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  • CLASSES

    Cell Surface Receptor Inhibitors
    MS Agents

    DEA CLASS

    Rx

    DESCRIPTION

    CD20-directed cytolytic monoclonal antibody which targets B-cells
    Used in adults for primary progressive MS and relapsing forms of MS, to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease
    Infusion reactions are common; pre-medication is needed prior to infusion

    COMMON BRAND NAMES

    OCREVUS

    HOW SUPPLIED

    OCREVUS Intravenous Inj Sol: 1mL, 30mg

    DOSAGE & INDICATIONS

    For the treatment of primary progressive or relapsing forms of multiple sclerosis, including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease.
    Intravenous dosage
    Adults

    300 mg IV infusion as a single dose, followed by a second 300 mg IV infusion 2 weeks later. Subsequent infusions of 600 mg IV are administered every 6 months. The first 600 mg dose is due 6 months after infusion 1 of the initial dose. Infusion rate modifications are necessary if infusion reactions occur, and depend on reaction severity. After completion of each infusion, monitor the patient for at least 1 hour. MISSED DOSES: If a planned infusion is missed, administer 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.

    MAXIMUM DOSAGE

    Adults

    600 mg/dose IV.

    Geriatric

    600 mg/dose IV.

    Adolescents

    Safety and efficacy have not been established.

    Children

    Safety and efficacy have not been established.

    Infants

    Not indicated.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Patients with mild hepatic impairment were included in clinical trials; it appears that no dosage adjustments are needed in these patients.

    Renal Impairment

    Patients with mild renal impairment were included in clinical trials; it appears that no dosage adjustments are needed in these patients.

    ADMINISTRATION

    Injectable Administration

    Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit. The ocrelizumab solution is clear or slightly opalescent, and colorless to pale brown.

    Intravenous Administration

    Preparation of infusion:
    Do not shake the ocrelizumab vial.
    Vials are preservative-free are intended for single-use only. Discard any solution in the vial that is not used to provide a dose.
    Withdraw the intended dose and dilute into an infusion bag of 0.9% Sodium Chloride Injection to a final concentration of approximately 1.2 mg/mL. Do not use other diluents, as their use has not been tested.
    Withdraw 10 mL (300 mg) and inject into 250 mL 0.9% Sodium Chloride Injection.
    Withdraw 20 mL (600 mg) and inject into 500 mL 0.9% Sodium Chloride Injection.
    No incompatibilities between ocrelizumab and polyvinyl chloride (PVC) or polyolefin (PO) bags and IV administration sets have been observed.
    Use the prepared solution immediately.
    Storage: If the solution is not used immediately, it may be refrigerated for up to 24 hours at 2 to 8 degrees C (36 to 46 degrees F) and 8 hours at room temperature up to 25 degrees C (77 degrees F), which includes infusion time. If the infusion cannot be completed within the same day, discard the remaining solution.
     
    Intravenous infusion administration:
    Administration can cause serious infusion-related reactions. Carefully monitor the patient during each infusion, and for at least 1 hour following the completion of each infusion.
    Administration needs to be by a healthcare professional with appropriate medical support to manage severe infusion reactions.
    Premedication: Premedicate 30 minutes prior to infusion with methylprednisolone 100 mg IV (or an equivalent corticosteroid) and 30 to 60 minutes prior to infusion with an antihistamine (e.g., diphenhydramine) to reduce the frequency and severity of infusion reactions. An antipyretic (e.g., acetaminophen) may also be considered.
    The content of the infusion bag must be at room temperature prior to infusion.
    Administer through a dedicated line using an infusion set with a 0.2 or 0.22 micron in-line filter.
    First 2 (300 mg) infusions: Administer at an initial rate of 30 mL/hour. Increase by 30 mL/hour every 30 minutes to a maximum rate of 180 mL/hour with a total infusion duration of 2.5 hours or longer.
    Subsequent infusions (600 mg)
    Option 1: Administer at an initial rate of 40 mL/hour. Increase by 40 mL/hour every 30 minutes to a maximum rate of 200 mL/hour with a total infusion duration of 3.5 hours or longer.
    Option 2: For use ONLY in patients with no history of a serious infusion reaction with any previous ocrelizumab infusion. Infuse over approximately 2 hours. Administer at an initial rate of 100 mL/hour for 15 minutes with subsequent rate increases to 200 mL/hour for 15 minutes, 250 mL/hour for 30 minutes, and 300 mL/hour for the remaining 60 minutes.
    Rate of infusion modifications in response to infusion reactions depend on reaction severity:
    Life-threatening or disabling infusion reactions: Immediately discontinue the infusion and provide appropriate supportive treatment. Permanently discontinue ocrelizumab.
    Severe infusion reactions: Immediately interrupt the infusion and provide appropriate supportive treatment. Wait until all symptoms have resolved before resuming infusion. When restarting, begin at one-half of the infusion rate at the time of infusion reaction onset. If this rate is tolerated, it may be increased according to recommended infusion rate titration guidelines. The rate modifications do not change the dose administered but do increase the duration of infusion time.
    Mild or moderate infusion reactions: Reduce the infusion rate to one-half of the rate at the onset of the infusion reaction and maintain the reduced rate for a minimum of 30 minutes. If this rate is tolerated, it may be increased according to recommended infusion rate titration guidelines. The rate modifications do not change the dose administered but do increase the duration of infusion time.
    Missed doses: If a planned infusion is missed, give ocrelizumab as soon as possible; do not wait until the next scheduled dose. Reset the dose schedule to give the next sequential dose 6 months after the missed dose. Doses must be separated by at least 5 months.

