Ciqorin

Package leaflet: Information for the user

Ciqorin 10 mg soft capsules, 25 mg soft capsules, 50 mg soft capsules, 100 mg soft capsules

Ciclosporin
Generic medicine
Please read this leaflet carefully before taking this medicine because it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, because it may be harmful.
• If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What Ciqorin is and what it is used for

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

• If you have received an organ transplant, bone marrow transplant, or stem cell transplant, the function of Ciqorin is to suppress your body's immune system. Ciqorin prevents rejection of the transplanted organ by blocking the development of certain cells that would normally attack the transplanted tissue.
• If you suffer from an autoimmune disease, in which your body's immune response attacks its own cells, Ciqorin suppresses this immune reaction. These diseases include sight-threatening eye disorders (endogenous uveitis, including Behçet's uveitis), severe cases of certain skin diseases (atopic dermatitis or eczema and psoriasis), severe rheumatoid arthritis, and a kidney disease known as nephrotic syndrome.

2. What you need to know before taking Ciqorin

If you are taking Ciqorin following a transplant, the medicine will only be prescribed by a doctor experienced in transplantation and/or autoimmune diseases.
The warning in this leaflet may vary depending on whether you are taking the medicine for a transplant or for an autoimmune disease.
Carefully follow all instructions provided by your doctor. These may differ from the general information contained in this leaflet.
Do not take Ciqorin

• if you are allergic to ciclosporin or any of the other ingredients of this medicine (listed in section 6).
• with products containing Hypericum perforatum (St. John’s wort).
• with medicines containing dabigatran etexilate (used to prevent blood clots after surgery) or bosentan and aliskiren (used to reduce high blood pressure).

Do not take Ciqorin and inform your doctor if any of the above conditions apply to you. If you are unsure, ask your doctor before taking Ciqorin.
Warnings and precautions
Before and during treatment with Ciqorin, inform your doctor immediately:

• if you have any signs of infection, such as fever or sore throat. Ciqorin suppresses the immune system and may also affect your body’s ability to fight infections.
• if you have liver problems.
• if you have kidney problems. Your doctor will regularly perform blood tests and, if necessary, may adjust your dose.
• if you develop high blood pressure. Your doctor will monitor your blood pressure regularly and, if needed, may prescribe a medicine to lower it.
• if you have low magnesium levels in your body. Your doctor may prescribe magnesium supplements, especially shortly after transplantation.
• if you have high potassium levels in your blood.
• if you have gout.
• if you require vaccination. If any of the above conditions apply to you, before or during treatment with Ciqorin, inform your doctor immediately.

Sun exposure and sun protection
Ciqorin suppresses the immune system. This increases the risk of developing cancer, particularly of the skin and lymphatic system. You should limit exposure to sunlight and UV light:

• by wearing appropriate protective clothing.
• by frequently applying a sunscreen with a high protection factor.

Monitoring during treatment with Ciqorin
Your doctor will monitor:

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

Additionally, if you are taking Ciqorin for a condition other than transplantation (intermediate uveitis or posterior uveitis and Behçet’s uveitis, atopic dermatitis, severe rheumatoid arthritis, or nephrotic syndrome), do not take Ciqorin:

• if you have kidney problems (except nephrotic syndrome).
• if you have an infection that is not controlled with therapy.
• if you have any type of cancer.
• if you have high blood pressure (hypertension) that is not controlled with therapy. If high blood pressure develops during treatment and cannot be controlled, Ciqorin must be discontinued by your doctor.

If any of the above conditions occur, do not take Ciqorin. If you are unsure, inform your doctor or pharmacist before taking Ciqorin.
If you are being treated for Behçet’s uveitis, your doctor will pay particular attention to whether you develop neurological symptoms (for example: increased forgetfulness, personality changes observed over time, psychiatric or mood disorders, burning sensation in limbs, reduced sensitivity in limbs, tingling in limbs, limb weakness, walking difficulties, headache with or without nausea and vomiting, vision disturbances including limited eye movement).
If you are elderly and being treated for psoriasis or atopic dermatitis, your doctor will monitor you closely. If Ciqorin has been prescribed for the treatment of psoriasis or atopic dermatitis, you must not be exposed to UVB radiation or phototherapy during treatment.
Children and adolescents
Ciqorin must not be administered to children for conditions other than transplantation, except for the treatment of nephrotic syndrome.
Elderly (65 years of age and over)
Experience with Ciqorin in elderly patients is limited. Your doctor must monitor proper kidney function. If you are over 65 years of age and suffer from psoriasis or atopic dermatitis, you should only be treated with Ciqorin if your condition is particularly severe.
Other medicines and Ciqorin
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
In particular, inform your doctor or pharmacist if you are taking any of the following medicines before or during treatment with Ciqorin:

• Medicines that may affect potassium levels. These include medicines containing potassium, potassium supplements, diuretics known as potassium-sparing diuretics, and certain medicines that lower blood pressure.
• Methotrexate. This is a medicine used to treat cancer, severe psoriasis, and severe rheumatoid arthritis.
• Medicines that may increase or decrease the level of ciclosporin (the active substance in Ciqorin) in the blood. Your doctor may monitor your ciclosporin blood levels when starting or stopping other medicines.
  • Medicines that may increase ciclosporin levels in the blood include: antibiotics (such as erythromycin or azithromycin), antifungals (voriconazole, itraconazole), medicines used for heart problems or high blood pressure (diltiazem, nicardipine, verapamil, amiodarone), metoclopramide (used for nausea), oral contraceptives, danazol (used to treat menstrual problems), medicines used to treat gout (allopurinol), cholic acid and derivatives (used to treat gallstones), protease inhibitors used to treat HIV, imatinib (used to treat leukemia or tumors), colchicine, telaprevir (used to treat hepatitis C), cannabidiol (uses include, among others, treatment of seizures).
  • Medicines that may decrease ciclosporin levels in the blood include: barbiturates (used to aid sleep), certain anticonvulsants (such as carbamazepine or phenytoin), octreotide (used to treat acromegaly or neuroendocrine tumors of the intestine), antibacterial medicines used to treat tuberculosis, orlistat (used to aid weight loss), herbal medicines containing St. John’s wort, ticlopidine (used after stroke), certain medicines that lower blood pressure (bosentan), and terbinafine (an antifungal medicine used to treat foot and nail infections).
• Medicines that may affect the kidneys. These include: antibacterial medicines (gentamicin, tobramycin, ciprofloxacin), antifungal medicines containing

amphotericin B, medicines used for urinary tract infections containing trimethoprim,
cancer medicines containing melphalan, medicines used to reduce stomach acid (acid secretion inhibitors of the H2-receptor antagonist type),
tacrolimus, painkillers (non-steroidal anti-inflammatory medicines such as diclofenac),
fibrates (used to lower blood fat levels).

• Nifedipine. It is used to treat high blood pressure and heart pain. If you are taking nifedipine during ciclosporin treatment, you may experience swollen gums that thicken around the teeth.
• Digoxin (used to treat heart problems), cholesterol-lowering medicines (HMG-CoA reductase inhibitors, also known as statins), prednisolone, etoposide (used to treat cancer), repaglinide (an antidiabetic medicine), immunosuppressants (everolimus, sirolimus), ambrisentan, and specific anticancer medicines called anthracyclines (e.g. doxorubicin).
• Mycophenolate sodium or mycophenolate mofetil (an immunosuppressant) and eltrombopag (used to treat bleeding disorders). If you experience any of the above conditions (or are unsure), inform your doctor or pharmacist before taking Ciqorin.

Hepatitis C
Inform your doctor if you have hepatitis C. Liver function may change during hepatitis C treatment and thus may affect ciclosporin blood levels. Your doctor may need to closely monitor your ciclosporin blood levels and adjust the dose of Ciqorin after starting hepatitis C treatment.
Ciqorin with food and drink
Do not take Ciqorin with grapefruit or grapefruit juice. These may affect the action of Ciqorin.
Pregnancy and breastfeeding
Ask your doctor or pharmacist for advice before taking this medicine.

