Version July 2025
Dosage guidance:
Safety: Prior to initiating therapy, evaluate need to administer age-appropriate vaccines according to immunization guidelines; screen all patients for hepatitis B virus (HBsAg and anti-HBc measurements) and for latent infections (eg, hepatitis, tuberculosis) in high-risk populations or in countries with a high tuberculosis burden. For patients who screen positive for latent infections, consult infectious disease or other appropriate specialists (eg, liver specialists) regarding treatment options before initiating therapy (Ref). Assess for infection prior to treatment initiation; delay treatment in patients with an active infection until the infection is resolved. Premedicate with dexamethasone (20 mg orally or equivalent corticosteroid) and an antihistamine (eg, desloratadine) 30 minutes prior to each infusion; may also consider premedication with acetaminophen.
Dosage form information: Do NOT substitute ocrelizumab (for IV administration) and ocrelizumab/hyaluronidase (for SUBQ administration); products have different dosing and are NOT interchangeable.
Multiple sclerosis, relapsing or primary progressive: SUBQ: ocrelizumab 920 mg/hyaluronidase 23,000 units once every 6 months.
Missed dose: If a dose is missed, administer as soon as possible. Reset the dose schedule to administer the next sequential dose 6 months after the missed dose is administered; doses must be separated by at least 5 months.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling; however, no significant change in pharmacokinetics was observed in patients with mild impairment.
There are no dosage adjustments provided in the manufacturer's labeling; however, no significant change in pharmacokinetics was observed in patients with mild impairment (Child-Turcotte-Pugh class A).
Hypogammaglobulinemia, prolonged and requiring IV immune globulin treatment or associated with severe opportunistic or recurrent infections: Consider discontinuing ocrelizumab/hyaluronidase.
Progressive multifocal leukoencephalopathy:
Signs/symptoms suggestive of progressive multifocal leukoencephalopathy: Withhold ocrelizumab/hyaluronidase treatment and perform appropriate diagnostics.
Confirmed progressive multifocal leukoencephalopathy: Discontinue ocrelizumab/hyaluronidase.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Reported in adults. Also, see individual agents.
>10%:
Gastrointestinal: Nausea (≤11%)
Local: Injection-site reactions (31% to 47%; including erythema at injection site, injection-site pruritus, pain at injection site, swelling at injection site)
Nervous system: Headache (≤11%)
Hypersensitivity to ocrelizumab, hyaluronidase, or any component of the formulation; active hepatitis B virus infection; history of life-threatening administration reaction to ocrelizumab.
Concerns related to adverse effects:
• GI toxicity: Immune-mediated colitis has occurred, including severe and acute-onset cases requiring hospitalization and/or surgery. The onset of symptoms (eg, new or persistent diarrhea, other GI symptoms) ranged from a few weeks to years following treatment initiation. Systemic corticosteroids were required in the majority of patients with colitis.
• Immunoglobulin reduction: Decrease in immunoglobulin levels may occur with use of ocrelizumab. Obtain quantitative serum immunoglobulins prior to therapy initiation; consult immunology experts prior to initiation for patients with low serum immunoglobulins. Monitor quantitative serum immunoglobulins during treatment, especially in patients with opportunistic or recurrent infections, and after discontinuation of therapy until B-cell repletion.
• Infection: Serious, including life-threatening or fatal, bacterial viral, parasitic, and fungal infections may occur during and/or following therapy. Assess for infections prior to treatment initiation, and screen for latent infections (eg, hepatitis, tuberculosis [TB]) in high-risk populations or in countries with a high TB burden. For patients who screen positive for latent infections, consult infectious disease or other specialists (eg, liver specialists) regarding treatment options before initiating therapy (AAN [Farez 2019]). In clinical studies, a slightly higher incidence of infections was reported in patients receiving IV ocrelizumab, compared to patients receiving the comparator drug or placebo. Over half of patients who received IV ocrelizumab experienced ≥1 infections. In multiple sclerosis (MS) patients, IV ocrelizumab is associated with an increased risk for respiratory tract infections (upper and lower), skin infections, and herpes-related infections, although was not associated with an increased risk of serious infections. Respiratory tract infections were predominantly mild to moderate and consisted mostly of upper respiratory tract infections and bronchitis.
