Sandimmun

Package leaflet: Information for the patient

Sandimmun, 50 mg/ml, concentrate for solution for infusion
cyclosporine
Please read all of this leaflet carefully before using this medicine, because it contains
important information for the patient.

• Keep this leaflet, so that you can read it again if necessary.
• If you have any further questions, please ask your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. This medicine may harm other people, even if their symptoms are the same.
• If you experience any adverse reactions, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of the leaflet

1. What Sandimmun is and what it is used for
2. Important information before using Sandimmun
3. How to use 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
This medicine is called Sandimmun. It contains the active substance cyclosporine. The concentrate is used to prepare a solution for intravenous administration. This medicine belongs to a group of medicines called immunosuppressive agents. These medicines are used to reduce the body's immune response.

What Sandimmun is used for and how it works
Sandimmun is used to control the activity of the immune system after organ transplantation, including bone marrow and stem cell transplantation. It prevents rejection of transplanted organs by blocking the development of certain cells which, under normal circumstances, would attack the transplanted tissues.

2. Important information before using Sandimmun

Sandimmun will only be prescribed by a doctor experienced in transplantation.
You must carefully follow all your doctor's instructions, which may differ from the general information
provided in this leaflet.

When not to use Sandimmun

• if the patient is allergic to cyclosporine or any of the other ingredients of this medicine (listed in section 6; see also section "Sandimmun contains castor oil and ethanol");
• with medicines 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 blood pressure). Do not take Sandimmun and tell your doctor if any of these apply to you. If in doubt, speak to your doctor before taking Sandimmun.

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

• the patient develops any signs of infection, such as fever or sore throat. Sandimmun suppresses the immune system and may also affect the body's ability to fight infections;
• the patient has liver disease;
• the patient has kidney disease. The doctor will order regular blood tests and may adjust the dose if necessary;
• the patient has high blood pressure. The doctor will monitor blood pressure regularly and may prescribe medication to lower it if needed;
• the patient has magnesium deficiency. The doctor may recommend magnesium supplements, especially shortly after surgery if the patient has received a transplant;
• the patient has high potassium levels in the blood;
• the patient has gout;
• the patient requires vaccination. If any of these situations occur before or during treatment with Sandimmun, inform the doctor immediately.

Protection from sunlight and sun exposure
Sandimmun suppresses the immune system, increasing the risk of developing malignant tumours,
particularly of the skin and lymphatic system. Limit exposure to sunlight and UV radiation by:

• wearing protective clothing;
• frequently applying high-protection sunscreen.

Talk to your doctor before taking Sandimmun if:

• the patient has current or past alcohol-related problems;
• the patient has epilepsy;
• the patient has any liver disease;
• the patient is pregnant;
• the patient is breastfeeding;
• this medicine has been prescribed for a child. If any of these situations apply to the patient (or if the patient is unsure), inform the doctor before taking Sandimmun. This is due to the alcohol content of this medicine (see also below "Sandimmun contains castor oil and ethanol").

Monitoring tests during treatment with Sandimmun
The doctor will monitor the following parameters:

• blood levels of cyclosporine, especially in transplant patients;
• blood pressure, before starting treatment and regularly during treatment;
• liver and kidney function;
• blood lipid (fat) levels. If you have any questions about how Sandimmun works or why it has been prescribed, speak to your doctor.

Children and adolescents
Experience with the use of Sandimmun in children is limited.

Elderly patients (65 years and older)
Experience with the use of Sandimmun in elderly patients is limited.
In these patients, the doctor should monitor kidney function.

Sandimmun with other medicines
Tell your doctor or pharmacist about all medicines the patient is currently taking or has recently taken,
as well as any medicines the patient plans to take.
In particular, inform your doctor or pharmacist if the patient is taking any of the following medicines
before or during treatment with Sandimmun:

