Package leaflet: Information for the patient

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

Keep this leaflet for possible future reference.
If you have any doubts, consult your doctor, pharmacist, or nurse.
This medicine has been prescribed for a specific individual. Do not share it with others. This medicine may harm other people, even if their symptoms are the same.
If the patient experiences any adverse reactions, including any not listed in this leaflet, inform your doctor, pharmacist, or nurse. See section 4.

Leaflet contents:

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

1. What Equoral is and what it is used for

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

What Equoral is used for and how it works

In patients who have undergone organ, bone marrow, or stem cell transplantation, the action of Equoral consists in controlling the immune system. Equoral 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, Equoral 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 known as nephrotic syndrome.

2. Important information before using Equoral

Patients receiving Equoral after transplantation will be prescribed this medicine exclusively by a physician experienced in transplantation and/or autoimmune diseases.
The instructions contained 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 Equoral

if the patient is allergic (hypersensitive) to ciclosporin or any of the other ingredients of the 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 take Equoral and inform the doctor if any of these situations apply to the patient. If in doubt, speak with the doctor before using Equoral.

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

the patient develops any signs of infection, such as fever or sore throat. Equoral 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 regularly monitor blood pressure 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 potassium levels in the blood;
the patient has gout;
the patient requires vaccination.

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

Protection against sunlight and UV radiation
Equoral suppresses the immune system, increasing the risk of developing malignant tumors, especially 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.

Talk to the doctor before using Equoral if:

the patient currently or previously had 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 using Equoral. This is due to the alcohol content in this medicine (see also below "Equoral contains ethanol").

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

blood levels of ciclosporin, especially in transplant patients;
blood pressure before starting treatment and regularly during treatment;
liver and kidney function;
blood lipid (fat) levels.

For any questions regarding the use of Equoral or the reasons for which it was prescribed, consult the doctor.

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

the patient has kidney disease (except nephrotic syndrome);
the patient has infections 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 Equoral.

Do not use Equoral if any of these situations apply to the patient. If in doubt, consult the doctor or pharmacist before using Equoral.

In patients being treated for uveitis in Behçet’s disease, the doctor will monitor the patient particularly closely if neurological symptoms occur (e.g., pronounced 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 Equoral has been prescribed for the treatment of psoriasis or atopic dermatitis, the patient must not expose themselves to UVB radiation or undergo phototherapy during treatment.

Hepatitis C
Inform the doctor if the patient has hepatitis C. During treatment for hepatitis C, liver function may change, which could affect blood levels of ciclosporin. Close monitoring of ciclosporin blood levels and dose adjustment may be necessary after starting treatment for hepatitis C.

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

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

Other medicines and Equoral
Inform the doctor or pharmacist about all medicines the patient is currently taking, has recently taken, or plans to take.

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

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 ciclosporin (the active substance in Equoral). The doctor may recommend monitoring ciclosporin blood levels when starting or stopping treatment with other medicines.
- Medicines that may increase ciclosporin 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 ciclosporin 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 loss), 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 (H₂-receptor antagonists), tacrolimus, painkillers (nonsteroidal anti-inflammatory drugs such as diclofenac), and medicines containing fibric acid (used to reduce blood fat levels, so-called fibrates).
Nifedipine. A medicine used to treat high blood pressure and angina. Using nifedipine during ciclosporin 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), consult the doctor or pharmacist before using Equoral.

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

Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or plans to become pregnant, she should consult the doctor before using this medicine.
Before using this medicine, consult the doctor or pharmacist.

Inform the doctor if the patient is pregnant or plans to become pregnant. Experience with using Equoral during pregnancy is limited. Generally, Equoral should not be used during pregnancy. If the patient must take this medicine, the doctor will discuss the benefits and risks associated with its use during pregnancy.
Inform the doctor if the patient is breastfeeding. Breastfeeding is not recommended during ciclosporin treatment, as ciclosporin, the active substance, passes into breast milk. This may affect the infant.

Driving and operating machinery
Drowsiness, disorientation, or blurred vision may occur after taking Equoral. Exercise caution when driving or operating machinery during treatment with Equoral until the patient knows how the medicine affects them.