- Hepatitis B reactivation: Screen for hepatitis B virus (HBV) in all patients (HBsAg and anti-HBc measurements) prior to treatment initiation. Postmarketing reports of hepatitis B reactivation in MS patients treated with ocrelizumab have been reported. Fulminant hepatitis, hepatic failure, and death caused by HBV reactivation have occurred in patients treated with other anti-CD20 monoclonal antibodies.
- Herpes infection: In clinical studies, herpes infections (herpes zoster, herpes simplex, oral herpes, genital herpes, and herpes virus infection) were reported more frequently in patients who received IV ocrelizumab compared to patients who received comparator drug, and oral herpes was reported more frequently with IV ocrelizumab than with placebo. Infections were predominantly mild to moderate in severity. Serious (some life-threatening) cases of herpes simplex virus and varicella zoster virus, including CNS infections (eg, encephalitis, meningitis), intraocular infections, and disseminated skin and soft tissue infections, have been reported. Serious herpes virus infections may occur at any time during treatment.
• Injection reactions: Injection-related reactions, including local (eg, erythema, pain, pruritus, swelling) and systemic (headache, nausea), may occur during injection or within 24 hours following injection. Reactions may be more frequent with the first injection. Serious infusion reactions leading to hospitalization have occurred with IV ocrelizumab; symptoms of ocrelizumab infusion reactions 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. Administer premedications (dexamethasone [or equivalent] and an antihistamine, with or without acetaminophen) to reduce the risk of injection reactions. Depending on the severity of the reaction, injection reactions may require infusion interruption or discontinuation; may also require symptomatic supportive management.
• Malignancy: Ocrelizumab may be associated with an increased risk of malignancy. Malignancies (including breast cancer) occurred more frequently in ocrelizumab-treated patients in clinical studies. Breast cancer occurred in 0.8% of females who received ocrelizumab and none of the females who received the comparator drug or placebo. Patients should follow standard breast cancer screening guidelines.
• Progressive multifocal leukoencephalopathy: Progressive multifocal leukoencephalopathy (PML) has been reported. PML is an opportunistic viral infection of the brain caused by the JC virus and usually leads to death or severe disability. PML typically only occurs in patients who are immunocompromised; however, patients who developed PML while taking ocrelizumab had no identifiable systemic medical condition resulting in immunosuppression, were not taking any concomitant immunomodulatory or immunosuppressant medications, and had not previously been treated with natalizumab. Symptoms progress over days to weeks and may include progressive weakness on one side of the body or clumsiness of limbs, vision disturbances, and mental status changes. Cases of PML have been diagnosed based on MRI findings and the detection of JC virus DNA in the cerebrospinal fluid without specific PML signs/symptoms. Monitoring with brain MRI for signs that may be consistent with PML may be beneficial and allow for an early diagnosis of PML.
Other warnings/precautions:
• Appropriate use: Ocrelizumab/hyaluronidase has not been studied in combination with other MS therapies. When initiating ocrelizumab/hyaluronidase after an immunosuppressive therapy or initiating an immunosuppressive following ocrelizumab/hyaluronidase therapy, consider the potential for increased immunosuppressive effects.