• Inform your doctor if you are pregnant or planning to become pregnant. Experience with Ciqorin during pregnancy is limited. In general, Ciqorin should not be taken during pregnancy. If taking this medicine is necessary, your doctor will discuss with you the benefits and potential risks of taking it during pregnancy.
• Inform your doctor if you are breastfeeding. Breastfeeding is not recommended during treatment with Ciqorin. This is because ciclosporin, the active ingredient, passes into breast milk. This may affect the baby.

Driving and using machines
You may feel drowsy, disoriented, or have blurred vision after taking Ciqorin. Be cautious when driving or operating machinery while taking Ciqorin until you know how this medicine affects you.
Ciqorin contains ethanol
10 mg
This medicine contains 15.95 mg of alcohol (ethanol) in each capsule.
25 mg
This medicine contains 39.86 mg of alcohol (ethanol) in each capsule.
50 mg
This medicine contains 79.75 mg of alcohol (ethanol) in each capsule.
100 mg
This medicine contains 159.50 mg of alcohol (ethanol) in each capsule.
The amount in 500 mg of this medicine (797.5 mg of ethanol) is equivalent to less than 20 ml of beer or 8 ml of wine. The small amount of alcohol in this medicine will not produce significant effects.
Ciqorin contains sorbitol
10 mg
This medicine contains 2.93 mg of sorbitol in each capsule.
25 mg
This medicine contains 4.92 mg of sorbitol in each capsule.
50 mg
This medicine contains 11.03 mg of sorbitol in each capsule.
100 mg
This medicine contains 19.06 mg of sorbitol in each capsule.
Ciqorin contains macrogol glycerol hydroxystearate
It may cause gastrointestinal disturbances and diarrhoea.

3. How to take Ciqorin

Take this medicine exactly as your doctor has told you. If you have any doubts, consult your doctor.
Do not take more than the recommended dose.
Your doctor will carefully adjust the dose of this medicine to your individual needs.
Taking too much medicine may affect kidney function. You will have regular blood tests and hospital visits, especially after a transplant. This will give you the opportunity to discuss your treatment and any problems you may have with your doctor.

How much Ciqorin to take
Your doctor will determine the correct dose of Ciqorin for you. It depends on your body weight and the reason why you are taking the medicine. Your doctor will also tell you how often to take the medicine.

• In adults: Organ, bone marrow or stem cell transplantation

  • The total daily dose is usually between 2 mg and 15 mg per kilogram of body weight. It should be divided into two doses.
  • Usually higher doses are used before and immediately after transplantation. Lower doses are used once the transplanted organ or bone marrow has stabilised.
  • Your doctor will adjust the dose to the appropriate level for you. To do this, your doctor may need to perform some blood tests. Endogenous uveitis
  • The total daily dose is usually between 5 mg and 7 mg per kilogram of body weight. It should be divided into two doses. Nephrotic syndrome
  • For adults, the total daily dose is usually 5 mg per kilogram of body weight. It should be divided into two doses. In patients with kidney problems, the initial daily dose should not exceed 2.5 mg per kilogram of body weight. Severe rheumatoid arthritis
  • The total daily dose is usually between 3 mg per kilogram of body weight and 5 mg per kilogram of body weight. It should be divided into two doses. Psoriasis and atopic dermatitis
  • The total daily dose is usually between 2.5 mg per kilogram of body weight and 5 mg per kilogram of body weight. It should be divided into two doses.

• In children: Nephrotic syndrome

  • For children, the total daily dose is usually 6 mg per kilogram of body weight. It should be divided into two doses. In patients with kidney problems, the initial daily dose should not exceed 2.5 mg per kilogram of body weight.

Follow your doctor's instructions exactly and never change the dose on your own initiative, even if you feel well.

Switching from oral cyclosporine to microemulsion oral cyclosporine
You may have previously taken another oral cyclosporine. Your doctor may decide to switch you to this medicine, Ciqorin.

