Source: European Medicines Agency (EU) Revision Year: 2020 Publisher: Roche Registration GmbH, Emil-Barell-Strasse 1, 79639, Grenzach-Wyhlen, Germany
Ocrevus is indicated for the treatment of adult patients with relapsing forms of multiple sclerosis (RMS) with active disease defined by clinical or imaging features (see section 5.1).
Ocrevus is indicated for the treatment of adult patients with early primary progressive multiple sclerosis (PPMS) in terms of disease duration and level of disability, and with imaging features characteristic of inflammatory activity (see section 5.1).
Ocrevus treatment should be initiated and supervised by specialised physicians experienced in the diagnosis and treatment of neurological conditions and who have access to appropriate medical support to manage severe reactions such as serious infusion-related reactions (IRRs).
The following two premedications must be administered prior to each Ocrevus infusion to reduce the frequency and severity of IRRs (see Infusion-related reactions in section 4.4 for additional steps to reduce IRRs):
100 mg intravenous methylprednisolone (or an equivalent) approximately 30 minutes prior to each Ocrevus infusion;
antihistamine approximately 30-60 minutes prior to each Ocrevus infusion;
In addition, premedication with an antipyretic (e.g paracetamol) may also be considered approximately 30-60 minutes prior to each Ocrevus infusion.
Initial Dose: 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 (Table 1).
Subsequent Doses: Subsequent doses of Ocrevus thereafter are administered as a single 600 mg intravenous infusion every 6 months (Table 1). The first subsequent dose of 600 mg 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 Ocrevus.
In case of IRRs during any infusion, see the following adjustments. Additional information on IRRs can be found in section 4.4.
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. Ocrevus must be permanently discontinued in these patients (see section 4.3).
If a patient experiences a severe IRR (such as dyspnea) 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.
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.
The above examples of dose interruption and slowing (for mild/moderate and severe IRRs) will result in a change in the infusion rate and increase the total duration of the infusion, but not the total dose. No dose reductions of Ocrevus are recommended.
If an infusion of Ocrevus is missed, it should be administered as soon as possible; do not wait until the next planned dose. The treatment interval of 6 months (with a minimum of 5 months) for Ocrevus should be maintained between doses (see Table 1).
Based on the limited data available (see section 5.1 and section 5.2), no posology adjustment is needed in patients over 55 years of age. Patients enrolled in the ongoing clinical trials continue to be dosed with 600 mg ocrelizumab every six months after they become 55 and older.
The safety and efficacy of Ocrevus in patients with renal impairment has not been formally studied. Patients with mild renal impairment were included in clinical trials. There is no experience in patients with moderate and severe renal impairment. Ocrevus is a monoclonal antibody and cleared via catabolism (i.e. breakdown into peptides and amino acids), and a change in dose is not expected to be required for patients with renal impairment (see section 5.2).
The safety and efficacy of Ocrevus in patients with hepatic impairment has not been formally studied. Patients with mild hepatic impairment were included in clinical trials. There is no experience in patients with moderate and severe hepatic impairment. Ocrevus is a monoclonal antibody and cleared via catabolism (rather than hepatic metabolism), and a change in dose is not expected to be required for patients with hepatic impairment (see section 5.2).
The safety and efficacy of Ocrevus in children and adolescents aged 0 to 18 years has not yet been established. No data are available.
After dilution, Ocrevus is administered as an intravenous infusion through a dedicated line. Ocrevus infusions should not be administered as an intravenous push or bolus.
Table 1. Dose and Schedule of Ocrevus:
| Amount of Ocrevus to be administered | Infusion instructions | ||
|---|---|---|---|
| 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 |
| Infusion 2 (2 weeks later) | 300 mg in 250 mL | 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. | |||
| Subsequent Doses (600 mg) once every 6 months | Single infusion | 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 | |||
Solutions of Ocrevus for intravenous infusion are prepared by dilution of the medicinal product into an infusion bag containing 0.9% sodium chloride, to a final concentration of approximately 1.2 mg/mL.For instructions on dilution of the medicinal product before administration see section 6.6.
Patients should be monitored during the infusion and for at least one hour after the completion of the infusion (see section 4.4).
There is limited clinical trial experience with doses higher than the approved intravenous dose of Ocrevus. The highest dose tested to date in MS patients is 2000 mg, administered as two 1000 mg intravenous infusions separated by 2 weeks (Phase II dose finding study in RRMS). The adverse drug reactions were consistent with the safety profile for Ocrevus in the pivotal clinical studies.
Please refer to section 4.8 for information about the Systemic Inflammatory Response Syndrome (SIRS) that occurred in a patient treated with Ocrevus 2000 mg.
There is no specific antidote in the event of an overdose; interrupt the infusion immediately and observe the patient for IRRs (see section 4.4).
Unopened vial: 24 months.
Diluted solution for intravenous infusion: Chemical and physical in-use stability has been demonstrated for 24 hours at 2-8°C and subsequently for 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 for 8 hours at room temperature, unless dilution is 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.
Store in a refrigerator (2°C–8°C).
Do not freeze.
Keep the vials in the outer carton in order to protect from light.
For storage conditions after dilution of the medicinal product, see section 6.3.
10 mL concentrate in a glass vial. Pack size of 1 or 2 vials. Not all pack sizes may be marketed.
Ocrevus should be prepared by a healthcare professional using aseptic technique. Do not shake the vial.
The product is intended for single use only.
Do not use the solution if discoloured or if the solution contains foreign particulate matter (see section 3 for a description of the solution).
Ocrevus medicinal product must be diluted before administration. Solutions of Ocrevus for intravenous administration are prepared by dilution of the drug product into an infusion bag containing isotonic 0.9% sodium chloride (300 mg/250 mL or 600 mg/500 mL), to a final drug concentration of approximately 1.2 mg/mL.
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.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
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