Ocrevus

Package leaflet: Information for the patient

Ocrevus 300 mg concentrate for solution for infusion

ocrelizumab
Please read this leaflet carefully before you are given this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor.
• If you get any side effects, including those not listed in this leaflet, tell your doctor or nurse. See section 4.

Contents of this leaflet

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

1. What Ocrevus is and what it is used for

What Ocrevus is
Ocrevus contains the active substance "ocrelizumab". It is a type of protein called a "monoclonal antibody". Antibodies work by binding to specific targets in the 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, particularly the nerves in the brain and spinal cord. In MS, the immune system (the body's defence system) does not work properly and attacks the protective layer (the so-called myelin sheath) that surrounds nerve cells, causing inflammation. Damage to the myelin sheath prevents nerves from functioning properly.
The symptoms of MS depend on which part of the central nervous system is affected and may include problems with walking and balance, weakness, numbness, double and blurred vision, poor coordination, and bladder problems.

• In relapsing forms of MS, patients experience repeated attacks of symptoms (relapses). Symptoms may appear suddenly within a few hours or develop slowly over several days. Symptoms fade or improve between relapses, but damage can accumulate over time, leading to permanent disability.
• In primary progressive MS, symptoms generally continue to worsen from the beginning of the disease.

How Ocrevus works
Ocrevus binds to specific B cells, a type of white blood cell that is part of the immune system and plays a role in MS. Ocrevus targets and removes these specific B cells. This reduces inflammation and attacks on the myelin sheath, decreases the likelihood of experiencing a relapse, and slows disease progression.

• In relapsing forms of MS (RMS), Ocrevus significantly reduces the number of attacks (relapses) and significantly slows disease progression. Ocrevus also significantly increases the likelihood that a patient will show no evidence of disease activity (brain lesions, relapses, and worsening disability).
• In primary progressive MS (PPMS), Ocrevus helps slow disease progression and reduce worsening of walking speed.

2. What you should know before being given Ocrevus

Do not be given Ocrevus if:

• you are allergic to ocrelizumab or to any of the other ingredients of this medicine (listed in section 6).
• you currently have an infection.
• you have been told you have serious problems with your immune system.
• you have a malignant tumour.

If you have any doubts, speak to your doctor before being given Ocrevus.
Warnings and precautions
Talk to your doctor before using Ocrevus if any of the following apply to you. Your
doctor may decide to delay treatment with Ocrevus, or may determine that you should not
receive Ocrevus if:

• You have an infection. Your doctor will wait until the infection has resolved before administering Ocrevus.
• You have previously had hepatitis B or are a carrier of the hepatitis B virus. Medicines such as Ocrevus can cause reactivation of the hepatitis B virus. Before treating you with Ocrevus, your doctor will check whether you are at risk of developing hepatitis B infection. Patients who have had hepatitis B or are carriers of the hepatitis B virus will have regular blood tests and be monitored by their doctor for signs of hepatitis B infection.
• You have a malignant tumour or have had one in the past. Your doctor may decide to delay treatment with Ocrevus. Effect on the immune system:
• Diseases affecting the immune system: if you have another disease that affects the immune system. It may not be possible to administer Ocrevus.
• Medicines affecting the immune system: if you have previously taken, are currently taking, or plan 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 treatment with Ocrevus or may ask you to stop taking these medicines before starting treatment with Ocrevus. For further information, see “Other medicines and Ocrevus” below.

Infusion-related reactions

• Infusion-related reactions are the most common side effect of Ocrevus.
• Tell your nurse or doctor immediately if you experience an infusion-related reaction (see section 4 for a list of infusion-related reactions). Infusion-related reactions may occur during the infusion or up to 24 hours afterwards.
• To reduce the risk of an infusion-related reaction, your doctor will give you medicines before each Ocrevus infusion (see section 3) and will closely monitor you during the infusion and for at least one hour after the infusion has been administered.

Infections

• Inform your doctor before being given Ocrevus if you suspect you have an infection. Your doctor will wait until the infection has resolved before administering Ocrevus.
• You may be more likely to develop infections while taking Ocrevus. This is because the immune cells targeted by Ocrevus also help fight infections.
• Before starting treatment with Ocrevus and before subsequent infusions, your doctor may ask you to have a blood test to check your immune system. If you have serious immune system problems, you may develop infections more frequently.
• If you are being treated with Ocrevus for primary progressive multiple sclerosis and have difficulty swallowing, Ocrevus may increase your risk of severe pneumonia.
• Tell your doctor or nurse immediately if during or after treatment with Ocrevus you notice any of the following signs of infection:
  • fever or chills
  • persistent cough
  • herpes (for example, cold sores, shingles, or genital herpes).
• Tell your doctor or nurse immediately if you think your MS is getting worse or if you notice new symptoms. There is a very rare but potentially life-threatening brain infection called “progressive multifocal leukoencephalopathy” (PML) that can cause symptoms similar to those of MS. PML can occur in patients treated with Ocrevus.
• Inform your partner or caregiver about your treatment with Ocrevus, as they may notice symptoms of PML that you do not, such as memory lapses, difficulty thinking, difficulty walking, loss of vision, or changes in the way you walk, which your doctor may need to investigate.

