ocrelizumab: package leaflet

What Ocrevus is
Ocrevus contains the active substance ‘ocrelizumab’. It is a type of protein called a ‘monoclonal antibody’. Antibodies work by attaching to specific targets in your body.
What Ocrevus is used for
Ocrevus is used to treat adults with:

Relapsing forms of multiple sclerosis (RMS)

Early primary progressive multiple sclerosis (PPMS)
Ocrevus is used to treat children and adolescents (aged 10 years and older) with relapsing forms of multiple sclerosis (RMS).
What is Multiple Sclerosis
Multiple Sclerosis (MS) affects the central nervous system, especially the nerves in the brain and spinal cord. In MS, the immune system (the body’s defence system) works incorrectly and attacks a protective layer (called myelin sheath) around nerve cells and causes inflammation. Breakdown of the myelin sheath stops the nerves working properly.
Symptoms of MS depend on which part of the central nervous system is affected and can include problems with walking and balance, weakness, numbness, double vision and blurring, poor coordination and bladder problems.

In relapsing forms of MS, the patient has repeated attacks of symptoms (relapses). The symptoms can appear suddenly within a few hours, or slowly over several days. The symptoms disappear or improve between relapses but damage may build up and lead to permanent disability.

In primary progressive MS, the symptoms generally continue to worsen from the start of the disease.

How does Ocrevus work
Ocrevus attaches to specific B cells, which are a type of white blood cells that are part of the immune system and play a role in MS. Ocrevus targets and removes those specific B cells. This reduces inflammation and attacks on the myelin sheath, reduces the chance of having a relapse and slows the progression of your disease.

In Relapsing forms of MS (RMS), Ocrevus helps to significantly reduce the number of attacks (relapses) and significantly slow down the progression of the disease. Ocrevus also significantly increases the chance of a patient having no evidence of disease activity (brain lesions, relapses and worsening of disability).

In Primary Progressive MS (PPMS), Ocrevus helps to slow down the progression of the disease and reduce deterioration in walking speed.

You must not be given Ocrevus:
 if you are allergic to ocrelizumab or any of the other ingredients of this medicine (listed in section 6).
 if you currently have an infection.
 if you have been told that you have severe problems with your immune system.
 if you have cancer.
If you are not sure, talk to your doctor before you are given Ocrevus.
Warnings and precautions
Talk to your doctor before you are given Ocrevus if any of the following apply to you. Your doctor may decide to delay your treatment with Ocrevus, or may decide you cannot receive Ocrevus if:
 you have an infection. Your doctor will wait until the infection is resolved before giving you Ocrevus.
 you have ever had hepatitis B or are a carrier of the hepatitis B virus. This is because medicines like Ocrevus can cause the hepatitis B virus to become active again. Before your Ocrevus treatment, your doctor will check if you are at risk of hepatitis B infection. Patients who have had hepatitis B or are carriers of the hepatitis B virus will have a blood test and will be monitored by a doctor for signs of hepatitis B infection.
 you have cancer or if you have had cancer in the past. Your doctor may decide to delay your treatment with Ocrevus.
Effect on the immune system:

Diseases that affect your immune system: if you have another disease which affects the immune system. You may not be able to receive Ocrevus.

Medicines that affect your immune system: if you have ever taken, are taking or are planning to take medicines that affect the immune system – such as chemotherapy, immunosuppressants or other medicines used to treat MS. Your doctor may decide to delay your treatment with Ocrevus or may ask you to stop such medicines before starting treatment with Ocrevus. See under ‘Other medicines and Ocrevus’, below for more information.

Infusion-related reactions

Infusion-related reactions are the most common side effect of Ocrevus treatment.

Tell your doctor or nurse straight away if you have any infusion-related reaction (see section 4 for a list of infusion-related reactions). Infusion-related reactions can happen during the infusion or up to 24 hours after the infusion.

To reduce the risk of infusion-related reaction, your doctor will give you other medicines before each infusion of Ocrevus (see section 3) and you will be closely monitored during the infusion and for at least one hour after the infusion has been given.
Infections

Talk to your doctor before you are given Ocrevus if you think you have an infection. Your doctor will wait until the infection is resolved before giving you Ocrevus.

You might get infections more easily with Ocrevus. This is because the immune cells that Ocrevus targets also help to fight infection.

Before you start treatment with Ocrevus and before subsequent infusions, your doctor may ask you to have a blood test to verify your immune system because infections may occur more frequently in case of severe problems with your immune system.

If you are treated with Ocrevus for primary progressive multiple sclerosis, and you have swallowing difficulties, Ocrevus may increase the risk of severe pneumonia.

Tell your doctor or nurse straight away if you have any of these signs of infection during or after Ocrevus treatment:
- fever or chills
- cough that does not go away
- herpes (such as cold sore, shingles or genital sores).

Tell your doctor or nurse straight away if you think your MS is getting worse or if you notice any new symptoms. This is because of a very rare and life-threatening brain infection, called ‘progressive multifocal leukoencephalopathy’ (PML), which can cause symptoms similar to those of MS. PML can occur in patients taking Ocrevus.

Tell your partner or carer about your Ocrevus treatment. They might notice symptoms of PML that you do not, such as memory lapses, trouble thinking, difficulty walking, sight loss, changes in the way you talk, which your doctor may need to investigate.
Vaccinations

Tell your doctor if you have recently been given any vaccine or might be given a vaccine in the near future.

While you are being treated with Ocrevus, you should not be given live or live attenuated vaccines (for example BCG for tuberculosis or vaccines against yellow fever).

Your doctor may recommend that you are given a seasonal influenza vaccine.

Your doctor will check if you need any vaccinations before you start treatment with Ocrevus.
Any vaccinations should be given at least 6 weeks before you start treatment with Ocrevus.
Liver Injury

Your doctor will take blood tests before you start treatment with Ocrevus and will repeat these tests 2 weeks later. After that, your doctor will take blood tests to check your liver function again if you have any symptoms of hepatic injury during treatment.

