Package Insert: Information for the Patient

XELJANZ 1 mg/ml Oral Solution

tofacitinib

Read this package insert carefully before starting to take this medicine, as it contains important information for you.

• Keep this package insert, as you may need to read it again.
• If you have any questions, consult your doctor or pharmacist.
• This medicine has been prescribed only for you, and you should not give it to others even if they have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are not listed in this package insert. See section 4.

In addition to this package insert, your doctor will also give you a patient information leaflet, which contains important safety information that you need to know before taking XELJANZ and during treatment with XELJANZ. Keep this patient information leaflet with you.

XELJANZ 1 mg/ml oral solution is a medication that contains the active ingredient tofacitinib.

XELJANZ 1 mg/ml oral solution is used for the treatment of active polyarticular idiopathic juvenile arthritis, a long-term disease that mainly causes joint pain and inflammation in patients 2 years of age and older.

XELJANZ 1 mg/ml oral solution is also used for the treatment of juvenile psoriatic arthritis, a condition that is an inflammatory joint disease, often accompanied by psoriasis, in patients 2 years of age and older.

XELJANZ 1 mg/ml oral solution may be used in combination with methotrexate when previous treatment for polyarticular idiopathic juvenile arthritis or juvenile psoriatic arthritis has not been effective or was not well tolerated. XELJANZ 1 mg/ml oral solution can also be taken as a single medication in cases where methotrexate treatment is not tolerated or is not recommended.

Do not take XELJANZ

• if you are allergic to tofacitinib or any of the other ingredients in this medicine
• (listed in section 6)
• if you have a serious infection such as blood infection or active tuberculosis
• if you have severe liver problems, such as cirrhosis (scarring of the liver)
• if you are pregnant or breastfeeding

Please contact your doctor if you have any doubts about any of the above points.

Warnings and precautions

Consult your doctor or pharmacist before starting to take XELJANZ:

• if you think you have an infection or have symptoms of an infection such as fever, sweating, chills, muscle aches, cough, difficulty breathing, appearance of mucus or changes in mucus, weight loss, hot, red, or painful skin, or sores on the body, difficulty or pain swallowing, diarrhea or stomach pain, burning sensation while urinating or frequent urination, or feeling very tired
• if you have a disease that increases the risk of infection (for example, diabetes, HIV/AIDS or a weakened immune system)
• if you have any type of infection, are receiving treatment for an infection, or have recurring infections. Inform your doctor immediately if you do not feel well. XELJANZ may reduce the body's ability to respond to infections and may worsen an existing infection or increase the risk of a new infection
• if you have or have had tuberculosis or have been in close contact with someone with tuberculosis. Your doctor will perform a tuberculosis test before starting treatment with XELJANZ and may repeat the test during treatment
• if you have chronic lung disease
• if you have liver problems
• if you have or have had hepatitis B or hepatitis C (viruses that affect the liver). The virus may become active while taking XELJANZ. Your doctor may perform blood tests for hepatitis before starting treatment with XELJANZ and while taking XELJANZ
• if you have ever had any type of cancer, and also if you currently smoke or have smoked in the past. XELJANZ may increase the risk of certain types of cancer. Cases of leukemia, lung cancer, and other types of cancer (such as breast cancer, skin cancer, prostate cancer, and pancreatic cancer) have been reported in patients treated with XELJANZ. If you develop cancer while on treatment with XELJANZ, your doctor will assess whether to interrupt treatment with XELJANZ
• if you have a known risk of fractures, for example, if you are over 65 years old, female, or taking corticosteroids (for example, prednisone)
• if you have a high risk of developing skin cancer. Your doctor may recommend regular skin checks while taking XELJANZ
• if you have had diverticulitis (a type of inflammation of the large intestine) or ulcers in the stomach or intestines (see section 4)
• if you have kidney problems
• if you plan to be vaccinated, inform your doctor. Certain types of vaccines should not be administered while taking XELJANZ. Before starting treatment with XELJANZ, you should be up to date on all recommended vaccinations. Your doctor will decide if you need to be vaccinated against herpes zoster
• if you have heart problems, high blood pressure, high cholesterol, and also if you currently smoke or have smoked in the past.

Cases of patients treated with XELJANZ who have developed blood clots in the lungs or veins have been reported. Your doctor will review your risk of developing blood clots in the lungs or veins and determine if XELJANZ is appropriate for you. If you have already had problems developing blood clots in the lungs and veins or have a higher risk of developing them [for example, if you are significantly overweight, have cancer, heart problems, diabetes, have had a heart attack (in the past 3 months), have had recent major surgery, are using hormonal contraceptives/hormone replacement therapy, have been identified with any coagulation disorder in you or your close relatives], if you currently smoke or have smoked in the past, your doctor may decide that XELJANZ is not suitable for you.

