Actemra

New Zealand - English - Medsafe (Medicines Safety Authority)

Active ingredient:
Tocilizumab 162 mg
Available from:
Roche Products (NZ) Ltd
INN (International Name):
Tocilizumab 162 mg
Dosage:
162 mg/0.9mL
Pharmaceutical form:
Solution for injection
Composition:
Active: Tocilizumab 162 mg Excipient: Arginine Arginine hydrochloride Histidine Histidine hydrochloride monohydrate Methionine Polysorbate 80 Water for injection
Prescription type:
Prescription
Manufactured by:
Genentech Inc
Therapeutic indications:
Actemra is indicated for the treatment of moderate to severe active rheumatoid arthritis (RA) in adult patients: - in combination with methotrexate (MTX) in those not previously treated with MTX - in combination with methotrexate (MTX) or other non-biological disease modifying anti-rheumatic drugs (DMARDs) in case of either an inadequate response or intolerance to previous therapy with one or more DMARDs - As monotherapy in case of intolerance to MTX or where continued treatment with MTX is inappropriate. Actemra has been shown to inhibit the progression of joint damage in adults, as measured by X-ray, when given in combination with methotrexate.
Product summary:
Package - Contents - Shelf Life: Syringe, prefilled type 1 glass, with needle safety device - 4 dose units - 24 months from date of manufacture stored at 2° to 8°C (Refrigerate, do not freeze) protect from light 8 hours not refrigerated stored at or below 30°C protect from light
Authorization number:
TT50-8074/2
Authorization date:
2013-03-05

Read the complete document

Actemra 210203

Consumer Medicine Information

Actemra

®

solution for subcutaneous injection

Tocilizumab

162 mg/0.9 mL solution for subcutaneous injection

What is in this leaflet

This leaflet answers some common questions about Actemra pre-filled syringe for subcutaneous

(under the skin) injection.

It does not contain all the available information.

It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you taking Actemra against

the benefits they expect it will have for you.

If you have any concerns about taking this medicine, ask your doctor or pharmacist.

Keep this leaflet.

You may need to read it again.

What Actemra is used for

Actemra contains the active ingredient tocilizumab.

Actemra belongs to a group of medicines called anti-rheumatic agents. There are many different

classes of anti-rheumatic agents. Actemra belongs to a class called monoclonal antibodies.

Monoclonal antibodies are proteins which specifically recognise and bind to other unique proteins in

the body.

Actemra is used to treat moderate to severe rheumatoid arthritis (RA) in adults.For RA, Actemra can

also prevent damage occurring to your joints and improve your ability to do your normal daily activities.

Actemra is also used to treat giant cell arteritis (GCA).

Some of the signs and symptoms of RA and GCA are caused by the actions of a protein called

interleukin-6 (IL-6) binding to the interleukin-6 receptor (IL-6R). Actemra works by binding and blocking

IL-6R thereby helping to relieve some of the signs and symptoms of RA and GCA.

Actemra is approved to treat GCA and RA, however your doctor may have prescribed Actemra for

another purpose.

Ask your doctor if you have any questions about why Actemra has been prescribed for you.

Actemra is not addictive.

This medicine is available only with a doctor’s prescription.

Before you use Actemra

When you must not use Actemra

Do not use Actemra if:

1.

you have had an allergic reaction to Actemra or any ingredients listed at the end of this

leaflet

Some of the symptoms of an allergic reaction may include shortness of breath, wheezing or

difficulty breathing, swelling of the face, lips, tongue or other parts of the body, and rash, itching or

hives on the skin.

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2.

you have had an allergic reaction to any other recombinant human or humanised

antibodies or proteins that are of hamster origin

3.

you have an active, severe infection

4.

the package is torn or shows signs of tampering

5.

the expiry date (EXP) printed on the pack has passed.

If you take this medicine after the expiry date has passed, it may not work as well.

If you are not sure if you should use Actemra, talk to your doctor.

Before you use Actemra

Tell your doctor if:

1.

you have an infection, or a history of a recurring or long-term infection

Actemra 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. This is particularly important if you have

diabetes or diverticulitis as you may have an increased risk of infection.

2.

you have any other health problems, especially the following:

liver disease such as viral hepatitis

tuberculosis

diverticulitis or intestinal ulcers

a low white blood cell count or a low platelet count

diabetes

raised blood pressure

high cholesterol or triglycerides

kidney disease

cancer

3.

you are pregnant or plan to become pregnant

It is not known whether Actemra is harmful to an unborn baby when taken by a pregnant

woman. If there is a need to take Actemra when you are pregnant your doctor will discuss the risks

and benefits to you and the unborn baby.

4.

you are breast-feeding or plan to breast-feed

It is not known whether Actemra passes into breast milk. It is recommended that you stop

breast-feeding while you are treated with Actemra.

5.

you are planning to have a vaccination or have recently had a vaccination

Certain types of vaccines should not be given while using Actemra.

6.

you are allergic to any other medicines, foods, dyes or preservatives

If you have not told your doctor about any of the above, tell them before you start taking

Actemra.

Use in Children

The safety and efficacy of Actemra given as a subcutaneous injection to patients below 18 years of

age have not been established.

Taking other medicines

Tell your doctor if you are taking any other medicines, including any that you have bought from

a pharmacy, supermarket or health food shop.

