Sandimmun

Package leaflet: Information for the patient

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

ciclosporin
Please read this leaflet carefully before 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, because it could be harmful.
• If you experience any side effect, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What is Sandimmun and what is it used for

What is Sandimmun
The name of this medicine is Sandimmun. 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 is used for and how Sandimmun works

• If you have received an organ transplant, a bone marrow transplant or a stem cell transplant, the function of Sandimmun is to suppress your body's immune system. Sandimmun prevents rejection of transplanted organs by inhibiting 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 blocks the immune reaction. These diseases include eye disorders that threaten 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 known as nephrotic syndrome.

2. What you should know before taking Sandimmun

If you are taking Sandimmun following a transplant, the medicine will be prescribed to you only by a doctor experienced in transplantation and/or autoimmune diseases.
The warnings provided 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 given by your doctor. These may differ from the general information contained in this leaflet.

Do not take Sandimmun:

• 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 and inform your doctor if any of the above conditions apply to you. If you are unsure, ask your doctor before taking Sandimmun.

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

• if you have any signs of infection, such as fever or sore throat. Sandimmun 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 necessary, 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 transplant surgery.
• if you have high levels of potassium in your blood.
• if you have gout.
• if you need vaccination. If any of the above conditions apply to you, before or during treatment with Sandimmun, inform your doctor immediately.

Sun exposure and sun protection
Sandimmun 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 a sunscreen with a high sun protection factor.

Inform your doctor before taking Sandimmun:

• if you have or have had alcoholism.
• 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 to a child. If you experience any of the above conditions (or are unsure), inform your doctor before taking Sandimmun. This is because this medicine contains alcohol (see the section below “Sandimmun contains ethanol”).

Monitoring during treatment with Sandimmun
Your doctor will monitor:

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

Additionally, if you are taking Sandimmun 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:

• if you have kidney problems (except nephrotic syndrome).
• if you have an infection that is not controlled with therapy.
• if you have any type of cancer.
• if you have high blood pressure (hypertension) that is not controlled with therapy. If high blood pressure develops during treatment and cannot be controlled, Sandimmun must be discontinued by your doctor. Do not take Sandimmun if any of the above conditions apply to you. If you are unsure, inform your doctor or pharmacist before taking Sandimmun.

If you are being treated for Behçet’s uveitis, your doctor will pay particular attention to whether you develop neurological symptoms (e.g.: increased forgetfulness, personality changes observed over time, psychiatric or mood disorders, burning sensation in limbs, reduced limb sensitivity, tingling in limbs, limb weakness, gait disturbances, 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 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 must not be administered to children for conditions other than transplantation, except for the treatment of nephrotic syndrome.

Elderly (65 years of age and over)
Experience with Sandimmun in elderly patients is limited. Your doctor must check that your kidneys are functioning properly. If you are over 65 years old and suffer from psoriasis or atopic dermatitis, you should be treated with Sandimmun only if your condition is particularly severe.

Other medicines and Sandimmun
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:

• Medicines that may affect potassium levels. These include medicines containing potassium, potassium supplements, diuretic tablets (diuretics) known as potassium-sparing diuretics, and certain medicines used to lower blood pressure.
• Methotrexate. This is a medicine used to treat tumours, severe psoriasis, and severe rheumatoid arthritis.
• Medicines that may increase or decrease ciclosporin (the active ingredient in Sandimmun) blood levels. Your doctor may monitor ciclosporin blood levels at the start or end of treatment with 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 leukaemia or tumours), 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 aid sleep), some anticonvulsant medicines (such as carbamazepine or phenytoin), octreotide (used to treat acromegaly or neuroendocrine tumours 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 have effects on the kidneys. These include: antibacterial medicines (gentamicin, tobramycin, ciprofloxacin), antifungal medicines containing amphotericin B, medicines used for urinary tract infections containing trimethoprim, anticancer medicines containing melphalan, medicines used to reduce stomach acid (acid secretion inhibitors of the H-receptor antagonist type), tacrolimus, painkillers (non-steroidal anti-inflammatory medicines such as diclofenac), fibric acid derivatives (used to reduce blood fat levels).
• Nifedipine. It is used to treat high blood pressure and heart pain. If you are taking nifedipine during ciclosporin treatment, you may experience swelling and thickening of the 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 coagulation disorders). If you experience any of the above conditions (or are unsure), inform your doctor or pharmacist before taking Sandimmun.

