heart pain. If you are taking nifedipine during ciclosporin treatment, you may develop swollen, thickened gums around your teeth.
Digoxin (used for heart problems), cholesterol-lowering medicines (HMG-CoA reductase inhibitors, also known as statins), prednisolone, etoposide (used to treat cancer), repaglinide (an antidiabetic medicine), immunosuppressants (everolimus, sirolimus), ambrisentan, and specific anticancer medicines called anthracyclines (e.g., doxorubicin).
Mycophenolate sodium or mycophenolate mofetil (an immunosuppressant) and eltrombopag (used to treat bleeding disorders). If you experience any of the above conditions (or are unsure), inform your doctor or pharmacist before taking Sandimmun Neoral.

Sandimmun Neoral with food and drinks
Do not take Sandimmun Neoral with grapefruit or grapefruit juice. These may affect the action of Sandimmun Neoral.

Pregnancy and breastfeeding
Ask your doctor or pharmacist for advice before taking this medicine.

Inform your doctor if you are pregnant or planning to become pregnant. Experience with Sandimmun Neoral during pregnancy is limited. In general, Sandimmun Neoral should not be taken during pregnancy. If use of this medicine is necessary, your doctor will discuss with you the benefits and potential 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 the infant.

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

Sandimmun Neoral contains ethanol
Sandimmun Neoral contains 94.70 mg of alcohol (ethanol) per ml, equivalent to 12% v/v. A 500 mg dose of Sandimmun Neoral contains 500 mg of ethanol, equivalent to approximately 13 ml of beer or 5 ml of wine. The small amount of alcohol in this medicine is unlikely to produce significant effects.

Sandimmun Neoral contains castor oil
Sandimmun Neoral contains castor oil, which may cause stomach upset and diarrhoea.

Sandimmun Neoral contains propylene glycol
This medicine contains 94.70 mg of propylene glycol per ml of oral solution.
If the child is less than 4 weeks old, speak with your doctor or pharmacist before administering this medicine, especially if the child is taking other medicines containing propylene glycol or alcohol.

3. How to take Sandimmun Neoral

Take this medicine exactly as directed by your doctor. If you have any doubts, consult your doctor.
Do not take more than the recommended dose.
Your doctor will carefully adjust the dose of this medicine according to your individual needs.
Taking too much medicine may affect kidney function. You will have regular blood tests and hospital visits, especially after a transplant. This will give you the opportunity to discuss with your doctor your treatment and any problems you may experience.

How much Sandimmun Neoral to take

In adults:
- Organ, bone marrow or stem cell transplantation
  - The total daily dose is usually between 2 mg and 15 mg per kilogram of body weight. It should be divided into two doses.
  - Higher doses are usually used before and immediately after transplantation. Lower doses are used once the transplanted organ or bone marrow has stabilized.
  - Your doctor will adjust the dose to the level appropriate for you. To do this, your doctor may need to perform certain blood tests.
- Endogenous uveitis
  - The total daily dose is usually between 5 mg and 7 mg per kilogram of body weight. It should be divided into two doses.
- Nephrotic syndrome
  - For adults, the total daily dose is usually 5 mg per kilogram of body weight. It should be divided into two doses. In patients with kidney problems, the initial daily dose should not exceed 2.5 mg per kilogram of body weight.
- Severe rheumatoid arthritis
  - The total daily dose is usually between 3 mg and 5 mg per kilogram of body weight. It should be divided into two doses.
- Psoriasis and atopic dermatitis
  - The total daily dose is usually between 2.5 mg and 5 mg per kilogram of body weight. It should be divided into two doses.
In children:
- Nephrotic syndrome
  - For children, the total daily dose is usually 6 mg per kilogram of body weight. It should be divided into two doses. In patients with kidney problems, the initial daily dose should not exceed 2.5 mg per kilogram of body weight.
  - Follow your doctor’s instructions exactly and never change the dose on your own initiative, even if you feel well.

Switching from Sandimmun to Sandimmun Neoral
You may have previously taken another medicine called Sandimmun soft gelatin capsules or Sandimmun oral solution. Your doctor may decide to switch you to this medicine, Sandimmun Neoral oral solution.

All these medicines contain ciclosporin as the active substance.
Compared to Sandimmun, Sandimmun Neoral is an improved formulation of ciclosporin. With Sandimmun Neoral, ciclosporin is better absorbed into the blood, and its absorption is less likely to be affected by food. This means that blood levels of ciclosporin will be more consistent with Sandimmun Neoral than with Sandimmun.

If your doctor switches your treatment from Sandimmun to Sandimmun Neoral:

Do not go back to taking Sandimmun unless your doctor tells you to.
After switching from Sandimmun to Sandimmun Neoral, your doctor will monitor you more closely for a short period. This is because of the change in how ciclosporin is absorbed into the blood. Your doctor will ensure that you are taking the correct dose for your individual needs.
You may experience some side effects. If this happens, contact your doctor or pharmacist. It may be necessary to reduce the dose. Never reduce the dose on your own initiative unless your doctor tells you to.