    STORAGE

    OCREVUS:
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Do not freeze
    - Protect from light
    - Refrigerate (between 36 and 46 degrees F)
    - Store in carton

    CONTRAINDICATIONS / PRECAUTIONS

    Infusion-related reactions

    Ocrelizumab is associated with a variety of infusion-related reactions, with severities ranging from mild to life-threatening. Ocrelizumab is contraindicated for use in patients with a history of a life-threatening infusion reaction to ocrelizumab. The drug must be administered under the close supervision of an experienced healthcare professional with access to appropriate medical support to manage severe reactions such as serious infusion reactions. While no fatal infusion reactions occurred during clinical trials, 0.3% of patients did experience serious reactions, some requiring hospitalization. The highest incidence of infusion reactions is associated with the first infusion. To reduce the risk of an infusion reaction, pre-medication with methylprednisolone (or an equivalent corticosteroid) and an antihistamine should be used. The addition of an antipyretic may also be considered. Infusion reactions did occur in patients who were pre-medicated during clinical trials. Observe patients for infusion reactions during the infusion and for 1 or more hours following infusion completion. Infusion reactions may occur up to 24 hours after the infusion. Dose adjustments are necessary for patients who experience infusion reactions, and adjustments are dependent on the severity of the reaction. For life-threatening reactions, immediately and permanently stop treatment. For less severe reactions, management may include temporarily stopping the infusion and/or reducing the infusion rate. In all cases, appropriate supportive treatment must be administered.

    Hepatitis, herpes infection, infection, progressive multifocal leukoencephalopathy, respiratory infection, viral infection

    Ocrelizumab increases a patient's susceptibility to infection due to suppression of the immune system. Patients are at increased risk for serious infection. Delay treatment with ocrelizumab until an active infection resolves. Serious cases of viral infection 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 with ocrelizumab during postmarketing experience. Some infections were life-threatening. A serious herpes infection may occur at any time during treatment. Be alert for the potential for respiratory infection, skin infection, or serious infections of other types. There were no reports of progressive multifocal leukoencephalopathy (PML) during clinical trials of ocrelizumab. However, PML has been observed in patients treated with other anti-CD20 antibodies and other MS therapies, and it has been associated with some risk factors (e.g., concomitant immunosuppression, immunocompromised patients). As PML usually leads to death or severe disability, it is of vital importance to withhold ocrelizumab and perform an appropriate diagnostic evaluation at the first sign or symptom of PML. Symptoms of PML are diverse, including progressive weakness on one side of the body, clumsiness of limbs, vision disturbances, confusion, or personality alterations from changes in thinking, memory, or orientation. MRI findings of PML may be apparent before clinical signs or symptoms. Hepatitis B reactivation has been reported in patients treated with ocrelizumab during postmarketing experience. Fulminant hepatitis, hepatic failure, and death caused by HBV reactivation have occurred in patients treated with other anti-CD20 antibodies. Ocrelizumab is contraindicated for use in patients with active hepatitis B infection. Perform HBV screening for all patients prior to treatment, and do not administer ocrelizumab to patients with active HBV confirmed by positive results for hepatitis B surface antigen (HBsAg) and hepatitis B surface antibody (anti-HB) tests. If patients are negative for HBsAg and positive for HB core antibody (HBcAb+) or are carriers of HBV (HBsAg+), consult liver disease experts before initiation and during treatment.

    Hypogammaglobulinemia, immunosuppression

    Perform testing for quantitative serum immunoglobulins before initiating ocrelizumab treatment. Consult immunology experts before initiating treatment with ocrelizumab in patients with low serum immunoglobulins (hypogammaglobulinemia). Monitor quantitative serum immunoglobulin concentrations during treatment and after treatment discontinuation, until B-cell repletion, especially in the setting of recurrent serious infections. Consider ocrelizumab discontinuation in patients with serious opportunistic or recurrent serious infections, and if prolonged hypogammaglobulinemia requires treatment with intravenous immunoglobulins. Ocrelizuamb decreased total immunoglobulins with the greatest decline seen in IgM concentrations; however, a decrease in IgG concentrations was associated with an increased rate of serious infections. When initiating ocrelizumab after an immunosuppressive therapy or initiating an immunosuppressive therapy after ocrelizumab treatment, consider the potential for increased immunosuppression. Ocrelizumab has not been studied in combination with other multiple sclerosis therapies.