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

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

• Inform your doctor if you are pregnant or intend to become pregnant. Experience with Sandimmun during pregnancy is limited. In general, Sandimmun should not be taken during pregnancy. If treatment with 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. This is because ciclosporin, the active ingredient, passes into breast milk. This may affect the baby.

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 ciclosporin blood levels and adjust the dose after starting hepatitis C treatment.

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

Sandimmun contains ethanol
Sandimmun contains 25, 50, 100 mg of alcohol (ethanol) per 25, 50, 100 mg capsule respectively, equivalent to 12.8% v/v. A 500 mg dose of Sandimmun 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 contains sorbitol
This medicine contains 30 mg of sorbitol in each 25 mg capsule
This medicine contains 62.4 mg of sorbitol in each 50 mg capsule
This medicine contains 103.8 mg of sorbitol in each 100 mg capsule

3. How to take Sandimmun

Take this medicine exactly as prescribed 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 be regularly monitored with blood tests and hospital visits, especially after a transplant. This will give you the opportunity to discuss your treatment and any problems you may have with your doctor.

How much Sandimmun to take

Your doctor will determine the correct dose of Sandimmun 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 it.

• 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, 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 appropriate level for you. To do this, your doctor may need to perform blood tests.
  • Endogenous uveitis
    • The total daily dose is usually between 5 mg and 7 mg per kilogram of body weight, divided into two doses.
  • Nephrotic syndrome
    • In adults, the total daily dose is usually 5 mg per kilogram of body weight, 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, 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, divided into two doses.

• In children:

  • Nephrotic syndrome
    • In children, the total daily dose is usually 6 mg per kilogram of body weight, 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.

If your doctor switches you from one oral formulation of ciclosporin 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. Your dose may need to be adjusted. Never change the dose on your own unless instructed by your doctor.

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

How to take Sandimmun
The daily dose 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
Your doctor will tell you how long you should take Sandimmun. 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 usually lasts 8 weeks.
Continue taking Sandimmun for as long as your doctor has instructed.
If you have any questions about how long to take Sandimmun, speak to your doctor or pharmacist.

If you take more Sandimmun than you should
If you accidentally take 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

• 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 missed dose.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone will experience them.
Some side effects can be serious
Contact 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.
• Changes in vision, 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, disorientation, reduced responsiveness, personality changes, restlessness, insomnia, vision disturbances, 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 (a sign of red blood cell breakdown), unexplained bruising or bleeding, feeling confused, disorientation, 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, contact your doctor.

Common: may affect up to 1 in 10 people.

• Seizures.
• Liver problems.
• High blood sugar levels.
• Fatigue.
• 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.
• Tingling or numbness sensation.
• Muscle pain, muscle spasms.
• Stomach ulcer.
• Overgrowth of the gums and covering of 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, contact 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, 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, contact your doctor.

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

• Nerve problems with numbness or tingling in fingers and toes.
• Inflammation of the pancreas with severe pain in the upper stomach.
• Muscle weakness, loss of muscle strength, leg, hand or generalised body muscle pain.
• 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 males. If any of these effects become severe, contact 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, contact 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 entire body.
• Bleeding under the skin or purple-coloured spots, sudden bleeding without apparent cause.
• Migraine or severe headache, often with malaise (nausea, vomiting) and sensitivity to light.
• Leg and foot pain.
• Hearing impairment. If any of these effects become severe, contact your doctor.

If you experience any side effect, including those not listed in this leaflet, consult 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 experience any side effect, including those not listed in this leaflet, consult 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.
Reporting side effects can help provide more information on the safety of this medicine.

5. How to store Sandimmun

• Keep this medicine out of the sight and reach of children.
• Do not use this medicine after the expiry date stated on the packaging.
• Do not store the capsules in a warm place. Store below 30°C.
• Leave the capsules in the blister pack. Remove the capsules only 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 you no longer use. This will help protect the environment.

6. Package contents and other information

What Sandimmun contains

• The active substance is ciclosporin. Each capsule contains 25 mg of ciclosporin.