• 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. Used in the treatment of cancer, severe psoriasis, and severe rheumatoid arthritis.
• Medicines that may increase or decrease blood levels of cyclosporine (the active substance in Sandimmun). The doctor may recommend monitoring cyclosporine blood levels when starting or stopping treatment with other medicines.
  • Medicines that may increase cyclosporine blood levels include: antibiotics (such as erythromycin or azithromycin), antifungal medicines (voriconazole, itraconazole), medicines used to treat heart disease or high blood pressure (diltiazem, nicardipine, verapamil, amiodarone), metoclopramide (used to treat nausea and vomiting), oral contraceptives, danazol (used to treat menstrual problems), medicines used to treat gout (allopurinol), cholic acid and its derivatives (used to treat gallstones), protease inhibitors used in HIV treatment, imatinib (used to treat leukaemia or tumours), colchicine, telaprevir (used to treat hepatitis C), cannabidiol (used among others to treat epileptic seizures).
  • Medicines that may decrease cyclosporine blood levels include: barbiturates (e.g. used as sedatives), certain anticonvulsants (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 aid weight loss), herbal products containing St. John's wort, ticlopidine (used after stroke), certain blood pressure-lowering medicines (bosentan), and terbinafine (an antifungal medicine used to treat foot and nail infections).
• Medicines affecting kidney function. These include: antibacterial medicines (gentamicin, tobramycin, ciprofloxacin), antifungal medicines containing amphotericin B, medicines used to treat urinary tract infections containing trimethoprim, anticancer medicines containing melphalan, medicines used to reduce stomach acid (H--receptor antagonists that inhibit acid secretion), tacrolimus, painkillers (non-steroidal anti-inflammatory drugs such as diclofenac), and medicines containing fibric acid (fibrates, used to reduce blood fat levels).
• Nifedipine. A medicine used to treat high blood pressure and angina. Taking nifedipine during cyclosporine treatment may cause gum swelling and overgrowth around the teeth.
• Digoxin (used to treat heart conditions), cholesterol-lowering medicines (HMG-CoA reductase inhibitors, also known as statins), prednisolone, etoposide (used to treat cancer), repaglinide (an antidiabetic medicine), immunosuppressive medicines (everolimus, sirolimus), ambrisentan, and specific anticancer medicines called anthracyclines (such as doxorubicin).
• Sodium mycophenolate or mycophenolate mofetil (an immunosuppressive medicine) and eltrombopag (used to treat bleeding disorders).

If any of these situations apply to the patient (or if the patient is unsure), speak to your doctor or pharmacist before taking Sandimmun.

Sandimmun with food and drink
Do not take Sandimmun with grapefruit or grapefruit juice, as they may affect how Sandimmun works.

Pregnancy and breastfeeding
Before taking this medicine, consult your doctor or pharmacist.

• Tell your doctor if the patient is pregnant or planning to become pregnant. Experience with the use of Sandimmun during pregnancy is limited. Generally, Sandimmun should not be used during pregnancy. If the patient needs to take this medicine, the doctor will discuss the benefits and risks of using it during pregnancy.
• Tell your doctor if the patient is breastfeeding. Breastfeeding is not recommended during treatment with Sandimmun, as cyclosporine, the active ingredient, passes into human milk and may affect the infant.

Hepatitis C
Inform your doctor if the patient has hepatitis C. Liver function may change during treatment for hepatitis C, which may affect cyclosporine blood levels. Careful monitoring of cyclosporine blood levels by the doctor and possible dose adjustment may be required after starting treatment for hepatitis C.

Driving and operating machinery
The patient may experience drowsiness, disorientation, or blurred vision after taking Sandimmun.
Exercise caution when driving or operating machinery during treatment with Sandimmun until the effect of the medicine on the patient is known.

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 millilitre, equivalent to 34.4% v/v. A 100 mg dose of Sandimmun contains 556 mg of ethanol, which corresponds to almost 14 ml of beer or 6 ml of wine. The small amount of alcohol in this medicine will not cause noticeable effects.

3. How to use Sandimmun

You must strictly follow all instructions given by your doctor. If in doubt, consult your doctor.
What dose of Sandimmun will be administered
Your doctor will determine the correct dose of Sandimmun for the patient. The dose depends on the patient's body weight and the condition being treated.

• The total daily dose is usually 3 to 5 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 stable function of the transplanted organ or bone marrow has been achieved.
• Your doctor will adjust the dose of Sandimmun to ensure it is optimal for the individual patient. For this purpose, blood tests may be necessary.