Switching from one oral ciclosporin formulation to another
After switching from one oral ciclosporin formulation to another:

Your doctor will monitor you more closely for a short period.
You may experience some side effects. If this happens, contact your doctor or pharmacist. It may be necessary to adjust the dose. Never change the dose on your own initiative unless your doctor tells you to.

When to take Sandimmun Neoral
Take Sandimmun Neoral at the same time every day. This is very important if you have had a transplant.

How to take Sandimmun Neoral
The daily doses must always be taken as two divided doses.

For initial use, follow steps 1–9.
For subsequent use, follow steps 5–9.

Opening a new bottle of Sandimmun Neoral oral solution

1. 2.	Lift the tab in the center of the aluminum ring. Completely remove the safety ring.
3. 4.	Remove the gray cap and discard it. Insert the cannula into the vial, pushing the white stopper fully into the vial neck.

Dose measurement

5. 6. 7.	Choose the syringe according to the volume of medicine to be measured: -For medicine volumes of 1 ml or less, use the 1 ml syringe. -For medicine volumes greater than 1 ml, use the 4 ml syringe. Insert the tip of the syringe into the white stopper. Pull back the plunger to draw up the correct amount of medicine. -Align the bottom of the plunger ring with the mark indicating the required amount of medicine. Push the plunger down and draw it up several times. -This will allow removal of any large air bubbles. The presence of a few small bubbles in the syringe is negligible and will not affect the dose in any way. Ensure that the correct amount of medicine is in the syringe. Then remove the syringe from the vial.
8. 9.	Transfer the drawn medicine from the syringe into a small glass container containing liquid, preferably orange or apple juice. -Make sure the syringe does not come into contact with the liquid in the container. -Stir and drink the entire contents of the glass immediately. After use, dry the outside of the syringe with a dry cloth. -Then store the syringe in its case. -Leave the white stopper and cannula in the vial. -Close the vial with the cap provided.

How long to take Sandimmun Neoral
Your doctor will tell you how long you should take Sandimmun Neoral. This depends on whether you are
taking the medicine after a transplant or for the treatment of a severe skin condition, rheumatoid arthritis,
uveitis, or nephrotic syndrome. For severe skin rash, the treatment duration is usually 8 weeks.
Continue taking Sandimmun Neoral for as long as your doctor has instructed you to do so.
If you have any questions about how long to take Sandimmun Neoral, speak with your doctor or pharmacist.

If you take more Sandimmun Neoral than you should
If you have accidentally taken too much medicine, inform your doctor immediately or go to the nearest
hospital emergency department. You may require medical treatment.

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 almost time for your next dose, skip the missed dose. Then continue as before.
Do not take a double dose to make up for the forgotten dose.

If you stop taking Sandimmun Neoral
Do not stop treatment with Sandimmun Neoral unless your doctor tells you to.
Continue taking Sandimmun Neoral even if you feel well. Stopping treatment with
Sandimmun Neoral may increase the risk of rejection of the transplanted organ.
If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Some side effects can be serious
Tell your doctor immediately if you experience any of the following serious side effects:

Like other medicines that affect the immune system, cyclosporine can affect the body's ability to fight infections and may cause tumours or other types of cancer, particularly of the skin. Signs of infection may include fever or sore throat.
Vision changes, loss 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 symptoms such as seizures, confusion, feeling disoriented, reduced responsiveness, personality changes, feeling agitated, insomnia, vision changes, blindness, coma, paralysis of part or all of the body, neck stiffness, loss of coordination with or without unusual speech or eye movements.
Swelling at the back of the eye. This may be associated with blurred vision. It may also affect vision due to increased pressure inside the head (benign intracranial hypertension).
Liver problems and liver damage, with or without yellowing of the skin and eyes, nausea, loss of appetite, and dark urine.
Kidney problems that may significantly reduce the amount of urine produced.
Low levels of red blood cells or platelets. Signs include paleness, feeling tired, difficulty breathing, dark urine (this is a sign of red blood cell breakdown), unexplained bruising or bleeding, feeling confused, feeling disoriented, reduced attention, and kidney problems.

Other side effects include:
Very common: May affect more than 1 in 10 people.

Kidney problems.
High blood pressure.
Headache.
Uncontrollable body tremors.
Excessive growth of body and facial hair.
High levels of lipids in the blood. If any of these effects become severe, tell your doctor.

Common: May affect up to 1 in 10 people.

Seizures.
Liver problems.
High blood sugar levels.
Tiredness.
Loss of appetite.
Nausea (feeling unwell), vomiting, stomach discomfort/pain, diarrhoea.
Excessive hair growth.
Acne, hot flushes.
Fever.
Low levels of white blood cells in the blood.
Numbness or tingling sensations.
Muscle pain, muscle spasms.
Stomach ulcer.
Overgrowth of the gums and covering of the teeth.
High levels of uric acid or potassium in the blood, low levels of magnesium in the blood. If any of these effects become severe, tell your doctor.