Do not use Actemra with other biological medicines used to treat RA, including infliximab, adalimumab,

etanercept, anakinra, abatacept, rituximab, certolizumab pegol and golimumab. It is unknown how

Actemra interacts with these medicines.

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Actemra may interfere with some medicines. These include:

warfarin, a medicine used to prevent blood clots

cyclosporin, a medicine used after organ transplants

atorvastatin and simvastatin, medicines used to reduce cholesterol levels

calcium channel blockers, such as amlodipine, which treat raised blood pressure

theophylline, a medicine used to treat bronchitis

phenytoin, a medicine used to treat epilepsy

benzodiazepines, such as diazepam, which treat anxiety

omeprazole, a medicine used to treat reflux disease and peptic ulcers

dextromethorphan, a cough medicine

These medicines may be affected by Actemra, or may affect how well the medicine works. You may

need to use different amounts of your medicine, or you may need to take different medicines. Your

doctor will advise you.

Your doctor or pharmacist has more information on medicines to be careful with or avoid while taking

Actemra.

Ask your doctor or pharmacist if you are not sure about this list of medicines.

How to use Actemra

Follow all directions given to you by your doctor or pharmacist carefully.

They may differ from the information contained in this leaflet.

Use Actemra exactly as your doctor has prescribed.

How much to inject

The recommended dose of Actemra to treat RA and GCA is 162 mg injected once a week.

The syringe is designed to deliver 162 mg per injection when used according to the instructions in this

leaflet.

Your doctor may test your blood to help guide your treatment. If you experience certain changes in your

blood tests, your doctor may decide to interrupt your treatment and reduce the frequency of dosing to

162 mg every 2 weeks or stop your treatment.

For RA, Actemra can be used in combination with methotrexate or other arthritis medications. Actemra

can also be used on its own if your doctor decides that methotrexate is inappropriate.

For GCA, Actemra is initially given in combination with a glucocorticoid medicine (such as prednisone).

Over the period of treatment with Actemra, your doctor should reduce the dose of glucocorticoid

medicine.

How to inject Actemra

Actemra is administered by subcutaneous injection. This means it is injected with a short needle into

the fatty tissue just under the skin.

The first injection of Actemra should always be given under the supervision of your healthcare

professional.

Your doctor may discuss with you whether it would be more convenient for you to inject Actemra

yourself at home, in which case, you or a caregiver would be instructed on how to give the injection.

This is a simple procedure and many patients prefer it.

Directions for self-injection

You should read these directions from beginning to end before starting so that you are familiar with

each step of the procedure. These instructions must be carefully followed. Consult with your healthcare

provider if you require further instructions. These instructions do not replace the instructions from your

healthcare provider. Your healthcare provider should show you how to prepare and inject properly

before you inject for the first time. Ask them any questions you may have.

Do not attempt to administer an injection until you are sure that you understand how to self-inject.

It is important to remain under your doctor’s care while using Actemra.

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The syringe is for single use only and should be safely discarded after use.

How to inject using the syringe

The syringe components:

Do not use if the syringe appears to be damaged.

Do not use if the medicine is cloudy, hazy, discoloured or contains particles.

Do not shake the syringe.

Do not try to open the syringe or take it apart.

Do not remove the needle cap until you are ready to inject.

Do not inject through clothing covering the skin.

Do not re-use the same syringe.

Do not touch the syringe trigger fingers as this may damage the syringe.

Gather what you will need:

Included in the pack:

pre-filled syringe

Not included in the pack:

Alcohol pad

Sterile cotton ball or gauze

Puncture-resistant container (also called a “sharps” container) for safe disposal of the needle

cap and used syringe.

Find a well-lit, clean, flat surface such as a table.

STEP 1. Visually check the syringe

Take the carton containing the syringes out of the refrigerator and remove one syringe from the carton.

Return the remaining syringes in the carton to the refrigerator.

Do not shake.

If there is foam in the medicine, put the syringe back in the carton in the refrigerator for use another

time and take a new syringe from the refrigerator.

Visually examine the syringe, as well as the medicine through the viewing window.

Do not use if the syringe appears to be damaged.

Do not use if the medicine is cloudy, hazy, discoloured or contains particles.

Check the expiration date on the carton and syringe to make sure that it has not expired (Fig. A). The

expiry date refers to the last day of that month.

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Do not use the syringe if the expiration date has passed.

Do not remove the syringe needle cap until step 5.

STEP 2. Allow the syringe to adjust to room temperature.

Place the syringe on a clean flat surface. Allow the syringe to warm up to room temperature which

should take 25 to 30 minutes.

Do not warm up the syringe in any other way.

STEP 3. Clean your hands

Wash your hands with soap and water. Cleanliness is vital during the injection procedure.

STEP 4. Choose and prepare an injection site

The recommended injection sites are the front and middle of your thighs and the lower part of your

abdomen below the navel (belly button), except for the five centimeter area directly around the navel. If

a caregiver is giving the injection, the outer area of the upper arms may also be used (Fig. B).

Use a different place each time you give yourself an injection at least 3 centimeters from the area you

used for your last injection.

Do not inject into areas that could be irritated by a belt or waistband. Do not inject into moles,

scars, bruises, or areas where the skin is tender, red, hard or not intact.

Clean the chosen injection area using the alcohol pad, to reduce the risk of infection (Fig. C). Let the

skin dry for approximately 10 seconds. Be sure not to touch the cleaned area prior to the injection. Do

not fan or blow on the cleaned area.