Vaccinations

• Inform your doctor if you have recently received any vaccine or if you may receive a vaccine in the near future.
• During treatment with Ocrevus, you must not receive live or live-attenuated vaccines (for example, the BCG vaccine for tuberculosis or vaccines against yellow fever).
• Your doctor may recommend that you receive a seasonal influenza vaccine.
• Your doctor will check whether you need any vaccinations before starting treatment with Ocrevus. Any vaccinations should be given at least 6 weeks before starting treatment with Ocrevus.

Children and adolescents
Ocrevus is not recommended for the treatment of children and adolescents under 18 years of age.
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
medicine.
In particular, inform your doctor:

• if you have previously taken, are currently taking, or plan to take medicines that affect the immune system – such as chemotherapy, immunosuppressants, or other medicines used to treat MS. The effect of these medicines on the immune system, when given together with Ocrevus, could be too strong. Your doctor may decide to delay treatment with Ocrevus or may ask you to stop taking these medicines before starting treatment with Ocrevus.
• if you are taking medicines for high blood pressure. Ocrevus may cause a drop in blood pressure. Your doctor may ask you to stop taking your blood pressure medicines within the 12 hours before your Ocrevus infusion.

If any of the above situations apply to you (or if you are unsure), speak to your doctor before being
given Ocrevus.
Pregnancy

• If you are pregnant, think you may be pregnant, or are planning to become pregnant, ask your doctor for advice before taking this medicine. This is because Ocrevus can cross the placenta and affect the unborn baby.
• Do not use Ocrevus if you are pregnant unless you have discussed this with your doctor first. Your doctor will weigh the benefits of treatment with Ocrevus against the possible risks to your baby.
• Talk to your doctor before vaccinating your baby.

Contraception in women
Women of childbearing potential should use contraceptive measures:

• during treatment with Ocrevus and
• for 4 months after the last infusion of Ocrevus.

Breast-feeding
Ocrevus may be used during breast-feeding. If you are given Ocrevus, talk to your doctor about the best way to breast-feed your baby.
Driving and using machines
It is not known whether Ocrevus affects your ability to drive or use tools or machines.
Your doctor will advise 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 (23 mg) of sodium per dose, i.e. essentially
“sodium-free”.

3. How Ocrevus is administered

Ocrevus will be administered to you by a doctor or nurse experienced in the use of this treatment, who will closely monitor you during the administration of the medicine in order to detect any possible adverse reactions. Ocrevus will always be given as a drop-by-drop infusion (intravenous infusion).

Medicines you must take before receiving Ocrevus
Before receiving Ocrevus, you will be given other medicines to prevent or reduce possible side effects, such as infusion-related reactions (see sections 2 and 4 for information on infusion-related reactions).
Before each infusion, you will receive a corticosteroid and an antihistamine, and you may also receive medicines to reduce fever.

Dosage and frequency of Ocrevus administration
You will receive a total dose of 600 mg of Ocrevus every 6 months.

• The first 600 mg dose of Ocrevus will be administered as two separate infusions (300 mg each), given 2 weeks apart. Each infusion will last approximately 2 hours and 30 minutes.
• Subsequent 600 mg doses of Ocrevus will be administered as a single infusion. Depending on the rate of the subsequent infusion, each infusion will last approximately 3 hours and 30 minutes or 2 hours.

How Ocrevus is administered

• Ocrevus will be administered by a doctor or nurse. It will be given as an infusion into a vein (intravenous infusion or i.v. infusion).
• You will be closely monitored during the administration of Ocrevus and for at least 1 hour after the infusion is completed, in case you experience any adverse effects such as infusion-related reactions. If you experience an infusion-related reaction, the infusion may be slowed down, temporarily suspended, or permanently discontinued depending on the severity (see sections 2 and 4 for information on infusion-related reactions).

If you miss an Ocrevus infusion

• If you miss an Ocrevus infusion, contact your doctor to reschedule it as soon as possible. Do not wait until your next scheduled infusion.
• To obtain the full benefit from Ocrevus, it is important that you receive each infusion at the correct time.

If you discontinue treatment with Ocrevus

• It is important that you continue treatment for as long as you and your doctor consider it beneficial for you.
• Some side effects may be related to low levels of B cells. After stopping treatment with Ocrevus, side effects may still occur until B cell levels return to normal. Your blood B cells will gradually return to normal levels. This may take from six months to two and a half years, or in rare cases up to several years.
• Before starting any other medicine, inform your doctor about the date of your last Ocrevus infusion.

If you have any questions about the use of this medicine, consult your doctor.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone 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 reactions are mild in intensity, but serious reactions can also occur.