• All these medicines contain cyclosporine as the active substance.
• Ciqorin is an improved, different formulation of cyclosporine. Cyclosporine is better absorbed into the blood with Ciqorin, and absorption is less likely to be affected by food intake. This means that cyclosporine blood levels will remain more stable with Ciqorin. If your doctor switches your medicine from oral cyclosporine to microemulsion oral cyclosporine:
• Do not go back to taking the previous medicine unless your doctor tells you to.
• After the switch, your doctor will monitor you more closely for a short period. This is due to the change in how cyclosporine is absorbed into the blood. Your doctor will ensure that you are taking the correct dose for your individual needs.
• You may experience some side effects. If this happens, contact your doctor or pharmacist. It may be necessary to reduce the dose. Never reduce the dose on your own initiative unless your doctor tells you to.

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 some side effects. If this happens, contact your doctor or pharmacist. It may be necessary to adjust the dose. Never change the dose on your own initiative unless your doctor tells you to.

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

How to take Ciqorin
The daily doses must always be taken as two divided doses.
Remove the capsules from the blister pack. Swallow the capsules whole with water.

How long to take Ciqorin
Your doctor will tell you how long you should take Ciqorin. This depends on whether you are taking the medicine after a transplant or for the treatment of a severe skin condition, rheumatoid arthritis, uveitis or nephrotic syndrome. For severe skin rash, the treatment duration is usually 8 weeks.
Continue taking Ciqorin for as long as your doctor has instructed you to do so.
If you have any questions about how long to take Ciqorin, speak to your doctor or pharmacist.

If you take more Ciqorin than you should
If you have taken too much medicine by accident, inform your doctor immediately or go to the nearest hospital emergency department. You may need medical treatment.

If you forget to take Ciqorin

• If you forget to take a dose, take it as soon as you remember. However, if it is almost time for your next dose, skip the missed dose and continue as before. Do not take a double dose to make up for the forgotten dose.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Some side effects can be serious
Tell your doctor immediately if you experience any of the following serious side effects:

• As with other medicines that affect the immune system, cyclosporine may affect the body's ability to fight infections and may cause tumours or other types of cancer, particularly of the skin. Signs of infection may include fever or sore throat.
• Changes in vision, loss of coordination, clumsiness, memory loss, difficulty speaking or understanding what others say, and muscle weakness. These could be signs of a brain infection called progressive multifocal leukoencephalopathy.
• Brain problems with symptoms such as seizures, confusion, disorientation, reduced responsiveness, personality changes, restlessness, insomnia, changes in vision, blindness, coma, paralysis of part or all of the body, neck stiffness, loss of coordination with or without unusual speech or eye movements.
• Swelling at the back of the eye. This may be associated with blurred vision. It may also affect vision due to increased pressure inside the head (benign intracranial hypertension).
• Liver problems and liver damage, with or without yellowing of the skin and eyes, nausea, loss of appetite, and dark urine.
• Kidney problems that may significantly reduce the amount of urine produced.
• Low levels of red blood cells or platelets. Signs include paleness, feeling tired, difficulty breathing, dark urine (a sign of red blood cell breakdown), unexplained bruising or bleeding, feeling confused, disoriented, reduced alertness, and kidney problems.

Other side effects include:
Very common side effects: may affect more than 1 in 10 people.

• Kidney problems.
• High blood pressure.
• Headache.
• Uncontrollable body tremors.
• Excessive growth of body and facial hair.
• High levels of lipids in the blood. If any of these effects become severe, tell your doctor.

Common side effects: may affect up to 1 in 10 people.

• Seizures.
• Liver problems.
• High blood sugar levels.
• Tiredness.
• Loss of appetite.
• Nausea (feeling unwell), vomiting, abdominal discomfort/pain, diarrhoea.
• Excessive hair growth.
• Acne, hot flushes.
• Fever.
• Low levels of white blood cells in the blood.
• Numbness or tingling sensation.
• Muscle pain, muscle spasms.
• Stomach ulcer.
• Overgrowth of the gums and covering of the teeth.
• High levels of uric acid or potassium in the blood, low levels of magnesium in the blood. If any of these effects become severe, tell your doctor.

Uncommon side effects: may affect up to 1 in 100 people.

• Symptoms of brain disorders including sudden seizures, mental confusion, insomnia, disorientation, vision problems, loss of consciousness, weakness in limbs, reduced movements.
• Skin rash.
• Generalised swelling.
• Weight gain.
• Low levels of red blood cells, low levels of platelets in the blood, which may increase the risk of bleeding. If any of these effects become severe, tell your doctor.