Tell your doctor immediately if you have any of these symptoms during or after Ocrevus treatment:
- new or worsening fatigue
- loss of appetite
- nausea
- vomiting
- abdominal discomfort

- unusual darkening of the urine
- yellowing of your skin or the whites of your eyes (jaundice)
Children and adolescents
Ocrevus is not intended to be used in children under 10 years old. This is because it has not been studied in this age group.
Other medicines and Ocrevus
Tell your doctor if you are taking, have recently taken or might take any other medicines.
In particular tell your doctor if:
 you have ever taken, are taking or are planning to take medicines that affect the immune system – such as chemotherapy, immunosuppressants or other medicines used to treat MS. The effect on the immune system of these medicines with Ocrevus could be too strong. Your doctor may decide to delay your treatment with Ocrevus or may ask you to stop such medicines before starting treatment with Ocrevus.
 you are taking medicines for high blood pressure. This is because Ocrevus may lower blood pressure. Your doctor may ask you to stop taking your blood pressure medicines for 12 hours before each Ocrevus infusion.
If any of the above apply to you (or you are not sure), talk to your doctor before you are given Ocrevus.
Pregnancy

If you are pregnant, think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking this medicine. This is because Ocrevus may cross the placenta and affect your baby.

Do not use Ocrevus if you are pregnant unless you have discussed this with your doctor. Your doctor will consider the benefit of you taking Ocrevus against the risk to your baby.

Talk to your doctor before vaccinating your baby.
Contraception for females
Females who could become pregnant must use contraception:
 during treatment with Ocrevus and
 for 4 months after your last infusion of Ocrevus.
Breast-feeding
Ocrevus can be used during breastfeeding. Talk to your doctor about the best way to feed your baby if you are given Ocrevus.
Driving and using machines
It is not known whether Ocrevus can affect your ability to drive or use tools or machines.
Your doctor will tell you whether your MS may affect your ability to drive or use tools and machines safely.
Ocrevus contains sodium
This medicine contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially ‘sodium- free’. Medicinal product will be prepared for administration with sodium-containing solution and this should be considered in relation to the total sodium intake of the patient from all sources per day.
Ocrevus contains polysorbate

This medicine contains 2 mg of polysorbate 20 in each vial, which is equivalent to 0.2 mg/mL.
Polysorbates may cause allergic reactions. Tell your doctor if you have any known allergies.

Ocrevus will be given to you by a doctor or nurse who is experienced with this treatment.
●
It will be given as a drip into a vein, this is called an intravenous infusion.
●
You will be closely monitored during your Ocrevus infusion and for at least 1 hour afterwards.
This is in case you have any side effects related to the infusion. The infusion may be slowed, paused or stopped if you have any side effects related to the infusion. This will depend on how severe your reaction is, see sections 2 and 4 for information about side effects related to the infusion Medicines you will have before you are given Ocrevus Before you are given Ocrevus, you will receive other medicines to prevent or reduce possible side effects such as infusion-related reactions (see sections 2 and 4 for information about infusion-related reactions).
You will receive a corticosteroid and an antihistamine before each infusion and you may also receive medicines to reduce fever.
How much and how often you will be given Ocrevus
Adults
You will be given a total dose of 600 mg of Ocrevus every 6 months.
●
The first 600 mg dose of Ocrevus will be given as 2 separate infusions (300 mg each), given 2 weeks apart. Each infusion will last about 2 hours 30 minutes.
●
The next 600 mg doses of Ocrevus will be given as a single infusion. Depending on the rate of the subsequent infusion, each infusion will either last about 3 hours 30 minutes or 2 hours.
Children and adolescents (aged 10 years and older)
The dose depends on body weight:
Children and adolescents with body weight below 35 kg:
●
Will be given a dose of 300 mg of Ocrevus every 6 months.
●
The first 300 mg dose of Ocrevus will be given as 2 separate infusions (150 mg each), given 2 weeks apart. Each infusion will last about 2 hours 30 minutes.
●
The next 300 mg doses of Ocrevus will be given as a single infusion. Each infusion will last about 2 hours 30 minutes.
●
Children who start on a 300 mg dose and subsequently reach a stable body weight of 35 kg or more should be switched to the 600 mg dose.
Children and adolescents with body weight equal to or above 35 kg:
●
Will be given a dose of 600 mg of Ocrevus every 6 months.
●
The first 600 mg dose of Ocrevus will be given as 2 separate infusions (300 mg each), given 2 weeks apart. Each infusion will last about 2 hours 30 minutes.
●
The next 600 mg doses of Ocrevus will be given as a single infusion. Each infusion will last about 3 hours 30 minutes.

If you miss an infusion of Ocrevus

If you miss an infusion of Ocrevus, talk to your doctor to arrange to have it as soon as possible.
Do not wait until your next planned infusion.

To get the full benefit of Ocrevus, it is important that you receive each infusion when it is due.
If you stop Ocrevus treatment

It is important to continue your treatment for as long as you and your doctor decide that it is helping you.

Some side effects can be related to having low B cells. After you stop Ocrevus treatment, you may still experience side effects until your B-cells return to normal. Your blood B-cells will gradually increase to normal levels. This can take from six months to two and a half years, or up to several years in rare cases.

Before you start any other medicines, tell your doctor when you had your last Ocrevus infusion.
If you have any further questions on the use of this medicine, ask your doctor.

Like all medicines, this medicine can cause side effects, although not everybody gets them.
The following side effects have been reported with Ocrevus:
Serious side effects:
Infusion-related reactions

Infusion-related reactions are the most common side effect of Ocrevus treatment (very common:
may affect more than 1 in 10 people). In most cases these are mild reactions but some serious reactions can happen.

