Tyenne 162 mg solution for injection in pre-filled pen

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only. Do not pass it onto others. It may harm them even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

In addition to this leaflet, you will be given a Patient Alert Card, which contains important safety information that you need to be aware of before and during treatment with Tyenne.

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

• if you or a child patient you look after are allergic to tocilizumab or any of the other ingredients of this medicine (listed in section 6).
• if you or a child patient you look after have an active, severe infection.

If either of these applies to you, tell a doctor. Do not use Tyenne.

Talk to your doctor, pharmacist or nurse before using Tyenne.

• If you experience allergic reactions such as chest tightness, wheezing, severe dizziness or lightheadedness, swelling of the lips, tongue, face or skin itching, hives or rash during or after the injection, then tell your doctor immediately.
• Do not take the next dose until you have informed your doctor AND your doctor has told you to take the next dose if you have experienced any allergic reaction symptoms after Tyenne administration.
• If you have any kind of infection, short- or long- term, or if you often get infections. Tell your doctor immediately if you feel unwell. Tyenne can reduce your body’s ability to respond to infections and may make an existing infection worse or increase the chance of getting a new infection.
• If you have had tuberculosis, tell your doctor. Your doctor will check for signs and symptoms of tuberculosis before starting Tyenne. If symptoms of tuberculosis (persistent cough, weight loss, listlessness, mild fever) or any other infection appear during or after therapy tell your doctor immediately.
• If you have had intestinal ulcers or diverticulitis, tell your doctor. Symptoms would include abdominal pain and unexplained changes in bowel habits with a fever.
• If you have liver disease, tell your doctor. Before you use Tyenne, your doctor may do a blood test to measure your liver function.
• If any patient has recently been vaccinated, or is planning a vaccination, tell your doctor. All patients should be up-to-date with all their vaccinations before they start treatment with Tyenne. Certain types of vaccines should not be given while receiving Tyenne.
• If you have cancer, tell your doctor. Your doctor will have to decide if you can still be given Tyenne.
• If you have risk factors for heart disease such as raised blood pressure and raised cholesterol levels, tell your doctor. These factors need to be monitored while receiving Tyenne.
• If you have moderate to severe kidney function problems, your doctor will monitor you.
• If you have persistent headaches.

Your doctor will perform a blood test before you receive Tyenne, to determine if you have a low white blood cell count, low platelet count or high liver enzymes.

Tyenne pre-filled pen is not recommended for use in children under 12 years of age.

Tyenne must not be given to children with sJIA (systemic juvenile idiopathic arthritis) weighing less than 10 kg.

If a child has a history of macrophage activation syndrome (activation and uncontrolled proliferation of specific blood cells), tell your doctor. Your doctor will have to decide if they can still be given Tyenne.

Tell your doctor if you are taking any other medicines, or have recently taken any. Tyenne can affect the way some medicines work, and the dose of these may require adjustment. If you are using medicines containing any of the following active substances, tell your doctor:

• methylprednisolone, dexamethasone, used to reduce inflammation
• simvastatin or atorvastatin, used to reduce cholesterol levels
• calcium channel blockers (such as amlodipine), used to treat high blood pressure
• theophylline, used to treat asthma
• warfarin or phenprocoumon, used as a blood thinning agents
• phenytoin, used to treat convulsions
• ciclosporin, used to suppress your immune system during organ transplants
• benzodiazepines (such as temazepam), used to relieve anxiety

Regarding vaccinations, please see the section on warnings above.

Due to lack of clinical experience, Tyenne is not recommended for use with other biological medicines for the treatment of RA, sJIA, pJIA or GCA.

Tyenne is not to be used in pregnancy unless clearly necessary. Talk to your doctor if you are pregnant, may be pregnant, or intend to become pregnant.

Women of childbearing potential must use effective contraception during and up to 3 months after treatment.

Stop breast-feeding if you are to be given Tyenne, and talk to your doctor. Leave a gap of at least 3 months after your last treatment before you start breast-feeding. It is not known whether Tyenne passes into breast milk.

This medicine can cause dizziness. If you feel dizzy, do not drive or use machines

The recommended dose for RA (rheumatoid arthritis) or GCA (giant cell arteritis) for adults is 162 mg (the content of 1 pre-filled pen) given once a week.

The usual dose of Tyenne depends on the patient’s weight.