Consult your doctor immediately if you experience sudden shortness of breath or difficulty breathing, chest pain or upper back pain, swelling in the legs or arms, pain or tenderness in the legs, or redness or change in color of the legs or arms while taking XELJANZ, as these may be signs of a blood clot in the lungs or veins.

Consult your doctor immediately if you experience severe changes in vision (blurred vision, partial or complete loss of vision), as this may be a sign of blood clots in the eyes.

Cases of patients treated with XELJANZ who have had a heart problem, including myocardial infarction, have been reported. Your doctor will assess your risk of developing a heart problem and determine if XELJANZ is suitable for you. Talk to your doctor immediately if you experience signs and symptoms of myocardial infarction, such as severe chest pain or pressure (which may radiate to the arms, jaw, neck, back, or stomach), difficulty breathing, cold sweat, dizziness, or sudden dizziness.

Additional control tests

Your doctor should perform blood tests before starting treatment with XELJANZ, after 4 to 8 weeks of treatment, and then every 3 months, to determine if you have a low white blood cell count (neutrophils or lymphocytes) or a low red blood cell count (anemia).

You should not take XELJANZ if your white blood cell count (neutrophils or lymphocytes) or red blood cell count is too low. If necessary, your doctor may suspend your treatment with XELJANZ to reduce the risk of infection (white blood cell count) or anemia (red blood cell count).

Your doctor may also perform other tests, for example, to monitor your cholesterol levels in the blood or to monitor the state of your liver. Your doctor should assess your cholesterol levels in the 8 weeks following the start of treatment with XELJANZ. Your doctor should perform periodic liver tests.

Older patients

The safety and efficacy of tofacitinib 1 mg/ml oral solution have not been established in older patients.

Asian patients

A higher number of herpes zoster cases have been observed in Japanese and Korean patients. Inform your doctor if you notice painful blisters on the skin.

You may also have a higher risk of developing certain lung problems. Inform your doctor if you experience any difficulty breathing.

Children and adolescents

This medicine should not be administered to patients under 2 years of age.

This medicine contains propylene glycol and should be used with caution in patients 2 years of age and older and only if recommended by your doctor (see "XELJANZ contains propylene glycol").

Other medicines and XELJANZ

Inform your doctor or pharmacist if you are taking, have taken recently, or may need to take any other medicine.

Inform your doctor if you have diabetes or are taking diabetes medications. Your doctor may decide that you need less diabetes medication while taking tofacitinib.

Some medicines should not be taken with XELJANZ. If taken with XELJANZ, they may alter the level of XELJANZ in your body, and the dose of XELJANZ may need to be adjusted. Inform your doctor if you are using medicines that contain any of the following active ingredients:

• antibiotics such as rifampicin, used to treat bacterial infections
• fluconazole, ketoconazole, used to treat fungal infections

XELJANZ should not be used with medicines that suppress the immune system, including biologic therapies (antibodies), such as those that inhibit tumor necrosis factor, interleukin-17, interleukin-12/interleukin-23, integrin antagonists, and strong immunosuppressive chemicals, including azathioprine, mercaptopurine, cyclosporine, and tacrolimus. The use of XELJANZ with these medicines may increase the risk of adverse effects, including infection.

People taking corticosteroids (for example, prednisone) may have a higher risk of developing serious infections and fractures.

Pregnancy and breastfeeding

If you are a woman of childbearing age, you should use effective contraception during treatment with XELJANZ and for at least 4 weeks after the last dose.

If you are pregnant or breastfeeding, or think you may be pregnant, or plan to become pregnant, consult your doctor before using this medicine. XELJANZ should not be used during pregnancy. Inform your doctor immediately if you become pregnant while taking XELJANZ.

If you are taking XELJANZ and breastfeeding, stop breastfeeding until you talk to your doctor about interrupting treatment with XELJANZ.

Driving and operating machinery

XELJANZ has no or limited effect on your ability to drive or operate machinery.

XELJANZ contains propylene glycol

This medicine contains 2.39 mg of propylene glycol in each ml of oral solution.

XELJANZ contains sodium benzoate

This medicine contains 0.9 mg of sodium benzoate in each ml of oral solution.

XELJANZ contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per ml; it is essentially "sodium-free".

This medicine has been provided and supervised by a specialist doctor who knows how to treat your condition.

Follow exactly the administration instructions for this medicine as indicated by your doctor, do not exceed the recommended dose. If in doubt, consult your doctor or pharmacist again.

The recommended dose in patients aged 2 years and older is based on the following classification according to weight (see Table 1):

Table 1: XELJANZ dosing for patients with juvenile idiopathic arthritis and JPs from 2 years of age:

Your doctor may reduce the dose if you have liver or kidney problems, or if you are taking certain medications. Your doctor may also temporarily or permanently interrupt treatment if blood tests show low white blood cell or red blood cell counts.