Tell your doctor or nurse straight away if you experience any signs or symptoms of an infusion-related reaction during the infusion or up to 24 hours after the infusion.
Symptoms can include, but are not limited to:
- itchy skin
- rash
- hives
- redness of the skin
- throat irritation or pain
- shortness of breath
- swelling of the throat
- flushing
- low blood pressure
- fever
- feeling tired
- headache
- feeling dizzy
- feeling sick (nausea)
- fast heart beat.

If you have an infusion-related reaction, you will be given medicines to treat it and the infusion may need to be slowed down or stopped. When the reaction has stopped, the infusion may be continued. If the infusion-related reaction is life-threatening, your doctor will permanently stop your treatment with Ocrevus.

Infections

You might get infections more easily with Ocrevus. The following infections have been seen in patients treated with Ocrevus in MS:
- Very common (may affect more than 1 in 10 people)
- sore throat and runny nose (upper respiratory tract infection)
- COVID-19
- flu
- Common (may affect up to 1 in 10 people)
- sinus infection
- bronchitis (bronchial tube inflammation)
- herpes infection (cold sore or shingles)
- infection of the stomach and bowel (gastroenteritis)
- respiratory tract infection
- infection of the lungs (pneumonia) caused by COVID-19 virus
- viral infection
- skin infection (cellulitis)
Some of them might be serious.

Tell your doctor or nurse straight away if you notice any of these signs of infection:
- fever or chills
- cough which does not go away
- herpes (such as cold sore, shingles and genital sores)
Other side effects:
Very common (may affect more than 1 in 10 people)
 decrease in specific proteins in the blood (immunoglobulins) which help protect against infection Common (may affect up to 1 in 10 people)  discharge from the eye with itching, redness and swelling (conjunctivitis)  cough  a build-up of thick mucus in the nose, throat or chest  low levels of a type of white blood cell (neutropenia) Not known (it is not known how often these side effects happen)  a reduction in white blood cells which can be delayed  damage to your liver, which may cause symptoms such as new or worsening fatigue, loss of appetite, nausea, vomiting, abdominal discomfort, unusual darkening of the urine, or yellowing of your skin or the whites of your eyes (jaundice) Reporting of side effects If you get any side effects, talk to your doctor 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.

Ocrevus will be stored by the healthcare professionals at the hospital or clinic under the following conditions:

This medicine is to be kept out of the sight and reach of children.


This medicine is not to be used after the expiry date which is stated on the outer carton and the vial label after ‘EXP’. The expiry date refers to the last day of that month.

This medicine is to be stored in a refrigerator (2 °C - 8 °C). It is not to be frozen. The vials are to be kept in the outer carton to protect them from light.
Ocrevus must be diluted before it is given to you. Dilution will be done by a healthcare professional. It is recommended that the product is used immediately after dilution. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the healthcare professional and would normally not be longer than 24 hours at 2 °C - 8 °C and subsequently 8 hours at room temperature.
Do not throw away any medicines via wastewater. These measures will help to protect the environment.

What Ocrevus contains
●
The active substance is ocrelizumab. Each vial contains 300 mg of ocrelizumab in 10 mL at a concentration of 30 mg/mL.
●
The other ingredients are sodium acetate trihydrate (see section 2 ‘Ocrevus contains sodium’), glacial acetic acid, trehalose dihydrate, polysorbate 20 and water for injections.
What Ocrevus looks like and contents of the pack

Ocrevus is a clear to slightly opalescent, and colourless to pale brown solution.

It is supplied as a concentrate for solution for infusion.

This medicine is available in packs containing 1 or 2 vials (vials of 10 mL concentrate). Not all pack sizes may be marketed.
Marketing Authorisation Holder
Roche Registration GmbH
Emil-Barell-Strasse 1
79639 Grenzach-Wyhlen
Germany
Manufacturer
Roche Pharma AG
Emil-Barell-Strasse 1
D-79639 Grenzach-Wyhlen
Germany
For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:
België/Belgique/Belgien
Luxembourg/Luxemburg
N.V. Roche S.A.
België/Belgique/Belgien
Tél/Tel: +32 (0) 2 525 82 11
Latvija
Roche Latvija SIA
Tel: +371 - 6 7039831
България
Рош България ЕООД
Тел: +359 2 474 5444
Lietuva
UAB “Roche Lietuva”
Tel: +370 5 2546799

Česká republika
Roche s. r. o.
Tel: +420 - 2 20382111
Magyarország
Roche (Magyarország) Kft.
Tel: +36 - 1 279 4500
Danmark
Roche Pharmaceuticals A/S
Tlf: +45 - 36 39 99 99
Nederland
Roche Nederland B.V.
Tel: +31 (0) 348 438000
Deutschland
Roche Pharma AG
Tel: +49 (0) 7624 140
Norge
Roche Norge AS
Tlf: +47 - 22 78 90 00
Eesti
Roche Eesti OÜ
Tel: + 372 - 6 177 380
Österreich
Roche Austria GmbH
Tel: +43 (0) 1 27739
Ελλάδα, Κύπρος
Roche (Hellas) A.E.
Ελλάδα
Τηλ: +30 210 61 66 100
Polska
Roche Polska Sp.z o.o.
Tel: +48 - 22 345 18 88
España
Roche Farma S.A.
Tel: +34 - 91 324 81 00
Portugal
Roche Farmacêutica Química, Lda
Tel: +351 - 21 425 70 00
France
Roche
Tél: +33 (0) 1 47 61 40 00
România
Roche România S.R.L.
Tel: +40 21 206 47 01
Hrvatska
Roche d.o.o.
Tel: +385 1 4722 333
Slovenija
Roche farmacevtska družba d.o.o.
Tel: +386 - 1 360 26 00
Ireland, Malta
Roche Products (Ireland) Ltd.
Ireland/L-Irlanda
Tel: +353 (0) 1 469 0700
Slovenská republika
Roche Slovensko, s.r.o.
Tel: +421 - 2 52638201
Ísland
Roche Pharmaceuticals A/S c/o Icepharma hf
Sími: +354 540 8000
Suomi/Finland
Roche Oy
Puh/Tel: +358 (0) 10 554 500
Italia
Roche S.p.A.
Tel: +39 - 039 2471
Sverige
Roche AB
Tel: +46 (0) 8 726 1200
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.