• Tell your doctor or nurse immediately if you experience any signs or symptoms of an infusion-related reaction during or up to 24 hours after the infusion. Symptoms include, but are not limited to:

  • itching of the skin
  • rash
  • hives
  • skin redness
  • throat irritation or pain
  • shortness of breath
  • swelling of the throat
  • flushing
  • low blood pressure
  • fever
  • feeling of fatigue
  • headache
  • dizziness
  • feeling unwell (nausea)
  • rapid heartbeat.

• If you experience an infusion-related reaction, you will be given medicines to treat it, and the infusion rate may need to be slowed or stopped. Once the reaction has resolved, the infusion may continue. If the infusion-related reaction is life-threatening, your doctor will permanently discontinue treatment with Ocrevus.

Infections

• You may be more likely to develop infections while receiving Ocrevus. The following infections have been observed in patients treated with Ocrevus for MS:
  • Very common (may affect more than 1 in 10 people)
  • sore throat and runny nose (inflammation of the upper respiratory tract)
  • influenza.
  • Common (may affect up to 1 in 10 people)
  • sinus infection
  • bronchitis (inflammation of the bronchi)
  • herpes infections (cold sores or shingles)
  • stomach and intestinal infection (gastroenteritis)
  • respiratory tract infection
  • viral infection
  • skin infection (cellulitis).

Some of these infections may be serious.

• Tell your doctor or nurse immediately if you notice any of the following signs of infection:
  • fever or chills
  • persistent cough
  • herpes (for example, on the lips, shingles, or genital herpes).

Other side effects:

Very common (may affect more than 1 in 10 people)

• reduction in specific proteins in the blood (immunoglobulins) that help protect against infections.

Common (may affect up to 1 in 10 people)

• eye discharge with itching, redness, and swelling (conjunctivitis)
• cough
• buildup of thick mucus in the nose, throat, or chest
• low levels of a type of white blood cells (neutropenia).

Not known (frequency cannot be estimated from the available data)

• a delayed reduction in white blood cells.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or nurse. You can also report side effects directly via the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Ocrevus

Ocrevus will be stored by healthcare professionals at the hospital or clinic under the following conditions:

• This medicinal product should be kept out of the sight and reach of children.
• This medicinal product must not be used after the expiry date stated on the carton and on the label of the vial after "Exp.". The expiry date refers to the last day of that month.
• This medicinal product must be stored in a refrigerator (2 °C - 8 °C). It must not be frozen. Vials should be kept in the outer packaging to protect them from light.

Ocrevus must be diluted before it is administered to you. Dilution will be performed by a healthcare professional. Immediate use of the diluted solution is recommended. If not used immediately, the storage times and conditions before use are the responsibility of the healthcare professional and should normally not exceed 24 hours at 2-8 °C, followed by up to 8 hours at room temperature.
Do not dispose of any medicine via wastewater. This will help protect the environment.

6. Package contents and other information

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 components are sodium acetate trihydrate (see section 2 “Ocrevus contains sodium”), glacial acetic acid, dithiothreitol dihydrate, polysorbate 20, and water for injections.

Description of the appearance of Ocrevus and contents of the pack

• Ocrevus is a solution ranging from clear to slightly opalescent, colourless to light brown.
• It is supplied as a concentrate for infusion solution.
• This medicinal product is available in packs containing 1 or 2 vials (10 mL concentrate vials). 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 further information about this medicinal product, contact the local representative of the Marketing Authorisation Holder:
België/Belgique/Belgien Lietuva
N.V. Roche S.A. UAB “Roche Lietuva”
Tél/Tel: +32 (0) 2 525 82 11 Tel: +370 5 2546799
България Luxembourg/Luxemburg
Рош България ЕООД (Voir/siehe Belgique/Belgien)
Тел: +359 2 474 5444
Česká republika Magyarország
Roche s. r. o. Roche (Magyarország) Kft.
Tel: +420 - 2 20382111 Tel: +36 - 1 279 4500
Danmark Malta
Roche Pharmaceuticals A/S (see Ireland)
Tlf: +45 - 36 39 99 99
Deutschland Nederland
Roche Pharma AG Roche Nederland B.V.
Tel: +49 (0) 7624 140 Tel: +31 (0) 348 438050
Eesti Norge
Roche Eesti OÜ Roche Norge AS
Tel: + 372 - 6 177 380 Tlf: +47 - 22 78 90 00
Ελλάδα Österreich
Roche (Hellas) A.E. Roche Austria GmbH
Τηλ: +30 210 61 66 100 Tel: +43 (0) 1 27739
España Polska
Roche Farma S.A. Roche Polska Sp.z o.o.
Tel: +34 - 91 324 81 00 Tel: +48 - 22 345 18 88
France Portugal
Roche Roche Farmacêutica Química, Lda
Tél: +33 (0) 1 47 61 40 00 Tel: +351 - 21 425 70 00
Hrvatska România
Roche d.o.o. Roche România S.R.L.
Tel: +385 1 4722 333 Tel: +40 21 206 47 01
Ireland Slovenija
Roche Products (Ireland) Ltd. Roche farmacevtska družba d.o.o.
Tel: +353 (0) 1 469 0700 Tel: +386 - 1 360 26 00
Ísland Slovenská republika
Roche Pharmaceuticals A/S Roche Slovensko, s.r.o.
c/o Icepharma hf Tel: +421 - 2 52638201
Sími: +354 540 8000
Italia Suomi/Finland
Roche S.p.A. Roche Oy
Tel: +39 - 039 2471 Puh/Tel: +358 (0) 10 554 500
Kύπρος Sverige
Roche (Hellas) A.E. Roche AB
Τηλ: +30 210 61 66 100 Tel: +46 (0) 8 726 1200
Latvija
Roche Latvija SIA
Tel: +371 - 6 7039831
Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu .
The following information is intended exclusively for healthcare professionals:
For further information, refer to the Summary of Product Characteristics.
To improve the traceability of biological medicinal products, the name and batch number of the administered product should be clearly recorded.
Dosage

