upadacitinib: package leaflet

For patients

Package leaflet, verbatim

Package leaflet: RINVOQ 15 mg prolonged-release tablets / RINVOQ 30 mg prolonged-release tablets / RINVOQ 45 mg prolonged-release tablets

1. How to puncture the foil

1a. Remove the cap from the bottle by pushing down and while still pushing, turn the cap anti-clockwise.
1b. Turn the cap over and place the cutting tool near the edge of the foil seal.

2. Push down to make a hole in the foil and

move the cutting tool round the edge of the foil to continue cutting the foil.

3. When you have taken your tablet, put the

cap back on and close the bottle.

If you have any further questions on 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.

Serious side effects
Talk to your doctor or get medical help straight away if you get any signs of:
- infection such as shingles or painful skin rash with blisters (herpes zoster) – common (may affect up to 1 in 10 people)
- infection of the lung (pneumonia), which may cause shortness of breath, fever, and a cough with mucus – common (may affect up to 1 in 10 people)
- infection in the blood (sepsis) – uncommon (may affect up to 1 in 100 people)
- allergic reaction (chest tightness, wheezing, swelling of the lips, tongue or throat, hives) – uncommon (may affect up to 1 in 100 people)

Other side effects
Talk to your doctor if you notice any of the following side effects:

Very common (may affect more than 1 in 10 people)
- throat and nose infections
- acne

anaemia
pain in your belly (abdomen)
fatigue (feeling unusually tired and weak)
headache (headache was very common in giant cell arteritis)
hives (urticaria)
urinary tract infection
rash
a spinning sensation (vertigo)
dizziness
infection of the lungs (bronchitis)
swelling of the feet and hands (peripheral oedema)

Uncommon (may affect up to 1 in 100 people)
- thrush in the mouth (white patches in the mouth)
- increased levels of triglycerides (a type of fat) in the blood, as shown in tests
- diverticulitis (painful inflammation of small pockets in the lining of your intestine)
- gastrointestinal perforation (a hole in the bowel)

Rare (may affect up to 1 in 1 000 people)
- changes in the colour of semen (mostly blue and less frequently green)

Additional side effects in adolescents with atopic dermatitis

Common
- warts (skin papilloma)

Reporting of side effects
If you get any 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 directly via the national reporting system listed in Appendix V. By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store RINVOQ

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 blister label and carton after ‘EXP’.

This medicine does not require any special temperature storage conditions.

Store in the original blister or bottle with the lid tightly closed in order to protect from moisture.

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.

6. Contents of the pack and other information

What RINVOQ contains

The active substance is upadacitinib.

RINVOQ 15 mg prolonged-release tablets
- Each prolonged-release tablet contains upadacitinib hemihydrate, equivalent to 15 mg upadacitinib.
- The other ingredients are:
- Core tablet: microcrystalline cellulose, mannitol, tartaric acid, hypromellose, silica colloidal anhydrous, magnesium stearate.
- Film coating: poly(vinyl alcohol), macrogol, talc, titanium dioxide (E171), iron oxide red (E172), iron oxide black (E172).

RINVOQ 30 mg prolonged-release tablets
- Each prolonged-release tablet contains upadacitinib hemihydrate, equivalent to 30 mg upadacitinib.
- The other ingredients are:
- Core tablet: microcrystalline cellulose, mannitol, tartaric acid, hypromellose, silica colloidal anhydrous, magnesium stearate.
- Film coating: poly(vinyl alcohol), macrogol, talc, titanium dioxide (E171), iron oxide red (E172).

RINVOQ 45 mg prolonged-release tablets
- Each prolonged-release tablet contains upadacitinib hemihydrate, equivalent to 45 mg upadacitinib.
- The other ingredients are:
- Core tablet: microcrystalline cellulose, mannitol, tartaric acid, hypromellose, silica colloidal anhydrous, magnesium stearate.
- Film coating: poly(vinyl alcohol), macrogol, talc, titanium dioxide (E171), iron oxide yellow (E172) and iron oxide red (E172).