• Immunizations: Administer live-attenuated or live vaccines at least 4 weeks and nonlive vaccines at least 2 weeks prior to treatment initiation. Avoid live-attenuated or live vaccines during treatment or after discontinuation until B-cell repletion; consider using live-attenuated vaccines only if risk of infection is high and nonlive vaccines are unavailable (AAN [Farez 2019]). Nonlive vaccines may be administered; however, consideration should be given to evaluating the immune response. Prior to administration of live-attenuated or live vaccinations in infants exposed to ocrelizumab/hyaluronidase in utero, confirm recovery of B-cell counts.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Subcutaneous [preservative free]:
Ocrevus Zunovo: Ocrelizumab 920 and hyaluronidase-ocsq 23,000 units/23 mL (23 mL)
No
Solution (Ocrevus Zunovo Subcutaneous)
920-23000MG-UT/23ML (per mL): $2,153.84
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Ocrelizumab/hyaluronidase (for SUBQ administration) and ocrelizumab (for IV administration) are NOT interchangeable; check vial labels to prevent medication errors.
SUBQ: Administer only via SUBQ injection. Premedicate with dexamethasone (or any equivalent corticosteroid) and an antihistamine (eg, desloratadine) 30 minutes prior to infusion; may also consider premedication with acetaminophen. Allow refrigerated product to reach room temperature prior to administration. If a mild to moderate injection-related reaction occurs, immediately interrupt injection and provide symptomatic treatment; continue injection only after resolution of symptoms and after consideration of risk versus benefit. Immediately and permanently discontinue injection and administer supportive therapy if life-threatening injection-related reaction occurs.
Before administration, attach syringe to winged/butterfly infusion set containing a 24- or 26-gauge needle for injection and a maximum priming volume of ≤0.8 mL. Ocrelizumab/hyaluronidase is compatible with polypropylene, polycarbonate, polyethylene, stainless steel, polyvinylchloride, and polyurethane. Prime the SUBQ infusion line with the drug product to eliminate air in the infusion line, stopping before the fluid reaches the needle. After priming, ensure syringe contains exactly 23 mL of drug solution; expel any excess volume from the syringe. Administer immediately to avoid needle clogging; do not store the prepared syringe that has been attached to the already primed SUBQ infusion set. Choose an injection site on abdomen a minimum of 2 inches from the navel, avoiding areas with moles or scars, or where skin is red, bruised, tender, or hard. Administer over a period of 10 minutes. Do not administer remaining priming volume in SUBQ infusion set. Monitor for signs/symptoms of injection reaction during and following administration (monitor for at least 1 hour following first injection; monitor for at least 15 minutes following subsequent injections).
Multiple sclerosis, relapsing or primary progressive: Treatment of primary progressive multiple sclerosis (MS) in adults and relapsing forms of MS, including clinically isolated syndrome, relapsing remitting disease, and active secondary progressive disease in adults.
Ocrevus Zunovo may be confused with Ocrevus.
Ocrelizumab/hyaluronidase may be confused with daratumumab/hyaluronidase, efgartigimod alfa/hyaluronidase, ocrelizumab, hyaluronidase, pertuzumab/trastuzumab/hyaluronidase, rituximab/hyaluronidase, trastuzumab/hyaluronidase.
