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OCREVUS IV Dosing
Assessments and recommended premedication
Administration

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OCREVUS and OCREVUS ZUNOVO Dosing and Administration Guide
OCREVUS ZUNOVO Dosing and Administration Video
OCREVUS ZUNOVO Dosing Information

OCREVUS® (ocrelizumab) #1 most-prescribed MS DMT in the US1

OCREVUS [IV] injection, for intravenous use

The first dose of OCREVUS [IV] is split between 2 treatments, for a total of 3 treatments in the first year.

OCREVUS [IV] Dosing2

Shorter 2-Hour Infusion2

2-hour infusion is available for patients who have not experienced serious IRs with any previous OCREVUS [IV] infusion2

Shorter 2-hour infusion option after initial dose*

OCREVUS® (ocrelizumab) initial dose and subsequent dosing schedule

*Infusion time may take longer if the infusion is interrupted or slowed.

Shorter 2-hour infusion is available after the initial dose for patients who have not experience serious infusion reactions with any previous OCREVUS IV infusion.†

Administering OCREVUS2

Premedication is 30 to 60 minutes, infusion is 2 hours or 3.5-4 hours, and observation is 60 minutes.

*Infusion time may take longer if the infusion is interrupted or slowed. No change in pre-medication, dose, formulation, or post-treatment monitoring between infusion timing options.2
†Per the ENSEMBLE Plus study protocol, serious infusion reactions included those that were fatal or life-threatening, required or prolonged hospitalization, resulted in persistent or significant by the trial investigator.2
‡For all doses, post-infusion monitoring with access to appropriate medical support to manage severe infusion reactions for at least one hour after infusion is recommended.2

Assessments and recommended premedications2

PRIOR TO THE FIRST DOSE OF OCREVUS [IV]
  • Perform hepatitis B virus screening
  • Test for quantitative serum immunoglobulins
  • Complete necessary vaccinations (4 weeks prior to live or live-attenuated vaccines and, when possible at least 2 weeks prior for non-live vaccines)

BEFORE EACH OCREVUS [IV] INFUSION

  • Determine whether there is an active infection. In case of active infection, delay infusion or OCREVUS [IV] until the infection resolves.

RECOMMENDED PREMEDICATION

Table describing the pre-medication steps for OCREVUS® (ocrelizumab)

Preparation and storage of the dilute solution for infusion

Administration2

OCREVUS [IV] is administered as an intravenous infusion through a dedicated line
Table describing the adminstration steps for OCREVUS® (ocrelizumab)

Infusion rate tables

OCREVUS® (ocrelizumab) initial dose (600 mg) administered as 2 infusions. 2.5-hour infusions start at a rate of 30mL/hr and increase the rate byt 30 mL/hr every 30 minutes to a maximum of 180 mL/hr.
OCREVUS® (ocrelizumab) subsequent dose (600 mg) once every 6 months. 3.5-to-4-hour infusions start at a rate of 40 mL/hr and increase the rate by 40 mL/hr every 30 minutes to a maximum of 200 mL/hr.

Solutions of OCREVUS [IV] 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 1/22 mg/mL.

*Administer the first subsequent dose 6 months after Infusion 1 of the initial dose.

Rate Modifications in the event of Infusion Reactions

Modify the infusion rate in response to the severity of the reaction

For infusion reactions that are not life-threatening, the change in infusion rate will increase the duration of the infusion but not the total dose.

For mild to moderate infusion reactions, reduce the infusion rate to half the rate of when the reacton began and maintain the reduced rate for at least 30 minutes. If tolerated, increase the infusion rate according to the initial infusion schedule. For severe reactions, interrupt the infusion immediately and provide supportive treatment. Only restart the infusion after all symtpoms have resolved, at half the infusion rate of when the reaction began. For life-threatening or disabling reactions, immediately stop infusion and provide appropriate supportive treatment. Permanently discontinue OCREVUS in these patients.