    Vaccination

    Administer all live or live-attenuated vaccinations according to current vaccination guidelines at least 4 weeks before initiation of ocrelizumab, and administer non-live vaccines at least 2 weeks before initiation whenever possible. Withhold vaccination with live or live-attenuated virus vaccines to patients during ocrelizumab treatment and until B-cell repletion. Ocrelizumab may interfere with the effectiveness of non-live virus vaccines. Attenuated antibody responses to tetanus toxoid-containing vaccine, pneumococcal polysaccharide, and pneumococcal conjugate vaccines, and seasonal influenza vaccine were observed in patients exposed to ocrelizumab at the time of vaccination during an open-label study. Do not administer live or live-attenuated vaccines to a newborn or infant born to mothers exposed to ocrelizumab while pregnant before confirming B-cell count recovery as measured by CD19+ B-cells; a newborn or infant may receive non-live vaccines as indicated before B-cell recovery; however, consider assessing the immune response to the vaccine.[61838] ACIP recommends that patients receiving any vaccination during immunosuppressive therapy or in the 2 weeks prior to starting therapy should be considered unimmunized and should be revaccinated a minimum of 3 months after discontinuation of therapy. Passive immunoprophylaxis with immune globulins may be indicated for immunocompromised persons instead of, or in addition to, vaccination.[43236]

    Breast cancer, new primary malignancy

    Ocrelizumab may increase the risk of developing a new primary malignancy. During controlled trials, malignancies, including breast cancer, occurred more frequently in patients given ocrelizumab compared to interferon beta-1a or placebo. Follow standard breast cancer screening guidelines. Use caution when treating patients with pre-existing or ongoing malignancies.

    Infants, neonates, pregnancy

    No adequate and well-controlled studies of ocrelizumab have been conducted during human pregnancy and the ability of the drug to cause fetal harm or affect reproductive capacity is unknown. Human IgG is known to cross the placental barrier; therefore, ocrelizumab may cross the placental barrier and cause fetal B-cell depletion and lymphocytopenia. During animal studies, depletion of B-lymphocytes in lymphoid tissues (spleen and lymph nodes) was observed in the fetuses of pregnant monkeys given ocrelizumab at doses of 2 times to 20 times the recommended human dose of 600 mg (on a mg/kg basis). Increased perinatal mortality was observed in the offspring of pregnant monkeys. The exact cause of death is unknown; however, the 2 neonates affected both had bacterial infections. Other adverse effects observed in the neonate monkeys include renal toxicity (glomerulopathy and inflammation), lymphoid follicle formation in the bone marrow, severe decreases in circulating B-lymphocytes, and reduced testicular weight. Do not administer live or live-attenuated vaccines to infants born to mothers exposed to ocrelizumab during pregnancy before confirming B-cell count recovery as measured by CD19+ B-cells. Neonates and infants may receive non-live vaccines as indicated before B-cell recovery; however, consider assessing the immune response to the vaccine. There is a pregnancy exposure registry that monitors outcomes in pregnant patients exposed to ocrelizumab; information about the registry can be obtained at www.ocrevuspregnancyregistry.com or by calling 1-833-872-4370.[61838]

    Contraception requirements, reproductive risk

    Ocrelizumab may pose a reproductive risk. Instruct females of childbearing age to avoid becoming pregnant while receiving the drug due to the potential for fetal harm. Discuss contraception requirements with the patient. Instruct patients that if they are pregnant or plan to become pregnant while receiving this drug that they should inform their healthcare provider. Women of childbearing potential should use effective contraception while receiving ocrelizumab therapy and for 6 months after the last infusion.

    Breast-feeding

    There are no data regarding use of ocrelizumab during breast-feeding and its excretion in human milk is unknown. Human IgG antibodies are excreted in human milk; therefore, the potential for absorption of ocrelizumab and subsequent B-cell depletion in the infant are unknown. Weigh the benefits of breast-feeding along with the mother's clinical need for ocrelizumab and any potential adverse effects on the breastfed infant or from the underlying maternal condition prior to using ocrelizumab. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    ADVERSE REACTIONS

    Severe

    bronchospasm / Rapid / Incidence not known
    anaphylactoid reactions / Rapid / Incidence not known
    laryngeal edema / Rapid / Incidence not known
    leukoencephalopathy / Delayed / Incidence not known
    hepatic failure / Delayed / Incidence not known
    progressive multifocal leukoencephalopathy / Delayed / Incidence not known
    hepatitis B exacerbation / Delayed / Incidence not known
    new primary malignancy / Delayed / Incidence not known

    Moderate

    infusion-related reactions / Rapid / 34.0-40.0
    depression / Delayed / 8.0-8.0
    peripheral edema / Delayed / 6.0-6.0
    hypotension / Rapid / Incidence not known
    sinus tachycardia / Rapid / Incidence not known
    erythema / Early / Incidence not known
    dyspnea / Early / Incidence not known
    meningitis / Delayed / Incidence not known
    hepatitis / Delayed / Incidence not known
    neutropenia / Delayed / Incidence not known
    immunosuppression / Delayed / Incidence not known
    hypogammaglobulinemia / Delayed / Incidence not known
    antibody formation / Delayed / Incidence not known

    Mild

    infection / Delayed / 58.0-70.0
    cough / Delayed / 7.0-7.0
    back pain / Delayed / 6.0-6.0
    diarrhea / Early / 6.0-6.0
    fatigue / Early / Incidence not known
    urticaria / Rapid / Incidence not known
    flushing / Rapid / Incidence not known
    dizziness / Early / Incidence not known
    nausea / Early / Incidence not known
    fever / Early / Incidence not known
    rash / Early / Incidence not known
    pruritus / Rapid / Incidence not known
    headache / Early / Incidence not known
    throat irritation / Early / Incidence not known