What RINVOQ looks like and contents of the pack

RINVOQ 15 mg prolonged-release tablets

RINVOQ 15 mg prolonged-release tablets are purple, oblong, biconvex tablets imprinted on one side with ‘a15’.

The tablets are provided in blisters or bottles.
RINVOQ is available in packs containing 28 or 98 prolonged-release tablets and in multipacks of 84 comprising 3 cartons, each containing 28 prolonged-release tablets.
Each calendar blister contains 7 tablets.

RINVOQ is available in bottles with desiccant containing 30 prolonged-release tablets, each pack contains 1 bottle (30 tablet pack) or 3 bottles (90 tablet pack).

RINVOQ 30 mg prolonged-release tablets

RINVOQ 30 mg prolonged-release tablets are red, oblong, biconvex tablets imprinted on one side with ‘a30’.

The tablets are provided in blisters or bottles.

RINVOQ is available in packs containing 28 or 98 prolonged-release tablets.
Each calendar blister contains 7 tablets.

RINVOQ is available in bottles with desiccant containing 30 prolonged-release tablets, each pack contains 1 bottle (30 tablet pack) or 3 bottles (90 tablet pack).

RINVOQ 45 mg prolonged-release tablets

RINVOQ 45 mg prolonged-release tablets are yellow to mottled yellow, oblong, biconvex tablets imprinted on one side with ‘a45’.

The tablets are provided in blisters or bottles.

RINVOQ is available in packs containing 28 prolonged-release tablets.
Each calendar blister contains 7 tablets.

RINVOQ is available in bottles with desiccant containing 28 prolonged-release tablets, each pack contains 1 bottle.

Not all pack sizes may be marketed.

Marketing Authorisation Holder
AbbVie Deutschland GmbH & Co. KG
Knollstrasse
67061 Ludwigshafen
Germany

Manufacturer
AbbVie S.r.l.
S.R. 148 Pontina, km 52 SNC
Aprilia (LT) 04011
Italy

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien
AbbVie SA
Tél/Tel: +32 10 477811
Lietuva
AbbVie UAB
Tel: +370 5 205 3023

България
АбВи ЕООД
Тел.:+359 2 90 30 430
Luxembourg/Luxemburg
AbbVie SA
Belgique/Belgien
Tél/Tel: +32 10 477811

Česká republika
AbbVie s.r.o.
Tel: +420 233 098 111
Magyarország
AbbVie Kft.
Tel.:+36 1 455 8600

Danmark
AbbVie A/S
Tlf.: +45 72 30-20-28
Malta
V.J.Salomone Pharma Limited
Tel: +356 21220174

Deutschland
AbbVie Deutschland GmbH & Co. KG
Tel: 00800 222843 33 (gebührenfrei)
Tel: +49 (0) 611 / 1720-0
Nederland
AbbVie B.V.
Tel: +31 (0)88 322 2843

Eesti
AbbVie OÜ
Tel: +372 623 1011
Norge
AbbVie AS
Tlf: +47 67 81 80 00

Ελλάδα
AbbVie ΦΑΡΜΑΚΕΥΤΙΚΗ Α.Ε.
Τηλ: +30 214 4165 555
Österreich
AbbVie GmbH
Tel: +43 1 20589-0

España
AbbVie Spain, S.L.U.
Tel: +34 91 384 09 10
Polska
AbbVie Sp. z o.o.
Tel.: +48 22 372 78 00

France
AbbVie
Tél: +33 (0) 1 45 60 13 00
Portugal
AbbVie, Lda.
Tel: +351 (0)21 1908400

Hrvatska
AbbVie d.o.o.
Tel + 385 (0)1 5625 501
România
AbbVie S.R.L.
Tel: +40 21 529 30 35

Ireland
AbbVie Limited
Tel: +353 (0)1 4287900
Slovenija
AbbVie Biofarmacevtska družba d.o.o.
Tel: +386 (1)32 08 060

