Celezon contains the active substance ruxolitinib.

Celezon is used to treat adult patients with an enlarged spleen or with symptoms related to myelofibrosis, a rare form of blood cancer.

Celezon is also used to treat adult patients with polycythaemia vera who are resistant to or intolerant of hydroxyurea.

Celezon is also used to treat patients 12 years of age and older and adults with graft-versus-host disease (GvHD). There are two forms of GvHD: an early form called acute GvHD that usually develops soon after the transplantation and can affect skin, liver and gastrointestinal tract, and a form called chronic GvHD, which develops later, usually weeks to months after the transplantation. Almost any organ can be affected by chronic GvHD.

How Celezon works

Enlargement of the spleen is one of the characteristics of myelofibrosis. Myelofibrosis is a disorder of the bone marrow, in which the marrow is replaced by scar tissue. The abnormal marrow can no longer produce enough normal blood cells and as a result the spleen becomes significantly enlarged. By blocking the action of certain enzymes (called Janus Associated Kinases), Celezon can reduce the size of the spleen in patients with myelofibrosis and relieve symptoms such as fever, night sweats, bone pain and weight loss in patients with myelofibrosis. Celezon can help reduce the risk of serious blood or vascular complications.

Polycythaemia vera is a disorder of the bone marrow, in which the marrow produce too many red blood cells. The blood becomes thicker as a result of the increased red blood cells. Celezon can relieve the symptoms, reduce spleen size and the volume of red blood cells produced in patients with polycythaemia vera by selectively blocking enzymes called Janus Associated Kinases (JAK1 and JAK2), thus potentially reducing the risk of serious blood or vascular complications.  

Graft-versus-host disease is a complication which occurs after transplantation when specific cells (T cells) in the donor’s graft (e.g. bone marrow) do not recognise the host cells/organs and attack them. By selectively blocking enzymes called Janus Associated Kinases (JAK1 and JAK2), Celezon reduces signs and symptoms of the acute and the chronic forms of graft-versus-host disease leading to disease improvement and survival of the transplanted cells.

If you have any questions about how Celezon works or why this medicine has been prescribed for you, ask your doctor.

Follow all your doctor’s instructions carefully. They may differ from the general information contained in this leaflet.

Do not take Celezon

·    If you are allergic to ruxolitinib or any of the other ingredients of this medicine (listed in section 6).

·    If you are pregnant or breast-feeding.

If either of the above applies to you, tell your doctor who will then decide whether you should start treatment with Celezon.

Warnings and precautions

Talk to your doctor or pharmacist before taking Celezon:

·    If you have any infections. It may be necessary to treat your infection before starting Celezon. It is important that you tell your doctor if you have ever had tuberculosis or if you have been in close contact with someone who has or has had tuberculosis. Your doctor may perform tests to see if you have tuberculosis or any other infections. It is important that you tell your doctor if you have ever had hepatitis B.

·    If you have any kidney problems. Your doctor may need to prescribe a different dose of Celezon.

·    If you have or have ever had any liver problems. Your doctor may need to prescribe a different dose of Celezon.

·    If you are taking other medicines (see section “Other medicines and Celezon”).

·    If you have ever had tuberculosis.

·    If you have ever had skin cancer.

Talk to your doctor or pharmacist during your treatment with Celezon:

·    If you experience unexpected bruising and/or bleeding, unusual tiredness, shortness of breath during exercise or at rest, unusually pale skin, or frequent infections (these are signs of blood disorders).

·    If you experience fever, chills or other symptoms of infections.

·    If you experience chronic coughing with blood-tinged sputum, fever, night sweats and weight loss (these can be signs of tuberculosis).

·    If you have any of the following symptoms or if anyone close to you notices that you have any of these symptoms: confusion or difficulty thinking, loss of balance or difficulty walking, clumsiness, difficulty speaking, decreased strength or weakness on one side of your body, blurred and/or loss of vision. These may be signs of a serious brain infection and your doctor may suggest further testing and follow-up.

·    If you develop painful skin rash with blisters (these are signs of shingles).

·    If you notice skin changes. This may require further observation, as certain types of skin cancer (non-melanoma) have been reported.

Blood tests

Before you start treatment with Celezon, your doctor will perform blood tests to determine the best starting dose for you. You will need to have further blood tests during treatment so that your doctor can monitor the amount of blood cells (white cells, red cells and platelets) in your body and assess how you are responding to the treatment and whether Celezon is having an unwanted effect on these cells. Your doctor may need to adjust the dose or stop treatment. Your doctor will carefully check if you have any signs or symptoms of infection before starting and during your treatment with Celezon. Your doctor will also regularly check the level of lipids (fat) in your blood.