INFUSION REACTIONS IN THE OPERA AND ORATORIAL TRIALS (controlled period)

3.5 to 4-hour infusion of OCREVUS [IV]: 99.7% of infusions did not result in serious IRs in the OPERA and ORATORIO studies [controlled period]2

Patients treated with Ocrevus in Opera and Oratorio. 60 to 66 percent had no IRs. 34 to 40 percent had any IR. .3 percent had serious IRs.
  • IRs were highest with the first infusion. Of the IRs that occurred, most were mild to moderate in severity3
  • 0.3% of patients with multiple sclerosis (MS) treated with OCREVUS [IV] experienced infusion reactions that were serious, some requiring hospitalization2

INFUSION REACTIONS IN THE ENSEMBLE PLUS STUDY

NO LIFE-THREATENING, FATAL OR SERIOUS IRs OCCURRED WITH OCREVUS [IV] IN THE ENSEMBLE PLUS STUDY2,4

The proportions of patients with IRs were similar between the 2 infusion protocols. 2 hour infusions had 24.4 percent and 3.5 to 4 hour infusions had 23.3 percent.
  • 2-hour infusion is available for patients who have not experienced serious infection reactions with any previous OCREVUS infusion
  • Overall, in all randomized doses, 27.1% of the patients in the 2-hour infusion group and 25.0% of the patients in the 3.5-hour infusion group reported mild or moderate infusion reactions; two infusion reactions were severe in intensity, with 1 severe infusion reaction (0.3%) reported in 1 patient in each group in this substudy.

ENSEMBLE PLUS evaluated the safety of OCREVUS [IV] 2-hour infusion2

A prospective, multicenter, randomized, double-blind, controlled, parallel-arm substudy of 580 patients with early RRMS, 81% (469/579) of increased patients received a single randomized infusion of OCREVUS for the primary analysis.

Per the ENSEMBLE protocol serious IRs included those that were fatal or life-threatening, required or prolonged hospitalization, resulted in persistent or significant disability or were deemed to be medically significant by the trial investigation.

Explore OCREVUS ZUNOVO

Ocrelizumab is also available in a subcutaneous formulation.

See OCREVUS ZUNOVO Dosing and Administration

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DMT=disease modifying therapy; PPMS=primary progressive multiple sclerosis; RMS=relapsing multiple sclerosis.

Quick links to resources

OCREVUS and OCREVUS ZUNOVO Dosing and Administration Guide
OCREVUS ZUNOVO Dosing and Administration Video
OCREVUS ZUNOVO Dosing Information

Important Safety Information & Indications

Indications

OCREVUS and OCREVUS ZUNOVO are 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.
Contraindications

Treatment with ocrelizumab is contraindicated in patients with active hepatitis B virus infection and in patients with a history of life-threatening administration reactions to ocrelizumab. OCREVUS ZUNOVO is also contraindicated in patients with a history of hypersensitivity to ocrelizumab, hyaluronidase, or any component of OCREVUS ZUNOVO.

Warnings and Precautions
Injection Reactions (OCREVUS ZUNOVO) OR Infusion Reactions (OCREVUS)

OCREVUS ZUNOVO can cause injection reactions, which can be local or systemic. Common symptoms of local injection reactions reported by patients treated with OCREVUS ZUNOVO in multiple sclerosis (MS) clinical trials included erythema, pain, swelling, and pruritus. Common symptoms of systemic injection reactions reported by patients included headache and nausea. In an open-label, active-controlled trial, injection reactions were more frequently reported with the first injection; 49% of patients experienced an injection reaction with the first injection.

In OCREVUS MS clinical trials, the incidence of infusion reactions in patients [who received methylprednisolone (or an equivalent steroid) and possibly other pre-medication to reduce the risk of infusion reactions prior to infusion] was 34% to 40%, with the highest incidence with the first infusion. There were no fatal infusion reactions, but 0.3% of intravenous ocrelizumab-treated MS patients experienced infusion reactions that were serious, some requiring hospitalization. Symptoms of infusion reactions can include pruritus, rash, urticaria, erythema, bronchospasm, throat irritation, oropharyngeal pain, dyspnea, pharyngeal or laryngeal edema, flushing, hypotension, pyrexia, fatigue, headache, dizziness, nausea, tachycardia, and anaphylaxis.

Monitor OCREVUS ZUNOVO patients during and after injections. Observe patients treated with OCREVUS for infusion reactions during the infusion and for at least one hour after completion of the infusion. Inform patients that administration reactions can occur during or within 24 hours of treatment.