• If the patient weighs less than 30 kg: the dose is 162 mg (the content of 1 pre-filled pen) once every 2 weeks
• If the patient weighs 30 kg or more: the dose is 162 mg (the content of 1 pre-filled pen) once every week

The usual dose of Tyenne depends on the patient’s weight.

• If the patient weighs less than 30 kg: the dose is 162 mg (the content of 1 pre-filled pen), once every 3 weeks
• If the patient weighs 30 kg or more: the dose is 162 mg (the content of 1 pre-filled pen), once every 2 weeks.

Tyenne is given by injection under the skin (subcutaneously). At the start, your doctor or nurse may inject Tyenne. However, your doctor may decide that you may inject Tyenne yourself. In this case you will get training on how to inject Tyenne yourself. Parents and carers will get training on how to inject Tyenne for patients who cannot inject themselves.

Talk to your doctor if you have any questions about giving yourself or an adolescent patient you look after an injection. You will find detailed “Instructions for administration” at the end of this leaflet.

Because Tyenne is given in one pre-filled pen, it is unlikely that you will receive too much.

However, if you are worried, talk to your doctor, pharmacist or nurse.

It is very important to use Tyenne exactly as prescribed by your doctor. Keep track of your next dose.

• If you miss your weekly dose within 7 days, take your dose on the next scheduled day.
• If you miss your once every other week dose within 7 days, inject a dose as soon as you remember and take your next dose at your regular scheduled time.
• If you miss your weekly or once every other week dose by more than 7 days, or you are not sure when to inject Tyenne, call your doctor or pharmacist.

It is very important to use Tyenne exactly as prescribed by the doctor. Keep track of the next dose.

• If a dose is missed within 7 days, inject a dose as soon as you remember and give the next dose at the regular scheduled time.
• If a dose is missed by more than 7 days, or you are not sure when to inject Tyenne, call the doctor or pharmacist.

You should not stop using Tyenne without discussing with your doctor first.

These are common: they may affect up to 1 in 10 people

Allergic reactions during or after injection:

• difficulty with breathing, chest tightness or light-headedness
• rash, itching, hives, swelling of the lips, tongue or face

If you notice any of these, tell your doctor immediately.

Signs of serious infections:

• fever and chills
• mouth or skin blisters
• stomach ache

Signs and symptoms of liver toxicity

These may affect up to 1 in 1000 people

• tiredness,
• abdominal pain,
• jaundice (yellow discoloration of skin or eyes)

If you notice any of these, tell your doctor as soon as possible.

Very common side effects:

These may affect 1 in 10 people or more

• upper respiratory tract infections with typical symptoms such as cough, blocked nose, runny nose, sore throat and headache,
• high blood fat (cholesterol) levels
• injection site reactions.

Common side effects:

These may affect up to 1 in 10 people

• lung infection (pneumonia)
• shingles (herpes zoster)
• cold sores (oral herpes simplex), blisters
• skin infection (cellulitis) sometimes with fever and chills
• rash and itching, hives
• allergic (hypersensitivity) reactions
• eye infection (conjunctivitis)
• headache, dizziness, high blood pressure
• mouth ulceration, stomach pain
• fluid retention (oedema) in the lower legs, weight increase
• cough, shortness of breath
• low white blood cell counts shown by blood tests (neutropenia, leucopenia)
• abnormal liver function tests (increased transaminases)
• increased bilirubin shown by blood tests
• low fibrinogen levels in the blood (a protein involved in blood clotting).

Uncommon side effects:

These may affect up to 1 in 100 people

• diverticulitis (fever, nausea, diarrhoea, constipation, stomach pain)
• red swollen areas in the mouth
• high blood fat (triglycerides)
• stomach ulcer
• kidney stones
• underactive thyroid.

Rare side effects:

These may affect up to1 in 1000 people

• Stevens-Johnson syndrome (skin rash, which may lead to severe blistering and peeling of the skin)
• fatal allergic reactions (anaphylaxis [fatal])
• inflammation of the liver (hepatitis), jaundice

Very rare side effects:

These may affect up to 1 in 10000 people

• low counts for white blood cells, red blood cells and platelets in blood tests.
• liver failure

Side effects in children and adolescents with sJIA or pJIA are generally similar to those in adults. Some side effects are seen more often in children and adolescents: inflamed nose and throat, headache, feeling sick (nausea) and lower white blood cell counts.

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 (see details below). By reporting side effects you can help provide more information on the safety of this medicine.

