Package leaflet: Information for the patient

Cyclaid, 25 mg, soft capsules
Cyclaid, 50 mg, soft capsules
Cyclaid, 100 mg, soft capsules
Cyclosporine
Please read carefully the entire leaflet before using the medicine, as it contains
important information for the patient.

Keep this leaflet, so that you can read it again if necessary.
If you have any doubts, please consult your doctor or pharmacist.
This medicine has been prescribed for a specific individual. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same.
If you experience any adverse effects, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Table of contents

What Cyclaid is and what it is used for
Important information before taking Cyclaid
How to take Cyclaid
Possible side effects
How to store Cyclaid
Contents of the pack and other information

1. What Cyclaid is and what it is used for

What Cyclaid is
This medicine is called Cyclaid. It contains the active substance cyclosporine. This medicine belongs to a group of medicines known as immunosuppressive agents. These medicines are used to reduce the body's immune response.

What Cyclaid is used for and how it works

In patients who have undergone organ, bone marrow, or stem cell transplantation, Cyclaid acts by controlling the immune system. Cyclaid prevents rejection of the transplanted organ by inhibiting the development of certain cells that would normally attack the transplanted tissue.
In patients with autoimmune diseases, in which the immune system attacks the body's own cells, Cyclaid suppresses this immune reaction. Such diseases include sight-threatening eye disorders (endogenous uveitis, including uveitis in Behçet's disease), severe cases of certain skin diseases (atopic dermatitis or eczema and psoriasis), severe rheumatoid arthritis, and a kidney disease called nephrotic syndrome.

2. Important information before using Cyclaid

Patients receiving Cyclaid will be prescribed this medicine exclusively by a physician experienced in transplantation and/or autoimmune diseases.
The recommendations in this leaflet may differ depending on whether the patient is taking this medicine due to organ transplantation or for the treatment of an autoimmune disease.
Carefully follow all instructions provided by the physician. These may differ from the general information contained in this leaflet.

When not to use Cyclaid:

if the patient is allergic to cyclosporine or any of the other ingredients of this medicine (listed in section 6),
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 use Cyclaid and inform the doctor if any of these situations apply to the patient. If in doubt, speak with the doctor before using Cyclaid.

Warnings and precautions
Before and during treatment with Cyclaid, immediately inform the doctor if:

the patient develops any signs of infection, such as fever or sore throat. Cyclaid suppresses the immune system and may reduce 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 develops high blood pressure. The doctor will monitor blood pressure regularly and may prescribe antihypertensive medication 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 levels of potassium in the blood.
the patient has gout.
the patient is due to be vaccinated.

If any of these situations occur before or during treatment with Cyclaid, inform the doctor immediately.

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

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

Inform the doctor before using Cyclaid if:

the patient has had problems related to alcohol consumption, currently or in the past,
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 the above situations apply to the patient (or the patient is unsure), inform the doctor before using Cyclaid, as this medicine contains alcohol (see also below "Cyclaid contains ethanol").

Monitoring tests during treatment with Cyclaid
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 there are any questions about how Cyclaid works or why it has been prescribed, consult the doctor.

Additionally, patients taking Cyclaid for indications other than post-transplantation
(intermediate or posterior uveitis and uveitis in Behçet's disease, atopic dermatitis, severe rheumatoid arthritis, or nephrotic syndrome) should not take Cyclaid if:

the patient has kidney disease (except nephrotic syndrome);
the patient has an infection that cannot be controlled with medication;
the patient has any malignant tumor;
the patient has untreated or uncontrolled high blood pressure (hypertension). If high blood pressure develops during treatment and cannot be controlled with medication, the doctor should discontinue Cyclaid. Do not use Cyclaid if any of these situations apply to the patient. If in doubt, consult the doctor or pharmacist before using Cyclaid.