Uncommon: May affect up to 1 in 100 people.

Symptoms of brain disorders including sudden attacks, mental confusion, insomnia, disorientation, vision disturbances, loss of consciousness, feeling of weakness in limbs, reduced movements.
Skin rash.
Generalised swelling.
Weight gain.
Low levels of red blood cells, low levels of platelets in the blood which may increase the risk of bleeding. If any of these effects become severe, tell your doctor.

Rare: May affect up to 1 in 1,000 people.

Nerve problems with numbness or tingling in the fingers of the hands and feet.
Inflammation of the pancreas with severe pain in the upper stomach.
Muscle weakness, loss of muscle strength, pain in the legs, hands or any part of the body.
Destruction of red blood cells, leading to kidney problems with symptoms such as swelling of the face, stomach, hands and/or feet, reduced urine volume, difficulty breathing, chest pain, seizures, loss of consciousness.
Changes in menstrual cycle, breast enlargement in men. If any of these effects become severe, tell your doctor.

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

Swelling at the back of the eye which may be associated with increased pressure inside the head and visual disturbances. If this effect becomes severe, tell your doctor.

Not known: Frequency cannot be estimated from the available data.

Severe liver problems with or without yellowing of the skin or eyes, nausea (feeling unwell), loss of appetite, dark urine, swelling of the face, feet, hands and/or whole body.
Bleeding under the skin or purple spots, sudden bleeding without apparent cause.
Migraine or severe headache, often with feeling unwell (nausea, vomiting) and sensitivity to light.
Pain in the legs and feet.
Hearing impairment. If any of these effects become severe, tell your doctor.

If you get any side effects, including ones not listed in this leaflet, talk to your doctor or pharmacist.
Additional 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 get any side effects, including ones not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Sandimmun Neoral

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the pack.
Store at room temperature (15°C–30°C).
Do not refrigerate. Do not store at temperatures below 20°C for more than 1 month. This is because the product contains oils which may solidify at low temperatures.
If the medicine has been accidentally refrigerated, allow it to reach room temperature before using again. The presence of floccules or small particles (sediment) in the medicine does not affect the efficacy or safety of the medicine. The dose can still be accurately measured with the syringe.
The contents of the bottle are stable for 2 months after opening. After 2 months, a new bottle must be used.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. This will help protect the environment.

6. Package contents and other information

What Sandimmun Neoral contains

The active substance is ciclosporin. One ml of oral solution contains 100 mg of ciclosporin.
The other components are: DL-alpha-tocopherol, absolute ethanol, propylene glycol, mono-di-glycerides of maize oil, macrogol glycerol hydroxystearate (Ph.Eur.) / polyoxyl 40 hydrogenated castor oil (USP).

Description of the appearance of Sandimmun Neoral and contents of the pack
Sandimmun Neoral is an oral solution. It is a clear, pale yellow to brownish liquid.

Pack containing 20 ml of oral solution
Pack containing 50 ml of oral solution
Pack containing 50 ml of oral solution with 1 oral dosing syringe
Pack containing 50 ml of oral solution with 2 oral dosing syringes
The 1 ml syringe is used to measure doses of 1 ml or less. Each mark on the syringe corresponds to 0.05 ml, which contains 5 mg of ciclosporin.
The 4 ml syringe is used to measure doses greater than 1 ml up to 4 ml. Each mark on the syringe corresponds to 0.1 ml, which contains 10 mg of ciclosporin.
Pack containing 250 ml (5 x 50) of oral solution

Not all pack sizes may be marketed.

Marketing Authorization Holder
Novartis Farma S.p.A.
Viale Luigi Sturzo, 43
20154 Milan MI
Italy

Manufacturer
Novartis Farma S.p.A.
Via Provinciale Schito 131
80058 Torre Annunziata NA
Italy
Novartis Farma S.p.A.
Viale Luigi Sturzo, 43
20154 Milan MI
Italy
Novartis Farmaceutica S.A.
Gran Vía de les Corts Catalanes, 764
08013 Barcelona
Spain

This medicinal product is authorized in the Member States of the European Economic Area and in the United Kingdom (Northern Ireland) under the following names:

Name	European Economic Area Member States
Sandimmun Neoral	Austria, Bulgaria, Cyprus, Czech Republic, Denmark, Greece, Spain, Finland, Croatia, Hungary, Iceland, Italy, Malta, Norway, Poland, Portugal, Romania, Sweden, Slovakia, Slovenia
Neoral	Ireland, Netherlands, United Kingdom (Northern Ireland)
Néoral	France
Neoral - Sandimmun	Belgium, Luxembourg
Sandimmun Optoral	Germany

Other sources of information
More detailed information about this medicine is available on the website of the Italian Medicines Agency
(http://www.aifa.gov.it/)