    DRUG INTERACTIONS

    Alemtuzumab: (Major) Ocrelizumab has not been studied in combination with other immunosuppressive or immune modulating therapies used for the treatment of multiple sclerosis, such as alemtuzumab. Concomitant use of ocrelizumab with alemtuzumab may increase the risk of immunosuppression. Avoid the use of these drugs together.
    Anifrolumab: (Major) Coadministration is not recommended. Anifrolumab has not been studied in combination with other biologic therapies including B-cell targeted therapies such as ocrelizumab. Potential concerns with use of these drugs together include an increased susceptibility to immunosuppression and serious infections, some of which might be fatal.
    Anthrax Vaccine: (Moderate) Administer all non-live vaccines at least 2 weeks before ocrelizumab initiation, whenever possible. Ocrelizumab may interfere with the effectiveness of non-live virus vaccines. Attenuated antibody responses to tetanus toxoid-containing vaccine, pneumococcal polysaccharide and pneumococcal conjugate vaccines, and seasonal influenza vaccine were observed in patients exposed to ocrelizumab at the time of vaccination during an open-label study. Infants born to mothers exposed to ocrelizumab during pregnancy may receive non-live vaccines as indicated before B-cell recovery; however, consider assessing the immune response to the vaccine. ACIP recommends that patients receiving any vaccination during immunosuppressive therapy or in the 2 weeks prior to starting therapy should be considered unimmunized and should be revaccinated a minimum of 3 months after discontinuation of therapy. Passive immunoprophylaxis with immune globulins may be indicated for immunocompromised persons instead of, or in addition to, vaccination.
    Bacillus Calmette-Guerin Vaccine, BCG: (Major) Due to the lack of clinical information related to the safety and efficacy of vaccine administration during ocrelizumab use, vaccination with live vaccines or live-attenuated vaccines is not recommended in patients taking ocrelizumab. Withhold vaccination with live or live-attenuated virus vaccines to patients during ocrelizumab treatment and until B-cell repletion. Administer all live or live-attenuated vaccinations according to current vaccination guidelines at least 4 weeks before initiation of ocrelizumab. Do not administer live or live-attenuated vaccines to infants born to mothers exposed to ocrelizumab during pregnancy before confirming B-cell count recovery as measured by CD19+ B-cells. ACIP recommends that patients receiving any vaccination during immunosuppressive therapy or in the 2 weeks prior to starting therapy should be considered unimmunized and should be revaccinated a minimum of 3 months after discontinuation of therapy. Passive immunoprophylaxis with immune globulins may be indicated for immunocompromised persons instead of, or in addition to, vaccination.
    Belimumab: (Major) Avoid use together. Belimumab has not been studied in combination with other biologic therapies including B-cell targeted therapies such as ocrelizumab. Therefore, belimumab use is not recommended in combination with biologic therapies. Potential concerns with use together include an increased susceptibility to immunosuppression and serious infections, some of which might be fatal.
    Betamethasone: (Moderate) Ocrelizumab has not been studied in combination with other immunosuppressive or immune modulating therapies used for the treatment of multiple sclerosis, including immunosuppressant doses of corticosteroids. Concomitant use of ocrelizumab with any of these therapies may increase the risk of immunosuppression. Monitor patients carefully for signs and symptoms of infection.
    Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine.
    Cortisone: (Moderate) Ocrelizumab has not been studied in combination with other immunosuppressive or immune modulating therapies used for the treatment of multiple sclerosis, including immunosuppressant doses of corticosteroids. Concomitant use of ocrelizumab with any of these therapies may increase the risk of immunosuppression. Monitor patients carefully for signs and symptoms of infection.
    Daclizumab: (Major) Avoid use of these drugs together. Ocrelizumab has not been studied in combination with other immunosuppressive or immune modulating therapies used for the treatment of multiple sclerosis. Concomitant use of ocrelizumab with any of these therapies may increase the risk of immunosuppression. Use caution when switching patients from long-acting therapies with immune effects such as daclizumab. The elimination half-life of daclizumab is approximately 20 days.
    Dexamethasone: (Moderate) Ocrelizumab has not been studied in combination with other immunosuppressive or immune modulating therapies used for the treatment of multiple sclerosis, including immunosuppressant doses of corticosteroids. Concomitant use of ocrelizumab with any of these therapies may increase the risk of immunosuppression. Monitor patients carefully for signs and symptoms of infection.
    Dimethyl Fumarate: (Moderate) Ocrelizumab has not been studied in combination with other immunosuppressive or immune modulating therapies used for the treatment of multiple sclerosis, such as dimethyl fumarate. Concomitant use of ocrelizumab with dimethyl fumarate may increase the risk of immunosuppression. Avoid the use of these drugs together.