STEP 5. Remove needle cap

Do not hold the syringe by the plunger while removing the needle cap.

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Hold the needle shield of the syringe firmly with one hand and pull off the needle cap with the other

hand (Fig. D). If you cannot remove the needle cap you should request the help of a caregiver or

contact your healthcare provider.

Do not touch the needle or let it touch any surface.

You may see a drop of liquid at the end of the needle. This is normal.

Throw away the needle cap in the sharps container.

Once the needle-cap is removed, the syringe should be used immediately to prevent the medicine from

drying out and blocking the needle. If it is not used within 5 minutes, the syringe should be disposed of

in the sharps container and a new syringe should be used.

Do not reattach the needle-cap after removal.

STEP 6. Give the injection

Hold the syringe comfortably in your hand. Be careful not to touch the syringe trigger fingers as this

may damage the syringe.

To be sure the needle can be inserted correctly under the skin, pinch a fold of loose skin at the clean

injection site with your free hand.

Do not hold or push on the plunger while inserting the needle into the skin.

Insert the needle all the way into the pinched skin at an angle between 45° to 90° with a quick, firm

action (Fig. E.).

It is important to choose the correct angle to ensure the medication is delivered under the skin (into

fatty tissue), otherwise the injection could be painful and the medication may not work.

Then keep the syringe in position and let go of the pinch of skin.

Hold the syringe with two fingers under the flange (or “wings”) and thumb on the plunger. Slowly inject

all of the medicine by gently pushing the plunger all the way down.

You must press the plunger all the way down to ensure you get the full dose of medication and to

ensure the trigger fingers are completely pushed to the side (Fig. F). If the plunger is not fully

depressed the needle shield will not extend to cover the needle when it is removed.

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Once the plunger is pushed all the way down, keep pressing down on the plunger to be sure all of the

medicine is injected before taking the needle out of the skin.

Keep pressing down on the plunger while you take the needle out of the skin at the same angle as

inserted (Fig G.).

Once the needle is removed completely from the skin, you can release the plunger. The needle will

retract allowing the needle shield to protect the needle (Fig H.).

If the needle is still exposed proceed carefully, and place the syringe into the sharps container to avoid

injury with the needle (see STEP 7).

If you see drops of blood at the injection site, you can press the sterile cotton ball or gauze over the

injection site for approximately 10 seconds.

Do not rub the injection site.

STEP 7. Safely dispose of the syringe

Do not try to re-cap your syringe.

Throw away used syringes in a sharps container (Fig I.). Ask your healthcare provider or pharmacist

for information about where you can get a sharps container or what other types of puncture-resistant

containers you can use to safely dispose of your used syringes, if you do not have one.

Do not throw away used syringes or the sharps container in household rubbish and do not

recycle them.

Dispose of the full container as instructed by your healthcare provider or pharmacist.

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

How long to use Actemra

The duration of treatment depends on how you are responding to the medicine. Your doctor will

discuss this with you.

Continue to use Actemra until your doctor tells you to stop.

If you forget to use it

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

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If you inject Actemra weekly and it is within 7 days of the dose you missed, you should skip the missed

dose. Inject your next dose as you would have on the originally scheduled day, had you not forgotten

the dose.

Do not give yourself two injections to make up for the injection that you missed.

If you inject Actemra every 2 weeks and it is within 7 days of the dose you missed, you should inject

the missed dose as soon as you remember. Inject the next dose as you would have on the originally

scheduled day, had you not forgotten the dose.

Do not give yourself two injections to make up for the injection that you missed.

If you inject Actemra every week or every 2 weeks and it has been more than 7 days since you missed

your dose, contact your healthcare provider for advice.

If you are not sure when to inject your next dose, contact your healthcare provider for advice.

In case of an overdose

If you think that you or anyone else may have used too much Actemra, immediately telephone

your doctor or Poisons Information Centre (telephone 0800 764 766 [0800 POISON]) for advice

or go to Accident and Emergency at your nearest hospital. Do this even if there are no signs of

discomfort or poisoning. You may need urgent medical attention.

Keep telephone numbers for these places handy.

While you are using Actemra

Things you must do

Tell your doctor immediately if you experience allergic reactions such as chest tightness,

wheezing, severe dizziness or light-headedness, swelling of the lips or skin rash during or after

using Actemra.

If you experience any allergic reaction symptoms after using Actemra, do not take the next

dose until you have informed your doctor AND your doctor has told you to take the next dose.

Tell your doctor immediately if you develop an infection while you are using Actemra.

The first signs of infection can include:

body aches, fever, chills

cough, chest discomfort/tightness, shortness of breath

redness, heat, unusual swelling of skin or joint

abdominal pain/tenderness and/or change in bowel function

Tell your doctor immediately if you develop severe blisters and bleeding in the lips, eyes,

mouth, nose and genitals while you are using Actemra.

Tell all doctors, dentists and pharmacists who are treating you that you are using Actemra.

Tell your doctor if you become pregnant while using Actemra.

Tell your doctor if you are breast-feeding while using Actemra.

Tell your doctor if you feel Actemra is not helping your condition.

Be sure to keep all of your appointments with your doctor so that your progress can be

checked.

Your doctor may test your blood to help guide your treatment.

Things you must not do

You should not breast-feed your infant during treatment with Actemra.