Children and adolescents

This medicine is not intended for use by children or adolescents aged below 18 years, who have the disease myelofibrosis or polycythaemia vera because it has not been studied in this age group.

For the treatment of graft-versus-host disease, Celezon can be used in patients 12 years and older.

 Other medicines and Celezon

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.

It is particularly important that you mention any of the following medicines containing any of the following active substances, as your doctor may need to adjust the Celezon dose for you.

The following may increase the risk of side effects with Celezon:

·    Some medicines used to treat infections. These include medicines used to treat fungal diseases (such as ketoconazole, itraconazole, posaconazole, fluconazole and voriconazole), medicines used to treat certain types of bacterial infections (antibiotics such as clarithromycin, telithromycin, ciprofloxacin, or erythromycin), medicines to treat viral infections, including HIV infection/AIDS (such as amprenavir, atazanavir, indinavir, lopinavir/ritonavir, nelfinavir, ritonavir, saquinavir), medicines to treat hepatitis C (boceprevir, telaprevir).

·    Nefazodone, a medicine to treat depression.

·    Mibefradil or diltiazem, medicines to treat hypertension and chronic angina pectoris.

·    Cimetidine, a medicine to treat heartburn.

The following may reduce the effectiveness of Celezon:

·    Avasimibe, a medicine to treat heart disease.

·    Phenytoin, carbamazepine or phenobarbital and other anti-epileptics used to stop seizures or fits.

·    Rifabutin or rifampicin, medicines used to treat tuberculosis (TB).

·    St. John’s wort (Hypericum perforatum), a herbal product used to treat depression.

 While you are taking Celezon

You should never start a new medicine without checking first with the doctor who prescribed Celezon. This includes prescription medicines, non-prescription medicines and herbal or alternative medicines.

Pregnancy and breast-feeding

Do not take Celezon during pregnancy. Talk to your doctor about how to take appropriate measures to avoid becoming pregnant during your treatment with Celezon.

Do not breast-feed while taking Celezon. Tell your doctor if you are breast-feeding.

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Driving and using machines

If you experience dizziness after taking Celezon, do not drive or use machines.

Celezon contains lactose and sodium

Celezon contains lactose. Each tablet of Celezon 5 mg, 10 mg, 15 mg, 20 mg and 25 mg Tablets contains 71.2 mg, 142.4 mg, 213.6 mg, 284.8 mg or 356 mg lactose; respectively. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.

Celezon contains sodium. Each tablet of Celezon 5 mg, 10 mg, 15 mg, 20 mg and 25 mg Tablets contains 0.24 mg, 0.49 mg, 0.73 mg, 0.98 mg or 1.22 mg sodium; respectively. This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium-free’.

Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure.

The dose of Celezon depends on the patient’s blood cell count. Your doctor will measure the amount of blood cells in your body and find the best dose for you, particularly if you have liver or kidney problems.

·    The recommended starting dose in myelofibrosis is 5 mg twice daily, 10 mg twice daily, 15 mg twice daily or 20 mg twice daily, depending on your blood cell count.

·    The recommended starting dose in polycythaemia vera and in graft-versus-host disease is 10 mg twice daily.

·    The maximum dose is 25 mg twice daily.

Your doctor will always tell you exactly how many Celezon tablets to take.

During the treatment your doctor may recommend a lower or higher dose to you if the results of blood tests show that this is necessary, if you have problems with your liver or kidneys, or if you also need treatment with certain other medicines.

If you receive dialysis, take either one single dose or two separate doses of Celezon only on dialysis days, after the dialysis has been completed. Your doctor will tell you if you should take one or two doses and how many tablets to take for each dose.

You should take Celezon every day at the same time, either with or without food.

You should continue taking Celezon for as long as your doctor tells you to. This is a long-term treatment.

Your doctor will regularly monitor your condition to make sure that the treatment is having the desired effect.

If you have questions about how long to take Celezon, talk to your doctor or pharmacist.

If you experience certain side effects (e.g. blood disorders), your doctor might need to change the amount of Celezon you have to take or tell you to stop taking Celezon for a while.

If you take more Celezon than you should

If you accidentally take more Celezon than your doctor prescribed, contact your doctor or pharmacist immediately.

If you forget to take Celezon

If you forgot to take Celezon simply take your next dose at the scheduled time. Do not take a double dose to make up for a forgotten dose.