Refer to individual components.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Abrocitinib: May increase immunosuppressive effects of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid
Alpha-/Beta-Agonists: Hyaluronidase may increase vasoconstricting effects of Alpha-/Beta-Agonists. Management: Do not use hyaluronidase to enhance the dispersion or absorption of alpha-/beta-agonists. Use of hyaluronidase for other purposes in patients receiving alpha-/beta-agonists may be considered as clinically indicated. Risk D: Consider Therapy Modification
Antihistamines: May decrease therapeutic effects of Hyaluronidase. Risk C: Monitor
Antithymocyte Globulin (Equine): Anti-CD20 B-Cell Depleting Therapies may increase adverse/toxic effects of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of anti-CD20 B-cell depleting therapy is reduced. Anti-CD20 B-Cell Depleting Therapies may increase immunosuppressive effects of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor
Antithymocyte Globulin (Equine): Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase adverse/toxic effects of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of immunosuppressive therapy is reduced. Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor
Baricitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Baricitinib. Risk X: Avoid
BCG Products: Anti-CD20 B-Cell Depleting Therapies may increase adverse/toxic effects of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Anti-CD20 B-Cell Depleting Therapies may decrease therapeutic effects of BCG Products. Risk X: Avoid
Brincidofovir: Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects of Brincidofovir. Risk C: Monitor
Brivudine: May increase adverse/toxic effects of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid
Chikungunya Vaccine (Live): Anti-CD20 B-Cell Depleting Therapies may decrease therapeutic effects of Chikungunya Vaccine (Live). Anti-CD20 B-Cell Depleting Therapies may increase adverse/toxic effects of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Chikungunya Vaccine (Live): Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase adverse/toxic effects of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects of Chikungunya Vaccine (Live). Risk X: Avoid
Cladribine: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Cladribine. Risk X: Avoid
Coccidioides immitis Skin Test: Coadministration of Immunosuppressants (Therapeutic Immunosuppressant Agents) and Coccidioides immitis Skin Test may alter diagnostic results. Management: Consider discontinuing therapeutic immunosuppressants several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider Therapy Modification
Corticosteroids (Systemic): May decrease therapeutic effects of Hyaluronidase. Management: Patients receiving corticosteroids (particularly at larger doses) may not experience the desired clinical response to standard doses of hyaluronidase. Larger doses of hyaluronidase may be required. Risk D: Consider Therapy Modification
COVID-19 Vaccines: Anti-CD20 B-Cell Depleting Therapies may decrease therapeutic effects of COVID-19 Vaccines. Management: Administer COVID-19 vaccine 2 to 4 weeks prior to the next scheduled dose of anti-CD20 therapy, if used chronically for the treatment of autoimmune disease. Revaccinate 6 months after completion of anti-CD20 therapy if used over a limited period. Risk D: Consider Therapy Modification
Dengue Tetravalent Vaccine (Live): Anti-CD20 B-Cell Depleting Therapies may increase adverse/toxic effects of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Anti-CD20 B-Cell Depleting Therapies may decrease therapeutic effects of Dengue Tetravalent Vaccine (Live). Risk X: Avoid
Denosumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Denosumab. Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and immunosuppressants. If combined, monitor for signs/symptoms of serious infections. Risk D: Consider Therapy Modification
Deucravacitinib: May increase immunosuppressive effects of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid
Efgartigimod Alfa: May decrease therapeutic effects of Fc Receptor-Binding Agents. Risk C: Monitor
Estrogen Derivatives: May decrease therapeutic effects of Hyaluronidase. Risk C: Monitor
Etrasimod: May increase immunosuppressive effects of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid
Filgotinib: May increase immunosuppressive effects of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid
Immunosuppressants (Cytotoxic Chemotherapy): May increase immunosuppressive effects of Ocrelizumab. Risk C: Monitor
Immunosuppressants (Miscellaneous Oncologic Agents): May increase immunosuppressive effects of Ocrelizumab. Risk C: Monitor
Immunosuppressants (Therapeutic Immunosuppressant Agents): May increase immunosuppressive effects of Ocrelizumab. Risk C: Monitor
Inebilizumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Inebilizumab. Risk C: Monitor
Influenza Virus Vaccines: Anti-CD20 B-Cell Depleting Therapies may decrease therapeutic effects of Influenza Virus Vaccines. Management: Administer influenza vaccines 2 weeks prior to starting anti-CD20 B-cell depleting therapies. Vaccination of patients treated with these agents in the past 6 months is not recommended. Risk D: Consider Therapy Modification
Leflunomide: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents. Risk D: Consider Therapy Modification
Local Anesthetics: Hyaluronidase may increase adverse/toxic effects of Local Anesthetics. Risk C: Monitor