How Sandimmun will be administered
This medicine will be diluted prior to administration with physiological saline solution or 5% glucose solution, in a ratio of 1:20 to 1:100, using appropriate aseptic techniques, and then given as a slow intravenous infusion lasting from 2 to 6 hours. Diluted infusion solutions must be discarded after 24 hours.
How long Sandimmun will be used
The treatment will be switched to oral cyclosporine (in capsule or oral solution form, both taken orally) as soon as possible.
Accidental overdose of Sandimmun
An excessive dose of this medicine may affect the kidneys. Regular blood tests and hospital visits will be necessary. This allows discussion with the doctor about the treatment and any problems the patient may experience.
If the patient thinks they have received too high a dose of Sandimmun, this must be reported to the doctor immediately.
If you have any further doubts regarding 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 will experience them.
Some side effects may be serious
You should immediately tell your doctor if the patient notices any of the following serious side effects:

• After intravenous administration of Sandimmun, symptoms of anaphylactic reactions have occurred. These reactions may include flushing of the face and upper chest, fluid in the lungs, shortness of breath, wheezing, changes in blood pressure (the patient may feel faint), and rapid heartbeat (tachycardia).
• Like other medicines affecting the immune system, cyclosporine may alter the body's ability to fight infections and may cause the development of tumours or other malignant neoplasms, particularly of the skin. Signs of infection may include fever or sore throat.
• Changes in vision, loss of coordination, motor incoordination, memory loss, difficulty speaking or understanding what others are saying, and muscle weakness. These may be symptoms of a brain infection called progressive multifocal leukoencephalopathy.
• Brain disorders with symptoms such as seizures, confusion, disorientation, reduced responsiveness, personality changes, agitation, insomnia, visual disturbances, blindness, coma, paralysis of part or all of the body, neck stiffness, loss of coordination with (or without) speech or eye movement disturbances.
• Swelling of the back of the eye. This may be associated with blurred vision. It may also affect vision due to increased pressure inside the head (non-tumour-related intracranial hypertension).
• Liver disorders and damage, with or without yellowing of the skin and eyes, nausea, loss of appetite, and dark urine.
• Kidney disorders, which may significantly reduce the amount of urine produced.
• Low number of red blood cells or platelets. Symptoms of these disorders include pale skin, feeling tired, breathlessness, dark urine (a sign of red blood cell breakdown), bruising or bleeding without obvious cause, feeling confused, disoriented, decreased alertness, and kidney problems.

Other side effects include:
Very common: may occur in more than 1 in 10 patients.

• Kidney function disorders;
• High blood pressure;
• Headache;
• Uncontrollable shaking of the body;
• Excessive growth of hair on the body and face;
• High levels of lipids in the blood.

If any of these symptoms occur, you should tell your doctor.
Common: may occur in up to 1 in 10 patients.

• Seizures (convulsions);
• Liver function disorders;
• High blood sugar levels;
• Fatigue;
• Loss of appetite;
• Nausea, vomiting, discomfort/pain in the abdomen, diarrhoea;
• Excessive hair growth;
• Skin rash, flushing;
• Fever;
• Low number of white blood cells;
• Numbness or tingling;
• Muscle pain, muscle cramps;
• Stomach ulcer;
• Overgrowth of the gums covering the teeth;
• High levels of uric acid and potassium in the blood, low levels of magnesium in the blood. If any of these symptoms occur, you should tell your doctor.

Uncommon: may occur in up to 1 in 100 patients.

• Symptoms of brain disorders, including sudden seizures, confusion, insomnia, disorientation, visual disturbances, loss of consciousness, feeling of limb weakness, movement disorders;
• Rash;
• Generalised swelling;
• Weight gain;
• Low number of red blood cells, low number of platelets, which may increase the risk of bleeding. If any of these symptoms occur, you should tell your doctor.

Rare: may occur in up to 1 in 1,000 patients.

• Nerve disorders with numbness or tingling in fingers of hands and feet;
• Pancreatitis with severe pain in the upper abdomen;
• Muscle weakness, loss of muscle strength, pain in legs or hands or other body muscles;
• Destruction of red blood cells, involving kidney disorders with symptoms such as swelling of the face, abdomen, hands and (or) feet, reduced urine output, difficulty breathing, chest pain, seizures, loss of consciousness;
• Changes in menstrual cycle, breast enlargement in men. If any of these symptoms occur, you should tell your doctor.