It is not known whether Actemra crosses into human milk.

Do not take any other medicines whether they require a prescription or not without first telling

your doctor or consulting a pharmacist.

Things to be careful of

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Be careful driving or operating machinery until you know how Actemra affects you.

Actemra has not been shown to impair the ability to drive or operate machinery.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are using

Actemra.

Actemra helps many patients with RA and GCA but it may have unwanted side effects. All medicines

can have side effects. Sometimes they are serious, most of the time they are not. You may need

medical treatment if you get some of the side effects.

Ask your doctor or pharmacist to answer any questions you may have.

Tell your doctor if you notice any of the following and they worry you:

mild fever and chills

high blood pressure (symptoms may include headache, dizziness, ringing in the ears)

rashes or itching

headache

cough

blocked or runny nose

sore throat

dizziness

nausea or indigestion

stomach pain

constipation

diarrhoea

cold sores

mouth or skin blisters

mouth ulcers

skin infection (redness, pain and/or swelling)

pain in the joints

injection site reactions

These are the more common side effects of Actemra. Mostly these are mild.

Tell your doctor immediately or go to your nearest Accident and Emergency Centre if you

notice any of the following:

difficulty breathing, chest tightness or wheezing

severe light-headedness

severe skin rash, itching, hives

swelling of the face, lips, mouth

signs of serious infection such as severe fever and chills, stomach ache or persistent

headaches

bleeding from the stomach or intestines. Signs and symptoms may include severe

stomach pain, vomiting blood or material that looks like coffee grounds, bleeding from your

rectum, black sticky bowel motions, bloody diarrhoea

severe blisters and bleeding in the lips, eyes, mouth, nose and genitals.

These are serious side effects. You may need urgent medical attention. Serious side effects are rare.

This is not a complete list of all possible side effects. Others may occur in some people and there may

be some side effects not yet known.

Tell your doctor if you notice anything else that is making you feel unwell, even if it is not on

this list.

Ask your doctor or pharmacist if you don’t understand anything in this list.

Do not be alarmed by this list of possible side effects. You may not experience any of them.

After using Actemra

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Storage

Store in a refrigerator (2°C to 8°C).

Once removed from the refrigerator, Actemra must be used within 8 hours and must be kept below

30°C. Once the needle cap is removed, the Actemra syringe must be used within five minutes.

Do not freeze.

Store the syringes in the carton to protect them from light and to keep them dry.

Do not use Actemra after the expiry date which is stated on the carton and syringe labels after

“EXP”. The expiry date refers to the last day of that month.

Disposal

The syringe is intended for single use only and must be thrown away after the injection.

Dispose of the syringes in a sharps container as instructed by your doctor, nurse or

pharmacist.

Do not put the used syringes in your normal household rubbish.

If your doctor tells you to stop using Actemra, or the product has passed its expiry date, ask

your pharmacist what to do with any medicine that is left over.

Product description

Availability

Actemra is available as:

A pre-filled syringe, 162mg/0.9mL, in packs of 4 syringes

Actemra is also available as a concentrated solution for intravenous infusion.

What Actemra looks like

Actemra is a clear to opalescent, colourless to pale yellow solution.

Ingredients

Active ingredient

tocilizumab (rch)

Inactive ingredients

polysorbate 80, histidine, histidine hydrochloride, arginine, arginine hydrochloride,

methionine, water for injections

Distributor

Actemra is distributed in New Zealand by:

Roche Products (New Zealand) Limited

PO Box 109113 Newmarket

Auckland 1149

NEW ZEALAND

Medical Enquiries: 0800 656 464

This leaflet was prepared on 03 February 2021.

Read the complete document

Actemra 210203

NEW ZEALAND DATA SHEET

1.

PRODUCT NAME

Actemra

20 mg/mL, concentrate for solution for intravenous (IV) infusion

Actemra

162 mg/0.9 mL, solution for subcutaneous (SC) injection

2.

QUALITATIVE AND QUANTITATIVE COMPOSITION

Concentrate for solution for IV infusion

Each vial contains 20 mg/mL tocilizumab (vials: 80 mg tocilizumab in 4 mL, 200 mg

tocilizumab in 10 mL and 400 mg tocilizumab in 20 mL).

Solution for SC injection

Each pre-filled syringe contains 162 mg/0.9 mL tocilizumab.

For the full list of excipients, see section 6.1.

3.

PHARMACEUTICAL FORM

Actemra concentrated solution for IV infusion is a clear to opalescent, colourless to pale

yellow sterile solution.

Actemra solution for SC injection is a clear to strongly opalescent, colourless to slightly

yellowish sterile solution.

4.

CLINICAL PARTICULARS

4.1

Therapeutic indications

Rheumatoid Arthritis (IV and SC formulations)

Actemra is indicated for the treatment of moderate to severe active rheumatoid arthritis (RA)

in adult patients:

in combination with methotrexate (MTX) in those not previously treated with MTX;

in combination with methotrexate (MTX) or other non-biological disease-modifying anti-

rheumatic drugs (DMARDs) in case of either an inadequate response or intolerance to

previous therapy with one or more DMARDs; or

as monotherapy in case of intolerance to MTX or where continued treatment with MTX is

inappropriate.

Actemra has been shown to inhibit the progression of joint damage in adults, as measured by

X-ray, when given alone or in combination with methotrexate.