Equoral contains ethanol
Equoral contains approximately 18.8% (by volume) ethanol (alcohol), equivalent to up to 798 mg per dose in transplant patients. This corresponds to nearly 20 ml of beer (5%) or 8.3 ml of wine (12%) per dose.
The alcohol in this medicine may alter the effects of other medicines. If the patient is taking other medicines, consult the doctor or pharmacist.
If the patient is alcohol-dependent, consult the doctor or pharmacist before using this medicine.
Alcohol may be harmful to patients with alcohol-related illness, epilepsy, brain damage, liver disease, or to pregnant or breastfeeding women. It may also be harmful if this medicine is given to children.

Equoral contains sorbitol
Equoral 25 mg contains 8.6 mg of sorbitol per capsule.
Equoral 50 mg contains 20.20 mg of sorbitol per capsule.
Equoral 100 mg contains 28.70 mg of sorbitol per capsule.
Sorbitol is a source of fructose. If the patient (or their child) has previously been diagnosed with intolerance to certain sugars or hereditary fructose intolerance, a rare genetic disorder in which the patient's body cannot break down fructose, the patient should contact the doctor before taking the medicine or giving it to a child.

Equoral contains castor oil (hydrogenated macrogolglycerides)
The medicine contains castor oil, which may cause indigestion and diarrhea.

3. How to use Equoral

This medicine should always be taken exactly as your doctor has instructed. If you are unsure, you should consult your doctor. Do not take more medicine than prescribed.
Your doctor will carefully adjust the dose of this medicine to your individual needs. Taking too much medicine may affect kidney function. You will have regular blood tests and hospital visits, especially after transplantation. These visits will provide an opportunity to discuss your treatment and any possible related problems with your doctor.

How much Equoral should be taken

Your doctor will determine the appropriate dose of Equoral for you. The dose depends on your body weight and the reason for which the medicine is being used. Your doctor will also inform you how often you should take this medicine.

In adults:

Organ, bone marrow or stem cell transplantation
The total daily dose usually ranges between 2 mg and 15 mg per kilogram of body weight. This is 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 ensure it is optimal for you. Blood tests may be necessary for this purpose.

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

Nephrotic syndrome
The total daily dose is usually 5 mg per kilogram of body weight. This 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 usually ranges between 3 mg and 5 mg per kilogram of body weight. This is divided into two doses.

Psoriasis and atopic dermatitis
The total daily dose usually ranges between 2.5 mg and 5 mg per kilogram of body weight. This is divided into two doses.

In children:

Nephrotic syndrome
The total daily dose is usually 6 mg per kilogram of body weight. This 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.

You must carefully follow your doctor's instructions and never change the dose on your own, even if you feel well.

Switching from another oral cyclosporine medicine to Equoral soft capsules
For patients already taking another oral medicine containing cyclosporine, your doctor may decide to switch to Equoral soft capsules.
All these medicines contain cyclosporine as the active ingredient.
Equoral is a different, improved formulation of cyclosporine. Cyclosporine is better absorbed into the blood from Equoral, and there is less likelihood that absorption will depend on food intake. This means that cyclosporine blood levels remain more stable when taking Equoral.

If your doctor switches you from one oral cyclosporine medicine to another:
Do not restart the previous medicine unless your doctor specifically instructs you to do so.
After the switch, your doctor will monitor your condition more closely for a short period due to changes in cyclosporine absorption into the blood. Your doctor will ensure you are receiving the appropriate dose for your needs.
You may experience certain side effects. If this occurs, inform your doctor or pharmacist. It may be necessary to reduce the dose of the medicine. Never reduce the dose on your own unless instructed by your doctor.

When to take Equoral
Equoral should be taken at the same time every day. This is very important for transplant patients.

How to take Equoral
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 take Equoral
Your doctor will inform you how long to take Equoral. This depends on whether you are taking the medicine after transplantation or for the treatment of severe skin diseases, rheumatoid arthritis, uveitis, or nephrotic syndrome. In the case of severe skin rash, treatment usually lasts 8 weeks.
Continue taking Equoral for as long as your doctor instructs.
If you have any questions about how long to take Equoral, speak with your doctor or pharmacist.

Taking more than the prescribed dose of Equoral
If you accidentally take more medicine than prescribed by your doctor, contact your doctor immediately or go to the nearest hospital emergency department. You may require medical assistance.

Missing a dose of Equoral
If you forget to take a dose, take it as soon as possible. However, if it is almost time for your 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 treatment with Equoral
Do not stop taking Equoral unless your doctor tells you to do so.
Continue taking Equoral even if you feel well. Stopping treatment with Equoral may increase the risk of transplant rejection.
If you have any further questions about using this medicine, consult your doctor or pharmacist.