Ísland
Vistor
Sími: +354 535 7000
Slovenská republika
AbbVie s.r.o.
Tel: +421 2 5050 0777

Italia
AbbVie S.r.l.
Tel: +39 06 928921
Suomi/Finland
AbbVie Oy
Puh/Tel: +358 (0)10 2411 200

Κύπρος
Lifepharma (Z.A.M.) Ltd
Τηλ.: +357 22 34 74 40
Sverige
AbbVie AB
Tel: +46 (0)8 684 44 600

Latvija
AbbVie SIA
Tel: +371 67605000

This leaflet was last revised in

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency web site:
https://www.ema.europa.eu.

Detailed information on this product is also available by scanning the QR code included below or on the outer carton with a smart phone. The same information is available on the following URL:
www.rinvoq.eu.

QR code to be included

To listen to or request a copy of this leaflet in <Braille>, <large print> or <audio>, please contact the local representative of the Marketing Authorisation Holder.

Package leaflet: RINVOQ 1 mg/ml oral solution

1. What RINVOQ is and what it is used for

RINVOQ is used to treat active polyarticular juvenile idiopathic arthritis in patients 2 years and older.
Polyarticular juvenile idiopathic arthritis is a disease that causes inflamed joints. If you have active polyarticular juvenile idiopathic arthritis, you may first be given other medicines. If these medicines do not work well enough, you will be given RINVOQ either alone or in combination with methotrexate to treat your polyarticular juvenile idiopathic arthritis.

RINVOQ can help to reduce pain, stiffness and swelling in your joints, and help to slow damage to the bone and cartilage in your joints. These effects can ease your normal daily activities and so improve your quality of life.

How RINVOQ works

RINVOQ contains the active substance upadacitinib. It belongs to a group of medicines called Janus kinase inhibitors. By reducing the activity of an enzyme called ‘Janus kinase’ in the body, RINVOQ lowers inflammation in polyarticular juvenile idiopathic arthritis.

2. What you need to know before you take RINVOQ

Do not take RINVOQ
- if you are allergic to upadacitinib or any of the other ingredients of this medicine (listed in section 6)
- if you have a severe infection (such as pneumonia or bacterial skin infection)
- if you have active tuberculosis (TB)
- if you have severe liver problems

if you are pregnant (see section Pregnancy, breast-feeding and contraception)

Warnings and precautions
Talk to your doctor or pharmacist before and during treatment with RINVOQ if:
- you have an infection or if you often get infections. Tell your doctor if you get symptoms such as fever, wounds, feeling more tired than usual or dental problems as these can be signs of infection. RINVOQ can reduce your body’s ability to fight infections and may make an existing infection worse or increase the chance of you getting a new infection. If you have diabetes or are 65 years of age or older you may have an increased chance of getting infections
- you have had tuberculosis or have been in close contact with someone with tuberculosis. Your doctor will test you for tuberculosis before starting RINVOQ and may retest during treatment
- you have had a herpes zoster infection (shingles), because RINVOQ may allow it to come back.
Tell your doctor if you get a painful skin rash with blisters as these can be signs of shingles
- you have ever had hepatitis B or C
- you have recently had or plan to have a vaccination (immunisation) - this is because live vaccines are not recommended while using RINVOQ
- you have or had in the past cancer, smoke or have smoked in the past, because your doctor will discuss with you if RINVOQ is appropriate for you
- new skin changes appear during or after taking RINVOQ. Your doctor may recommend that you have regular skin examinations while taking RINVOQ because non-melanoma skin cancer has been observed in patients taking RINVOQ
- have, or have had, heart problems, because your doctor will discuss with you if RINVOQ is appropriate for you
- your liver does not work as well as it should
- you have previously had blood clots in the veins of your legs (deep vein thrombosis) or lungs (pulmonary embolism) or have an increased risk for developing this (for example: if you had recent major surgery, if you use hormonal contraceptives\hormonal replacement therapy, if a blood clotting disorder is identified in you or your close relatives). Your doctor will discuss with you if RINVOQ is appropriate for you. Tell your doctor if you get sudden shortness of breath or difficulty breathing, chest pain or pain in upper back, swelling of the leg or arm, leg pain or tenderness, or redness or discolouration in the leg or arm as these can be signs of blood clots in the veins
- you experience sudden changes to your eyesight. You should seek medical advice straight away if you have sudden symptoms such as blurry vision, partial or complete loss of vision, as these may be a sign of blocked blood flow in the eyes
- you have kidney problems
- you have unexplained stomach (abdominal) pain, have or have had diverticulitis (painful inflammation of small pockets in the lining of your intestine) or ulcers in your stomach or intestines, or are taking non-steroidal anti-inflammatory medicines.

