OCREVUS

OCREVUS- ocrelizumab injection
Genentech, Inc.

1 INDICATIONS AND USAGE

OCREVUS is indicated for the treatment of:

• Relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults
• Primary progressive MS, in adults

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 ImmunoglobulinsPrior 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 Volume *	Infusion Rate and Duration †
* 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. † Infusion time may take longer if the infusion is interrupted or slowed [see Dosage and Administration (2.5)]. ‡ Administer the first Subsequent Dose 6 months after Infusion 1 of the Initial Dose. § [see Adverse Reactions (6.1) and Clinical Studies (14.3)].
Initial Dose (two infusions)	Infusion 1	300 mg in 250 mL	Start at 30 mL per hour Increase by 30 mL per hour every 30 minutes Maximum: 180 mL per hour Duration: 2.5 hours or longer
	Infusion 2(2 weeks later)	300 mg in 250 mL
Subsequent Doses (one infusion)every 6 months)‡	Option 1 Infusion of approximately 3.5 hours duration †	600 mg in 500 mL	Start at 40 mL per hour Increase by 40 mL per hour every 30 minutes Maximum: 200 mL per hour Duration: 3.5 hours or longer
	OR
	Option 2(If no prior serious infusion reaction with any previous OCREVUS infusion)§Infusion of approximately 2 hours duration †	600 mg in 500 mL	Start at 100 mL per hour for the first 15 minutes Increase to 200 mL per hour for the next 15 minutes Increase to 250 mL per hour for the next 30 minutes Increase to 300 mL per hour for the remaining 60 minutesDuration: 2 hours or longer

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 [see Dosage and Administration (2.2)]. If this rate is tolerated, increase the rate as described in Table 1. 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. This change in rate will increase the total duration of the infusion but not the total dose.