In patients being treated for uveitis in Behçet's disease, the doctor will closely monitor the patient if neurological symptoms occur (e.g., increased forgetfulness, personality changes during treatment, psychiatric disorders or mood disturbances, burning sensation in the limbs, reduced sensation in the limbs, tingling in the limbs, limb weakness, gait disturbances, headache with or without nausea and vomiting, visual disturbances including limited eye movement).

The doctor will closely monitor treatment in elderly patients and in patients being treated for psoriasis or atopic dermatitis. If Cyclaid has been prescribed for the treatment of psoriasis or atopical dermatitis, the patient must not expose themselves to UVB radiation or undergo phototherapy during treatment.

Children and adolescents
Cyclaid should not be given to children for non-transplantation-related diseases, except for the treatment of nephrotic syndrome.

Elderly patients (65 years of age and older)
Experience with the use of Cyclaid in elderly patients is limited. In these patients, the doctor should monitor kidney function. Patients aged 65 years and older with psoriasis or atopic dermatitis should only be treated with Cyclaid if their disease is particularly severe.

Cyclaid and other medicines
Inform the 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.

Specifically, inform the doctor or pharmacist if the patient is taking any of the following medicines before or during treatment with Cyclaid:

Medicines that may affect potassium levels. These include potassium-containing medicines, potassium supplements, 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 Cyclaid). The doctor may recommend monitoring cyclosporine blood levels when starting or stopping 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 vomiting), oral contraceptives, danazol (used to treat menstrual disorders), 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 leukemia or tumors), 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 sleeping pills), certain anticonvulsants (such as carbamazepine or phenytoin), octreotide (used to treat acromegaly or neuroendocrine intestinal tumors), antibacterial medicines used to treat tuberculosis, orlistat (used for weight reduction), herbal medicines 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 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\textsubscript{2}-receptor antagonists), tacrolimus, painkillers (non-steroidal anti-inflammatory drugs such as diclofenac), medicines containing fibric acid (used to reduce blood fats, known as fibrates).
Nifedipine. A medicine used to treat high blood pressure and angina. Using nifedipine during cyclosporine treatment may cause gum swelling and overgrowth around the teeth.
Digoxin (used to treat heart disease), 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). If any of these situations apply to the patient (or the patient is unsure), consult the doctor or pharmacist before using Cyclaid.

Cyclaid with food and drink
Do not take Cyclaid with grapefruit or grapefruit juice, as they may affect the action of Cyclaid.

Pregnancy and breastfeeding
Consult the doctor or pharmacist before taking any medicine. The doctor will discuss with the patient the risks associated with taking Cyclaid during pregnancy.
Inform the doctor if the patient is pregnant or planning to become pregnant.
Experience with the use of Cyclaid during pregnancy is limited. Generally, Cyclaid should not be used during pregnancy. If it is necessary for the patient to take this medicine, the doctor will discuss the benefits and risks of using it during pregnancy.
Inform the doctor if the patient is breastfeeding. Breastfeeding is not recommended during treatment with Cyclaid, as cyclosporine, the active substance, passes into breast milk and may affect the breastfed infant.

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

Driving and operating machinery
Cyclaid contains alcohol, which may impair the ability to drive or operate machinery.

Cyclaid contains macrogolglycerol hydroxystearate, which may cause stomach irritation and diarrhea.

Cyclaid contains ethanol
This medicine contains 25 mg, 50 mg, or 100 mg of alcohol (ethanol) in each capsule containing 25 mg, 50 mg, or 100 mg of cyclosporine, respectively. A 500 mg dose of cyclosporine contains 500 mg of ethanol, equivalent to less than 13 ml of beer or 5 ml of wine.
The small amount of alcohol in this medicine will not cause noticeable effects.

Cyclaid contains propylene glycol
The medicine contains 47.25 mg of propylene glycol in each 25 mg capsule.
The medicine contains 79 mg of propylene glycol in each 50 mg capsule.
The medicine contains 136.5 mg of propylene glycol in each 100 mg capsule.
Before administering the medicine to a child under 4 weeks of age, consult the doctor or pharmacist, especially if the child is taking other medicines containing propylene glycol or alcohol.