• The other components are:
  o Capsule contents: absolute ethanol, interesterified corn oil, refined corn oil.
  o Capsule shell: red iron oxide (E172), titanium dioxide (E171), glycerol 85%, sorbitol syrup, gelatin.

• The active substance is ciclosporin. Each capsule contains 50 mg of ciclosporin.

• The other components are:
  o Capsule contents: absolute ethanol, interesterified corn oil, refined corn oil.
  o Capsule shell: yellow iron oxide (E172), titanium dioxide (E171), glycerol 85%, sorbitol syrup, gelatin.

• The active substance is ciclosporin. Each capsule contains 100 mg of ciclosporin.

• The other components are:
  o Capsule contents: absolute ethanol, interesterified corn oil, refined corn oil.
  o Capsule shell: red iron oxide (E172), titanium dioxide (E171), glycerol 85%, sorbitol syrup, gelatin.

Description of the appearance of Sandimmun and contents of the pack
Sandimmun 25 mg soft capsules are pink, oval-shaped.
Sandimmun 50 mg soft capsules are golden yellow, elongated in shape.
Sandimmun 100 mg soft capsules are pale pink, elongated in shape.
Sandimmun 25 mg, 50 mg and 100 mg soft capsules
Pack sizes: 30, 50 soft capsules
Pack size: 500 (10 x 50) soft capsules
Not all pack sizes may be marketed.

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

Manufacturer
Novartis Farma S.p.A.
Via Provinciale Schito 131
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

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

Other sources of information
More detailed information about this medicinal product is available on the website of the Italian Medicines Agency (http://www.aifa.gov.it/)
Package leaflet: information for the patient

Sandimmun 100 mg/ml oral solution

ciclosporin
Please read this leaflet carefully before 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, 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, because it could be harmful.
• If you experience any side effects, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What Sandimmun is and what it is used for

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

• If you have received an organ transplant, a bone marrow transplant or a stem cell transplant, the function of Sandimmun is to suppress your body's immune system. Sandimmun 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 blocks this immune reaction. Such 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

If you are taking Sandimmun following a transplant, the medicine will be prescribed to you only by a
physician experienced in transplantation and/or autoimmune diseases.
The warning provided 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 given by your doctor. These may differ from the general information
contained in this leaflet.
Do not take Sandimmun:

• 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 and inform your doctor if any of the above conditions apply to you. If you
are unsure, consult your doctor before taking Sandimmun.
Warnings and precautions
Before and during treatment with Sandimmun, inform your doctor immediately:

• if you have any signs of infection, such as fever or sore throat. Sandimmun 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 magnesium levels in your body. Your doctor may prescribe magnesium supplements, especially shortly after transplant surgery.
• if you have high potassium levels in your blood.
• if you have gout.
• if you need vaccination. If any of the above conditions apply to you, before or during treatment with Sandimmun, inform your doctor immediately.

Sun exposure and sun protection
Sandimmun 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:

• 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 experience any of the conditions listed above (or are uncertain), inform your doctor before taking Sandimmun. This is because this medicine contains alcohol (see section below “Sandimmun contains ethanol”).

Monitoring during treatment with Sandimmun
Your doctor will monitor:

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

Additionally, if you are taking Sandimmun 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:

• if you have kidney problems (except 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 therapy. If high blood pressure develops during treatment and cannot be controlled, Sandimmun must be discontinued by your doctor. Do not take Sandimmun if any of the above conditions apply to you. If you are unsure, inform your doctor or pharmacist before taking Sandimmun.

If you are being treated for Behçet's uveitis, your doctor will pay particular attention to any neurological symptoms (for example: increasing forgetfulness, personality changes over time, psychiatric or mood disorders, burning sensation in limbs, reduced limb sensitivity, tingling in limbs, limb weakness, gait disturbances, 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 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 must not be administered to children for conditions other than transplantation, except for the treatment of nephrotic syndrome.
Elderly (65 years of age and over)
Experience with Sandimmun 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 should only be considered if the condition is particularly severe.
Other medicines and Sandimmun
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:

• Medicines that may affect potassium levels. These include medicines containing potassium, potassium supplements, diuretic tablets (diuretics) known as potassium-sparing diuretics, and certain medicines used to lower blood pressure.
• Methotrexate. This is a medicine used to treat cancer, severe psoriasis, and severe rheumatoid arthritis.
• Medicines that may increase or decrease ciclosporin (the active substance in Sandimmun) blood levels. Your doctor may monitor ciclosporin blood levels at the start or end of treatment with 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 in HIV treatment, 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 intestinal tumors), 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, anticancer medicines containing melphalan, medicines used to reduce stomach acid (acid secretion inhibitors such as H-receptor antagonists), 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 coagulation disorders). If you experience any of the above conditions (or are uncertain), inform your doctor or pharmacist before taking Sandimmun.