If you have juvenile idiopathic arthritis polyarticular or psoriatic arthritis, your doctor may change your XELJANZ 5 ml oral solution twice a day treatment to XELJANZ 5 mg film-coated tablets twice a day.

XELJANZ is for oral use. You can take XELJANZ with or without food.

Try to take XELJANZ at the same time every day (morning and night).

If you take more XELJANZ than you should

If you take more than the recommended dose of XELJANZ 1 mg/ml oral solution, inform your doctor or pharmacist immediately.

If you forget to take XELJANZ

Do not take a double dose to make up for the missed dose. Take the next dose at the usual time and continue as before.

If you interrupt treatment with XELJANZ

Do not stop taking XELJANZ without consulting your doctor.

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

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

Some may be serious and require medical attention.

Side effects in patients with juvenile idiopathic polyarticular arthritis and juvenile psoriatic arthritis were consistent with those observed in adult patients with rheumatoid arthritis, with the exception of some infections (flu, pharyngitis, sinusitis, viral infection) and gastrointestinal or general disorders (abdominal pain, nausea, vomiting, fever, headache, cough), which were more frequent in the pediatric population with juvenile idiopathic arthritis.

Possible serious side effects

In rare cases, infections can be fatal. Cases of lung cancer, leukemia, and myocardial infarction have also been reported.

If you notice any of the following serious side effects, inform your doctor immediately.

The signs of severe infection (frequent) include

• fever and chills
• cough
• skin blisters
• stomach pain
• persistent headache

The signs of ulcers or holes (perforations) in the stomach (infrequent) include

• fever
• stomach pain or abdominal pain
• blood in stool
• unjustified changes in bowel habits

Stomach or intestinal ulcers occur more frequently in patients who are also being treated with nonsteroidal anti-inflammatory drugs or corticosteroids (e.g. prednisone).

The signs of allergic reactions (unknown frequency) include

• chest tightness
• asthma
• severe dizziness or vertigo
• swelling of the lips, tongue, or throat
• urticaria (pruritus and hives)

The signs of blood clots in the lungs, veins, or eyes (infrequent: venous thromboembolism) include

• sudden shortness of breath or difficulty breathing
• chest pain or upper back pain
• swelling of the legs or arms
• pain or tenderness in the legs
• redness or change in color of legs or arms
• severe changes in vision

The signs of myocardial infarction (infrequent) include

• chest pain or pressure (which may radiate to the arms, jaw, neck, or back)
• difficulty breathing
• cold sweat
• sudden dizziness or lightheadedness

Other side effectsthat have been observed with XELJANZ are listed below.

Frequent(may affect up to 1 in 10 patients): respiratory infections (pneumonia and bronchitis), shingles, nasal, throat, or tracheal infections (nasopharyngitis), flu, sinusitis, urinary tract infections (cystitis), sore throat (pharyngitis), elevated muscle enzymes in the blood (signs of muscle problems), stomach pain (abdominal pain) (which may be due to stomach inflammation), vomiting, diarrhea, nausea, indigestion, low white blood cell count, low red blood cell count (anemia), swelling of the feet and hands, headache, high blood pressure (hypertension), cough, skin rash.

Infrequent(may affect up to 1 in 100 patients): lung cancer, tuberculosis, kidney infection, skin infection, herpes simplex or oral ulcers (herpes labial), elevated creatinine in the blood (a possible sign of kidney problems), elevated cholesterol (including LDL), fever, fatigue (fatigue), weight gain, dehydration, muscle tear, tendinitis, joint swelling, joint sprain, abnormal sensations, insomnia, sinus congestion, shortness of breath or difficulty breathing, skin redness, itching, fatty liver, painful inflammation of small pouches that protrude from the intestinal lining (diverticulitis), viral infections, viral infections affecting the intestine, some types of non-melanoma skin cancer.

Rare(may affect up to 1 in 1,000 patients): blood infection (sepsis), lymphoma (cancer of the white blood cells), disseminated tuberculosis affecting bones and other organs, other unusual infections, joint infections, elevated liver enzymes in the blood (sign of liver problems), muscle and joint pain.

Very rare(may affect up to 1 in 10,000 patients): tuberculosis affecting the brain and spinal cord, meningitis, infection of soft tissues and fascia.

In general, fewer side effects were observed in rheumatoid arthritis when XELJANZ was administered alone compared to when it was combined with methotrexate.

Reporting side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect that does not appear in this prospectus. You can also report them directly through thenational notification system included in theAppendix V. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

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

Do not use this medication after the expiration date that appears on the carton or in the bottle. The expiration date is the last day of the month indicated.

This medication does not require any special storage temperature.

Store in the original bottle and packaging to protect it from light.

Dispose of after 60 days from the first opening

Do not use this medication if you observe that the solution shows visible signs of deterioration.