3. How to use Cyclaid

This medicine should always be used as directed by the doctor. If in doubt, consult the
doctor.
Do not take more medicine than prescribed.
The doctor will adjust the dose of this medicine according to the patient's condition. Excessive amounts of the medicine may affect
kidney function. The patient should attend regular blood tests and hospital visits, especially
after transplantation. The patient will have the opportunity to discuss the treatment and any
related problems with the doctor.
How much Cyclaid should be taken
The doctor will adjust the dose of Cyclaid for the patient. The dose depends on the patient's body weight and the reason for which the medicine is being used. The treating doctor will also inform the patient 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 is divided into two doses.
Higher doses are usually used before and immediately after transplantation. Lower doses are used after achieving stable function of the transplanted organ or bone marrow.
The doctor will adjust the dose of the medicine to make it optimal for the individual patient. For this purpose, blood tests may be necessary.

Endogenous uveitis

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

Nephrotic syndrome

The total daily dose is usually 5 mg per kilogram of body weight. It is divided into two doses. In patients with kidney disease, the first 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 is divided into two doses.

Psoriasis and atopic dermatitis

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

In children:
Nephrotic syndrome

The total daily dose is usually 6 mg per kilogram of body weight. It is divided into two doses. In patients with kidney disease, the first daily dose should not exceed 2.5 mg per kilogram of body weight. The patient must strictly follow the doctor's instructions and never change the dose of the medicine independently, even if feeling well.

If the doctor switches from one oral cyclosporine medicine to another
After switching from one oral form of cyclosporine to another:
The doctor will closely monitor the patient's condition for a short period.
Certain adverse effects may occur. If this happens, inform the
doctor or pharmacist. A dose adjustment may be necessary. Never
change the dose independently unless instructed by the doctor.
When to take Cyclaid
Cyclaid should be taken at the same time every day. This is very important for patients after
transplantation.
How to take Cyclaid
The daily dose should always be taken in two divided doses. Remove the capsules from the blister pack.
Swallow the capsules whole with water.
How long to use Cyclaid
The doctor will inform the patient how long to use Cyclaid. This depends on whether the patient is taking
the medicine after transplantation or for the treatment of severe skin diseases, rheumatoid arthritis, uveitis, or nephrotic syndrome. In the case of severe rash, treatment usually lasts 8 weeks.
Continue taking Cyclaid for as long as directed by the doctor.
If there are any questions about how long to use Cyclaid, discuss them with the doctor or pharmacist.
Taking more than the recommended dose of Cyclaid
If an excessive amount of medicine has been taken by accident, contact the doctor immediately or go to the emergency department of the nearest hospital.
Medical help may be required.
Missing a dose of Cyclaid
If a dose of medicine is missed, take it as soon as possible. If it is almost time for the next dose, skip the missed dose.
Then continue taking the medicine as before.
Do not take a double dose to make up for a missed dose.
Stopping Cyclaid
Do not stop taking Cyclaid unless instructed by the doctor.
Continue taking Cyclaid even if the patient feels well. Stopping treatment with Cyclaid may increase the risk of rejection of the transplanted organ.
If there are any further doubts regarding the use of this medicine, consult the doctor or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
Some adverse reactions may be serious
You should immediately tell your doctor if the patient notices any of the following serious adverse reactions:
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, especially of the skin. Signs of infection may include fever or sore throat.
Visual disturbances, 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 disorders.
Swelling of the back of the eye. This may result in blurred vision. It may also affect vision due to increased pressure in the head (non-neoplastic intracranial hypertension).
Liver disorders with or without jaundice (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 include: pale skin, feeling tired, shortness of breath, dark urine (a sign of red blood cell breakdown), bruising or bleeding without apparent cause, feeling confused, feeling disoriented, reduced alertness, and kidney disorders.
Other adverse reactions include:
Very common adverse reactions: may affect more than 1 in 10 patients.
Kidney function disorders.
High blood pressure.
Headache.
Uncontrollable body tremor.
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 adverse reactions: may affect 1 to 10 in 100 patients.
Seizures (convulsions).
Liver function disorders.
High blood sugar levels.
Fatigue.
Loss of appetite.
Nausea, vomiting, abdominal pain, constipation, diarrhoea.
Hirsutism (excessive hair growth).
Acne, sudden flushing.
Fever.
Low white blood cell count.
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 adverse reactions: may affect 1 to 10 in 1,000 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 red blood cell count, low platelet count, which may increase the risk of bleeding.
If any of these symptoms occur, you should tell your doctor.
Rare adverse reactions: may affect 1 to 10 in 10,000 patients.
Nervous system disorders with numbness or tingling of fingers of hands and feet.
Pancreatitis with severe pain in the upper abdomen.
Muscle weakness, loss of muscle strength, pain in leg or hand muscles or other body muscles.
Destruction of red blood cells, including 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 adverse reactions: may affect 1 to 10 in 100,000 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.
Other adverse reactions with unknown frequency: frequency cannot be estimated from available data.
Severe liver disorders with or without yellowing of eyes or skin, nausea, loss of appetite, dark urine, swelling of the face, feet, hands and (or) entire body.
Subcutaneous bleeding or purple spots on the skin, sudden bleeding without apparent cause.
Migraine or severe headache, often with nausea or vomiting and sensitivity to light.
Pain in legs and feet.
Hearing impairment.
If any of these symptoms occur, you should tell your doctor.
Additional adverse reactions in children and adolescents
No additional adverse reactions are expected in children and adolescents compared to adults.
Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, you should tell your doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions of the 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 Adverse reactions can also be reported to the marketing authorisation holder. Reporting adverse reactions helps provide more information on the safety of the medicine.