If you notice any of the following serious side effects, tell a doctor straight away:
- symptoms such as a rash (hives), trouble breathing, or swelling of your lips, tongue, or throat, you may be having an allergic reaction. Some people taking RINVOQ had serious allergic reactions. If you have any of these symptoms during treatment with RINVOQ, stop taking RINVOQ and get emergency medical help straight away
- severe stomach pain especially accompanied by fever, nausea, and vomiting.

Blood tests
You will need blood tests before you start taking RINVOQ, or while you are taking it. This is to check for a low red blood cell count (anaemia), low white blood cell count (neutropenia or lymphopenia), high blood fat (cholesterol) or high levels of liver enzymes. The tests are to check that treatment with RINVOQ is not causing problems.

Elderly
There is a higher rate of infection in patients aged 65 years of age and older. Tell your doctor as soon as you notice any signs or symptoms of an infection.

Patients 65 years of age and older may be at increased risk of infections, heart problems including heart attack, and some types of cancer. Your doctor will discuss with you if RINVOQ is appropriate for you.

Children and adolescents

RINVOQ is not recommended for use in children under 2 years of age or weighing less than 10 kg with polyarticular juvenile idiopathic arthritis. This is because it has not been studied in these patients.

Other medicines and RINVOQ
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. This is because some medicines may reduce how well RINVOQ works or may increase the risk of getting side effects. It is very important to talk to your doctor or pharmacist if you are taking any of the following:
- medicines to treat fungal infections (such as itraconazole, posaconazole or voriconazole)
- medicines to treat bacterial infections (such as clarithromycin)
- medicines to treat Cushing’s syndrome (such as ketoconazole)
- medicines to treat tuberculosis (such as rifampicin)
- medicines to treat seizures or fits (such as phenytoin)
- medicines that affect your immune system (such as azathioprine, 6-mercaptopurine, ciclosporin and tacrolimus)
- medicines that may increase your risk of gastrointestinal perforation or diverticulitis such as non-steroidal anti-inflammatory medicines (usually used to treat painful and/or inflammatory conditions of muscle or joints), and/or opioids (used to treat severe pain), and/or corticosteroids (usually used to treat inflammatory conditions)
- medicines to treat diabetes or if you have diabetes. Your doctor may decide if you need less anti-diabetic medicine while taking upadacitinib.

If any of the above apply to you or you are not sure, talk to your doctor or pharmacist before taking RINVOQ.

Pregnancy, breast-feeding and contraception

Pregnancy
RINVOQ must not be used during pregnancy.

Breast-feeding
If you are breast-feeding or are planning to breast-feed, talk to your doctor before taking this medicine.
You should not use RINVOQ while breast-feeding as it is not known if this medicine passes into breast milk. You and your doctor should decide if you will breast-feed or use RINVOQ. You should not do both.

Contraception
If you are a woman of child-bearing potential, you must use effective contraception to avoid becoming pregnant while taking RINVOQ and for at least 4 weeks after your last dose of RINVOQ. If you become pregnant during this time, you must talk to your doctor straight away.

If your child has her first menstrual period while taking RINVOQ, you should inform the doctor.

Driving and using machines
Do not drive or use machines if you experience dizziness or a spinning sensation (vertigo) when taking RINVOQ until they resolve.