Medications should not be thrown down the drain or in the trash. Ask your pharmacist how to dispose of the containers and medications that you no longer need. This will help protect the environment.

Composition of XELJANZ

• The active ingredient is tofacitinib.
• Each ml contains 1 mg of tofacitinib (as tofacitinib citrate).
• The other components are grape aroma [which contains propylene glycol (E1520) (see section 2 “XELJANZ contains propylene glycol”), glycerin (E422) and natural flavors], hydrochloric acid, lactic acid (E270), purified water, sodium benzoate (E211) (see section 2 “XELJANZ contains sodium benzoate” and “XELJANZ contains sodium”), sucralose (E955) and xylitol (E967).

Appearance of the product and contents of the pack

XELJANZ 1 mg/ml oral solution is a clear, colourless solution.

The oral solution 1 mg/ml is presented in 250 ml HDPE bottles of white colour containing 240 ml of oral solution. Each pack contains an HDPE bottle, a bottle adapter and an oral dosing syringe with graduations of 3.2 ml, 4 ml and 5 ml.

Marketing authorisation holder

Pfizer Europe MA EEIG

Boulevard de la Plaine 17

1050 Bruxelles

Belgium

Responsible for manufacturing

Pfizer Service Company BVBA

Hoge Wei 10

1930 Zaventem

Belgium

You can request more information about this medicine by contacting the local representative of the marketing authorisation holder:

Last update of this leaflet:

Other sources of information

The detailed information on this medicine is available on the website of the European Medicines Agency:http://www.ema.europa.eu.

7. Instructions for the use of XELJANZ oral solution

Read these Instructions for Use before starting to take XELJANZ oral solution. There may be new information.

Important information about the dosing of XELJANZ oral solution

Always use the oral dosing syringe provided with XELJANZ oral solution to measure and administer the prescribed dose. If you are unsure, ask a healthcare professional or pharmacist to show you how to measure the prescribed dose.

How should XELJANZ be stored?

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

Discard any remaining XELJANZ oral solution after 60 days.

To help you remember when to discard the XELJANZ bottle, you can write the date of the first use on the bottle and then:

Date of first use ____/____/____.

Before each use:

Wash your hands with water and soap and place the contents of the box on a clean and flat surface.

Each pack of XELJANZ oral solution contains

• 1 bottle adapter
• 1 XELJANZ oral solution bottle
• 1 oral dosing syringe

Step 1. Remove the bottle from the pack

Remove the XELJANZ oral solution bottle from the pack.

Step 2. Open the bottle

Open the bottle. Remove the sealed cap from the top of the bottle (only the first time).

Do not throw away the child-resistant cap.

Note: there is no need to shake the bottle before use.

Step 3. Insert the bottle adapter

Remove the bottle adapter and oral dosing syringe from the plastic wrapper. With the bottle on a flat surface, push the tapered end of the bottle adapter with your thumbs until it reaches the bottom of the bottle neck while holding the bottle firmly.

Note: do not remove the bottle adapter after it has been inserted.

Step 4. Remove air from the oral dosing syringe

Push the plunger of the oral dosing syringe all the way down to remove any excess air.

Step 5. Insert the oral dosing syringe

Insert the oral dosing syringe vertically into the bottle through the opening of the bottle adapter until it is firmly in place.

Step 6. Extract the dose from the bottle

With the oral dosing syringe in place, turn the bottle upside down. Pull the plunger back.

If you see air bubbles in the oral dosing syringe, press the plunger all the way down to return the oral solution to the bottle. Then, extract the prescribed dose of oral solution.

Step 7. Remove the oral dosing syringe

Place the bottle upright on a flat surface. Remove the oral dosing syringe from the bottle adapter by pulling the syringe barrel upwards.

Step 8. Check the extracted dose

Check that you have extracted the correct dose in the oral dosing syringe.

If the dose is not correct, insert the tip of the oral dosing syringe firmly into the bottle adapter. Push the plunger all the way down to return the oral solution to the bottle. Repeat steps 6 and 7.

Step 9. Take the XELJANZ dose

Place the tip of the oral dosing syringe into the inside of the patient's cheek.

Push the plunger slowly all the way down to administer all the medicine from the oral dosing syringe. Make sure the patient has time to swallow the medicine.

Step 10. Close the bottle

Close the bottle tightly by turning the child-resistant cap in a clockwise direction, leave the bottle adapter where it is.

Put the bottle back in the pack and close it to protect the XELJANZ oral solution from light.

Step 11. Clean the oral dosing syringe

Remove the plunger from the syringe barrel by pulling the plunger and barrel in opposite directions.

Wash both with water after each use.

Allow them to air dry; then put the oral dosing syringe back with the oral solution in the pack.

Store the oral dosing syringe with the XELJANZ oral solution.

Do not discard the oral dosing syringe.