Sandimmun with food and drinks
Do not take Sandimmun with grapefruit or grapefruit juice. These can affect the action of Sandimmun.
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 during pregnancy is limited. In general, Sandimmun should not be taken during pregnancy. If treatment with 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. 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. Be cautious when driving or operating machinery while taking Sandimmun until you know how it affects you.
Sandimmun contains ethanol
Sandimmun contains 100 mg of alcohol (ethanol) per ml, equivalent to 12.6% v/v. A 500 mg dose of Sandimmun contains 500 mg of ethanol, equivalent to 13 ml of beer or 5 ml of wine.
The small amount of alcohol in this medicine will not produce significant effects.

3. How to take Sandimmun

Take this medicine exactly as prescribed 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 be regularly monitored with blood tests and hospital visits, especially after a transplant. This will give you the opportunity to discuss your treatment and any problems you may experience with your doctor.

How much Sandimmun to take
Your doctor will determine the correct dose of Sandimmun 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 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 appropriate level 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 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 initiative, even if you feel well.

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 instructed by your doctor.

When to take Sandimmun
Take Sandimmun every day at the same time. This is very important if you have had a
transplant.
How to take Sandimmun
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 vial of Sandimmun oral solution

Dosage measurement

How long to take Sandimmun
Your doctor will tell you how long you should take Sandimmun. 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 duration of treatment is usually 8 weeks.
Continue taking Sandimmun for as long as your doctor has instructed you to do so.
If you have any questions about how long to take Sandimmun, talk to your doctor or pharmacist.

If you take more Sandimmun 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 need medical treatment.

If you forget to take Sandimmun

• 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
Do not stop treatment with Sandimmun unless your doctor tells you to.
Continue taking Sandimmun even if you feel well. Stopping treatment with Sandimmun 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 everyone gets them.
Some side effects can be serious
Tell your doctor immediately if you experience any of the following serious side effects:

• As with other medicines that affect the immune system, cyclosporine 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 say, and muscle weakness. These could be signs of a brain infection called progressive multifocal leucoencephalopathy.
• Brain problems with symptoms such as seizures, confusion, feeling disoriented, reduced responsiveness, personality changes, feeling agitated, insomnia, vision disturbances, 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 (a sign of red blood cell breakdown), bruising or bleeding without obvious cause, 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 side 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 sensation.
• 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 side 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 the 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 side effects become severe, tell your doctor.

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

• Nervous system problems with numbness or tingling in fingers of hands and feet.
• Inflammation of the pancreas with severe pain in the upper stomach.
• Muscle weakness, loss of muscle strength, pain in 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, enlargement of breast gland in men. If any of these side 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 side 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-coloured 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 side effects become severe, tell your doctor.

If you experience any side effect, 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 experience any side effect, 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 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

• 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 below 30°C.
• Do not refrigerate.
• If the medicine is accidentally placed in the refrigerator, 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 vial are stable for 2 months after opening. After 2 months, a new vial 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 contains

• The active substance is cyclosporine. One ml of oral solution contains 100 mg of cyclosporine.
• The other components are absolute ethanol, interesterified corn oil, refined corn oil.

Description of the appearance of Sandimmun and contents of the pack
Sandimmun is a solution for oral use. It is a clear, yellow to yellowish-brown liquid with a slight, very fine sediment.

• 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 cyclosporine.
• 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 cyclosporine.