Methotrexate: May increase immunosuppressive effects of Ocrelizumab. Risk C: Monitor
Mumps- Rubella- or Varicella-Containing Live Vaccines: Anti-CD20 B-Cell Depleting Therapies may increase adverse/toxic effects of Mumps- Rubella- or Varicella-Containing Live Vaccines. Specifically, the risk of vaccine-associated infection may be increased. Anti-CD20 B-Cell Depleting Therapies may decrease therapeutic effects of Mumps- Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid
Nadofaragene Firadenovec: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase adverse/toxic effects of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid
Natalizumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Natalizumab. Risk X: Avoid
Nipocalimab: May decrease therapeutic effects of Fc Receptor-Binding Agents. Risk C: Monitor
Ofatumumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Ofatumumab. Risk C: Monitor
Phenylephrine (Systemic): Hyaluronidase may increase vasoconstricting effects of Phenylephrine (Systemic). Management: Do not use hyaluronidase to enhance the dispersion or absorption of phenylephrine. Use of hyaluronidase for other purposes in patients receiving phenylephrine may be considered as clinically indicated. Risk D: Consider Therapy Modification
Pidotimod: Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects of Pidotimod. Risk C: Monitor
Pimecrolimus: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Pimecrolimus. Risk X: Avoid
Poliovirus Vaccine (Live/Trivalent/Oral): Anti-CD20 B-Cell Depleting Therapies may increase adverse/toxic effects of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Anti-CD20 B-Cell Depleting Therapies may decrease therapeutic effects of Poliovirus Vaccine (Live/Trivalent/Oral). Risk X: Avoid
Polymethylmethacrylate: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase hypersensitivity effects of Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider Therapy Modification
Rabies Vaccine: Anti-CD20 B-Cell Depleting Therapies may decrease therapeutic effects of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider Therapy Modification
Ritlecitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Ritlecitinib. Risk X: Avoid
Rozanolixizumab: May decrease therapeutic effects of Fc Receptor-Binding Agents. Risk C: Monitor
Ruxolitinib (Topical): Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Ruxolitinib (Topical). Risk X: Avoid
Salicylates: May decrease therapeutic effects of Hyaluronidase. Risk C: Monitor
Sipuleucel-T: Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants prior to initiating sipuleucel-T therapy. Risk D: Consider Therapy Modification
Tacrolimus (Topical): Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Tacrolimus (Topical). Risk X: Avoid
Talimogene Laherparepvec: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase adverse/toxic effects of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid
Tertomotide: Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects of Tertomotide. Risk X: Avoid
Tofacitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Tofacitinib. Management: Coadministration of tofacitinib with potent immunosuppressants is not recommended. Use with non-biologic disease-modifying antirheumatic drugs (DMARDs) was permitted in psoriatic arthritis clinical trials. Risk X: Avoid
Typhoid Vaccine: Anti-CD20 B-Cell Depleting Therapies may increase adverse/toxic effects of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Anti-CD20 B-Cell Depleting Therapies may decrease therapeutic effects of Typhoid Vaccine. Risk X: Avoid
Ublituximab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Ublituximab. Risk C: Monitor
Upadacitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Upadacitinib. Risk X: Avoid
Vaccines (Live): Anti-CD20 B-Cell Depleting Therapies may increase adverse/toxic effects of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Anti-CD20 B-Cell Depleting Therapies may decrease therapeutic effects of Vaccines (Live). Risk X: Avoid
Vaccines (Non-Live/Inactivated/Non-Replicating): Anti-CD20 B-Cell Depleting Therapies may decrease therapeutic effects of Vaccines (Non-Live/Inactivated/Non-Replicating). Management: Give non-live/inactivated/non-replicating vaccines at least 2 weeks prior to initiation or 6 months after anti-CD20 B-cell depleting therapies. If vaccinated prior to B cell recovery, consider assessing immune response to vaccination. Risk D: Consider Therapy Modification
Yellow Fever Vaccine: Anti-CD20 B-Cell Depleting Therapies may increase adverse/toxic effects of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Anti-CD20 B-Cell Depleting Therapies may decrease therapeutic effects of Yellow Fever Vaccine. Risk X: Avoid
Zoster Vaccine (Live/Attenuated): Anti-CD20 B-Cell Depleting Therapies may increase adverse/toxic effects of Zoster Vaccine (Live/Attenuated). Specifically, the risk of vaccine-associated infection may be increased. Anti-CD20 B-Cell Depleting Therapies may decrease therapeutic effects of Zoster Vaccine (Live/Attenuated). Risk X: Avoid
Zoster Vaccine (Live/Attenuated): Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase adverse/toxic effects of Zoster Vaccine (Live/Attenuated). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects of Zoster Vaccine (Live/Attenuated). Risk X: Avoid
Patients who could become pregnant should use effective contraception during therapy and for 6 months after the last dose of ocrelizumab and hyaluronidase.
