Jakavi ® 20 mg Tablets

JAKAVI contains the active substance ruxolitinib. JAKAVI is used to treat adult patients with an enlarged spleen or with symptoms related to myelofibrosis, a rare form of blood cancer. JAKAVI is also used to treat adult patients with polycythaemia vera who are resistant to or intolerant of hydroxyurea. JAKAVI is also used to treat patients 12 years of age and older and adults with graft - versus - host disease (GvHD). This disease occurs after transplantation of blood or bone marrow from a healthy donor to a patient and comes with a variety of troublesome symptoms concerning many organs. 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, around three months after the transplantation. It frequently causes symptoms in the skin, liver, mouth, lungs, gastrointestinal tract, neuromuscular system, or genitourinary tract. In the skin it causes a dry, itchy rash, which is raised and is like alligator skin. There also may be hair loss, decrease in sweating, and premature greying of the hair. Mouth dryness is a common symptom. It may progress to food sensitivity, such that spicy and acid foods may sting. The eyes may also be involved with dryness, irritation and redness. Almost any organ can be affected by chronic GvHD.

How JAKAVI works Myelofibrosis is a disorder of the bone marrow, in which the marrow is replaced by scar tissue. The abnormal bone marrow can no longer produce enough normal blood cells and as a result, the spleen starts to produce blood cells which cause a significant increase in the size of the spleen. By blocking the action of certain enzymes (called Janus Associated Kinases), JAKAVI can reduce the size of the spleen and relieve symptoms such as fever, night sweats, bone pain and weight loss. Polycythaemia vera is a disorder of the bone marrow, in which the marrow produces too many red blood cells. The blood becomes thicker as a result of the increased red blood cells in the blood vessels which increases the risk of serious blood and vascular complications. JAKAVI, by blocking certain enzymes called Janus Associated Kinases (JAK 1 and JAK 2), suppresses the over production of red blood cells by the bone marrow which relieves the disease symptoms, reduces spleen size, and the overproduction of red blood cells which reduces 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) don’t recognize the host cells/organs and attack them. By selectively blocking enzymes called Janus Associated Kinases JAK1 and JAK2, JAKAVI is effective to reduce 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 JAKAVI works or why it has been prescribed for you, ask your doctor.

Follow all the doctor’s instructions carefully. Do not take JAKAVI − 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 your baby − if you have an acute infection − if you have latent/dormant/silent tuberculosis of your lungs or other organs − if you have HIV − if you have acute hepatitis B or have had Hepatitis B which are not well controlled with appropriate treatment − if you are to be immunised with a live attenuated bacterial or viral vaccine − if you have a blood haemoglobin of 8 g/dL or less − if you have a blood platelet count of 50,000 mm3 or less − if you have a total neutrophil count of 500 mm3 or less − if you have a skin cancer called basal cell carcinoma or squamous cell carcinoma − if you are 18 years of age or below If either of the above applies to you, tell your doctor who will then decide whether you should start treatment with JAKAVI.

Warnings and precautions

The infections, skin cancers and blood abnormalities listed in the “Do not take JAKAVI section” will first have to be cured/resolved, improved, well-controlled or reversed before you can start treatment with JAKAVI. Talk to your doctor or pharmacist before taking JAKAVI − if you have any infections. It is necessary to treat your infection before starting JAKAVI. (see “Do not take JAKAVI ”) 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 (see “Do not take JAKAVI ”). 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 or ever had hepatitis B. (see “Do not take JAKAVI ”). − if you have any kidney problems. Your doctor may need to prescribe a different dose of JAKAVI. − if you have or have ever had any liver problems. Your doctor may need to prescribe a different dose of JAKAVI. − if you are taking other medicines (see section “Other medicines and JAKAVI ) − if you have ever had skin cancer. (see “Do not take JAKAVI ”) Talk to your doctor or pharmacist during your treatment with JAKAVI − if you experience unexpected bruising, or a swelling containing clotted or partially clotted blood under your skin (haematoma) 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 JAKAVI, 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 JAKAVI 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 JAKAVI. Your doctor will also regularly check the level of lipids (fat) in your blood. Blood tests will also be done to check on your hepatitis B status. Stopping JAKAVI When you stop taking JAKAVI, the myelofibrosis symptoms may come back. Your doctor may want to gradually reduce the amount of JAKAVI taken each day, before stopping it completely.