RINVOQ contains sodium benzoate
This medicine contains 0.3 mg sodium benzoate in each ml of oral solution.

RINVOQ contains sodium
This medicine contains less than 1 mmol sodium (23 mg) per ml, that is to say essentially ‘sodium- free’.

3. How to take RINVOQ

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

How much RINVOQ to take

The recommended dose is based on body weight.

Patient weight
Dose and schedule
10 to < 20 kg
3 mg (3 ml oral solution) twice a day
20 to < 30 kg
4 mg (4 ml oral solution) twice a day
≥ 30 kg
6 mg (6 ml oral solution) twice a day

How to take

Take the oral solution twice a day by mouth (see section 7 Instructions for use)
To help you remember to take RINVOQ, take it at the same time every day.
The oral solution can be taken with or without food.
Avoid food or drink containing grapefruit whilst you are taking (or being treated with) RINVOQ as these may make side effects more likely, by increasing the amount of medicine in your body.

If you take more RINVOQ than you should
If you take more RINVOQ than you should, contact your doctor. You may get some of the side effects listed in section 4.

If you forget to take RINVOQ
- If you miss a dose, take it as soon as you remember and then continue with the next dose at its regular time.
- If it is almost time for the next dose, do not take the missed dose. Take the next dose at its regular time.
- Do not take a double dose to make up for a forgotten dose.

If you stop taking RINVOQ
Do not stop taking RINVOQ unless your doctor tells you to stop taking it.

If you have any further questions on 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.

Other side effects
Talk to your doctor if you notice any of the following side effects:

Very common (may affect more than 1 in 10 people)
- throat and nose infections
- acne

Common (may affect up to 1 in 10 people)
- non-melanoma skin cancer
- cough
- fever
- cold sores (herpes simplex)
- feeling sick in the stomach (nausea)
- increase in an enzyme called creatine kinase, shown by blood tests
- low white blood cell counts shown in blood tests
- increased levels of cholesterol (a type of fat in the blood) as shown in tests
- increased levels of liver enzymes, shown by blood tests (sign of liver problems)
- weight gain
- inflammation (swelling) of the hair follicles
- flu (influenza)
- anaemia
- pain in your belly (abdomen)
- fatigue (feeling unusually tired and weak)
- headache (headache was very common in giant cell arteritis)
- hives (urticaria)
- urinary tract infection
- rash
- a spinning sensation (vertigo)
- dizziness
- infection of the lungs (bronchitis)
- swelling of the feet and hands (peripheral oedema)

Rare (may affect up to 1 in 1 000 people)
- changes in the colour of semen (mostly blue and less frequently green)

5. How to store RINVOQ

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 bottle label and carton after ‘EXP’.

This medicine does not require any special temperature storage conditions.

Keep the bottle in the outer carton in order to protect from light.

Throw away any remaining oral solution 60 days after first opening the bottle.

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.

6. Contents of the pack and other information

What RINVOQ contains

The active substance is upadacitinib.
- Each 1 ml of oral solution contains upadacitinib hemihydrate, equivalent to 1 mg upadacitinib.
- The other ingredients are:
- citric acid anhydrous, purified water, sodium benzoate (see section 2), sodium citrate dihydrate, and sucralose.

What RINVOQ looks like and contents of the pack

RINVOQ 1 mg/ml oral solution is a clear, colourless to light yellow solution.

The oral solution is provided in HDPE bottles with a child-resistant cap.

Each bottle contains 180 ml of solution. The bottle is packaged in a carton with one press-in bottle adapter and one 10 ml oral dosing syringe with markings at each ml.

Marketing Authorisation Holder
AbbVie Deutschland GmbH & Co. KG
Knollstrasse
67061 Ludwigshafen
Germany

Manufacturer
AbbVie S.r.l.
S.R. 148 Pontina, km 52 SNC
Aprilia (LT) 04011

Italy

AbbVie Deutschland GmbH & Co. KG
Knollstrasse
67061 Ludwigshafen
Germany