Ocrelizumab is a humanized monoclonal antibody (IgG1). Human IgG crosses the placenta. Fetal exposure is dependent upon the IgG subclass, maternal serum concentrations, placental integrity, newborn birth weight, and GA, generally increasing as pregnancy progresses. The lowest exposure would be expected during the period of organogenesis and the highest during the third trimester (Clements 2020; Palmeira 2012; Pentsuk 2009).
Transient peripheral B-cell depletion and lymphocytopenia have been reported in infants with in utero exposure to other anti-CD20 antibodies.
Also refer to the Ocrelizumab and Hyaluronidase monographs for additional information.
Ocrelizumab is present in breast milk (Anderson 2023); it is not known if hyaluronidase is present in breast milk.
Ocrelizumab is a humanized monoclonal antibody (IgG1). Human IgG is present in breast milk; concentrations are dependent upon IgG subclass and postpartum age (Anderson 2021). The potential for peripheral B-cell depletion in the breastfeeding infant is not known. According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother.
Also refer to the Ocrelizumab and Hyaluronidase monographs for additional information.
Hepatitis B virus (HBV) screening in all patients: Hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc) tests (prior to therapy initiation); do not administer to patients with active HBV confirmed by positive results for HBsAg and anti-HB tests; for patients who are negative for HBsAg and positive for HB core antibody (HBcAb+) or are carriers of HBV (HBsAg+), consult a liver disease specialist prior to initiating and during therapy.
Perform latent infection screening (eg, hepatitis, tuberculosis [TB]) in high-risk populations or in countries with high TB burden (baseline). Monitor quantitative serum immunoglobulins (baseline, throughout treatment as clinically necessary, especially in patients with opportunistic or recurrent infections, after discontinuation of therapy until B-cell repletion). Assess for active infection prior to treatment. Monitor for injection reactions (during injection and for ≥1 hour following the first injection, and ≥15 minutes following subsequent injections). Monitor for signs/symptoms of immune-mediated colitis, infection, malignancy, and progressive multifocal leukoencephalopathy (PML). Perform brain MRI (at first signs/symptoms suggestive of PML and as clinically indicated to monitor for early signs of PML).
Ocrelizumab: Ocrelizumab is a recombinant humanized IgG monoclonal antibody directed against B-cells that express the cell surface antigen CD20; CD20 is present on pre-B and mature B lymphocytes. B-cells are thought to influence the course of multiple sclerosis through antigen presentation, autoantibody production, cytokine regulation, and formation of ectopic lymphoid aggregates in the meninges (Hauser 2017). Ocrelizumab selectively targets and binds with high affinity to the cell surface to deplete CD20 expressing B-cells through antibody-dependent cell-mediated phagocytosis and cytotoxicity, as well as complement-mediated cytolysis (Hauser 2017; Montalban 2017).
Hyaluronidase: Enzymatically modifies the permeability of connective tissue through hydrolysis of hyaluronic acid, one of the chief components of tissue cement, which offers resistance to diffusion of liquids through tissues; hyaluronidase increases the distribution/dispersion and absorption of locally injected or extravasated IV medications.
Distribution: Vd: 2.78 L.
Metabolism: Antibodies are primarily cleared by catabolism.
Half-life elimination: 20 days.
Time to peak: ~4 days.