    Diphtheria Toxoid, Tetanus Toxoid, Acellular Pertussis Vaccine, DTaP; Haemophilus influenzae type b Conjugate Vaccine; Hepatitis B Vaccine, Recombinant; Inactivated Poliovirus Vaccine, IPV: (Moderate) Administer all non-live vaccines at least 2 weeks before ocrelizumab initiation, whenever possible. Ocrelizumab may interfere with the effectiveness of non-live virus vaccines. Attenuated antibody responses to tetanus toxoid-containing vaccine, pneumococcal polysaccharide and pneumococcal conjugate vaccines, and seasonal influenza vaccine were observed in patients exposed to ocrelizumab at the time of vaccination during an open-label study. Infants born to mothers exposed to ocrelizumab during pregnancy may receive non-live vaccines as indicated before B-cell recovery; however, consider assessing the immune response to the vaccine. ACIP recommends that patients receiving any vaccination during immunosuppressive therapy or in the 2 weeks prior to starting therapy should be considered unimmunized and should be revaccinated a minimum of 3 months after discontinuation of therapy. Passive immunoprophylaxis with immune globulins may be indicated for immunocompromised persons instead of, or in addition to, vaccination.
    Diphtheria Toxoid, Tetanus Toxoid, Acellular Pertussis Vaccine, DTaP; Haemophilus influenzae type b Conjugate Vaccine; Inactivated Poliovirus Vaccine, IPV: (Moderate) Administer all non-live vaccines at least 2 weeks before ocrelizumab initiation, whenever possible. Ocrelizumab may interfere with the effectiveness of non-live virus vaccines. Attenuated antibody responses to tetanus toxoid-containing vaccine, pneumococcal polysaccharide and pneumococcal conjugate vaccines, and seasonal influenza vaccine were observed in patients exposed to ocrelizumab at the time of vaccination during an open-label study. Infants born to mothers exposed to ocrelizumab during pregnancy may receive non-live vaccines as indicated before B-cell recovery; however, consider assessing the immune response to the vaccine. ACIP recommends that patients receiving any vaccination during immunosuppressive therapy or in the 2 weeks prior to starting therapy should be considered unimmunized and should be revaccinated a minimum of 3 months after discontinuation of therapy. Passive immunoprophylaxis with immune globulins may be indicated for immunocompromised persons instead of, or in addition to, vaccination.
    Diphtheria Toxoid, Tetanus Toxoid, Acellular Pertussis Vaccine, DTaP; Hepatitis B Vaccine, Recombinant; Inactivated Poliovirus Vaccine, IPV : (Moderate) Administer all non-live vaccines at least 2 weeks before ocrelizumab initiation, whenever possible. Ocrelizumab may interfere with the effectiveness of non-live virus vaccines. Attenuated antibody responses to tetanus toxoid-containing vaccine, pneumococcal polysaccharide and pneumococcal conjugate vaccines, and seasonal influenza vaccine were observed in patients exposed to ocrelizumab at the time of vaccination during an open-label study. Infants born to mothers exposed to ocrelizumab during pregnancy may receive non-live vaccines as indicated before B-cell recovery; however, consider assessing the immune response to the vaccine. ACIP recommends that patients receiving any vaccination during immunosuppressive therapy or in the 2 weeks prior to starting therapy should be considered unimmunized and should be revaccinated a minimum of 3 months after discontinuation of therapy. Passive immunoprophylaxis with immune globulins may be indicated for immunocompromised persons instead of, or in addition to, vaccination.
    Diphtheria Toxoid, Tetanus Toxoid, Acellular Pertussis Vaccine, DTaP; Inactivated Poliovirus Vaccine, IPV: (Moderate) Administer all non-live vaccines at least 2 weeks before ocrelizumab initiation, whenever possible. Ocrelizumab may interfere with the effectiveness of non-live virus vaccines. Attenuated antibody responses to tetanus toxoid-containing vaccine, pneumococcal polysaccharide and pneumococcal conjugate vaccines, and seasonal influenza vaccine were observed in patients exposed to ocrelizumab at the time of vaccination during an open-label study. Infants born to mothers exposed to ocrelizumab during pregnancy may receive non-live vaccines as indicated before B-cell recovery; however, consider assessing the immune response to the vaccine. ACIP recommends that patients receiving any vaccination during immunosuppressive therapy or in the 2 weeks prior to starting therapy should be considered unimmunized and should be revaccinated a minimum of 3 months after discontinuation of therapy. Passive immunoprophylaxis with immune globulins may be indicated for immunocompromised persons instead of, or in addition to, vaccination.
    Diphtheria Toxoid; Tetanus Toxoid Adsorbed, DT, Td: (Moderate) Administer all non-live vaccines at least 2 weeks before ocrelizumab initiation, whenever possible. Ocrelizumab may interfere with the effectiveness of non-live virus vaccines. Attenuated antibody responses to tetanus toxoid-containing vaccine, pneumococcal polysaccharide and pneumococcal conjugate vaccines, and seasonal influenza vaccine were observed in patients exposed to ocrelizumab at the time of vaccination during an open-label study. Infants born to mothers exposed to ocrelizumab during pregnancy may receive non-live vaccines as indicated before B-cell recovery; however, consider assessing the immune response to the vaccine. ACIP recommends that patients receiving any vaccination during immunosuppressive therapy or in the 2 weeks prior to starting therapy should be considered unimmunized and should be revaccinated a minimum of 3 months after discontinuation of therapy. Passive immunoprophylaxis with immune globulins may be indicated for immunocompromised persons instead of, or in addition to, vaccination.
