Equoral

Package leaflet: Information for the patient

Warning! Keep the leaflet. Information on the immediate packaging in a foreign language
Equoral (Ciclosporina Teva)
100 mg/ml, oral solution
Ciclosporinum
Equoral and Ciclosporina Teva are different trade names for the same medicine.
Please read the leaflet carefully 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 questions, please consult your doctor, pharmacist, or nurse.
• 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 reactions, including any adverse reactions not listed in this leaflet, inform your doctor, pharmacist, or nurse. See section 4.

Table of contents of the leaflet:

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

1. What is Equoral and what is it used for

What is Equoral
This medicine is called Equoral. It contains the active substance ciclosporin. This medicine belongs to a group of medicines called immunosuppressants. These medicines are used to reduce the body's immune response.
What Equoral is used for and how Equoral works

• In patients who have undergone organ, bone marrow, or stem cell transplantation, the action of Equoral is to control the immune system. Equoral prevents rejection of the transplanted organ by blocking 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 stops 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 Equoral

Patients receiving Equoral 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 given by the physician. These may differ from the general information contained in this leaflet.

When not to use Equoral

• if the patient is allergic to cyclosporine 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 tell your doctor if this applies to the patient. If in doubt, speak with the doctor before using Equoral.

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

• the patient develops any signs of infection, such as fever or sore throat. Equoral 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 develops high blood pressure. The doctor will regularly monitor the patient's blood pressure and may prescribe antihypertensive medication if necessary;
• 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 requires vaccination. If any of these conditions occur before or during treatment with Equoral, inform the doctor immediately.

Protection from sunlight and solar radiation
Equoral 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 sunscreen with a high sun protection factor.

Talk to the doctor before using Equoral if:

• the patient has alcohol-related problems, 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 these situations apply to the patient (or the patient is unsure), inform the doctor before using Equoral. This is due to the ethanol content of this medicine (see also below "Equoral contains anhydrous ethanol").

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

• blood cyclosporine levels, 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 Equoral works or why it has been prescribed, consult the doctor.

Additionally, patients taking Equoral for indications other than post-transplantation
(intermediate or posterior 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 tumour;
• 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 treated for uveitis in Behçet's disease, the doctor will monitor the patient particularly closely if neurological symptoms occur (e.g. marked 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 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.

Inform the doctor if the patient has hepatitis C. During treatment of hepatitis C, liver function may change, which could affect cyclosporine blood levels. Close monitoring of cyclosporine 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 diseases, 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. Elderly patients (aged 65 and over) with psoriasis or atopic dermatitis should only be treated with Equoral if their disease is particularly severe.

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

In particular, 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, 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 cyclosporine (the active substance in Equoral) blood levels. 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 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).
  • 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 tumours), 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 (H\2-receptor antagonists), tacrolimus, painkillers (nonsteroidal anti-inflammatory drugs such as diclofenac), medicines containing fibric acid (used to reduce blood fat levels, known as fibrates).
• 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).

If any of these situations apply to the patient (or 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 have a child, she should consult the doctor before using this medicine. The doctor will discuss the risks associated with taking Equoral during pregnancy.

• Tell 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 it is necessary for the patient to take this medicine, the doctor will discuss the benefits and risks of using Equoral during pregnancy.
• Tell the doctor if the patient is breastfeeding. If the patient is taking Equoral, she should not breastfeed, as cyclosporine, the active substance, passes into breast milk. This may affect the infant.

Driving and operating machinery
Equoral contains alcohol. This may affect the ability to drive and operate machinery.

Equoral contains anhydrous ethanol
Equoral contains approximately 15.2% (by volume) ethanol (alcohol), equivalent to up to 600 mg per dose in transplant patients. This is equivalent to nearly 15.2 ml of beer or 6.3 ml of wine (12%) per dose.
The alcohol in this medicine may alter the effect 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 macrogolglycerol hydroxystearate
The medicine contains macrogolglycerol hydroxystearate, which may cause indigestion and diarrhoea.

3. How to use Equoral

This medicine should always be taken exactly as prescribed by your doctor. If in doubt, 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 of the medicine may affect kidney function. You will attend regular blood tests and hospital visits, especially after transplantation. These visits will provide an opportunity to discuss your treatment and any potential 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, divided into two doses.
• Higher doses are typically used before and immediately after transplantation. Lower doses are used once the transplanted organ or bone marrow function has stabilized.
• Your doctor will adjust the dose to achieve optimal therapy for you. Blood tests may be necessary for this purpose.

Endogenous uveitis of the eye

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

Nephrotic syndrome

The total daily dose is usually 5 mg per kilogram of body weight, 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, 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, divided into two doses.

• In children:

Nephrotic syndrome

The total daily dose is usually 6 mg per kilogram of body weight, divided into two doses. In patients with kidney disease, the first daily dose should not exceed 2.5 mg per kilogram of body weight.

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

For patients already taking another oral cyclosporine medicine (soft capsules or oral solution), your doctor may decide to switch your treatment to Equoral oral solution.
All these medicines contain cyclosporine as the active ingredient.
Equoral is a different, improved cyclosporine formulation. Cyclosporine is better absorbed into the blood from Equoral, and there is less likelihood that absorption will be affected by food intake. This means that cyclosporine blood levels remain more stable when using Equoral.

If your doctor switches you from another oral cyclosporine medicine to Equoral:

• Do not restart the previous medicine unless instructed by your doctor.
• After switching from another cyclosporine medicine to Equoral, your doctor will monitor you more closely for a short period. This is 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 adverse effects. If this occurs, inform your doctor or pharmacist. A dose reduction may be necessary. Never reduce the dose on your own unless instructed by your doctor.