The following information is intended for healthcare professionals only:
Read the SmPC for additional information.
In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.
Posology

Initial dose
In adults, the initial 600 mg dose is administered as two separate intravenous infusions; first as a 300 mg infusion, followed 2 weeks later by a second 300 mg infusion (see Table 3).
In paediatric patients (aged 10 years and older), the initial dose is administered according to the patient’s body weight (see Table 4):
●
Paediatric patients with body weight less than 35 kg: The initial 300 mg dose is administered as two separate intravenous infusions: first as a 150 mg infusion, followed 2 weeks later by a second 150 mg infusion.
●
Paediatric patients with body weight 35 kg or more: The initial 600 mg dose is administered as two separate intravenous infusions: first as a 300 mg infusion, followed 2 weeks later by a second 300 mg infusion.
●
Subsequent doses
In adults, subsequent doses of ocrelizumab thereafter are administered as a single 600 mg intravenous infusion every 6 months (see Table 3).
In paediatric patients (aged 10 years and older), subsequent doses of ocrelizumab thereafter are administered as a single intravenous infusion every 6 months according to the patient’s body weight (see Table 4):
●
Paediatric patients with body weight less than 35 kg: 300 mg.
●
Paediatric patients with body weight 35 kg or more: 600 mg.
Paediatric patients who start on a 300 mg dose and subsequently reach a stable body weight of 35 kg or more should be switched to the 600 mg dose.
The first subsequent dose should be administered six months after the first infusion of the initial dose.
A minimum interval of 5 months should be maintained between each dose of ocrelizumab.
Figure 1 Dose and schedule of Ocrevus for adult patients and paediatric patients with body weight 35 kg or more

Figure 2 Dose and schedule of Ocrevus for paediatric patients with body weight less than 35 kg Management of IRRs before the infusion ● Treatment should be initiated and supervised by an experienced healthcare professional with access to appropriate medical support to manage severe reactions such as serious infusion- related reactions (IRRs), hypersensitivity reactions and/or anaphylactic reactions.
●
Premedication for IRRs
The two following premedications must be administered prior to each ocrelizumab infusion to reduce the frequency and severity of IRRs (Table 1):
● intravenous methylprednisolone (or an equivalent);
● antihistamine;
In addition, premedication with an antipyretic (e.g., paracetamol) may also be considered prior to each infusion.
●
Hypotension, as a symptom of IRR, may occur during infusions. Therefore, withholding of antihypertensive treatments should be considered for 12 hours prior to and throughout each Ocrevus infusion. Patients with a history of congestive heart failure (New York Heart Association III & IV) were not studied.
Table 1
Premedication prior to Ocrevus intravenous infusion
Premedication
Timing
Methylprednisolone intravenous
(or an equivalent) approximately 30 minutes prior to
Ocrevus intravenous infusion
Antihistamine
(e.g. diphenhydramine) approximately 30-60 minutes prior to
Ocrevus intravenous infusion
Antipyretic (e.g. acetaminophen/paracetamol) may be considered approximately 30-60 minutes prior to Ocrevus intravenous infusion Instructions for dilution ● The product should be prepared by a healthcare professional using aseptic technique. Do not shake the vial. A sterile needle and syringe should be used to prepare the diluted infusion solution.
●
The product is intended for single use only.

●
Concentrate may contain fine translucent and/or reflective particles associated with enhanced opalescence. Do not use the concentrate if discoloured or if the concentrate contains foreign particulate matter.
●
Medicinal product must be diluted before administration. Solutions for intravenous administration are prepared by dilution of the concentrate into an infusion bag containing sodium chloride 9 mg/mL (0.9%) solution for infusion according to Table 2.
●
Discard any unused portion left in the vial.
●
The diluted infusion solution must be administered using an infusion set with a 0.2 or 0.22 micron in-line filter.
●
Prior to the start of the intravenous infusion, the content of the infusion bag should be at room temperature to avoid an infusion reaction due to the administration of the solution at low temperatures.
Table 2
Dilution of Ocrevus
Dose of Ocrevus
Volume of
Ocrevus
Volume of 0.9% sodium chloride
Final concentration
150 mg
5 mL
250 mL
0.6 mg/mL
300 mg
10 mL
250 mL
1.2 mg/mL
600 mg
20 mL
500 mL
1.2 mg/mL
Method of administration
●
After dilution, treatment is administered as an intravenous infusion through a dedicated line.
●
Infusions should not be administered as an intravenous push or bolus.

Table 3
Dose and schedule for adult patients
Amount of ocrelizumab to be administered
Infusion instruction
Initial dose
(600 mg) divided into 2 infusions
Infusion 1
300 mg in 250 mL

Initiate the infusion at a rate of
30 mL/hour for 30 minutes

The rate can be increased in
30 mL/hour increments every
30 minutes to a maximum of
180 mL/hour.