    Diphtheria/Tetanus Toxoids; Pertussis Vaccine: (Moderate) Administer all non-live vaccines at least 2 weeks before ocrelizumab initiation, whenever possible. Ocrelizumab may interfere with the effectiveness of non-live virus vaccines. Attenuated antibody responses to tetanus toxoid-containing vaccine, pneumococcal polysaccharide and pneumococcal conjugate vaccines, and seasonal influenza vaccine were observed in patients exposed to ocrelizumab at the time of vaccination during an open-label study. Infants born to mothers exposed to ocrelizumab during pregnancy may receive non-live vaccines as indicated before B-cell recovery; however, consider assessing the immune response to the vaccine. ACIP recommends that patients receiving any vaccination during immunosuppressive therapy or in the 2 weeks prior to starting therapy should be considered unimmunized and should be revaccinated a minimum of 3 months after discontinuation of therapy. Passive immunoprophylaxis with immune globulins may be indicated for immunocompromised persons instead of, or in addition to, vaccination.
    Diphtheria/Tetanus Toxoids; Pertussis Vaccine; Haemophilus influenzae type b Conjugate Vaccine: (Moderate) Administer all non-live vaccines at least 2 weeks before ocrelizumab initiation, whenever possible. Ocrelizumab may interfere with the effectiveness of non-live virus vaccines. Attenuated antibody responses to tetanus toxoid-containing vaccine, pneumococcal polysaccharide and pneumococcal conjugate vaccines, and seasonal influenza vaccine were observed in patients exposed to ocrelizumab at the time of vaccination during an open-label study. Infants born to mothers exposed to ocrelizumab during pregnancy may receive non-live vaccines as indicated before B-cell recovery; however, consider assessing the immune response to the vaccine. ACIP recommends that patients receiving any vaccination during immunosuppressive therapy or in the 2 weeks prior to starting therapy should be considered unimmunized and should be revaccinated a minimum of 3 months after discontinuation of therapy. Passive immunoprophylaxis with immune globulins may be indicated for immunocompromised persons instead of, or in addition to, vaccination.
    Diroximel Fumarate: (Moderate) Ocrelizumab has not been studied in combination with other immunosuppressive or immune modulating therapies used for the treatment of multiple sclerosis, such as diroximel fumarate. Concomitant use of ocrelizumab with diroximel fumarate may increase the risk of immunosuppression. Avoid the use of these drugs together.
    Glatiramer: (Moderate) Ocrelizumab has not been studied in combination with other immunosuppressive or immune modulating therapies used for the treatment of multiple sclerosis, such as glatiramer. Concomitant use of ocrelizumab with glatiramer may increase the risk of immunosuppression. Avoid the use of these drugs together.
    Haemophilus influenzae type b Conjugate Vaccine: (Moderate) Administer all non-live vaccines at least 2 weeks before ocrelizumab initiation, whenever possible. Ocrelizumab may interfere with the effectiveness of non-live virus vaccines. Attenuated antibody responses to tetanus toxoid-containing vaccine, pneumococcal polysaccharide and pneumococcal conjugate vaccines, and seasonal influenza vaccine were observed in patients exposed to ocrelizumab at the time of vaccination during an open-label study. Infants born to mothers exposed to ocrelizumab during pregnancy may receive non-live vaccines as indicated before B-cell recovery; however, consider assessing the immune response to the vaccine. ACIP recommends that patients receiving any vaccination during immunosuppressive therapy or in the 2 weeks prior to starting therapy should be considered unimmunized and should be revaccinated a minimum of 3 months after discontinuation of therapy. Passive immunoprophylaxis with immune globulins may be indicated for immunocompromised persons instead of, or in addition to, vaccination.
    Haemophilus influenzae type b Conjugate Vaccine; Hepatitis B Vaccine, Recombinant: (Moderate) Administer all non-live vaccines at least 2 weeks before ocrelizumab initiation, whenever possible. Ocrelizumab may interfere with the effectiveness of non-live virus vaccines. Attenuated antibody responses to tetanus toxoid-containing vaccine, pneumococcal polysaccharide and pneumococcal conjugate vaccines, and seasonal influenza vaccine were observed in patients exposed to ocrelizumab at the time of vaccination during an open-label study. Infants born to mothers exposed to ocrelizumab during pregnancy may receive non-live vaccines as indicated before B-cell recovery; however, consider assessing the immune response to the vaccine. ACIP recommends that patients receiving any vaccination during immunosuppressive therapy or in the 2 weeks prior to starting therapy should be considered unimmunized and should be revaccinated a minimum of 3 months after discontinuation of therapy. Passive immunoprophylaxis with immune globulins may be indicated for immunocompromised persons instead of, or in addition to, vaccination.
    Hepatitis A Vaccine, Inactivated: (Moderate) Administer all non-live vaccines at least 2 weeks before ocrelizumab initiation, whenever possible. Ocrelizumab may interfere with the effectiveness of non-live virus vaccines. Attenuated antibody responses to tetanus toxoid-containing vaccine, pneumococcal polysaccharide and pneumococcal conjugate vaccines, and seasonal influenza vaccine were observed in patients exposed to ocrelizumab at the time of vaccination during an open-label study. Infants born to mothers exposed to ocrelizumab during pregnancy may receive non-live vaccines as indicated before B-cell recovery; however, consider assessing the immune response to the vaccine. ACIP recommends that patients receiving any vaccination during immunosuppressive therapy or in the 2 weeks prior to starting therapy should be considered unimmunized and should be revaccinated a minimum of 3 months after discontinuation of therapy. Passive immunoprophylaxis with immune globulins may be indicated for immunocompromised persons instead of, or in addition to, vaccination.