If you stop taking Celezon

If you interrupt your treatment with Celezon your symptoms related to myelofibrosis or polycythaemia vera may come back. In graft-versus-host disease, a reduction in your dose or stopping your treatment with Celezon is possible if you respond to treatment and your doctor will supervise this procedure. Therefore, you should not stop taking Celezon or change the dose without discussing it with your doctor.

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

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Most of the side effects of ruxolitinib are mild to moderate and will generally disappear after a few days to a few weeks of treatment.

Myelofibrosis and polycythaemia vera

Some side effects could be serious.

Seek medical help immediately prior to taking the next scheduled dose if you experience the following serious side effects:

Very common (may affect more than 1 in 10 people)

·    Any sign of bleeding in the stomach or intestine, such as passing black or bloodstained stools, or vomiting blood

·    Unexpected bruising and/or bleeding, unusual tiredness, shortness of breath during exercise or at rest, unusually pale skin, or frequent infections (possible symptoms of blood disorders)

·    Painful skin rash with blisters (possible symptoms of shingles (herpes zoster))

·    Fever, chills or other symptoms of infections

·    Low level of red blood cells (anaemia), low level of white blood cells (neutropenia) or low level of platelets (thrombocytopenia)

Common (may affect up to 1 in 10 people):

·    Any sign of bleeding in the brain, such as sudden altered level of consciousness, persistent headache, numbness, tingling, weakness or paralysis

Other side effects with ruxolitinib

Other possible side effects include the following listed below. If you experience these side effects talk to your doctor or pharmacist.

Very common (may affect more than 1 in 10 people):

·    High level of cholesterol or fat in the blood (hypertriglyceridaemia)

·    Abnormal liver function test results

·    Dizziness

·    Headache

·    Urinary tract infections

·    Weight gain

·    Fever, cough, difficult or painful breathing, wheezing, pain in chest when breathing (possible symptoms of pneumonia)

·    High blood pressure (hypertension), which may also be the cause of dizziness and headaches

·    Constipation

·    High level of lipase in the blood

Common (may affect up to 1 in 10 people):

·    Reduced number of all three types of blood cells – red blood cells, white blood cells, and platelets (pancytopenia)

·    Frequently passing wind (flatulence)

Uncommon (may affect up to 1 in 100 people):

·    Tuberculosis

·    Recurrence of hepatitis B infection (which can cause yellowing of the skin and eyes, dark brown-colored urine, right-sided stomach pain, fever and feeling nauseous or being sick)

Graft-versus-host disease (GvHD)

Some side effects could be serious.

Seek medical help immediately prior to taking the next scheduled dose if you experience the following serious side effects:

Very common (may affect more than 1 in 10 people):

•    Fever, pain, redness, and/or difficulty breathing (possible symptoms of an infection with the cytomegalovirus (cytomegalovirus infection))

•    Fever, pain when urinating (possible symptoms of a urinary tract infection)

•    Fast heart rate, fever, confusion and rapid breathing (possible symptoms of sepsis, which is a serious condition that occurs in response to an infection that causes widespread inflammation)

•    Tiredness, fatigue, pale skin (possible symptoms of anaemia which is caused by low level of red blood cells), frequent infections, fever, chills, sore throat or mouth ulcers due to infections (possible symptoms of neutropenia which is caused by low level of white blood cells), spontaneous bleeding or bruising (possible symptoms of thrombocytopenia which is caused by low levels of platelets) 

•    Low counts of all three types of blood cells - red blood cells, white blood cells, and platelets (pancytopenia)  

Other side effects

Other possible side effects include the following listed below. If you experience these side effects talk to your doctor or pharmacist.

Very common (may affect more than 1 in 10 people):

·    High level of cholesterol (hypercholesterolaemia) 

·    Headache 

·    High blood pressure (hypertension) 

·    Feeling sick (nausea) 

·    Abnormal liver function test results 

·    Increased blood level of enzyme from muscle potentially indicating muscle damage and/or muscle breakdown (increased blood creatine phosphokinase) 

·    Increased blood level of creatinine, a substance normally eliminated by the kidneys into the urine, which may mean that your kidneys are not functioning properly (increased blood creatinine)

Common (may affect up to 1 in 10 people):

·    Fever, pain, redness, and/or difficulty breathing (possible symptoms of infection with BK virus)

·    Weight gain 

·    Constipation

Keep this medicine out of the sight and reach of children.

Store below 30°C.

Store in the original package.

Do not use this medicine after the expiry date which is stated on the package after “EXP”. The expiry date refers to the last day of that month.

Do not use this medicine if you notice any visible signs of deterioration.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.