Each infusion should be given over approximately 2.5 hours.
Infusion 2
(2 weeks later)
300 mg in 250 mL
Subsequent doses
(600 mg) single infusion once every
6 months
Option 1
Infusion of approx. 3.5 hours duration
600 mg in 500 mL

Initiate the infusion at a rate of
40 mL/hour for 30 minutes

The rate can be increased in
40 mL/hour increments every
30 minutes to a maximum of
200 mL/hour

Each infusion should be given over approximately 3.5 hours.
OR
Option 2
Infusion of approx.
2 hours duration
600 mg in 500 mL

Initiate the infusion at a rate of
100 mL/hour for the first
15 minutes

Increase the infusion rate to
200 mL/hour for the next
15 minutes

Increase the infusion rate to
250 mL/hour for the next
30 minutes 

Increase the infusion rate to
300 mL/hour for the remaining
60 minutes

Each infusion should be given over approximately 2 hours.
Table 4
Dose and schedule for paediatric patients (aged 10 years and older)
Infusion
Amount of ocrelizumab to be administered
Infusion instruction
Body weight < 35 kg
Initial dose divided into 2 infusions
Infusion 1
150 mg in 250 mL

Initiate the infusion at a rate of
30 mL/hour

Thereafter, the rate can be increased in 30 mL/hour
Infusion 2
150 mg

Management of IRRs during and after the infusion
Patients should be monitored during the infusion and for at least one hour after the completion of the infusion.
During the infusion

Infusion adjustments in case of IRRs
In case of IRRs during any infusion, see the following adjustments.
Life-threatening IRRs
If there are signs of a life threatening or disabling IRR during an infusion, such as acute hypersensitivity or acute respiratory distress syndrome the infusion must be stopped immediately and the patient should receive appropriate treatment. The infusion must be permanently discontinued in these patients.
Severe IRRs
If a patient experiences a severe IRR (such as dyspnoea) or a complex of flushing, fever, and throat pain symptoms, the infusion should be interrupted immediately and the patient should receive symptomatic treatment. The infusion should be restarted only after all symptoms have resolved. The initial infusion rate at restart should be half of the infusion rate at the time of onset of the reaction. No infusion adjustment is necessary for subsequent new infusions, unless the patient experiences an IRR.
Infusion
Amount of ocrelizumab to be administered
Infusion instruction
(2 weeks later) in 250 mL increments every 30 minutes to a maximum of 180 mL/hour  Each infusion should be given over approximately 2.5 hour Subsequent doses Single infusion once every 6 months 300 mg in 250 mL Body weight ≥ 35 kg Initial dose divided into 2 infusions Infusion 1 300 mg in 250 mL  Initiate the infusion at a rate of 30 mL/hour  Thereafter, the rate can be increased in 30 mL/hour increments every 30 minutes to a maximum of 180 mL/hour  Each infusion should be given over approximately 2.5 hour Infusion 2 (2 weeks later) 300 mg in 250 mL Subsequent doses Single infusion once every 6 months 600 mg in 500 mL  Initiate the infusion at a rate of 40 mL/hour.

Thereafter, the rate can be increased in 40 mL/hour increments every 30 minutes to a maximum of 200 mL/hour  Each infusion should be given over approximately 3.5 hours

Mild to moderate IRRs
If a patient experiences a mild to moderate IRR (e.g., headache), the infusion rate should be reduced to half the rate at the onset of the event. This reduced rate should be maintained for at least 30 minutes. If tolerated, the infusion rate may then be increased according to the patient’s initial infusion rate. No infusion adjustment is necessary for subsequent new infusions, unless the patient experiences an IRR.

Patients who experience severe pulmonary symptoms, such as bronchospasm or asthma exacerbation, must have their infusion interrupted immediately and permanently. After administering symptomatic treatment, monitor the patient until the pulmonary symptoms have resolved because initial improvement of clinical symptoms could be followed by deterioration.

Hypersensitivity may be clinically indistinguishable from an IRR in terms of symptoms. If a hypersensitivity reaction is suspected during infusion, the infusion must be stopped immediately and permanently.
After the infusion

Patients should be observed for at least one hour after the completion of the infusion for any symptom of an IRR.

Physicians should alert patients that an IRR can occur within 24 hours of infusion.
Shelf life
Unopened vial
2 years
Diluted solution for intravenous infusion
●
Chemical and physical in-use stability has been demonstrated for 24 hours at 2-8 °C and subsequently 8 hours at room temperature.
●
From a microbiological point of view, the prepared infusion should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2-8 °C and subsequently 8 hours at room temperature, unless dilution undertaken in controlled and validated aseptic conditions.
●
In the event an intravenous infusion cannot be completed the same day, the remaining solution should be discarded.

What Ocrevus is
Ocrevus contains the active substance ‘ocrelizumab’. It is a type of protein called a ‘monoclonal antibody’. Antibodies work by attaching to specific targets in your body.
What Ocrevus is used for
Ocrevus is used to treat adults with:

Relapsing forms of multiple sclerosis (RMS)

Early primary progressive multiple sclerosis (PPMS)
What is Multiple Sclerosis
Multiple Sclerosis (MS) affects the central nervous system, especially the nerves in the brain and spinal cord. In MS, the immune system (the body’s defence system) works incorrectly and attacks a protective layer (called myelin sheath) around nerve cells and causes inflammation. Breakdown of the myelin sheath stops the nerves working properly.
Symptoms of MS depend on which part of the central nervous system is affected and can include problems with walking and balance, weakness, numbness, double vision and blurring, poor coordination and bladder problems.

In relapsing forms of MS, the patient has repeated attacks of symptoms (relapses). The symptoms can appear suddenly within a few hours, or slowly over several days. The symptoms disappear or improve between relapses but damage may build up and lead to permanent disability.

In primary progressive MS, the symptoms generally continue to worsen from the start of the disease.

How does Ocrevus work
Ocrevus attaches to specific B cells, which are a type of white blood cells that are part of the immune system and play a role in MS. Ocrevus targets and removes those specific B cells. This reduces inflammation and attacks on the myelin sheath, reduces the chance of having a relapse and slows the progression of your disease.

In Relapsing forms of MS (RMS), Ocrevus helps to significantly reduce the number of attacks (relapses) and significantly slow down the progression of the disease. Ocrevus also significantly increases the chance of a patient having no evidence of disease activity (brain lesions, relapses and worsening of disability).

In Primary Progressive MS (PPMS), Ocrevus helps to slow down the progression of the disease and reduce deterioration in walking speed.