Giant Cell Arteritis (SC formulation only)

Actemra is indicated for the treatment of giant cell arteritis (GCA) in adult patients.

Polyarticular Juvenile Idiopathic Arthritis (pJIA) (IV formulation only)

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Actemra is indicated for the treatment of active polyarticular juvenile idiopathic arthritis in

patients 2 years of age and older who have shown an inadequate response to methotrexate

(MTX) or were intolerant to MTX. Actemra can be given alone or in combination with MTX.

Systemic Juvenile Idiopathic Arthritis (IV formulation only)

Actemra is indicated for the treatment of active systemic juvenile idiopathic arthritis (sJIA) in

patients 2 years of age and older, who have responded inadequately to previous therapy with

NSAIDs and systemic corticosteroids. Actemra can be given alone or in combination with

methotrexate (MTX).

4.2

Dose and method of administration

General

Treatment should be initiated by healthcare professionals experienced not only in the

diagnosis and treatment of RA, GCA, pJIA or sJIA but also in the use of biological therapies

for this condition.

For adult patients with RA, Actemra may be administered as an IV infusion or a SC injection.

For adult patients with GCA, Actemra is administered as a SC injection.

For patients with pJIA or sJIA, Actemra is administered as an IV infusion.

Actemra IV formulation is not intended for SC administration. Actemra SC formulation is not

intended for IV administration.

Actemra should be diluted by a healthcare professional with sterile 0.9% w/v sodium chloride

solution using aseptic technique (see section 4.2, Method of Administration).

The recommended duration of the IV infusion is 1 hour.

During IV infusion, and for 30 minutes post-infusion with Actemra, the patient must be

closely monitored at all times for any signs or symptoms of a hypersensitivity reaction.

Should any such reaction occur then appropriate urgent responses and treatments are to be

initiated. The necessary equipment, treatments and protocols sufficient to initiate the

management of acute anaphylaxis are to be in place along with the availability of

appropriately trained personnel. There must be continued education and training of the health

care professionals who administer the infusions. As part of the informed consent process

patients should be made aware of the risk of anaphylaxis and the equipment, treatments and

protocols in place to manage this risk.

Substitution by any other biological medicinal product requires the consent of the prescribing

physician.

Dose

Rheumatoid Arthritis in Adults (IV and SC formulation)

Intravenous dosing regimen

The recommended dose of Actemra for adult patients is 8 mg/kg given once every 4 weeks as

an IV infusion.

For individuals whose body weight is more than 100 kg, doses exceeding 800 mg per

infusion are not recommended (see section 5.2 Pharmacokinetics).

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Actemra can be used alone or in combination with MTX and/or other non-biological

DMARDs.

Subcutaneous dosing regimen

The recommended dose for adult patients is 162 mg given once every week as a

subcutaneous injection.

Actemra can be used alone or in combination with MTX and/or other non-biological

DMARDs.

Patients transitioning from IV Actemra therapy to SC administration should administer the

first SC dose at the time of the next scheduled IV dose under the supervision of a qualified

healthcare professional.

The first injection should be performed under the supervision of a qualified healthcare

professional. After proper training in injection technique, patients may self-inject with

Actemra if their treating healthcare professional determines that it is appropriate.

Assess suitability of patient for SC home use and instruct patients to inform a healthcare

professional if they experience any symptoms of allergic reaction. Patients should seek

immediate medical attention if they develop symptoms of serious allergic reactions (see

section 4.4, Hypersensitivity Reactions).

Dose Modification Recommendations for RA

Liver enzyme abnormalities

Lab Value

Action

> 1 to 3 x ULN

Dose modify concomitant DMARDs if appropriate

For patients receiving intravenous Actemra with persistent increases in

this range, reduce Actemra dose to 4 mg/kg or interrupt Actemra until

ALT/AST have normalized

Restart with 4 mg/kg or 8 mg/kg, as clinically appropriate.

For patients receiving subcutaneous Actemra with persistent increases

in this range, reduce Actemra injection frequency to every other week

or interrupt Actemra until ALT/AST have normalized. Restart with

weekly injection or injection every other week, as clinically

appropriate.

> 3 to 5 x ULN

Interrupt Actemra dosing until < 3 x ULN and follow

recommendations above for > 1 to 3 x ULN

For persistent increases > 3 x ULN, discontinue Actemra (confirmed

by repeat testing, see Precautions – Hepatic Transaminase and

Laboratory Effects),

> 5 x ULN

Discontinue Actemra

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Low absolute neutrophil count (ANC)

Lab Value

(cells x 10

9

/L)

Action

ANC > 1

Maintain dose

ANC 0.5 to 1

Interrupt Actemra dosing

For patients receiving intravenous Actemra, when ANC > 1 x 10

resume Actemra at 4 mg/kg and increase to 8 mg/kg as clinically

appropriate.

For patients receiving subcutaneous Actemra, when ANC > 1 x 10

resume Actemra injection every other week and increase frequency to

every week, as clinically appropriate.

ANC < 0.5

Discontinue Actemra

Low platelet count

Lab Value

(cells x 10

9

/L)

Action

50 to 100

Interrupt Actemra dosing

For patients receiving intravenous Actemra, when platelet count is >

100 x 10

/L resume Actemra at 4 mg/kg and increase to 8 mg/kg as

clinically appropriate.