Ireland

UK

or search for MHRA Yellow Card in the Google Play or Apple App Store

• The active substance is tocilizumab. Each pre-filled pen contains 162 mg tocilizumab in 0.9 mL.
• The other ingredients are L-arginine, L-histidine, L-lactic acid, sodium chloride, polysorbate 80, hydrochloric acid (E507) and/or sodium hydroxide (E524), water for injections.

Tyenne is a solution for injection. The solution is clear and colourless to pale yellow.

Tyenne is supplied as a 0.9 mL pre-filled pen containing 162 mg tocilizumab solution for injection.

Each pack contains 1 or 4 pre-filled pens with multipacks containing 12 (3 packs of 4) pre-filled pens. Not all pack sizes may be marketed.

For EU:

For GB:

Read and follow the Instructions for Use that come with your Tyenne pre-filled pen before you start using it and each time you get a refill. There may be new information. This information does not replace talking to your doctor about your medical condition or treatment.

If you have any questions about using your Tyenne pre-filled pen, please call your doctor .

Important information

• Read the patient information that comes with your pre-filled pen for important information you need to know before using it.
• Before you use the pre-filled pen for the first time, make sure your doctor shows you the right way to use it.
• Do not try to take apart the Tyenne pre-filled pen at any time.
• Always inject Tyenne the way your doctor taught you to.

• The pre-filled pen is for self-injection or administration with the help of a caregiver.
• The pre-filled pen is for use at home.
• When injecting Tyenne, children may self-inject if both the doctor and caregiver find it appropriate.
• Do not reuse the pre-filled pen. The pre-filled pen is for single-dose (1-time) use only.
• Do not share your pre-filled pen with another person. You may give another person an infection or get an infection from them.
• Do not remove the pre-filled pen clear cap until you are ready to inject.
• Do not use the pre-filled pen if it shows any signs of damage or if it has been dropped.

• Store Tyenne in the refrigerator between 2°C to 8°C.
• Store unused pre-filled pens in the original carton to protect from light.
• Do not freeze. If Tyenne freezes,throw it away in a sharp disposal container.
• Keep Tyenne out of exposure to heat or direct sunlight.
• Keep the pre-filled pen out of reach and sight of children.
• Tyenne may be stored at room temperature between 20°C to 25°C in the carton it comes in for up to 14 days.
• Throw away (dispose of) Tyenne in a sharp disposal or puncture-resistant container if it has been out of the refrigerator more than 14 days. Once stored at room temperature, do not place back in the refrigerator.

• When travelling on an airplane, always check with your airline and your doctor about bringing injectable medicine with you. Always carry Tyenne in your carry-on luggage because the aircraft luggage area can be very cold and Tyenne could freeze.

1.1 Prepare a clean, flat surface, such as a table or counter top, in a well-lit area.
1.2 Gather the following supplies (not included) (see Figure A):

• A sterile cotton ball or gauze
• An alcohol swab
• A sharps disposal container (see Step 8, “Throw away your pre-filled pen”).

1.3 Remove the carton containing the pre-filled pen from the refrigerator.
Do not keep your pre-filled pen out of the refrigerator for more than 14 days without use.
1.4 Check the expiration date on the carton to make sure the date has not passed (see Figure B).
Do not use the pre-filled pen if the expiration date has passed.

1.5 Remove the sealed tray from the carton. Check the sealed tray for any signs of damage, and make sure the expiration date on the tray has not passed.
Do not use the pre-filled pen if the expiration date has passed, because it may not be safe.
Do not use the pre-filled pen if the tray looks damaged or like it has been opened.
1.6 Let the sealed tray sit on the prepared surface for 45 minutes before use to allow the medicine in the pre-filled pen to reach room temperature (see Figure C).

Note: Not doing so could cause your injection to feel uncomfortable and it could take longer to inject.

Do not warm in any other way, such as in a microwave, hot water, or direct sunlight.

Keep Tyenne out of the reach of children.

1.7 Peel the seal off of the tray (see Figure D), and invert the tray to remove the single-use pre-filled pen (see Figure E).

Do not remove the clear cap of the pre-filled pen until you are ready to inject to avoid injury.

2.1 Check the pre-filled pen to make sure it is not cracked or damaged (see Figure F).

Do not use if the pre-filled pen shows signs of damage or if it has been dropped.

2.2 Check the pre-filled pen label to make sure that:

• The name on the pre-filled pen says Tyenne
• The expiration date (EXP) on the pre-filled pen has not passed (see Figure G).