5. How to store Cyclaid medicine

Keep the medicine out of the sight and reach of children.
This medicine does not require special storage temperature conditions.
Store in the original packaging to protect from light and moisture.
The capsules should be kept in blisters. The packaging should be opened immediately before
taking the medicine.
Do not use this medicine after the expiry date stated on the blister and carton after:
"EXP". The expiry date refers to the last day of the stated month.
After opening the blister, a characteristic smell of the medicine may be noticeable. This is normal and does not mean that the capsules are unsuitable for use.
Medicines must not be disposed of via the sewage system or in household waste. Ask your pharmacist how to dispose of medicines no longer in use. Such measures will help protect the environment.

6. Contents of the pack and other information

What Cyclaid contains
The active substance is cyclosporine. Each soft capsule contains 25 mg, 50 mg or 100 mg of cyclosporine.
The other ingredients are:
Capsule contents: absolute ethanol, all-rac-α-tocopheryl acetate (E 307), ethylene glycol monoethyl ether, oleic acid polyglycol glycerides, polyoxyl 15 hydroxystearate.
Capsule shell: gelatin, glycerol, propylene glycol, titanium dioxide (E171), iron oxide black (E172) (only in 25 mg and 100 mg).

What Cyclaid looks like and contents of the pack
Cyclaid is available in three strengths:
25 mg: grey soft capsule.
50 mg: white soft capsule.
100 mg: grey soft capsule.
Packaged in blisters of Aluminium/Aluminium, containing 50 or 60 soft capsules.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Aurovitas Pharma Polska Sp. z o.o.
ul. Sokratesa 13D lok. 27
01-909 Warsaw
Poland

Manufacturer
Morningside Pharmaceuticals Ltd.
5 Pavilion Way, Castle Business Park
Loughborough
Leicestershire, LE11 5GW
United Kingdom
Monteresearch s.r.l
Via IV Novembre n.92
20021 – Bollate (MI)
Italy
Medis International a.s., production plant Bolatice
Průmyslová 961/16
747 23 Bolatice
Czech Republic