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

• Nerve problems with numbness or tingling in fingers and toes.
• Inflammation of the pancreas with severe pain in the upper stomach.
• Muscle weakness, loss of muscle strength, pain in the legs, hands, or any part of the body.
• Destruction of red blood cells, leading to kidney problems with symptoms such as swelling of the face, stomach, hands and/or feet, reduced urine volume, difficulty breathing, chest pain, seizures, loss of consciousness.
• Changes in menstrual cycle, breast enlargement in men. If any of these effects become severe, tell your doctor.

Very rare side effects: may affect up to 1 in 10,000 people.

• Swelling at the back of the eye which may be associated with increased pressure inside the head and visual disturbances. If this effect becomes severe, tell your doctor.

Not known: Frequency cannot be estimated from the available data.

• Severe liver problems with or without yellowing of the skin or eyes, nausea (feeling unwell), loss of appetite, dark urine, swelling of the face, feet, hands and/or the whole body.
• Bleeding under the skin or purple spots, sudden unexplained bleeding.
• Migraine or severe headache often with nausea, vomiting, and sensitivity to light.
• Pain in the lower limbs.
• Hearing impairment. If any of these effects become severe, tell your doctor.

Additional side effects in children and adolescents
No additional side effects are expected in children and adolescents compared to adults.
Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Ciqorin

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and blister after
EXP.
The expiry date refers to the last day of that month.
Store below 30°C. Do not freeze. Keep in the original packaging to protect the medicine from light and moisture.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Ciqorin contains

• The active substance is cyclosporine. 10 mg Each soft capsule contains 10 mg of cyclosporine. 25 mg Each soft capsule contains 25 mg of cyclosporine. 50 mg Each soft capsule contains 50 mg of cyclosporine. 100 mg Each soft capsule contains 100 mg of cyclosporine.
• The other components of the capsule contents are macrogol glycerol hydroxystearate, glycerol monolinoleate, diethylene glycol monoethyl ether, anhydrous ethanol and D,L-α-tocopherol.
• The other components of the capsule shell are 10 mg gelatin, glycerol (85 percent), liquid sorbitol (non-crystallizable) (E420), glycine, titanium dioxide (E171) and light liquid paraffin.

Description of the appearance of Ciqorin and contents of the pack
10 mg
Opaque white to whitish capsules containing an oily liquid from colourless to slightly yellowish.
Approximate dimensions: 9.0 x 5.5 mm.
25 mg
Opaque yellow capsules containing an oily liquid from colourless to slightly yellowish. Approximate dimensions: 12.2 x 7.6 mm.
50 mg
Opaque yellow-brown capsules containing an oily liquid from colourless to slightly yellowish. Approximate dimensions: 20.7 x 7.8 mm.
100 mg
Opaque brown capsules containing an oily liquid from colourless to slightly yellowish. Approximate dimensions: 24.7 x 9.9 mm.
10 + 25 + 50 mg
Capsules are available in packs of 20, 30, 50, 50x1, 60, 90 and 100 in OPA/Alu/PVC – aluminium blisters.
100 mg
Capsules are available in packs of 20, 30, 30x1, 50, 50x1, 60, 90 and 100 in OPA/Alu/PVC – aluminium blisters.
Not all pack sizes may be marketed.
Marketing Authorisation Holder and Manufacturer
Teva Italia S.r.l. - Piazzale Luigi Cadorna, 4 - 20123 Milan, Italy
Responsible manufacturer for batch release
Teva Czech Industries s.r.o.
Ostravska 29, c.p. 305 - 74770 Opava-Komarov
Czech Republic
TEVA Pharmaceutical Works Private Limited Company
Pallagi út 13, 4042 – Debrecen
Hungary
Pharmachemie B.V.
Swensweg 5, 2031 GA Haarlem
The Netherlands
Merckle GmbH
Ludwig-Merckle-Straße 3, 89143 Blaubeuren
Germany
Teva Operations Poland Sp. z o.o.
ul. Mogilska 80, 31-546 Krakow
Poland