• Initial dose

The initial dose of 600 mg is administered as two separate intravenous infusions: the first 300 mg infusion is followed 2 weeks later by a second 300 mg infusion.

• Subsequent doses

Subsequent doses of ocrelizumab are administered as a single 600 mg intravenous infusion every 6 months (see Table 1). The first subsequent 600 mg dose should be administered 6 months after the first infusion of the initial dose. A minimum interval of 5 months should be maintained between ocrelizumab doses.
Figure 1. Ocrevus dosing

Management of IRRs prior to infusion

• Treatment must be initiated and supervised by a healthcare professional experienced in the management of severe reactions, including infusion-related reactions (IRRs), hypersensitivity reactions, and/or anaphylactic reactions, with immediate access to appropriate medical support measures.
• Premedication for IRRs

Prior to each ocrelizumab infusion, the following two premedications should be administered to reduce the frequency and severity of IRRs:

• 100 mg methylprednisolone (or equivalent) administered intravenously approximately 30 minutes before each infusion;
• an antihistamine administered approximately 30–60 minutes before each infusion. Administration of an antipyretic (e.g., paracetamol) may also be considered approximately 30–60 minutes before each infusion.
• Hypotension may occur during infusions as a symptom of IRR. Therefore, consideration should be given to withholding antihypertensive treatments in the 12 hours prior to each Ocrevus infusion and during the infusion itself. Patients with a history of congestive heart failure (New York Heart Association class III and IV) have not been studied.

Instructions for dilution

• The product must be prepared by a healthcare professional using aseptic technique. Do not shake the vial. Use sterile needles and syringes to prepare the diluted infusion solution.
• The product is for single use only.
• The concentrate may contain small translucent and/or reflective particles associated with increased opalescence. Do not use the concentrate if there are changes in colour or if foreign particles are present.
• The medicine must be diluted before administration. Intravenous infusion solutions are prepared by diluting the concentrate in an infusion bag containing isotonic sodium chloride 9 mg/mL (0.9%) solution for injection (300 mg/250 mL or 600 mg/500 mL), to achieve a final ocrelizumab concentration of approximately 1.2 mg/mL.
• The diluted infusion solution must be administered using an infusion set with an in-line filter of 0.2 or 0.22 micron.
• Prior to starting the intravenous infusion, the contents of the infusion bag should be at room temperature to avoid infusion reactions due to administration of cold solution.

Method of administration

• After dilution, treatment is administered as an intravenous infusion through a dedicated line.
• Infusions must not be administered as rapid intravenous injection or intravenous bolus.

Table 1: Dosage

Management of IRRs during and after infusion
Patients must be monitored during the infusion and for at least one hour after completion of the infusion.

During infusion

• Modification of infusion in case of IRR

In case of IRR during any infusion, refer to the following modification guidelines.
Potentially life-threatening IRR
If signs of a potentially life-threatening or disabling IRR are observed during an infusion, such as acute hypersensitivity or acute respiratory distress syndrome, the infusion must be stopped immediately and the patient must receive appropriate treatment. In these patients, the infusion must be permanently discontinued (see section 4.3).

Severe IRR
If a patient experiences a severe IRR (e.g., dyspnea) or a combination of symptoms including flushing, fever, and sore throat, the infusion must be stopped immediately and symptomatic treatment administered. The infusion may be resumed only after all symptoms have resolved. The initial infusion rate must be half the rate used at the time the reaction occurred. For subsequent infusions, no modification of the infusion rate is required unless the patient experiences an IRR.

Mild to moderate IRR
If a patient experiences a mild to moderate IRR (e.g., headache), the infusion rate must be reduced to half the rate used at the time the event occurred. This reduced rate must be maintained for at least 30 minutes. If tolerated, the infusion rate may then be increased according to the patient's initial infusion rate. For subsequent infusions, no modification of the infusion is required unless the patient experiences an IRR.

• Patients who develop severe pulmonary symptoms, such as bronchospasm or asthma exacerbation, must immediately and permanently discontinue the infusion. After administration of symptomatic treatment, the patient should be monitored until pulmonary symptoms resolve, as an initial improvement in clinical symptoms may be followed by worsening.
• Clinically, hypersensitivity may be indistinguishable from an IRR. In case of suspected hypersensitivity reaction during infusion, the infusion must be immediately and permanently discontinued.