    Hepatitis A Vaccine, Inactivated; Hepatitis B Vaccine, Recombinant: (Moderate) Administer all non-live vaccines at least 2 weeks before ocrelizumab initiation, whenever possible. Ocrelizumab may interfere with the effectiveness of non-live virus vaccines. Attenuated antibody responses to tetanus toxoid-containing vaccine, pneumococcal polysaccharide and pneumococcal conjugate vaccines, and seasonal influenza vaccine were observed in patients exposed to ocrelizumab at the time of vaccination during an open-label study. Infants born to mothers exposed to ocrelizumab during pregnancy may receive non-live vaccines as indicated before B-cell recovery; however, consider assessing the immune response to the vaccine. ACIP recommends that patients receiving any vaccination during immunosuppressive therapy or in the 2 weeks prior to starting therapy should be considered unimmunized and should be revaccinated a minimum of 3 months after discontinuation of therapy. Passive immunoprophylaxis with immune globulins may be indicated for immunocompromised persons instead of, or in addition to, vaccination.
    Hepatitis B Vaccine, Recombinant: (Moderate) Administer all non-live vaccines at least 2 weeks before ocrelizumab initiation, whenever possible. Ocrelizumab may interfere with the effectiveness of non-live virus vaccines. Attenuated antibody responses to tetanus toxoid-containing vaccine, pneumococcal polysaccharide and pneumococcal conjugate vaccines, and seasonal influenza vaccine were observed in patients exposed to ocrelizumab at the time of vaccination during an open-label study. Infants born to mothers exposed to ocrelizumab during pregnancy may receive non-live vaccines as indicated before B-cell recovery; however, consider assessing the immune response to the vaccine. ACIP recommends that patients receiving any vaccination during immunosuppressive therapy or in the 2 weeks prior to starting therapy should be considered unimmunized and should be revaccinated a minimum of 3 months after discontinuation of therapy. Passive immunoprophylaxis with immune globulins may be indicated for immunocompromised persons instead of, or in addition to, vaccination.
    Human Papillomavirus 9-Valent Vaccine: (Moderate) Administer all non-live vaccines at least 2 weeks before ocrelizumab initiation, whenever possible. Ocrelizumab may interfere with the effectiveness of non-live virus vaccines. Attenuated antibody responses to tetanus toxoid-containing vaccine, pneumococcal polysaccharide and pneumococcal conjugate vaccines, and seasonal influenza vaccine were observed in patients exposed to ocrelizumab at the time of vaccination during an open-label study. Infants born to mothers exposed to ocrelizumab during pregnancy may receive non-live vaccines as indicated before B-cell recovery; however, consider assessing the immune response to the vaccine. ACIP recommends that patients receiving any vaccination during immunosuppressive therapy or in the 2 weeks prior to starting therapy should be considered unimmunized and should be revaccinated a minimum of 3 months after discontinuation of therapy. Passive immunoprophylaxis with immune globulins may be indicated for immunocompromised persons instead of, or in addition to, vaccination.
    Human Papillomavirus Bivalent Vaccine: (Moderate) Administer all non-live vaccines at least 2 weeks before ocrelizumab initiation, whenever possible. Ocrelizumab may interfere with the effectiveness of non-live virus vaccines. Attenuated antibody responses to tetanus toxoid-containing vaccine, pneumococcal polysaccharide and pneumococcal conjugate vaccines, and seasonal influenza vaccine were observed in patients exposed to ocrelizumab at the time of vaccination during an open-label study. Infants born to mothers exposed to ocrelizumab during pregnancy may receive non-live vaccines as indicated before B-cell recovery; however, consider assessing the immune response to the vaccine. ACIP recommends that patients receiving any vaccination during immunosuppressive therapy or in the 2 weeks prior to starting therapy should be considered unimmunized and should be revaccinated a minimum of 3 months after discontinuation of therapy. Passive immunoprophylaxis with immune globulins may be indicated for immunocompromised persons instead of, or in addition to, vaccination.
    Human Papillomavirus Quadrivalent Vaccine: (Moderate) Administer all non-live vaccines at least 2 weeks before ocrelizumab initiation, whenever possible. Ocrelizumab may interfere with the effectiveness of non-live virus vaccines. Attenuated antibody responses to tetanus toxoid-containing vaccine, pneumococcal polysaccharide and pneumococcal conjugate vaccines, and seasonal influenza vaccine were observed in patients exposed to ocrelizumab at the time of vaccination during an open-label study. Infants born to mothers exposed to ocrelizumab during pregnancy may receive non-live vaccines as indicated before B-cell recovery; however, consider assessing the immune response to the vaccine. ACIP recommends that patients receiving any vaccination during immunosuppressive therapy or in the 2 weeks prior to starting therapy should be considered unimmunized and should be revaccinated a minimum of 3 months after discontinuation of therapy. Passive immunoprophylaxis with immune globulins may be indicated for immunocompromised persons instead of, or in addition to, vaccination.
    Hydrocortisone: (Moderate) Ocrelizumab has not been studied in combination with other immunosuppressive or immune modulating therapies used for the treatment of multiple sclerosis, including immunosuppressant doses of corticosteroids. Concomitant use of ocrelizumab with any of these therapies may increase the risk of immunosuppression. Monitor patients carefully for signs and symptoms of infection.