Pack size: 20 ml, 50 ml oral solution
Pack size: 50 ml oral solution with 2 oral dosing syringes
Not all pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer
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

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:

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/)
Package leaflet: information for the patient

Sandimmun 50 mg/ml concentrate for solution for infusion

ciclosporin
Please read this leaflet carefully before 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 others, even if they have the same symptoms as yours, because it could be harmful.
• If you experience any side effect, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What Sandimmun is and what it is used for

What Sandimmun is
The name of the medicine is Sandimmun. It contains the active substance ciclosporin. The concentrate is used
to prepare a solution that is administered by intravenous infusion. Ciclosporin belongs to a group of medicines
known as immunosuppressive agents. These medicines are used to reduce the body's immune responses.
What Sandimmun is used for and how Sandimmun works
Sandimmun is used to control the body's immune system after an organ transplant, including bone marrow
and stem cell transplants. It prevents rejection of transplanted organs by blocking the development of certain cells
that would normally attack the transplanted tissue.

2. What you need to know before taking Sandimmun

Sandimmun will only be prescribed to you by a doctor experienced in transplantation.
Carefully follow all instructions provided by your doctor. These may differ from the general information
contained in this leaflet.
Do not take Sandimmun:

• If you are allergic to ciclosporin or to any of the other ingredients of this medicine (listed in section 6; see also the section below “Sandimmun contains castor oil and ethanol”).
• 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 and inform your doctor if any of the above conditions apply to you. If you are
unsure, ask your doctor before taking Sandimmun.
Warnings and precautions
Before and during treatment with Sandimmun, inform your doctor immediately:

• If you have any signs of infection, such as fever or sore throat. Sandimmun 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 medication 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, inform your doctor immediately.

Sun exposure and sun protection
Sandimmun 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 sun protection factor.

Inform your doctor before taking Sandimmun:

• If you have or have had alcoholism.
• 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 experience any of the conditions listed above (or are unsure), inform your doctor before taking Sandimmun. This is because this medicine contains alcohol (see the section below “Sandimmun contains castor oil and ethanol”).

Monitoring during treatment with Sandimmun

• Your doctor will check:
• Ciclosporin levels in your blood, especially if you have undergone transplantation,
• Blood pressure before starting treatment and regularly during treatment,
• How well your liver and kidneys are functioning,
• Lipids in your blood (fats). If you have any questions about how Sandimmun works or why this medicine has been prescribed for you, ask your doctor.

Children and adolescents
Experience with Sandimmun in children is limited.
Elderly (65 years of age and over)
Experience with Sandimmun in elderly patients is limited. Your doctor must monitor proper kidney function.
Other medicines and Sandimmun
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:

• Medicines that may affect potassium levels. These include medicines containing potassium, potassium supplements, diuretic tablets (diuretics) known as potassium-sparing diuretics, and certain medicines used to lower blood pressure.

• Methotrexate. This is a medicine used to treat cancer, severe psoriasis, and severe rheumatoid arthritis.

• Medicines that may increase or decrease ciclosporin levels (the active substance in Sandimmun) in the blood. Your doctor may monitor ciclosporin blood levels at the start or end of treatment with other medicines.

• Medicines that may increase ciclosporin levels in the 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 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 levels in the blood include: barbiturates (used to aid 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, anticancer 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. It is used to treat high blood pressure and heart pain. If you are taking nifedipine during ciclosporin treatment, you may experience swelling and thickening of the gums around your teeth.

• Digoxin (used to treat heart problems), cholesterol-lowering medicines (HMG-CoA reductase inhibitors, also called 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 blood clotting disorders). If you experience any of the above conditions (or are unsure), inform your doctor or pharmacist before taking Sandimmun.

Sandimmun with food and drink
Do not take Sandimmun with grapefruit or grapefruit juice. These may affect the action of Sandimmun.
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 during pregnancy is limited. In general, Sandimmun 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. This is because ciclosporin, the active ingredient, passes into breast milk. This may affect the baby.

Hepatitis C
Inform your doctor if you have hepatitis C. Your liver function may change during treatment for hepatitis C, which may affect ciclosporin blood levels. Your doctor may need to closely monitor your blood levels of ciclosporin and adjust the dose after starting treatment for hepatitis C.
Driving and using machines
You may feel drowsy, disoriented, or experience blurred vision after taking Sandimmun.
Be cautious when driving or operating machinery while taking Sandimmun until you know how it affects you.
Sandimmun contains castor oil and ethanol
Sandimmun concentrate for solution for infusion contains castor oil, which may cause severe allergic reactions.
Sandimmun concentrate for solution for infusion contains 278 mg of alcohol (ethanol) in each ml, equivalent to 34.4% v/v. A 100 mg dose of Sandimmun contains 556 mg of ethanol. This is equivalent to almost 14 ml of beer or 6 ml of wine.
The small amount of alcohol in this medicine will not produce significant effects.