After infusion

• Patients must be monitored for at least one hour after completion of the infusion to detect any symptoms of an IRR.
• Physicians must inform patients about the possibility that an IRR may occur within 24 hours following the infusion.

Shelf life
Intact vial
2 years

Diluted solution for intravenous infusion

• Chemical and physical in-use stability has been demonstrated for 24 hours at 2–8 °C, followed by 8 hours at room temperature.
• From a microbiological standpoint, the prepared infusion solution should be used immediately. If not used immediately, the duration and conditions of storage prior to use are the responsibility of the user and normally should not exceed 24 hours at 2–8 °C, followed by 8 hours at room temperature, unless the dilution is carried out under controlled and validated aseptic conditions.
• If intravenous infusion cannot be performed on the same day, any remaining solution must be discarded.

Patient information leaflet

Ocrevus 920 mg solution for injection

ocrelizumab
Please read this leaflet carefully before you are given this medicine because
it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor or nurse. See section 4.
• This medicine has been prescribed for you only. Do not pass it on to other people, even if their symptoms are the same as yours, because it may be harmful.

Contents of this leaflet

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

1. What Ocrevus is and what it is used for

What Ocrevus is
Ocrevus contains the active substance "ocrelizumab". It is a type of protein called a "monoclonal antibody". Antibodies work by binding to specific targets in the 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, particularly the nerves in the brain and spinal cord. In MS, the immune system (the body's defence system) does not work properly and attacks the protective layer (the so-called myelin sheath) that surrounds nerve cells, causing inflammation. Damage to the myelin sheath prevents nerves from functioning properly.
The symptoms of MS depend on which part of the central nervous system is affected and may include problems with walking and balance, weakness, numbness, double and blurred vision, poor coordination, and bladder problems.

• In relapsing forms of MS, patients experience repeated attacks of symptoms (relapses). Symptoms may appear suddenly within a few hours or gradually over several days. Symptoms fade or improve between relapses, but damage can accumulate and lead to permanent disability.
• In primary progressive MS, symptoms generally continue to worsen from the beginning of the disease.

How Ocrevus works
Ocrevus binds to specific B cells, a type of white blood cell that is part of the immune system and plays a role in MS. Ocrevus targets and eliminates these specific B cells. This reduces inflammation and attacks on the myelin sheath, decreases the likelihood of relapses, and slows disease progression.

• In relapsing forms of MS (RMS), Ocrevus significantly reduces the number of attacks (relapses) and significantly slows disease progression. Ocrevus also significantly increases the likelihood that a patient will show no evidence of disease activity (brain lesions, relapses, and worsening disability).
• In primary progressive MS (PPMS), Ocrevus helps slow disease progression and reduce worsening walking speed.

2. What you need to know before you are given Ocrevus

Do not receive Ocrevus:

• if you are allergic to ocrelizumab or to any of the other ingredients of this medicine (listed in section 6).
• if you currently have an infection.
• if you have been diagnosed with severe immune system disorders.
• if you have a malignant tumour.

If you have any doubts, consult your doctor before receiving Ocrevus.
Warnings and precautions
Talk to your doctor before using Ocrevus if any of the following apply to you. Your
doctor may decide to delay administration of Ocrevus treatment, or may
determine that you should not receive Ocrevus if:

• You have an infection. Your doctor will wait until the infection has resolved before administering Ocrevus.
• You have previously had hepatitis B or are a carrier of the hepatitis B virus. Medicines such as Ocrevus can cause reactivation of the hepatitis B virus. Before treating you with Ocrevus, your doctor will check whether you are at risk of developing hepatitis B infection. Patients who have had hepatitis B or are carriers of the hepatitis B virus will undergo regular blood tests and be monitored by the doctor for signs of hepatitis B infection.
• You have a malignant tumour or have had one in the past. Your doctor may decide to delay treatment with Ocrevus. Effect on the immune system:
• Diseases affecting the immune system: if you have another disease that affects the immune system. It may not be possible to administer Ocrevus to you.
• Medicines affecting the immune system: if you have previously taken, are currently taking, or plan 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 treatment with Ocrevus or may ask you to stop taking these medicines before starting Ocrevus treatment. For further information, see “Other medicines and Ocrevus” below.

Infusion-related reactions

• Infusion-related reactions are the most common side effect of Ocrevus when administered as a subcutaneous injection (under the skin).
• Inform your nurse or doctor immediately if you experience an infusion-related reaction (see section 4 for a list of infusion-related reactions). Infusion-related reactions may occur during the injection or up to 24 hours afterwards.
• To reduce the risk of an infusion-related reaction, your doctor will administer certain medicines before each Ocrevus injection (see section 3) and will closely monitor you during the infusion and for at least one hour after the initial infusion.