4. Possible adverse reactions

Like any medicine, this medicine may cause adverse reactions, although not everyone experiences 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 incontinence, 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.
Disorders of the brain 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 be associated with blurred vision. It may also affect vision due to increased pressure in the head (non-neoplastic intracranial hypertension).
Liver disorders and liver damage with yellowing of the skin and eyes, nausea, loss of appetite, and dark urine, or without these symptoms.
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 of fatigue, shortness of breath, dark urine (a sign of red blood cell breakdown), development of bruises or bleeding without apparent cause, feeling of confusion, feeling of disorientation, reduced alertness, and kidney problems.
Other adverse reactions include:
Very common adverse reactions: may affect more than 1 in 10 people.
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.

Common adverse reactions: may affect 1 to 10 in 100 people.

Seizures (convulsions).
Liver function disorders.
High blood sugar levels.
Fatigue.
Loss of appetite.
Nausea, vomiting, discomfort and/or abdominal pain, diarrhoea.
Excessive hair growth.
Acne, 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.

Uncommon adverse reactions: may affect 1 to 10 in 1,000 people.

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.

Rare adverse reactions: may affect 1 to 10 in 10,000 people.

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, muscle 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.

Very rare adverse reactions: may affect 1 to 10 in 100,000 people.

Swelling of the back of the eye, which may be associated with increased pressure inside the head and visual disturbances.

Other adverse reactions occurring with unknown frequency: frequency cannot be estimated from the available data.

Severe liver disorders with yellowing of eyes or skin or without, nausea, loss of appetite, dark urine, swelling of the face, feet, hands and (or) the whole 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.
Hearing impairment.
Pain in legs and feet.

If any adverse reactions occur, including any adverse reactions not listed in this leaflet, you should tell your doctor or pharmacist.
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 adverse reactions not listed in this leaflet, you should inform your doctor, pharmacist or nurse.
Adverse reactions can be reported directly to the Department of Monitoring Adverse Reactions of Medicinal Products, 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 directly to the responsible entity.
By reporting adverse reactions, more information on the safety of the medicine can be collected.

5. How to store the medicine Equoral

Keep the medicine out of the sight and reach of children.
Store below 25°C in the original, tightly closed packaging.
Do not store in the refrigerator, do not freeze.
Keep capsules in the original packaging until use to protect them from light. After opening the blister pack, a characteristic odour may be noticed. This is normal and does not mean the capsules are unsuitable for use.
Do not use this medicine after the expiry date stated on the packaging after: Expiry (EXP). The expiry date refers to the last day of the stated month.
Medicines must not be disposed of via the sewage system or in household waste.
Ask your pharmacist how to dispose of medicines no longer required. Such measures help protect the environment.

6. Contents of the pack and other information

What Equoral contains

The active substance is cyclosporine.
- Equoral 25 mg: each capsule contains 25 mg of cyclosporine.
- Equoral 50 mg: each capsule contains 50 mg of cyclosporine.
- Equoral 100 mg: each capsule contains 100 mg of cyclosporine.
Other components are: anhydrous ethanol, polyglyceryl polyricinoleate (n = 3), polyglyceryl polyricinoleate (n = 10), hydrogenated castor oil macrogolglycerides, D,L-(alpha) tocopherol. Components of the gelatin capsule: gelatin, glycerol, non-crystallizing sorbitol, glycine, iron oxide, titanium dioxide.

What Equoral looks like and contents of the pack
Equoral 25 mg: yellow, flexible gelatin capsules, oval-shaped, size 12.5 x 8 mm,
containing a yellowish to yellowish-brown oily liquid.
Equoral 50 mg: yellow ochre, flexible gelatin capsules, elongated shape, size 21 x 8 mm,
containing a yellowish to yellowish-brown oily liquid.
Equoral 100 mg: brown, flexible gelatin capsules, elongated shape, size 26 x 8 mm,
containing a yellowish to yellowish-brown oily liquid.
Pack contains 50 capsules in blisters, packed in a cardboard box.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Teva Pharmaceuticals Polska Sp. z o.o.
Emilii Plater 53 Street
00-113 Warsaw
tel.: (22) 345 93 00

Manufacturer
Teva Czech Industries s.r.o.
Ostravská 29
747 70 Opava-Komarov
Czech Republic

Teva Operations Poland Sp. z o.o.
Mogilska 80 Street
31-546 Kraków