You must not be given Ocrevus:
 if you are allergic to ocrelizumab or any of the other ingredients of this medicine (listed in section 6).
 if you currently have an infection.
 if you have been told that you have severe problems with your immune system.
 if you have cancer.
If you are not sure, talk to your doctor before you are given Ocrevus.
Warnings and precautions
Talk to your doctor before you are given Ocrevus if any of the following apply to you. Your doctor may decide to delay your treatment with Ocrevus, or may decide you cannot receive Ocrevus if:
 you have an infection. Your doctor will wait until the infection is resolved before giving you Ocrevus.
 you have ever had hepatitis B or are a carrier of the hepatitis B virus. This is because medicines like Ocrevus can cause the hepatitis B virus to become active again. Before your Ocrevus treatment, your doctor will check if you are at risk of hepatitis B infection. Patients who have had hepatitis B or are carriers of the hepatitis B virus will have a blood test and will be monitored by a doctor for signs of hepatitis B infection.
 you have cancer or if you have had cancer in the past. Your doctor may decide to delay your treatment with Ocrevus.
Effect on the immune system:

Diseases that affect your immune system: if you have another disease which affects the immune system. You may not be able to receive Ocrevus.

Medicines that affect your immune system: if you have ever taken, are taking or are planning to take medicines that affect the immune system – such as chemotherapy, immunosuppressants or other medicines used to treat MS. Your doctor may decide to delay your treatment with Ocrevus or may ask you to stop such medicines before starting treatment with Ocrevus. See under ‘Other medicines and Ocrevus’, below for more information.

Injection reactions

Injection reactions are the most common side effect of Ocrevus treatment given as an injection under your skin (subcutaneous injection).

Tell your doctor or nurse straight away if you have any injection reaction (see section 4 for a list of injection reactions). Injection reactions can happen during the injection or up to 24 hours after the injection.

To reduce the risk of injection reactions, your doctor will give you other medicines before each injection of Ocrevus (see section 3) and you will be observed during the injection and for at least one hour after the initial injection has been given.
Infections

Talk to your doctor before you are given Ocrevus if you think you have an infection. Your doctor will wait until the infection is resolved before giving you Ocrevus.

You might get infections more easily with Ocrevus. This is because the immune cells that Ocrevus targets also help to fight infection.

Before you start treatment with Ocrevus and before subsequent injections, your doctor may ask you to have a blood test to verify your immune system because infections may occur more frequently in case of severe problems with your immune system.

If you are treated with Ocrevus for primary progressive multiple sclerosis, and you have swallowing difficulties, Ocrevus may increase the risk of severe pneumonia.

Tell your doctor or nurse straight away if you have any of these signs of infection during or after Ocrevus treatment:
- fever or chills
- cough that does not go away
- herpes (such as cold sore, shingles or genital sores).

Tell your doctor or nurse straight away if you think your MS is getting worse or if you notice any new symptoms. This is because of a very rare and life-threatening brain infection, called ‘progressive multifocal leukoencephalopathy’ (PML), which can cause symptoms similar to those of MS. PML can occur in patients taking Ocrevus.

Tell your partner or carer about your Ocrevus treatment. They might notice symptoms of PML that you do not, such as memory lapses, trouble thinking, difficulty walking, sight loss, changes in the way you talk, which your doctor may need to investigate.
Vaccinations

Tell your doctor if you have recently been given any vaccine or might be given a vaccine in the near future.

While you are being treated with Ocrevus, you should not be given live or live attenuated vaccines (for example BCG for tuberculosis or vaccines against yellow fever).

Your doctor may recommend that you are given a seasonal influenza vaccine.

Your doctor will check if you need any vaccinations before you start treatment with Ocrevus.
Any vaccinations should be given at least 6 weeks before you start treatment with Ocrevus.
Liver Injury

Your doctor will take blood tests before you start treatment with Ocrevus and will take blood tests to check your liver function again if you have any symptoms of hepatic injury during treatment.

Tell your doctor immediately if you have any of these symptoms during or after Ocrevus treatment:
- new or worsening fatigue
- loss of appetite
- nausea
- vomiting

- abdominal discomfort
- unusual darkening of the urine
- yellowing of your skin or the whites of your eyes (jaundice)
Children and adolescents
Subcutaneous Ocrevus is not intended to be used in children and adolescents younger than 18 years old. This is because it has not yet been studied in this age group.
Other medicines and Ocrevus
Tell your doctor if you are taking, have recently taken or might take any other medicines.
In particular tell your doctor if:
 you have ever taken, are taking or are planning to take medicines that affect the immune system – such as chemotherapy, immunosuppressants or other medicines used to treat MS. The effect on the immune system of these medicines with Ocrevus could be too strong. Your doctor may decide to delay your treatment with Ocrevus or may ask you to stop such medicines before starting treatment with Ocrevus.
If any of the above apply to you (or you are not sure), talk to your doctor before you are given Ocrevus.
Pregnancy

If you are pregnant, think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking this medicine. This is because Ocrevus may cross the placenta and affect your baby.

Do not use Ocrevus if you are pregnant unless you have discussed this with your doctor. Your doctor will consider the benefit of you taking Ocrevus against the risk to your baby.

Talk to your doctor before vaccinating your baby.
Contraception for women
Women who could become pregnant must use contraception:
 during treatment with Ocrevus and
 for 4 months after your last dose of Ocrevus.
Breast-feeding
Ocrevus can be used during breastfeeding. Talk to your doctor about the best way to feed your baby if you are given Ocrevus.
Driving and using machines
It is not known whether Ocrevus can affect your ability to drive or use tools or machines.
Your doctor will tell you whether your MS may affect your ability to drive or use tools and machines safely.
Ocrevus contains sodium
This medicine contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially ‘sodium- free’.
Ocrevus contains polysorbate
This medicine contains 13.8 mg of polysorbate 20 in each vial, which is equivalent to 0.6 mg/mL.
Polysorbates may cause allergic reactions. Tell your doctor if you have any known allergies.