Infections

• Inform your doctor before receiving Ocrevus if you suspect you have an infection. Your doctor will wait until the infection has resolved before administering Ocrevus.
• You may be more prone to infections while receiving Ocrevus. This is because the immune cells targeted by Ocrevus also help fight infections.
• Before starting Ocrevus treatment and before subsequent injections, your doctor may ask you to have a blood test to check your immune system. If you have serious immune system problems, you may be more likely to develop infections.
• If you are being treated with Ocrevus for primary progressive multiple sclerosis and have difficulty swallowing, Ocrevus may increase your risk of severe pneumonia.
• Inform your doctor or nurse immediately if, during or after treatment with Ocrevus, you notice any signs of infection such as:
  • fever or chills
  • persistent cough
  • herpes (e.g. cold sores, shingles, or genital herpes).
• Inform your doctor or nurse immediately if you think your MS is worsening or if you notice new symptoms. There is a very rare but potentially fatal brain infection called “progressive multifocal leukoencephalopathy” (PML) that can cause symptoms similar to those of MS. PML can occur in patients treated with Ocrevus.
• Inform your partner or caregiver about your Ocrevus treatment, as they may notice PML symptoms that you do not, such as memory lapses, difficulty thinking, difficulty walking, loss of vision, or changes in walking pattern, which your doctor may need to investigate.

Vaccinations

• Inform your doctor if you have recently received any vaccine or if you are likely to receive a vaccine in the near future.
• During treatment with Ocrevus, you must not receive live or live-attenuated vaccines (e.g. the BCG vaccine for tuberculosis or vaccines against yellow fever).
• Your doctor may recommend that you receive a seasonal influenza vaccine.
• Your doctor will check whether you need any vaccinations before starting Ocrevus treatment. Any vaccinations should be given at least 6 weeks before starting Ocrevus treatment.

Children and adolescents
Ocrevus is not recommended for the treatment of children and adolescents under 18 years of age.
This is because it has not yet been studied in this age group.
Other medicines and Ocrevus
Inform your doctor if you are taking, have recently taken, or might take any other
medicines.
In particular, inform your doctor:

• if you have previously taken, are currently taking, or plan to take medicines that affect the immune system—such as chemotherapy, immunosuppressants, or other medicines used to treat MS. The effect of these medicines on the immune system, when administered with Ocrevus, may be too strong. Your doctor may decide to delay treatment with Ocrevus or may ask you to stop taking these medicines before starting Ocrevus treatment.

If any of the above situations apply to you (or if you are unsure), speak with your doctor before receiving
Ocrevus.
Pregnancy

• If you are pregnant, think you may be pregnant, or are planning to become pregnant, consult your doctor before taking this medicine. This is because Ocrevus can cross the placenta and may affect the unborn child.
• Do not use Ocrevus during pregnancy unless you have discussed it with your doctor first. Your doctor will assess the benefits of Ocrevus treatment against the potential risks to your unborn child.
• Talk to your doctor before vaccinating your baby.

Contraception in women
Women of childbearing potential should use contraceptive measures:

• during treatment with Ocrevus and
• for 4 months after the last dose of Ocrevus.

Breast-feeding
Ocrevus may be used during breast-feeding. If you are given Ocrevus,
discuss with your doctor the best feeding options for your baby.
Driving and using machines
It is not known whether Ocrevus affects your ability to drive or use tools or machines.
Your doctor will advise 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 (23 mg) of sodium per dose, i.e. essentially
“sodium-free”.

3. How Ocrevus is administered

Medicines you must take before receiving Ocrevus
Before receiving Ocrevus, you will be given other medicines to prevent or reduce possible side effects, such as infusion-related reactions (see sections 2 and 4 for information on infusion-related reactions).
Before each infusion, you will receive a corticosteroid and an antihistamine, and you may also receive medicines to reduce fever.

What dose and how often you will receive Ocrevus
You will be given a total dose of 920 mg of Ocrevus every 6 months.

How Ocrevus is administered

• Ocrevus will be administered by a doctor or nurse. It will be given as an injection under the skin (subcutaneous injection).
• The injections will be given in the abdomen over approximately 10 minutes.
• The doctor or nurse will ensure that each injection is administered in the abdominal area, in areas where the skin is not red, bruised, tender, or hard, and avoiding areas with moles or scars.
• You will be closely monitored during the administration of Ocrevus and for at least 1 hour after the initial infusion, in case you experience side effects such as infusion-related reactions. If you experience an infusion-related reaction, the infusion may be temporarily paused or permanently discontinued depending on its severity (see sections 2 and 4 for information on infusion-related reactions).

If you miss an Ocrevus infusion

• If you miss an Ocrevus infusion, contact your doctor to schedule the missed dose as soon as possible. Do not wait until your next scheduled infusion.
• To get the full benefit from Ocrevus, it is important that you receive each infusion at the correct time.

If you stop treatment with Ocrevus

• It is important that you continue treatment for as long as you and your doctor consider it beneficial.
• Some side effects may be related to low levels of B-cells. After stopping treatment with Ocrevus, side effects may still occur until B-cell levels return to normal. Your blood B-cells will gradually return to normal levels. This may take from six months to two and a half years, or in rare cases up to several years.
• Before starting any other medicine, inform your doctor about the date of your last dose of Ocrevus.