3. How to take Sandimmun

Follow your doctor's instructions exactly. If you have any doubts, consult your doctor.
How much Sandimmun will be given to you
Your doctor will determine the correct dose of Sandimmun for you. This dose depends on your body weight and the reason why you are receiving the medicine.

• The total daily dose is usually between 3 mg and 5 mg per kilogram of body weight. It should be divided into two doses.
• Usually, higher doses are used before and shortly after transplantation. Lower doses are used once the transplanted organ or bone marrow has stabilized.
• Your doctor will adjust the dose to the appropriate level for you. To do this, your doctor may need to perform some blood tests.

How Sandimmun will be used
The medicine will be diluted before use with physiological saline or 5% glucose solution and then administered to you as a slow intravenous infusion.
How long Sandimmun will be used
You will be switched to cyclosporine in the form of capsules or oral solution (both taken by mouth) as soon as possible.
If you have been given more Sandimmun than you should have
Too much medicine can affect how well your kidneys work. You will be regularly monitored with blood tests and hospital visits. This will give you the opportunity to discuss your treatment and any problems you may have with your doctor.
If you think you have been given too much, inform your doctor immediately.
If you have any other questions about the use of this medicine, ask 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:

• Signs of anaphylactoid reactions have occurred following intravenous administration of Sandimmun. These reactions may present as facial and upper chest flushing, fluid in the lungs, shortness of breath, wheezing, changes in blood pressure (you may feel faint), and rapid heartbeat (tachycardia).
• Like other medicines that affect the immune system, cyclosporine 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 say, and muscle weakness. These may be signs of a brain infection called progressive multifocal leukoencephalopathy.
• Brain problems with symptoms such as seizures, confusion, disorientation, poor 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 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 (a sign of red blood cell breakdown), unexplained bruising or bleeding, feeling confused, disorientation, 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 side 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 side 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 side effects become severe, tell your doctor.

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

• Nerve problems with numbness or tingling in fingers and toes.
• Inflammation of the pancreas with severe pain in the upper stomach.
• Muscle weakness, loss of muscle strength, pain in 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 side 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 side 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 the whole body.
• Bleeding under the skin or purple spots, sudden unexplained bleeding.
• Migraine or severe headache, often with nausea, vomiting, and sensitivity to light.
• Leg and foot pain.
• Hearing impairment. If any of these side effects become severe, tell your doctor.

If you experience any side effect, 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 experience any side effect, 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 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

• Keep this medicine out of the sight and reach of children.
• Do not use this medicine after the expiry date stated on the pack.
• This medicine does not require any special storage temperature.
• Once the vial has been opened, the contents must be used immediately or stored in the refrigerator (2°C - 8°C).
• After dilution, the solution must be used immediately or stored in the refrigerator (2°C - 8°C) and discarded after 24 hours.
• Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Sandimmun contains

• The active substance is cyclosporine. One ml of concentrate for solution for infusion contains 50 mg of cyclosporine.
• The other components are: absolute ethanol, polyoxyl 40 hydrogenated castor oil.

Description of the appearance of Sandimmun and contents of the pack
Sandimmun concentrate for solution for infusion is supplied in vials containing 1 ml or 5 ml of concentrate. The concentrate is a clear, oily, yellow/brown liquid. It is used by the doctor or nurse to prepare a solution which will be administered to you by slow intravenous infusion.
Pack of 10 vials containing 1 ml
Pack of 10 vials containing 5 ml
It is possible that not all pack sizes are marketed.

Marketing Authorisation Holder and Manufacturer
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
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 authorised in the European Economic Area and in the United Kingdom (Northern Ireland) under the following names:

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/)
Instructions for opening vials of Sandimmun 50 mg/ml concentrate for solution for infusion:
To properly open the vials, follow the instructions below: