Posology : מינונים

2     DOSAGE AND ADMINISTRATION
2.1 Assessments Prior to First Dose of OCREVUS
Hepatitis B Virus Screening
Prior to initiating OCREVUS, perform Hepatitis B virus (HBV) screening. OCREVUS is contraindicated in patients with active HBV confirmed by positive results for HBsAg and anti-HBV tests. For patients who are negative for surface antigen [HBsAg] and positive for HB core antibody [HBcAb+] or are carriers of HBV [HBsAg+], consult liver disease experts before starting and during treatment [see Warnings and Precautions (5.2)].
Serum Immunoglobulins
Prior to initiating OCREVUS, perform testing for quantitative serum immunoglobulins [see Warnings and Precautions (5.4)]. For patients with low serum immunoglobulins, consult immunology experts before initiating treatment with OCREVUS.


Vaccinations
Because vaccination with live-attenuated or live vaccines is not recommended during treatment and after discontinuation until B-cell repletion, administer all immunizations according to immunization guidelines at least 4 weeks prior to initiation of OCREVUS for live or live-attenuated vaccines and, whenever possible, at least 2 weeks prior to initiation of OCREVUS for non-live vaccines [see Warnings and Precautions (5.2) and Clinical Pharmacology (12.2)].
2.2 Preparation Before Every Infusion
Infection Assessment
Prior to every infusion of OCREVUS, determine whether there is an active infection. In case of active infection, delay infusion of OCREVUS until the infection resolves [see Warnings and Precautions (5.2)].
Recommended Premedication
Pre-medicate with 100 mg of methylprednisolone (or an equivalent corticosteroid) administered intravenously approximately 30 minutes prior to each OCREVUS infusion to reduce the frequency and severity of infusion reactions [see Warnings and Precautions (5.1)]. Pre-medicate with an antihistamine (e.g., diphenhydramine) approximately 30-60 minutes prior to each OCREVUS infusion to further reduce the frequency and severity of infusion reactions.
The addition of an antipyretic (e.g., acetaminophen) may also be considered.
2.3 Recommended Dosage and Dose Administration
Administer OCREVUS under the close supervision of an experienced healthcare professional with access to appropriate medical support to manage severe reactions such as serious infusion reactions.
•   Initial dose: 300 mg intravenous infusion, followed two weeks later by a second 300 mg intravenous infusion.
•   Subsequent doses: single 600 mg intravenous infusion every 6 months.
•   Observe the patient for at least one hour after the completion of the infusion [see Warnings and Precautions (5.1)].


Table 1         Recommended Dose, Infusion Rate, and Infusion Duration for RMS and PPMS 
Amount and Volume1                  Infusion Rate and Duration3

300 mg            • Start at 30 mL per hour
Infusion 1
Initial Dose                              in 250 mL           • Increase by 30 mL per hour every 30 minutes
(two infusions)
Infusion 2               300 mg            • Maximum: 180 mL per hour (2 weeks later)          in 250 mL           • Duration: 2.5 hours or longer • Start at 40 mL per hour
Option 1
• Increase by 40 mL per hour every 30
Infusion of              600 mg              minutes in 500 mL approximately                                • Maximum: 200 mL per hour 3.5 hours duration 3                                • Duration: 3.5 hours or longer 
OR
Subsequent          Option 2
Doses          (If no prior                                • Start at 100 mL per hour for the first 15 (one infusion)        serious                                    minutes every 6 months)2      infusion                                  • Increase to 200 mL per hour for the next 15 reaction with                                  minutes any previous               600 mg
OCREVUS                                     • Increase to 250 mL per hour for the next 30 infusion)4             in 500 mL             minutes
• Increase to 300 mL per hour for the
Infusion of                                  remaining 60 minutes approximately
2 hours                                    Duration: 2 hours or longer duration 3
1
Solutions of OCREVUS for intravenous infusion are prepared by dilution of the drug product into an infusion bag containing 0.9% Sodium Chloride Injection, to a final drug concentration of approximately 1.2 mg/mL.
2
Administer the first Subsequent Dose 6 months after Infusion 1 of the Initial Dose.
3
Infusion time may take longer if the infusion is interrupted or slowed [see Dosage and Administration (2.5)].
4
[see Adverse Reactions (6.1) and Clinical Studies (14.3)].

2.4 Delayed or Missed Doses
If a planned infusion of OCREVUS is missed, administer OCREVUS as soon as possible; do not wait until the next scheduled dose. Reset the dose schedule to administer the next sequential dose 6 months after the missed dose is administered. Doses of OCREVUS must be separated by at least 5 months [see Dosage and Administration (2.3)].
2.5 Dose Modifications Because of Infusion Reactions
Dose modifications in response to infusion reactions depends on the severity.
Life-threatening Infusion Reactions
Immediately stop and permanently discontinue OCREVUS if there are signs of a life-threatening or disabling infusion reaction [see Warnings and Precautions (5.1)]. Provide appropriate supportive treatment.


Severe Infusion Reactions
Immediately interrupt the infusion and administer appropriate supportive treatment, as necessary [see Warnings and Precautions (5.1)]. Restart the infusion only after all symptoms have resolved. When restarting, begin at half of the infusion rate at the time of onset of the infusion reaction. If this rate is tolerated, increase the rate as described in Table 1 [see Dosage and Administration (2.3)]. This change in rate will increase the total duration of the infusion but not the total dose.
Mild to Moderate Infusion Reactions
Reduce the infusion rate to half the rate at the onset of the infusion reaction and maintain the reduced rate for at least 30 minutes [see Warnings and Precautions (5.1)]. If this rate is tolerated, increase the rate as described in Table 1 [see Dosage and Administration (2.3)]. This change in rate will increase the total duration of the infusion but not the total dose.
2.6 Preparation and Storage of the Dilute Solution for Infusion
Preparation
OCREVUS must be prepared by a healthcare professional using aseptic technique. A sterile needle and syringe should be used to prepare the diluted infusion solution.
Visually inspect for particulate matter and discoloration prior to administration. Do not use the solution if discolored or if the solution contains discrete foreign particulate matter. Do not shake.
Withdraw intended dose and further dilute into an infusion bag containing 0.9% Sodium Chloride Injection, to a final drug concentration of approximately 1.2 mg/mL.
•   Withdraw 10 mL (300 mg) of OCREVUS and inject into 250 mL
•   Withdraw 20 mL (600 mg) of OCREVUS and inject into 500 mL
Do not use other diluents to dilute OCREVUS since their use has not been tested. The product contains no preservative and is intended for single use only.
Storage of Infusion Solution
Prior to the start of the intravenous infusion, the content of the infusion bag should be at room temperature.
Use the prepared infusion solution immediately. If not used immediately, chemical and physical in use stability has been demonstrated for 24 hours (in the refrigerator) at 2°C–8°C and 8 hours at room temperature (up to 25°C), which includes infusion time. In the event an intravenous infusion cannot be completed the same day, discard the remaining solution.
From 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°C to 8°C and 8 hours at room temperature, unless dilution is undertaken in controlled and validated aseptic conditions.
No incompatibilities between OCREVUS and polyvinyl chloride (PVC) or polyolefin (PO) bags and intravenous (IV) administration sets have been observed.
Administration
Administer the diluted infusion solution through a dedicated line using an infusion set with a 0.2 or 0.22 micron in-line filter.