If you have any questions about the use of this medicine, consult your doctor.

4. Possible side effects

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 administered as subcutaneous injection (very common: may affect more than 1 in 10 people). In most cases, these reactions are mild or moderate in severity, but some serious reactions have occurred with Ocrevus administered as intravenous infusion (intravenous infusion).
• Tell your doctor or nurse immediately if you experience any signs or symptoms of an infusion-related reaction during or up to 24 hours after the infusion. Symptoms include, but are not limited to:
  • itching of the skin
  • rash
  • hives
  • skin redness
  • pain or swelling at the injection site
  • throat irritation or pain
  • shortness of breath
  • swelling of the throat
  • flushing
  • low blood pressure
  • fever
  • feeling of fatigue
  • headache
  • dizziness
  • feeling unwell (nausea)
  • rapid heartbeat.
• If you experience an infusion-related reaction, you will be given medicines to treat it, and it may be necessary to stop the infusion. If the infusion-related reaction is life-threatening, your doctor will permanently discontinue treatment with Ocrevus.

Infections

• You may be more likely to develop infections while taking Ocrevus. The following infections have been observed in patients treated with Ocrevus for MS:
  • Very common (may affect more than 1 in 10 people)
  • sore throat and runny nose (upper respiratory tract inflammation)
  • influenza.
  • Common (may affect up to 1 in 10 people)
  • sinus infection
  • bronchitis (inflammation of the bronchi)
  • herpes infections (cold sores or shingles)
  • stomach and intestinal infection (gastroenteritis)
  • respiratory tract infection
  • viral infection
  • skin infection (cellulitis).

Some of these infections may be serious.

• Tell your doctor or nurse immediately if you notice any signs of infection, such as:
  • fever or chills
  • persistent cough
  • herpes (for example, on the lips, shingles, or genital herpes).

Other side effects:

Very common (may affect more than 1 in 10 people)

• reduction in specific proteins in the blood (immunoglobulins) that help protect against infections.

Common (may affect up to 1 in 10 people)

• eye discharge with itching, redness, and swelling (conjunctivitis)
• cough
• buildup of thick mucus in the nose, throat, or chest
• low levels of a type of white blood cells (neutropenia).

Not known (frequency cannot be estimated from the available data)

• delayed-onset reduction in white blood cells.

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, talk to your doctor or nurse. You can also report side effects directly via the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Ocrevus

Ocrevus will be stored by healthcare professionals at the hospital or clinic under the following conditions:

• This medicinal product should be kept out of the sight and reach of children.
• This medicinal product must not be used after the expiry date stated on the carton and on the label of the vial after "Exp.". The expiry date refers to the last day of that month.
• This medicinal product must be stored in a refrigerator (2 °C - 8 °C). It must not be frozen. Vials should be kept in the outer carton to protect them from light and must not be shaken.

Do not dispose of any medicinal product via wastewater. This will help protect the environment.

6. Package Contents and Other Information

What Ocrevus Contains

• The active substance is ocrelizumab. Each vial contains 920 mg of ocrelizumab in 23 mL (40 mg/mL).
• The other components are recombinant human hyaluronidase (rHuPH20), sodium acetate trihydrate (see section 2 “Ocrevus contains sodium”), glacial acetic acid, α,α-trehalose dihydrate, polysorbate 20, L-methionine, and water for injections.

Description of the Appearance of Ocrevus and Contents of the Package

• Ocrevus is a solution ranging from clear to slightly opalescent, colourless to light brown.
• It is supplied as an injectable solution.
• Ocrevus is available in packs containing 1 glass vial.

Marketing Authorization 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 further information about this medicinal product, please contact the local representative of the marketing authorization holder:

België/Belgique/Belgien Lietuva
N.V. Roche S.A. UAB “Roche Lietuva”
Tél/Tel: +32 (0) 2 525 82 11 Tel: +370 5 2546799

България Luxembourg/Luxemburg
Рош България ЕООД (See/siehe Belgique/Belgien)
Тел: +359 2 474 5444

Česká republika Magyarország
Roche s. r. o. Roche (Magyarország) Kft.
Tel: +420 - 2 20382111 Tel: +36 - 1 279 4500

Danmark Malta
Roche Pharmaceuticals A/S (see Ireland)
Tlf: +45 - 36 39 99 99

Deutschland Nederland
Roche Pharma AG Roche Nederland B.V.
Tel: +49 (0) 7624 140 Tel: +31 (0) 348 438050

Eesti Norge
Roche Eesti OÜ Roche Norge AS
Tel: + 372 - 6 177 380 Tlf: +47 - 22 78 90 00

Ελλάδα Österreich
Roche (Hellas) A.E. Roche Austria GmbH
Τηλ: +30 210 61 66 100 Tel: +43 (0) 1 27739