Do not use the pre-filled pen if the name on the label is not Tyenne or the expiration date on the label has passed.

2.3 Look at the medicine in the viewing window. Make sure it is clear and colorless to pale yellow and does not contain flakes or particles (see Figure H).

Note: Air bubbles in the medicine are normal.

Do not inject if the liquid is cloudy, discolored, or has lumps or particles in it because it may not be safe to use.

3.1 Wash your hands well with soap and water, then dry them with a clean towel (see Figure I).

4.1 If you are giving yourself the injection, you can use:

• The front of your upper thigh
• The abdomen, except within 5 cm around the belly button (navel)
• If a caregiver is giving the injection, they can use the outer area of the upper arm (see Figure J).

Note: Choose a different site for each injection to reduce redness, irritation or other skin problems.

Do not inject into skin that is sore (tender), bruised, red, hard, scaly, or has lesions, moles, scars, or stretch marks or tattoos.

Do not use the pre-filled pen through clothing.

5.1 Wipe the skin where you want to inject with an alcohol swab to clean it (see Figure K).

Let the skin dry.

Do not blow on or touch the site after cleaning.

6.1 When you are ready to inject, hold the pre-filled pen in one hand with the clear cap on top, pointing straight up.

Using your other hand, firmly pull the clear cap straight off without twisting (see Figure L).

Note: Use the pre-filled pen right away after removing the cap to avoid contamination.

Do not try to recap the needle at any time, even at the end of the injection.

Do not touch the needle cover (the orange part located at the tip of the pre-filled pen) because this might cause an accidental needle stick.

6.2 Throw away the clear cap.
6.3 Rotate the pre-filled pen so that the orange needle cover points downwards.
6.4 Position your hand on the pre-filled pen so that you can see the window.
6.5 Place the pre-filled pen against your skin at a 90-degree (straight) angle (see Figure M).

Note: To make sure you inject under the skin (into fatty tissue), do not hold the pre-filled pen at an angle.

Note: You do not need to pinch your skin.

To make sure you inject the full dose, read all of the steps from 6.6 to 6.9 before you start:

6.6 In a single motion, push the pre-filled pen firmly against your skin until you hear a first click. The orange plunger rod will move through the window during the injection (this means the injection has started) (see Figure N).
6.7 WAIT and hold the pre-filled pen in place until you hear a second click. This may take up to 10 seconds. Continue to HOLD (see Figure O).
6.8 Wait and slowly count to 5 after you hear the second click. Continue to HOLD the pre-filled pen in place to make sure you inject a full dose (see Figure P).
Do not lift the pre-filled pen until you are sure 5 seconds has passed, and the injection is complete.

6.9 While holding the pre-filled pen in place, check the window to make sure the orange plunger rod has fully appeared in the viewing window, and has stopped moving (see Figure Q).

Note: If the orange plunger rod did not come all the way down or you believe you did not get a full injection, call your doctor. Do not try to repeat the injection with a new pre-filled pen.

7.1 When the injection is complete, lift the pre-filled pen straight away from your skin (see Figure R).

Note: The needle cover will slide down and cover the needle.

Do not recap the pre-filled pen.

7.2 Check the window to make sure the orange plunger rod came all the way down (see Figure S).

Note: If the orange plunger rod did not come all the way down or you believe you did not get a full injection, call your doctor. Do not try to repeat the injection with a new pre-filled pen.

7.3 If you see blood on the injection site, press gauze or a cotton ball against the skin until the bleeding stops (see Figure T).

Do not rub the injection site.

8.1 Put your used pre-filled pen in a sharps disposal container right away after use (see Figure U).

Do not put the clear cap back on the pre-filled pen.

Do not throw away (dispose of) your pre-filled pen in your household trash.

Do not reuse the pre-filled pen.

If you do not have a sharps disposal container, you can use a household container that is:

• made of a heavy-duty plastic,
• can be closed with a tight-fitting, puncture-resistant lid, without sharps being able to come out,
• upright and stable during use,
• leak-resistant, and
• properly labeled to warn of hazardous waste inside the container.

When your sharps disposal container is almost full, you will need to follow your local guidelines for the right way to dispose of your sharps disposal container.

Do not throw away (dispose of) your used sharps disposal container in your household trash unless your local guidelines permit this.

Do not recycle your used sharps disposal container.

Always keep the sharps disposal container out of reach of children.

9.1 Record your injection date and site (see Figure V).

Note: This is to help you remember when and where to do your next injection.