Reducing the Risk and Managing Injection or Infusion Reactions

For OCREVUS ZUNOVO, administer oral pre-medication (e.g., dexamethasone or an equivalent corticosteroid, and an antihistamine) at least 30 minutes prior to each OCREVUS ZUNOVO injection to reduce the risk of injection reactions. The addition of an antipyretic (e.g., acetaminophen) may also be considered.

For OCREVUS, administer pre-medication (e.g., methylprednisolone or an equivalent corticosteroid, and an antihistamine) to reduce the frequency and severity of infusion reactions. The addition of an antipyretic (e.g., acetaminophen) may also be considered.

Management recommendations depend on the type and severity of the reaction. For life-threatening reactions, immediately and permanently stop OCREVUS ZUNOVO or OCREVUS and administer appropriate supportive treatment. For less severe OCREVUS ZUNOVO injection reactions, the injection should be interrupted immediately, and the patient should receive symptomatic treatment. The injection should be completed at the healthcare provider’s discretion and only after all symptoms have resolved. For less severe OCREVUS infusion reactions, management may involve temporarily stopping the infusion, reducing the infusion rate, and/or administering symptomatic treatment.

Infections

Serious, including life-threatening or fatal, bacterial, viral, parasitic and fungal infections have been reported in patients receiving ocrelizumab. An increased risk of infections (including serious and fatal bacterial, fungal, and new or reactivated viral infections) has been observed in patients during and following completion of treatment with anti-CD20 B-cell depleting therapies.

A higher proportion of OCREVUS-treated patients experienced infections compared to patients taking REBIF or placebo. In RMS trials, 58% of OCREVUS-treated patients experienced one or more infections compared to 52% of REBIF-treated patients. In the PPMS trial, 70% of OCREVUS -treated patients experienced one or more infections compared to 68% of patients on placebo. OCREVUS was not associated with an increased risk of serious infections in MS patients in controlled trials.

Ocrelizumab increases the risk for upper respiratory tract infections, lower respiratory tract infections, skin infections, and herpes-related infections. Delay administration of ocrelizumab in patients with an active infection until the infection has resolved.

Respiratory Tract Infections

A higher proportion of OCREVUS-treated patients experienced respiratory tract infections compared to patients taking REBIF or placebo. In RMS trials, 40% of OCREVUS-treated patients experienced upper respiratory tract infections compared to 33% of REBIF-treated patients, and 8% of OCREVUS-treated patients experienced lower respiratory tract infections compared to 5% of REBIF-treated patients. In the PPMS trial, 49% of OCREVUS-treated patients experienced upper respiratory tract infections compared to 43% of patients on placebo and 10% of OCREVUS-treated patients experienced lower respiratory tract infections compared to 9% of patients on placebo. The infections were predominantly mild to moderate and consisted mostly of upper respiratory tract infections and bronchitis.

Herpes

In active-controlled (RMS) clinical trials, herpes infections were reported more frequently in OCREVUS-treated patients than in REBIF-treated patients, including herpes zoster (2.1% vs. 1.0%), herpes simplex (0.7% vs. 0.1%), oral herpes (3.0% vs. 2.2%), genital herpes (0.1% vs. 0%), and herpes virus infection (0.1% vs. 0%). Infections were predominantly mild to moderate in severity. In the placebo-controlled (PPMS) clinical trial, oral herpes was reported more frequently in the OCREVUS-treated patients than in the patients on placebo (2.7% vs 0.8%).

Serious cases of infections caused by herpes simplex virus and varicella zoster virus, including central nervous system infections (encephalitis and meningitis), intraocular infections, and disseminated skin and soft tissue infections, have been reported in the postmarketing setting in multiple sclerosis patients receiving ocrelizumab. Serious herpes virus infections may occur at any time during treatment with ocrelizumab. Some cases were life-threatening.

If serious herpes infections occur, treatment with ocrelizumab should be discontinued or withheld until the infection has resolved, and appropriate treatment should be administered.