For patients receiving subcutaneous Actemra, when platelet count is >

100 x 10

/L resume Actemra injection every other week and increase

frequency to every week, as clinically appropriate.

< 50

Discontinue Actemra

Giant Cell Arteritis (SC formulation only)

The recommended dose of Actemra for adult patients with GCA is 162 mg given once every

week as a subcutaneous injection, in combination with a tapering course of glucocorticoids.

Actemra can be used alone following discontinuation of glucocorticoids.

In the event of patients experiencing a relapse of GCA during the course of Actemra therapy,

the treating physician should consider re-introducing and/or escalating the dose of

concomitant glucocorticoids (or restarting glucocorticoid therapy if it has been discontinued)

according to best medical judgement/treatment guidelines.

The first injection should be performed under the supervision of a qualified healthcare

professional. After proper training in injection technique, patients may self-inject with

Actemra if their treating healthcare professional determines that it is appropriate.

Assess suitability of patient for SC home use and instruct patients to inform a healthcare

professional if they experience any symptoms of allergic reaction. Patients should seek

immediate medical attention if they develop symptoms of serious allergic reactions (see

section 4.4, Hypersensitivity Reactions).

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Dose Modification Recommendations for GCA

Liver enzyme abnormalities

Lab Value

Action

> 1 to 3x ULN

Dose modify concomitant immunomodulatory agents if appropriate.

For patients with persistent increases in this range, reduce Actemra

injection frequency to every other week or interrupt Actemra until

ALT/AST have normalised. Restart with weekly injection or injection

every other week, as clinically appropriate.

> 3 to 5x ULN

Interrupt Actemra dosing until < 3x ULN and follow

recommendations above for >1 to 3x ULN

For persistent increases > 3x ULN (confirmed by repeat testing, see

section 4.4, Hepatic Transaminase and Laboratory Effect), discontinue

Actemra.

> 5x ULN

Discontinue Actemra.

Low absolute neutrophil count (ANC)

Lab Value

(cells x 10

9

/L)

Action

ANC > 1

Maintain dose.

ANC 0.5 to 1

Interrupt Actemra dosing

When ANC > 1 x 10

/L resume Actemra injection every other week

and increase frequency to every week, as clinically appropriate.

ANC < 0.5

Discontinue Actemra.

Low platelet count

Lab Value

(cells x 10

9

/L)

Action

50 to 100

Interrupt Actemra dosing

When platelet count is > 100 x 10

/L resume Actemra injection every

other week and increase frequency to every week, as clinically

appropriate.

< 50

Discontinue Actemra.

Polyarticular Juvenile Idiopathic Arthritis (pJIA) (IV formulation only)

The recommended dose of Actemra for patients with pJIA is:

10 mg/kg for patients below 30 kg,

8 mg/kg for patients ≥ 30 kg,

given once every four weeks as an IV infusion. A change in dose should only be based on a

consistent change in the patient’s body weight over time. Actemra can be used alone or in

combination with MTX.

Systemic Juvenile Idiopathic Arthritis (IV formulation only)

The recommended dose of Actemra for patients with sJIA is:

12 mg/kg for patients below 30 kg,

8 mg/kg for patients ≥ 30 kg,

given once every two weeks as an IV infusion. A change in dose should only be based on a

consistent change in the patient’s body weight over time. Actemra can be used alone or in

combination with MTX.

Actemra 210203

Dose Modification Recommendations for pJIA and sJIA

Dose reduction of Actemra has not been studied in the pJIA or sJIA population. Dose

interruptions of Actemra for laboratory abnormalities are recommended in patients with pJIA

or sJIA and are similar to what is outlined above for patients with RA (see section 4.4,

Haematological Abnormalities). If appropriate, concomitant MTX and/or other medications

should be dose modified or stopped and Actemra dosing interrupted until the clinical

situation has been evaluated. In pJIA or sJIA the decision to discontinue Actemra for a

laboratory abnormality should be based upon the medical assessment of the individual

patient.

Special populations

Paediatric Populations

The safety and efficacy in paediatric patients below the age of 2 years old have not been

established.

Elderly

No dose adjustment is required in elderly patients aged 65 years and older.

Renal impairment

No dose adjustment is required in patients with mild or moderate renal impairment (see

section 5.2, Pharmacokinetics in Special Populations). Actemra has not been studied in

patients with severe renal impairment.

Hepatic impairment

The safety and efficacy of Actemra has not been studied in patients with hepatic impairment

(see section 4.4, Active Hepatic Disease and Hepatic Impairment) and therefore no dose

recommendations can be made.

Method of Administration

Concentrated solution for intravenous infusion

Parenteral medications should be inspected visually for particulate matter or discolouration

prior to administration.

Only solutions which are clear to opalescent, colourless to pale yellow and free of visible

particles must be infused.

Use a sterile needle and syringe to prepare Actemra IV formulations.

Rheumatoid Arthritis

From a 100 mL infusion bag, withdraw a volume of 0.9% sodium chloride solution equal to

the volume of the Actemra solution required for the patient’s dose, and discard. Withdraw the

required amount of Actemra (0.4 mL per kg of the patient’s body weight) under aseptic

conditions and add to the infusion bag. To mix the solution, gently invert the bag to avoid

foaming.

sJIA patients below 30 kg

From a 50 mL infusion bag, withdraw a volume of 0.9% sodium chloride solution equal to

0.6 mL/kg of the patient’s body weight and discard. This volume should be replaced in the

saline bag with an equal volume of Actemra under aseptic conditions. To mix the solution,

gently invert the bag to avoid foaming.