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

After switching from one oral cyclosporine formulation to another:

• Your doctor will monitor you more closely for a short period.
• You may experience certain adverse effects. If this occurs, inform your doctor or pharmacist. A dose adjustment may be necessary. Never change 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 especially important for transplant patients.

How to take Equoral

The daily dose should always be taken in two divided doses.

• For first use, perform the steps described in points 1 to 7.
• For subsequent uses, perform the steps described in points 4 to 7.

Starting a new bottle of Equoral oral solution

The dose of Equoral should be measured using the provided syringe and diluted with orange juice or another non-alcoholic beverage (grapefruit juice is contraindicated) in a 1:20 ratio. Use glass or porcelain containers for dilution. Plastic containers are not recommended. The prepared drink should be consumed entirely in one go. Any residue remaining in the container should be mixed with a small amount of the diluting liquid and consumed. After use, wipe the outside of the syringe with a paper towel and return it to its protective cover. Do not wash the dosing syringe with water, alcohol, or other liquids. The dosing syringe should only be used when completely dry.

Instructions for using the dosing set are provided below:

1. Unscrew the cap

2. Press the dosing insert with tube into the bottle neck. This insert will remain in place throughout the duration of treatment.

3. Insert the syringe into the opening of the insert with tube and use the plunger to draw up the prescribed amount of medicine. If air bubbles form, remove them by repeating the process of drawing the liquid into the syringe and expelling it back into the bottle, then draw up the prescribed amount again.

4. Dilute the measured amount of medicine with orange juice or another non-alcoholic beverage (do not use grapefruit juice) in a 1:20 ratio. Use a glass or porcelain container for dilution (plastic containers are not recommended). The prepared solution should be consumed immediately and entirely; add a small amount of water to the remaining medicine at the bottom of the container and drink it.

5. Immediately after measuring the correct amount of medicine, close the bottle tightly with the cap.

6. After using the syringe, wipe its tip with a dry tissue and return it to the plastic tube. Never rinse the syringe with water, ethanol, or any other liquid. The syringe should only be used when completely dry.

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 cases of severe rash, treatment usually lasts 8 weeks.

Continue taking Equoral for as long as your doctor prescribes.

If you have any questions about how long to take Equoral, speak with your doctor or pharmacist.

Taking more than the recommended dose of Equoral

If you accidentally take more medicine than prescribed, contact your doctor immediately or go to the nearest hospital emergency department. You may require medical attention.

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 instructed by your doctor.
Continue taking Equoral even if you feel well. Stopping treatment with Equoral may increase the risk of rejection of the transplanted organ.

If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse reactions

Like any medicine, 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:

• As with 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.
• Changes in vision, loss of coordination, motor weakness, 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 in the head (non-neoplastic intracranial hypertension).
• Liver disorders and damage, with or without jaundice (yellowing of the skin and eyes), nausea, loss of appetite, and dark urine.
• Kidney disorders, which may greatly reduce the amount of urine produced.
• Low number of red blood cells or platelets. Symptoms of these disorders include pale skin, feeling tired, shortness of breath, dark urine (a sign of red blood cell breakdown), easy bruising or bleeding without apparent cause, confusion, 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, abdominal pain, constipation, 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 in the 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, 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 at 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.

If any adverse reactions occur, including any not listed in this leaflet, you should tell your doctor or pharmacist.
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, pharmacist or nurse. 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
Reporting adverse reactions helps to provide more information on the safety of the medicine.

5. How to store the medicine Equoral

Keep the medicine out of the sight and reach of children.
Store below 25°C.
Do not use the solution for longer than 3 months after first opening the bottle.
The oral solution Equoral 100 mg/ml may become cloudy when stored below 20°C. In such a case,
warming the medicine to room temperature (25°C) is recommended to remove the cloudiness.
Any cloudiness of the solution does not affect its efficacy or dosing.
Do not use this medicine after the expiry date stated on the packaging. The expiry date refers to the last day of the specified month.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the pack and other information

What Equoral contains

• The active substance is cyclosporine. 1 ml of solution contains 100 mg of cyclosporine.
• Other ingredients are: anhydrous ethanol, polyglyceryl 3-oleate, polyglyceryl 10-oleate, macrogol hydroxystearate glyceryl.

What Equoral looks like and contents of the pack
Equoral is an oily oral solution, yellow to brownish-yellow in colour.
The pack contains 50 ml of solution in a bottle made of amber glass with a cap and a dosing set
consisting of a syringe and a dosing insert with a tube, placed in a sealed tube inside a cardboard box.
For further information, please contact the responsible party or the parallel importer.
Responsible party in Portugal, country of export:
Teva Pharma - Produtos Farmacêuticos, Lda.
Lagoas Park, Edifício 5 A, Piso 2
2740-245 Porto Salvo, Portugal
Manufacturer:
Teva Czech Industries s.r.o.
Ostravska 29, c.p. 305
747 70 Opava-Komarov, Czech Republic
Parallel importer:
Delfarma Sp. z o.o.
ul. Św. Teresy od Dzieciątka Jezus 111
91-222 Łódź
Repackaged in:
Delfarma Sp. z o.o.
ul. Św. Teresy od Dzieciątka Jezus 111
91-222 Łódź
Portugal, country of export, marketing authorisation number: 4877882
Parallel import authorisation number: 177/22