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Ocrelizumab- Ocrevus™

Ocrelizumab- OCREVUS™ injection
[ Usual Diluents ] [ Standard Dilution ] [ Storage and Stability ]
DESCRIPTION CLINICAL PHARMACOLOGY INDICATIONS AND USAGE
CONTRAINDICATIONS PRECAUTIONS ADVERSE REACTIONS
DOSAGE AND ADMINISTRATION HOW SUPPLIED WARNINGS
PRESCRIBING HIGHLIGHTS:  Please see package insert for additional information and possible updates to ensure safe and effective use of this medication. The authors make no claims of the accuracy of the information contained herein; and these suggested doses are not a substitute for clinical judgment. Neither GlobalRPh Inc. nor any other party involved in the preparation of this program shall be liable for any special, consequential, or exemplary damages resulting in whole or part from any user's use of or reliance upon this material. Please read the disclaimer carefully BEFORE accessing or using this site. BY ACCESSING OR USING THIS SITE, YOU AGREE TO BE BOUND BY THE TERMS AND CONDITIONS SET FORTH IN THE DISCLAIMER.  

Drug UPDATES:   [Drug information  /  PDF]  
PACKAGE INSERT -Dosing:  Click (+) next to Dosage and Administration section (drug info link)

 

Usual Diluents top of page

NS

Standard Dilutions   [Amount of drug] [Infusion volume] [Infusion rate] top of page

[300mg]  [250 ml]  [See table below]
[600mg]  [500 ml]  [See table below]

Table 1 Recommended Dose, Infusion Rate, and Infusion Duration for RMS and PPMS
Amount and Volume* Infusion Rate and Duration†
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)		 One infusion every 6 months‡ 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
*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.  

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.

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.

WARNINGS  top of page

See warnings and precautions below.

DESCRIPTION  top of page

Description:
Ocrelizumab is a recombinant humanized monoclonal antibody directed against CD20-expressing B-cells. Ocrelizumab is a glycosylated immunoglobulin G1 (IgG1) with a molecular mass of approximately 145 kDa.

OCREVUS (ocrelizumab) Injection for intravenous infusion is a preservative-free, sterile, clear or slightly opalescent, and colorless to pale brown solution supplied in single-dose vials. Each mL of solution contains 30 mg ocrelizumab, glacial acetic acid (0.25 mg), polysorbate 20 (0.2 mg), sodium acetate trihydrate (2.14 mg), and trehalose dihydrate (40 mg) at pH 5.3.

CLINICAL PHARMACOLOGY: top of page

Mechanism of Action:
The precise mechanism by which ocrelizumab exerts its therapeutic effects in multiple sclerosis is unknown, but is presumed to involve binding to CD20, a cell surface antigen present on pre-B and mature B lymphocytes. Following cell surface binding to B lymphocytes, ocrelizumab results in antibody-dependent cellular cytolysis and complement-mediated lysis.

INDICATIONS AND USAGE  top of page

INDICATIONS AND USAGE:
OCREVUS is a CD20-directed cytolytic antibody indicated for the treatment of patients with relapsing or primary progressive forms of multiple sclerosis

CONTRAINDICATIONS top of page

Contraindications:
Active hepatitis B virus infection
History of life-threatening infusion reaction to OCREVUS

PRECAUTIONS top of page

WARNINGS AND PRECAUTIONS:

  1. Infusion reactions: Management recommendations for infusion reactions depend on the type and severity of the reaction. Permanently discontinue OCREVUS if a life-threatening or disabling infusion reaction occurs (2.3, 5.1)
  2. Infections: Delay OCREVUS administration in patients with an active infection until the infection is resolved. Vaccination with live-attenuated or live vaccines is not recommended during treatment with OCREVUS and after discontinuation, until B-cell repletion (5.2)
  3. Malignancies: An increased risk of malignancy, including breast cancer, may exist with OCREVUS (5.3)

ADVERSE REACTIONS top of page

ADVERSE REACTIONS:

The most common adverse reactions were:

  • RMS (incidence >/=10% and > REBIF): upper respiratory tract infections and infusion reactions (6.1)
  • PPMS (incidence >/=10% and > placebo): upper respiratory tract infections, infusion reactions, skin infections, and lower respiratory tract infections (6.1)

    To report SUSPECTED ADVERSE REACTIONS, contact Genentech at 1-888-835-2555 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

See PACKAGE INSERT for PATIENT COUNSELING INFORMATION and Medication Guide.

DOSAGE AND ADMINISTRATION  top of page

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)].

Vaccinations
Because vaccination with live-attenuated or live vaccines is not recommended during treatment and after discontinuation until B-cell repletion, administer all necessary immunizations according to immunization guidelines at least 6 weeks prior to initiation of OCREVUS [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]. PDF

Table 1 Recommended Dose, Infusion Rate, and Infusion Duration for RMS and PPMS
Amount and Volume* Infusion Rate and Duration†
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)		 One infusion every 6 months‡ 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
*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.  

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.

2.6 Preparation and Storage of the Dilute Solution for Infusion
Preparation
OCREVUS must be prepared by a healthcare professional using aseptic technique.

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.

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.

HOW SUPPLIED  top of page

DOSAGE FORMS AND STRENGTHS:
Injection: 300 mg/10 mL (30 mg/mL) in a single-dose vial. 

Storage and Stability top of page

OCREVUS (ocrelizumab) injection is a preservative-free, sterile, clear or slightly opalescent, and colorless to pale brown solution supplied as a carton containing one 300 mg/10 mL (30 mg/mL) single-dose vial (NDC 50242-150-01).

Store OCREVUS vials at 2°C–8°C (36°F–46°F) in the outer carton to protect from light. Do not freeze or shake.

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, store up to 24 hours in the refrigerator at 2°C–8°C (36°F–46°F) and 8 hours at room temperature up to 25°C (77°F), which includes infusion time. In the event an intravenous infusion cannot be completed the same day, discard the remaining solution.

No incompatibilities between OCREVUS and polyvinyl chloride (PVC) or polyolefin (PO) bags and intravenous (IV) administration sets have been observed.
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Ocrelizumab- Ocrevus™