Actemra 210203

pJIA patients below 30 kg

From a 50 mL infusion bag, withdraw a volume of 0.9% sodium chloride solution equal to

0.5 mL/kg of the patient’s body weight and discard. This volume should be replaced in the

saline bag with an equal volume of Actemra under aseptic conditions. To mix the solution,

gently invert the bag to avoid foaming.

pJIA and sJIA patients ≥ 30 kg

From a 100 mL infusion bag, withdraw a volume of 0.9% sodium chloride solution equal to

the volume of the Actemra solution required for the patient’s dose. Withdraw the required

amount of Actemra (0.4 mL per kg of the patient’s body weight) under aseptic conditions and

dilute in a 100 mL infusion bag containing sterile, non-pyrogenic 0.9% sodium chloride

solution. To mix the solution, gently invert the bag to avoid foaming.

Solution for Subcutaneous Injection

Subcutaneous Actemra formulation is administered with a single-use pre-filled syringe.

The recommended injection sites (abdomen, thigh and upper arm) should be rotated and

injections should never be given into moles, scars, or areas where the skin is tender, bruised,

red, hard or not intact.

If a patient misses a weekly injection of Actemra within 7 days of the scheduled dose, they

should be instructed to take the missed dose on the next scheduled day. If a patient misses a

biweekly (i.e. every other week) injection of Actemra within 7 days of the scheduled dose,

they should be instructed to take the missed dose immediately and the next dose on the next

scheduled day.

Do not use if the medicine is cloudy or contains particles, is any colour besides colourless to

slightly yellowish, or any part of the pre-filled syringe appears to be damaged.

Actemra should not be shaken.

After removing the pre-filled syringe from the refrigerator, the pre-filled syringe should be

allowed to reach room temperature by waiting for 25 to 30 minutes, before injecting. After

removing the cap the injection should be started within 5 minutes.

4.3

Contraindications

Actemra is contraindicated in patients with:

known hypersensitivity to any component of the product or with a history of any reaction

consistent with hypersensitivity to any component of the product, Chinese hamster ovary

cell products or other recombinant human or humanised antibodies

active, severe infections (see section 4.4, Infections)

4.4

Special warnings and precautions for use

In order to improve the traceability of biological medicinal products, the trade name and

batch number of the administered product should be clearly recorded (or stated) in the patient

file.

Actemra 210203

All Indications

Infections

Serious and sometimes fatal infections have been reported in patients receiving

immunosuppressive agents including Actemra (see section 4.8). Actemra treatment should

not be initiated in patients with active infections (see section 4.3). If a patient develops a

serious infection, administration of Actemra should be interrupted until the infection is

controlled. Physicians should exercise caution when considering the use of Actemra in

patients with a history of recurring or chronic infection, or with underlying conditions (e.g.

diverticulitis, diabetes) which may predispose patients to infections.

Vigilance for the timely detection of serious infection is recommended for patients receiving

immunosuppressive agents, such as Actemra, for moderate to severe RA, GCA, pJIA or sJIA

as signs and symptoms of acute inflammation may be lessened, due to suppression of the

acute phase reaction. The effects of Actemra on C-reactive protein (CRP), neutrophils and

signs and symptoms of infection should be considered when evaluating a patient for a

potential infection. Patients (which include younger children who may be less able to

communicate their symptoms) and parents/guardians of minors with pJIA or sJIA should be

instructed to contact a physician immediately when any symptoms suggesting infection

appear, in order to assure rapid evaluation and appropriate treatment.

The use of Actemra is not recommended in patients with HIV, positive core antibody for

hepatitis B, prior HCV infection, or symptomatic EBV infection. Viral reactivation (e.g.

hepatitis B) has been reported with biologic therapies for RA. In clinical studies with

Actemra, patients who screened positive for hepatitis were excluded.

In the long term RA exposure population, the overall rate of serious infections (bacterial,

viral and fungal) was 4.7 events per 100 patient years. Reported serious infections, some with

fatal outcome, included active tuberculosis, which may present with intrapulmonary or

extrapulmonary disease, invasive pulmonary infections, including candidiasis, aspergillosis,

coccidioidomycosis and pneumocystis jirovecii, pneumonia, cellulitis, herpes zoster,

gastroenteritis, diverticulitis, sepsis and bacterial arthritis. Cases of opportunistic infections

have been reported.

Complications of Diverticulitis

Events of diverticular perforation as complications of diverticulitis have been reported in

patients treated with Actemra. Actemra should be used with caution in patients with previous

history of intestinal ulceration or diverticulitis. Patients presenting with symptoms potentially

indicative of complicated diverticulitis, such as abdominal pain, should be evaluated

promptly for early identification of gastrointestinal perforation.

Tuberculosis

As recommended for other biological treatments for all patients should be screened for latent

tuberculosis (TB) infection prior to starting Actemra therapy. Patients with latent TB should

be treated with standard anti-mycobacterial therapy before initiating Actemra.

Vaccinations

Live and live attenuated vaccines should not be given concurrently with Actemra as clinical

safety has not been established.

No data are available on the secondary transmission of infection from persons receiving live

vaccines to patients receiving Actemra.