España Polska
Roche Farma S.A. Roche Polska Sp.z o.o.
Tel: +34 - 91 324 81 00 Tel: +48 - 22 345 18 88

France Portugal
Roche Roche Farmacêutica Química, Lda
Tél: +33 (0) 1 47 61 40 00 Tel: +351 - 21 425 70 00

Hrvatska România
Roche d.o.o. Roche România S.R.L.
Tel: +385 1 4722 333 Tel: +40 21 206 47 01

Ireland Slovenija
Roche Products (Ireland) Ltd. Roche farmacevtska družba d.o.o.
Tel: +353 (0) 1 469 0700 Tel: +386 - 1 360 26 00

Ísland Slovenská republika
Roche Pharmaceuticals A/S Roche Slovensko, s.r.o.
c/o Icepharma hf Tel: +421 - 2 52638201
Sími: +354 540 8000

Italia Suomi/Finland
Roche S.p.A. Roche Oy
Tel: +39 - 039 2471 Puh/Tel: +358 (0) 10 554 500

Kύπρος Sverige
Roche (Hellas) A.E. Roche AB
Τηλ: +30 210 61 66 100 Tel: +46 (0) 8 726 1200

Latvija
Roche Latvija SIA
Tel: +371 - 6 7039831

Other Sources of Information
More detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu.

The following information is intended exclusively for healthcare professionals:
For more information, refer to the Summary of Product Characteristics.
To improve traceability of biological medicinal products, the name and batch number of the administered product must be clearly documented.
To avoid administration errors, it is important to check the medicine labels to ensure that the correct formulation (intravenous or subcutaneous) is administered to the patient as prescribed.
Before administration, the medicinal product should be inspected visually for particulate matter and discoloration.
This medicinal product is for single use only and must be prepared by a healthcare professional using aseptic technique.
No incompatibilities have been observed between this medicinal product and polypropylene (PP), polycarbonate (PC), polyethylene (PE), polyvinyl chloride (PVC), polyurethane (PUR), or stainless steel.

Syringe Preparation

• Before use, remove the vial from the refrigerator to allow the solution to reach room temperature.
• Withdraw the entire contents of Ocrevus injectable solution from the vial using a syringe and a transfer needle (a 21G needle is recommended).
• Remove the transfer needle and connect a subcutaneous infusion set (e.g. with wings/butterfly) containing a 24–26G needle for injection. Use a subcutaneous infusion set with a residual volume of not more than 0.8 mL for administration.
• Prime the subcutaneous infusion line with the drug solution to remove air from the line, stopping before the liquid reaches the needle.
• Ensure that the syringe contains exactly 23 mL of medicinal product solution after insertion and expulsion of any excess volume from the syringe.
• Administer immediately to avoid needle clogging. Do not store the prepared syringe connected to a previously filled subcutaneous infusion set.

If the dose is not administered immediately, refer to the section below “Storage of the Syringe”.

Storage of the Syringe

• If the dose is not to be administered immediately, use aseptic technique to withdraw the entire contents of Ocrevus injectable solution from the vial into a syringe, ensuring that the dose volume (23 mL) and the priming volume of the subcutaneous infusion set are accounted for. Replace the transfer needle with a syringe cap. Do not connect a subcutaneous infusion set during storage.
• Chemical and physical in-use stability has been demonstrated for 30 days at a temperature of 2 °C to 8 °C, and additionally for 8 hours without light protection at ≤30 °C.
• From a microbiological standpoint, the product should be used immediately after transfer from the vial to the syringe. If not used immediately, the duration and conditions of storage prior to use are the responsibility of the user and normally should not exceed 24 hours at a temperature of 2 °C to 8 °C, unless the preparation was carried out under controlled and validated aseptic conditions.
• If the syringe has been stored in the refrigerator, allow it to reach room temperature before administration.

Method of Administration
Ocrevus 920 mg injectable solution is not intended for intravenous administration and must always be administered as a subcutaneous injection by a healthcare professional.
Patients may start treatment with ocrelizumab administered either intravenously or subcutaneously. Patients currently receiving intravenous ocrelizumab may continue with intravenous ocrelizumab or switch to Ocrevus 920 mg injectable solution.
Before administration, the medicinal product must be removed from the refrigerator to allow the solution to reach room temperature. For instructions on use and handling of the medicinal product before administration, refer to section 6.6.
The 920 mg dose must be administered via subcutaneous injection into the abdomen over approximately 10 minutes. Use of a subcutaneous infusion set (e.g. with wings/butterfly) is recommended. Do not administer to the patient the residual volume retained in the subcutaneous infusion set.
The injection site should be the abdomen, excluding the area within 5 cm around the navel. Injections must never be administered into areas where the skin shows signs of redness, bruising, tenderness, or hardness, or where moles or scars are present.
Ocrevus injectable solution must always be administered by a healthcare professional. After the first dose, patients should be monitored for at least one hour with access to appropriate medical equipment to manage severe reactions such as IRs. For subsequent doses, the need for post-injection monitoring should be determined at the discretion of the treating physician (see section 4.4).