Medicines you will have before you are given Ocrevus
Before you are given Ocrevus, you will receive other medicines to prevent or reduce possible side effects such as injection reactions (see sections 2 and 4 for information about injection reactions).
You will receive a corticosteroid and an antihistamine before each injection and you may also receive medicines to reduce fever.
How much and how often you will be given Ocrevus
You will be given a total dose of 920 mg of Ocrevus every 6 months.
How Ocrevus is given

Ocrevus will be given to you by a doctor or a nurse. It will be given as an injection under your skin (subcutaneous injection).

Injections will be given in the stomach in approximately 10 minutes.

Your doctor or nurse will make sure each injection is given in the stomach, where the skin is not red, bruised, tender, hard, or areas where there are moles or scars.

You will be observed while you are being given Ocrevus and for at least one hour after the initial injection has been given. This is in case you have any side effects such as injection reactions. The injection may be temporarily stopped or permanently stopped if you have an injection reaction, depending on how serious it is (see sections 2 and 4 for information about injection reactions).
If you miss an injection of Ocrevus

If you miss an injection of Ocrevus, talk to your doctor to arrange to have it as soon as possible.
Do not wait until your next planned injection.

To get the full benefit of Ocrevus, it is important that you receive each injection when it is due.
If you stop Ocrevus treatment

It is important to continue your treatment for as long as you and your doctor decide that it is helping you.

Some side effects can be related to having low B cells. After you stop Ocrevus treatment, you may still experience side effects until your B-cells return to normal. Your blood B-cells will gradually increase to normal levels. This can take from six months to two and a half years, or up to several years in rare cases.

Before you start any other medicines, tell your doctor when you had your last Ocrevus dose.
If you have any further questions on the use of this medicine, ask your doctor.

Like all medicines, this medicine can cause side effects, although not everybody gets them.
The following side effects have been reported with Ocrevus:

Serious side effects:
Injection reactions

Injection reactions are the most common side effect of Ocrevus treatment given as a subcutaneous injection (very common: may affect more than 1 in 10 people). In most cases these are mild or moderate reactions but serious reactions have happened with Ocrevus treatment given as an infusion in a vein (intravenous infusion).

Tell your doctor or nurse straight away if you experience any signs or symptoms of an injection reaction during the injection or up to 24 hours after the injection. Symptoms can include, but are not limited to:
- itchy skin
- rash
- hives
- redness of the skin
- pain or swelling at the injection site
- throat irritation or pain
- shortness of breath
- swelling of the throat
- flushing
- low blood pressure
- fever
- feeling tired
- headache
- feeling dizzy
- feeling sick (nausea)
- fast heart beat.

If you have an injection reaction, you may be given medicines to treat it and the injection may need to be stopped. If the injection reaction is life-threatening, your doctor will permanently stop your treatment with Ocrevus.
Infections

You might get infections more easily with Ocrevus. The following infections have been seen in patients treated with Ocrevus in MS:
- Very common (may affect more than 1 in 10 people)
- sore throat and runny nose (upper respiratory tract infection)
- COVID-19
- flu
- Common (may affect up to 1 in 10 people)
- sinus infection
- bronchitis (bronchial tube inflammation)
- herpes infection (cold sore or shingles)
- infection of the stomach and bowel (gastroenteritis)
- respiratory tract infection
- infection of the lungs (pneumonia) caused by COVID-19 virus
- viral infection
- skin infection (cellulitis)
Some of them might be serious.

Tell your doctor or nurse straight away if you notice any of these signs of infection:
- fever or chills
- cough which does not go away
- herpes (such as cold sore, shingles and genital sores)

Other side effects:
Very common (may affect more than 1 in 10 people)
 decrease in specific proteins in the blood (immunoglobulins) which help protect against infection Common (may affect up to 1 in 10 people)  discharge from the eye with itching, redness and swelling (conjunctivitis)  cough  a build-up of thick mucus in the nose, throat or chest  low levels of a type of white blood cell (neutropenia) Not known (it is not known how often these side effects happen)  a reduction in white blood cells which can be delayed  damage to your liver, which may cause symptoms such as new or worsening fatigue, loss of appetite, nausea, vomiting, abdominal discomfort, unusual darkening of the urine, or yellowing of your skin or the whites of your eyes (jaundice) Reporting of side effects If you get any side effects, talk to your doctor 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.

Ocrevus will be stored by the healthcare professionals at the hospital or clinic under the following conditions:

This medicine is to be kept out of the sight and reach of children.

This medicine is not to be used after the expiry date which is stated on the outer carton and the vial label after ‘EXP’. The expiry date refers to the last day of that month.

This medicine is to be stored in a refrigerator (2 oC – 8 oC). It is not to be frozen. The vials are to be kept in the outer carton to protect them from light. Do not shake.
Do not throw away any medicines via wastewater. These measures will help to protect the environment.

What Ocrevus contains

The active substance is ocrelizumab. Each vial contains 920 mg of ocrelizumab in 23 mL (40 mg/mL).

The other ingredients are recombinant human hyaluronidase (rHuPH20), sodium acetate trihydrate (see section 2 ‘Ocrevus contains sodium’), glacial acetic acid, α,α-trehalose dihydrate, polysorbate 20, methionine and water for injections.
What Ocrevus looks like and contents of the pack

Ocrevus is a clear to slightly opalescent, and colourless to pale brown solution.

It is supplied as a solution for injection.