Actemra 210203

It is recommended that all patients, particularly paediatric or elderly patients be brought up to

date with all immunisations in agreement with current immunisation guidelines prior to

initiating Actemra therapy. The interval between live vaccinations and initiation of Actemra

therapy should be in accordance with current vaccination guidelines regarding

immunosuppressive agents.

In a randomised open-label study, adult RA patients treated with Actemra and MTX were

able to mount an effective response to both the 23-valent pneumococcal polysaccharide and

tetanus toxoid vaccines which was comparable to the response seen in patients on MTX only.

Hypersensitivity Reactions

Serious hypersensitivity reactions, including anaphylaxis, have been reported in association

with Actemra (see section 4.8, Infusion Reactions). In the post-marketing setting, events of

serious hypersensitivity and anaphylaxis, have occurred in patients treated with a range of

doses of Actemra, with or without concomitant therapies, premedication and/or a previous

hypersensitivity reaction.

In the post marketing setting, cases with a fatal outcome have been reported with intravenous

Actemra. These events have occurred as early as the first infusion of Actemra (see section 4.3

and 4.8, Post-Marketing Experience). Appropriate treatment should be available for

immediate use in the event of an anaphylactic reaction during infusion with Actemra. If an

anaphylactic reaction or other serious hypersensitivity reaction occurs, administration of

Actemra should be stopped immediately and Actemra should be permanently Discontinued.

Patients with a history of any reaction consistent with hypersensitivity to any component of

the product must not be re-challenged with Actemra (see section 4.3).

Viral Reactivation

Viral reactivation (e.g. hepatitis B virus) has been reported with biologic therapies for RA. In

clinical studies with Actemra, patients who screened positive for hepatitis were excluded.

Active Hepatic Disease and Hepatic Impairment

Treatment with Actemra particularly when administered concomitantly with MTX, may be

associated with elevations in hepatic transaminases therefore caution should be exercised

when considering treatment of patients with active hepatic disease or hepatic impairment (see

sections 4.2, Special Populations and section 4.8, Laboratory Abnormalities).

Viral reactivation (e.g. hepatitis B) has been reported with biologic therapies for RA. In

clinical studies with Actemra, patients who screened positive for hepatitis were excluded.

Hepatotoxicity

Mild and moderate elevations of hepatic transaminases and bilirubin have been reported with

Actemra treatment (see section 4.8). An increased frequency of these elevations was observed

when potentially hepatotoxic drugs (e.g. MTX) were used in combination with Actemra.

There is a potential risk of hepatotoxicity with use of Actemra.

Serious drug-induced liver injury, including acute liver failure, hepatitis and jaundice, have

been observed with Actemra (see section 4.8). Serious hepatic injury occurred between 2 weeks

to more than 5 years after initiation of Actemra. Cases of liver failure resulting in liver

transplantation have been reported.

Actemra 210203

Particular caution should be exercised when considering initiation of Actemra treatment in

patients with elevated ALT or AST above 1.5 x ULN. In patients with baseline ALT or AST

above 5 x ULN, treatment with Actemra is not recommended.

In RA, GCA, pJIA and sJIA, ALT /AST should be monitored every 4 to 8 weeks for the first

6 months of treatment followed by every 12 weeks thereafter. For recommended dose

modifications, including Actemra discontinuation, based on transaminases levels, see section

4.2.

For ALT or AST elevations > 3 to 5 x ULN, confirmed by repeat testing, Actemra treatment

should be interrupted. Once the patient’s hepatic transaminases are below 3 x ULN,

treatment with Actemra may recommence at 4 or 8 mg/kg for the IV formulation or weekly

injection or injection every other week for the SC formulation.

Haematological Abnormalities

Decreases in neutrophil and platelet counts have occurred following treatment with Actemra

8 mg/kg in combination with MTX (see section 4.8, Laboratory Abnormalities). There may

be an increased risk of neutropenia in patients who have previously been treated with a TNF

antagonist.

Caution should be exercised when considering initiation of Actemra treatment in patients

with a low neutrophil or platelet count (i.e. ANC < 2 x 10

/L or platelet count below 100 x

/L). In patients with an ANC below 0.5 x 10

/L or a platelet count < 50 x 10

/L treatment

is not recommended (see section 4.4, Effects of Laboratory Tests).

Severe neutropenia may be associated with an increased risk of serious infections, although

there has been no clear association between decreases in neutrophils and the occurrence of

serious infections in clinical trials with Actemra to date.

In RA and GCA, neutrophils and platelets should be monitored 4 to 8 weeks after start of

therapy and thereafter according to standard clinical practice. For recommended dose

modifications based on ANC and platelet counts, see section 4.2.

In pJIA and sJIA neutrophils and platelets should be monitored at the time of the second

infusion and thereafter according to good clinical practice (see section 4.2).

Lipid Parameters

Elevations in lipid parameters including total cholesterol, low density lipoprotein (LDL), high

density lipoprotein (HDL) and triglycerides were observed in patients treated with Actemra

(see section 4.8, Elevations in Lipid Parameters). In the majority of patients, there was no

increase in atherogenic indices, and elevations in total cholesterol responded to treatment

with lipid lowering agents.

Assessment of lipid parameters should be performed in patients 4 to 8 weeks following

initiation of Actemra therapy. Patients should be managed according to local clinical

guidelines for management of hyperlipidaemia.

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