Children and adolescents

JAKAVI is not intended for use by children or adolescents, who have the disease myelofibrosis or polycythaemia vera. For the treatment of graft - versus - host disease, JAKAVI can be used in patients 12 years and older.

Other medicines and JAKAVI

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 JAKAVI dose for you. The following may increase the risk of side effects with JAKAVI: − 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 JAKAVI: − 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 JAKAVI you should never start a new medicine without checking first with the doctor who prescribed JAKAVI. This includes prescription medicines, non-prescription medicines and herbal or alternative medicines.

Do not share medicines prescribed for you with any other person. Always take JAKAVI exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure. The dose of JAKAVI depends on your 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 15 mg twice daily or 20 mg twice daily, depending on your blood cell count. − The recommended starting dose in polycythaemia vera is 10 mg twice daily. − The maximum dose is 25 mg twice daily. Your doctor will always tell you exactly how many and what strength of JAKAVI 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 JAKAVI 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 JAKAVI every day at the same time, either with or without food.

You should continue taking JAKAVI 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 JAKAVI, 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 JAKAVI you have to take or tell you to stop taking JAKAVI for a while. If you take more JAKAVI than you should If you accidentally take more JAKAVI than your doctor prescribed, contact your doctor or pharmacist immediately. If you forget to take JAKAVI If you forgot to take JAKAVI 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 JAKAVI If you interrupt your treatment with JAKAVI your myelofibrosis and polycythemia vera related symptoms may come back. In GvHD, dose reduction or completely stopping JAKAVI is possible if you respond to treatment and your doctor will supervise this process. Therefore, you should not stop taking JAKAVI without discussing it with your doctor.

JAKAVI can have side effects. Not all side effects reported for JAKAVI are included in this leaflet. Should your general health worsen or if you experience any untoward effects while taking JAKAVI, please consult your health care provider for advice. If any of the following happens, stop taking JAKAVI and tell your doctor immediately or go to the casualty department at your nearest hospital: Frequent: − any sign of bleeding in the brain, such as sudden altered level of consciousness, persistent headache, numbness, tingling, weakness or paralysis; − any sign of bleeding in the stomach or intestine, such as passing black or bloodstained stools, or vomiting blood; − unexpected bruising or a swelling containing clotted or partially clotted blood under your skin (haematoma) 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) or very low levels of all types of blood cells (pancytopenia); − Low levels of blood cells may present with fatigue/tiredness, paleness, bruising, swellings under your skin and bleeding and make you very susceptible to infections.

Other side effects with JAKAVI Frequent: − high level of cholesterol or fat in the blood (hypertriglyceridemia); − abnormal liver function test results; − dizziness; − headache; − fever, pain when urinating as signs of an infection of the urinary tract (urinary tract infections); − weight gain; − high blood pressure (hypertension), which may also be the cause of dizziness and headaches; − fever, cough, difficult or painful breathing, wheezing, pain in chest when breathing (possible symptoms of pneumonia); − frequently passing wind (flatulence); − constipation; − rash of small fluid-filled blisters, appearing on reddened skin, signs of shingles (herpes zoster); − bruising.

Less frequent: − Tuberculosis; − reactivation of Hepatitis B infection. If you notice any side effects not mentioned in this leaflet, please inform your doctor or pharmacist. Reporting of side effects If you get side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects to SAHPRA via the “6.04 Adverse Drug Reaction Reporting Form”, found online under SAHPRA’s publications: https://www.sahpra.org.za/Publications/Index/8. By reporting side effects, you can help provide more information on the safety of JAKAVI.

Keep this medicine out of the sight and reach of children. Do not use this medicine after the expiry date which is stated on the carton or blister after “EXP”. Do not store above 25 °C. Protect from moisture. Store in the original package. 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.