Hepatitis B Virus Reactivation

Hepatitis B virus (HBV) reactivation has been reported in MS patients treated with ocrelizumab in the postmarketing setting. Fulminant hepatitis, hepatic failure, and death caused by HBV reactivation have occurred in patients treated with anti-CD20 antibodies. Perform HBV screening in all patients before initiation of treatment with ocrelizumab. Do not administer ocrelizumab to patients with active HBV confirmed by positive results for HBsAg and anti-HB 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.

Possible Increased Risk of Immunosuppressant Effects With Other Immunosuppressants

When initiating treatment with ocrelizumab after an immunosuppressive therapy or initiating an immunosuppressive therapy after ocrelizumab-containing products, consider the potential for increased immunosuppressive effect. Treatment with ocrelizumab has not been studied in combination with other MS therapies.

Vaccinations

Administer all immunizations according to immunization guidelines at least 4 weeks prior to initiation of ocrelizumab treatment for live or live-attenuated vaccines and, whenever possible, at least 2 weeks prior to initiation of ocrelizumab treatment for non-live vaccines. Ocrelizumab may interfere with the effectiveness of non-live vaccines. The safety of immunization with live or live-attenuated vaccines following treatment with ocrelizumab has not been studied, and vaccination with live-attenuated or live vaccines is not recommended during treatment and until B-cell repletion.

Vaccination of Infants Born to Mothers Treated With Ocrelizumab Products During Pregnancy

In infants of mothers exposed to ocrelizumab during pregnancy, do not administer live or live-attenuated vaccines before confirming the recovery of B-cell counts as measured by CD19+ B-cells. Depletion of B-cells in these infants may increase the risks from live or live-attenuated vaccines.

You may administer non-live vaccines, as indicated, prior to recovery from B-cell depletion, but you should consider assessing vaccine immune responses, including consultation with a qualified specialist, to assess whether a protective immune response was mounted.

Progressive Multifocal Leukoencephalopathy

Cases of progressive multifocal leukoencephalopathy (PML) have been reported in patients with MS treated with ocrelizumab in the postmarketing setting. PML is an opportunistic viral infection of the brain caused by the JC virus (JCV) that typically occurs only in patients who are immunocompromised, and that usually leads to death or severe disability. PML has occurred in ocrelizumab-treated patients who had not been treated previously with natalizumab, (which has a known association with PML), were not taking any immunosuppressive or immunomodulatory medications associated with risk of PML prior to or concomitantly with ocrelizumab and did not have any known ongoing systemic medical conditions resulting in compromised immune system function.

JCV infection resulting in PML has also been observed in patients treated with other anti-CD20 antibodies and other MS therapies.

At the first sign or symptom suggestive of PML, withhold treatment with ocrelizumab-containing products and perform an appropriate diagnostic evaluation. Typical symptoms associated with PML are diverse, progress over days to weeks, and include progressive weakness on one side of the body or clumsiness of limbs, disturbance of vision, and changes in thinking, memory, and orientation leading to confusion and personality changes. 

Magnetic resonance imaging (MRI) findings may be apparent before clinical signs or symptoms of PML. Monitoring with MRI for signs consistent with PML may be useful, and any suspicious findings should lead to further investigation to allow for an early diagnosis of PML, if present. If PML is confirmed, treatment with ocrelizumab should be discontinued.

Reduction in Immunoglobulins

As expected with any B-cell depleting therapy, decreased immunoglobulin levels are observed with ocrelizumab treatment. The pooled data of OCREVUS clinical studies (RMS and PPMS) and their open-label extensions (up to approximately 7 years of exposure) have shown an association between decreased levels of immunoglobulin G (IgG<LLN) and increased rates of serious infections. Monitor the levels of quantitative serum immunoglobulins during treatment with ocrelizumab and after discontinuation of treatment, until B-cell repletion, and especially in the setting of recurrent serious infections. Consider discontinuing treatment with ocrelizumab- in patients with serious opportunistic or recurrent serious infections, and if prolonged hypogammaglobulinemia requires treatment with intravenous immunoglobulins.

Malignancies

An increased risk of malignancy with ocrelizumab may exist. In controlled trials, malignancies, including breast cancer, occurred more frequently in OCREVUS-treated patients. Breast cancer occurred in 6 of 781 females treated with OCREVUS and none of 668 females treated with REBIF or placebo. Patients should follow standard breast cancer screening guidelines.