Ocrevus is available in a pack containing 1 glass vial.
Marketing Authorisation Holder

Roche Registration GmbH
Emil-Barell-Strasse 1
79639 Grenzach-Wyhlen
Germany
Manufacturer
Roche Pharma AG
Emil-Barell-Strasse 1
D-79639 Grenzach-Wyhlen
Germany
For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:
België/Belgique/Belgien
Luxembourg/Luxemburg
N.V. Roche S.A.
België/Belgique/Belgien
Tél/Tel: +32 (0) 2 525 82 11
Latvija
Roche Latvija SIA
Tel: +371 - 6 7039831
България
Рош България ЕООД
Тел: +359 2 474 5444
Lietuva
UAB “Roche Lietuva”
Tel: +370 5 2546799
Česká republika
Roche s. r. o.
Tel: +420 - 2 20382111
Magyarország
Roche (Magyarország) Kft.
Tel: +36 - 1 279 4500
Danmark
Roche Pharmaceuticals A/S
Tlf: +45 - 36 39 99 99
Nederland
Roche Nederland B.V.
Tel: +31 (0) 348 438000
Deutschland
Roche Pharma AG
Tel: +49 (0) 7624 140
Norge
Roche Norge AS
Tlf: +47 - 22 78 90 00
Eesti
Roche Eesti OÜ
Tel: + 372 - 6 177 380
Österreich
Roche Austria GmbH
Tel: +43 (0) 1 27739
Ελλάδα, Κύπρος
Roche (Hellas) A.E.
Ελλάδα
Τηλ: +30 210 61 66 100
Polska
Roche Polska Sp.z o.o.
Tel: +48 - 22 345 18 88
España
Roche Farma S.A.
Tel: +34 - 91 324 81 00
Portugal
Roche Farmacêutica Química, Lda
Tel: +351 - 21 425 70 00
France
Roche
Tél: +33 (0) 1 47 61 40 00
România
Roche România S.R.L.
Tel: +40 21 206 47 01
Hrvatska
Roche d.o.o.
Tel: +385 1 4722 333
Slovenija
Roche farmacevtska družba d.o.o.
Tel: +386 - 1 360 26 00

Ireland, Malta
Roche Products (Ireland) Ltd.
Ireland/L-Irlanda
Tel: +353 (0) 1 469 0700
Slovenská republika
Roche Slovensko, s.r.o.
Tel: +421 - 2 52638201
Ísland
Roche Pharmaceuticals A/S c/o Icepharma hf
Sími: +354 540 8000
Suomi/Finland
Roche Oy
Puh/Tel: +358 (0) 10 554 500
Italia
Roche S.p.A.
Tel: +39 - 039 2471
Sverige
Roche AB
Tel: +46 (0) 8 726 1200
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.

--------------------------------------------------------------------------------------------------------------------------- The following information is intended for healthcare professionals only:
Read the SmPC for additional information.
In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.
It is important to check the product labels to ensure that the correct formulation (intravenous or subcutaneous) is being administered to the patient by the correct route, as prescribed.
The medicinal product should be inspected visually to ensure there is no particulate matter or discolouration prior to administration.
The medicinal product is for single use only and should be prepared by a healthcare professional using aseptic technique.
No incompatibilities between this medicinal product and polypropylene (PP), polycarbonate (PC), polyethylene (PE), polyvinyl chloride (PVC), and polyurethane (PUR) and stainless steel have been observed.
Preparation of the syringe

Prior to use, the vial should be removed from the refrigerator to allow the solution to come to room temperature.

Withdraw the entire contents of Ocrevus solution for injection from the vial with a syringe and transfer needle (21G recommended).

Remove the transfer needle and attach a subcutaneous infusion set (e.g., winged/butterfly) containing a 24-26G needle for injection. Use a subcutaneous infusion set with residual hold-up volume NOT exceeding 0.8 mL for administration.

Prime the subcutaneous infusion line with the solution for injection to eliminate the air in the infusion line and stop before the fluid reaches the needle.

Ensure the syringe contains exactly 23 mL of the solution after priming and expelling any excess volume from the syringe.

Administer immediately to avoid needle clogging. Do not store the prepared syringe that has been attached to the already-primed subcutaneous infusion set.
If the dose is not administered immediately, refer to “Storage of the syringe” below.
Storage of the syringe

If the dose is not to be administered immediately, use aseptic technique to withdraw the entire contents of Ocrevus solution for injection from the vial into the syringe to account for the dose volume (23 mL) and priming volume for the subcutaneous infusion set. Replace the transfer needle with a syringe closing cap. Do not attach a subcutaneous infusion set for storage.

Chemical and physical in-use stability has been demonstrated for 30 days at 2 °C to 8 °C and additionally for 8 hours unprotected from light at ≤30 °C.

From a microbiological point of view, the product should be used immediately once transferred from the vial to the syringe. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and normally not longer than 24 hours at 2 °C to 8 °C, unless the preparation has taken place in controlled and validated aseptic conditions.

If the syringe was stored in a refrigerator, allow the syringe to reach room temperature prior to administration.

Method of administration
Ocrevus 920 mg solution for injection is not intended for intravenous administration and should always be administered via a subcutaneous injection by a healthcare professional.
Patients may start treatment using intravenous or subcutaneous ocrelizumab and patients currently receiving intravenous ocrelizumab may continue treatment with intravenous ocrelizumab or transition to Ocrevus 920 mg solution for injection.
Prior to administration, the medicinal product should be removed from refrigeration to allow the solution to come to room temperature.
The 920 mg dose should be administered as a subcutaneous injection in the abdomen in approximately 10 minutes. Use of a subcutaneous infusion set (e.g., winged/butterfly) is recommended. Any residual hold-up volume remaining in the subcutaneous infusion set should not be administered to the patient.
The injection site should be the abdomen, except for 5 cm around the navel. Injections should never be given into areas where the skin is red, bruised, tender, or hard, or areas where there are moles or scars.
Ocrevus solution for injection should always be administered by a healthcare professional. For the initial dose, post-injection monitoring with access to appropriate medical support to manage severe reactions such as IRs, for at least one hour after injection is recommended. For subsequent doses, the need for post-injection monitoring is at the treating physician’s discretion.