Very rare: may occur in up to 1 in 10,000 patients.

• Swelling of the back of the eye, which may be associated with increased pressure inside the head and visual disturbances. If any of these symptoms occur, you should tell your doctor.

Frequency not known: frequency cannot be estimated from available data.

• Severe liver disorders with or without yellowing of the eyes or skin, nausea, loss of appetite, dark urine, swelling of the face, feet, hands and (or) the entire body;
• Bleeding under the skin or purple spots on the skin, sudden bleeding without obvious cause;
• Migraine or severe headache, often with nausea or vomiting and sensitivity to light;
• Pain in legs and feet. If any of these symptoms occur, you should tell your doctor.

If any side effects occur, including any not listed in this leaflet, you should tell 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 any side effects occur, including any not listed in this leaflet, you should tell your doctor or pharmacist. Side effects can be reported directly to the Department of Monitoring Adverse Drug Reactions, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C
02-222 Warsaw
Tel.: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Side effects can also be reported to the marketing authorisation holder.
Reporting side effects helps provide more information on the safety of this medicine.

5. How to store Sandimmun

• Keep this medicine out of sight and reach of children.
• Do not use this medicine after the expiry date stated on the packaging.
• There are no special storage temperature requirements for this medicine.
• After opening the ampoule, the contents should be diluted using appropriate aseptic techniques and administered immediately by trained medical personnel. If the diluted solution is not administered immediately, it may be stored at 2°C to 8°C (in a refrigerator), provided that the total storage and infusion time is less than 24 hours. Discard any unused diluted solutions.
• Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. This will help protect the environment.

6. Contents of the package and other information

What the medicine Sandimmun contains

• The active substance is cyclosporine. One ml of concentrate for solution for infusion contains 50 mg of cyclosporine.
• The other ingredients are: anhydrous ethanol, polyoxyethylated castor oil.

What Sandimmun looks like and contents of the pack
Sandimmun concentrate for solution for infusion is available in ampoules containing
1 ml of concentrate. The concentrate is a clear, brownish-yellow, oily liquid. It is administered
by a doctor or nurse to prepare an infusion solution for slow intravenous infusion.
The clinical pack contains 10 ampoules of 1 ml each.
Marketing Authorisation Holder
Novartis Poland Sp. z o.o.
ul. Marynarska 15
02-674 Warsaw
Tel. + 48 22 375 48 88
Manufacturer/Importer
Novartis Pharma GmbH
Jakov-Lind-Straße 5, Top 3.05
1020 Vienna
Austria
Novartis Pharma S.A.S.
8-10 rue Henri Sainte-Claire Deville
92500 Rueil-Malmaison
France
Novartis (Hellas) S.A.C.I.
12th km National Road Athens-Lamia
14451 Metamorphoses
Greece
Novartis Farmaceutica SA
Gran Via de les Corts Catalanes, 764
08013 Barcelona
Spain
Novartis Pharma B.V.
Haaksbergweg 16
1101 BX Amsterdam
The Netherlands
Novartis Pharma GmbH
Sophie-Germain-Strasse 10
90443 Nuremberg
Germany
Novartis Farma - Produtos Farmacêuticos S.A.
Avenida Professor Doutor Cavaco Silva, n.10E
Taguspark
2740-255 Porto Salvo
Portugal
Novartis Sverige AB
Torshamnsgatan 48
164 40 Kista
Sweden
Novartis Hungária Kft.
Bartók Béla út 43-47.
1114 Budapest
Hungary
Novartis Farma S.p.A.
Via Provinciale Schito 131
80058 Torre Annunziata, NA
Italy
Novartis Farma S.P.A.
Largo Umberto Boccioni,1
21040 Origgio (VA)
Italy
This medicinal product is authorised in the European Economic Area countries and in the United Kingdom (Northern Ireland)
under the following names:
The Netherlands Sandimmune
Austria, Belgium, Croatia, Czech Republic, Denmark, Finland, France, Sandimmun
Germany, Greece, Hungary, Iceland, Ireland, Italy, Luxembourg,
Norway, Poland, Portugal, Slovakia, Slovenia, Spain,
Sweden, United Kingdom (Northern Ireland)
Other sources of information
Detailed information on this medicine is available on the website
https://www.gov.pl/web/urpl.