Immune-Mediated Colitis

Immune-mediated colitis, which can present as a severe and acute-onset form of colitis, has been reported in patients receiving ocrelizumab in the postmarketing setting. Some cases of colitis were serious, requiring hospitalization, with a few patients requiring surgical intervention. Systemic corticosteroids were required in many of these patients. The time from treatment initiation to onset of symptoms in these cases ranged from a few weeks to years. Monitor patients for immune-mediated colitis during ocrelizumab treatment and evaluate promptly if signs and symptoms that may indicate immune-mediated colitis, such as new or persistent diarrhea or other gastrointestinal signs and symptoms, occur.

Use in Specific Populations
Pregnancy

There are no adequate data on the developmental risk associated with use of ocrelizumab in pregnant women. There are no data on B-cell levels in human neonates following maternal exposure to ocrelizumab-containing products. However, transient peripheral B-cell depletion and lymphocytopenia have been reported in infants born to mothers exposed to other anti-CD20 antibodies during pregnancy. Ocrelizumab is a humanized monoclonal antibody of an immunoglobulin G1 subtype and immunoglobulins are known to cross the placental barrier.

Lactation

There are no data on the presence of ocrelizumab or hyaluronidase in human milk, the effects on the breastfed infant, or the effects of the drug on milk production. Ocrelizumab was excreted in the milk of ocrelizumab-treated monkeys. Human IgG is excreted in human milk, and the potential for absorption of ocrelizumab to lead to B-cell depletion in the infant is unknown. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for ocrelizumab and any potential adverse effects on the breastfed infant from ocrelizumab or from the underlying maternal condition.

Females and Males of Reproductive Potential

Women of childbearing potential should use effective contraception while receiving ocrelizumab and for 6 months after the last dose of ocrelizumab. Instruct patients that if they are pregnant or plan to become pregnant while taking OCREVUS or OCREVUS ZUNOVO, they should inform their healthcare provider.

Most Common Adverse Reactions

In patients treated with OCREVUS:

  • RMS: The most common adverse reactions (≥10% and >REBIF): upper respiratory tract infections and infusion reactions.
  • PPMS: The most common adverse reactions (≥10% and >placebo): upper respiratory tract infections, infusion reactions, skin infections, and lower respiratory tract infections.

The most common adverse reaction observed with OCREVUS ZUNOVO in patients with RMS and PPMS was injection reactions (incidence of 49%).

You may report side effects to the FDA at (800) FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Genentech at (888) 835-2555.

Please see additional Important Safety Information throughout and click here for full OCREVUS Prescribing Information and Medication Guide. For OCREVUS ZUNOVO, click here for full Prescribing Information and Medication Guide.

    • Data on file. Genentech, Inc. November 2023.

      Data on file. Genentech, Inc. November 2023.

    • OCREVUS [prescribing information]. South San Francisco, CA: Genentech, Inc. 2024.

      OCREVUS [prescribing information]. South San Francisco, CA: Genentech, Inc. 2024.

    • De Seze J, Arnold DJ, Bar-Or A, et al; OPERA I, OPERA II and ORATORIO clinical investigators. Infusion-related reactions with ocrelizumab in relapsing multiple sclerosis and primary progressive multiple sclerosis. Poster presented at: 32nd Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS); September 14-17, 2016; London, United Kingdom. Poster P720.

      De Seze J, Arnold DJ, Bar-Or A, et al; OPERA I, OPERA II and ORATORIO clinical investigators. Infusion-related reactions with ocrelizumab in relapsing multiple sclerosis and primary progressive multiple sclerosis. Poster presented at: 32nd Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS); September 14-17, 2016; London, United Kingdom. Poster P720.

    • Hartung HP; ENSEMBLE Steering Committee members and study investigators. Ocrelizumab shorter infusion: Primary results from the ENSEMBLE PLUS substudy in patients with MS. Neurol Neuroimmunol Neuroinflamm. 2020;7(5):e807

      Hartung HP; ENSEMBLE Steering Committee members and study investigators. Ocrelizumab shorter infusion: Primary results from the ENSEMBLE PLUS substudy in patients with MS. Neurol Neuroimmunol Neuroinflamm. 2020;7(5):e807