    Influenza Virus Vaccine: (Moderate) Administer all non-live vaccines at least 2 weeks before ocrelizumab initiation, whenever possible. Ocrelizumab may interfere with the effectiveness of non-live virus vaccines. Attenuated antibody responses to tetanus toxoid-containing vaccine, pneumococcal polysaccharide and pneumococcal conjugate vaccines, and seasonal influenza vaccine were observed in patients exposed to ocrelizumab at the time of vaccination during an open-label study. Infants born to mothers exposed to ocrelizumab during pregnancy may receive non-live vaccines as indicated before B-cell recovery; however, consider assessing the immune response to the vaccine. ACIP recommends that patients receiving any vaccination during immunosuppressive therapy or in the 2 weeks prior to starting therapy should be considered unimmunized and should be revaccinated a minimum of 3 months after discontinuation of therapy. Passive immunoprophylaxis with immune globulins may be indicated for immunocompromised persons instead of, or in addition to, vaccination.
    Interferon Beta-1a: (Moderate) Ocrelizumab has not been studied in combination with other immunosuppressive or immune modulating therapies used for the treatment of multiple sclerosis, such as interferon beta-1a or interferon beta-1b. Concomitant use of ocrelizumab with interferon beta may increase the risk of immunosuppression.
    Interferon Beta-1b: (Moderate) Ocrelizumab has not been studied in combination with other immunosuppressive or immune modulating therapies used for the treatment of multiple sclerosis, such as interferon beta-1a or interferon beta-1b. Concomitant use of ocrelizumab with interferon beta may increase the risk of immunosuppression.
    Intranasal Influenza Vaccine: (Major) Due to the lack of clinical information related to the safety and efficacy of vaccine administration during ocrelizumab use, vaccination with live vaccines or live-attenuated vaccines is not recommended in patients taking ocrelizumab. Withhold vaccination with live or live-attenuated virus vaccines to patients during ocrelizumab treatment and until B-cell repletion. Administer all live or live-attenuated vaccinations according to current vaccination guidelines at least 4 weeks before initiation of ocrelizumab. Do not administer live or live-attenuated vaccines to infants born to mothers exposed to ocrelizumab during pregnancy before confirming B-cell count recovery as measured by CD19+ B-cells. ACIP recommends that patients receiving any vaccination during immunosuppressive therapy or in the 2 weeks prior to starting therapy should be considered unimmunized and should be revaccinated a minimum of 3 months after discontinuation of therapy. Passive immunoprophylaxis with immune globulins may be indicated for immunocompromised persons instead of, or in addition to, vaccination. (Moderate) Administer all non-live vaccines at least 2 weeks before ocrelizumab initiation, whenever possible. Ocrelizumab may interfere with the effectiveness of non-live virus vaccines. Attenuated antibody responses to tetanus toxoid-containing vaccine, pneumococcal polysaccharide and pneumococcal conjugate vaccines, and seasonal influenza vaccine were observed in patients exposed to ocrelizumab at the time of vaccination during an open-label study. Infants born to mothers exposed to ocrelizumab during pregnancy may receive non-live vaccines as indicated before B-cell recovery; however, consider assessing the immune response to the vaccine. ACIP recommends that patients receiving any vaccination during immunosuppressive therapy or in the 2 weeks prior to starting therapy should be considered unimmunized and should be revaccinated a minimum of 3 months after discontinuation of therapy. Passive immunoprophylaxis with immune globulins may be indicated for immunocompromised persons instead of, or in addition to, vaccination.
    Japanese Encephalitis Virus Vaccine: (Moderate) Administer all non-live vaccines at least 2 weeks before ocrelizumab initiation, whenever possible. Ocrelizumab may interfere with the effectiveness of non-live virus vaccines. Attenuated antibody responses to tetanus toxoid-containing vaccine, pneumococcal polysaccharide and pneumococcal conjugate vaccines, and seasonal influenza vaccine were observed in patients exposed to ocrelizumab at the time of vaccination during an open-label study. Infants born to mothers exposed to ocrelizumab during pregnancy may receive non-live vaccines as indicated before B-cell recovery; however, consider assessing the immune response to the vaccine. ACIP recommends that patients receiving any vaccination during immunosuppressive therapy or in the 2 weeks prior to starting therapy should be considered unimmunized and should be revaccinated a minimum of 3 months after discontinuation of therapy. Passive immunoprophylaxis with immune globulins may be indicated for immunocompromised persons instead of, or in addition to, vaccination.
    Live Vaccines: (Major) Due to the lack of clinical information related to the safety and efficacy of vaccine administration during ocrelizumab use, vaccination with live vaccines or live-attenuated vaccines is not recommended in patients taking ocrelizumab. Withhold vaccination with live or live-attenuated virus vaccines to patients during ocrelizumab treatment and until B-cell repletion. Administer all live or live-attenuated vaccinations according to current vaccination guidelines at least 4 weeks before initiation of ocrelizumab. Do not administer live or live-attenuated vaccines to infants born to mothers exposed to ocrelizumab during pregnancy before confirming B-cell count recovery as measured by CD19+ B-cells. ACIP recommends that patients receiving any vaccination during immunosuppressive therapy or in the 2 weeks prior to starting therapy should be considered unimmunized and should be revaccinated a minimum of 3 months after discontinuation of therapy. Passive immunoprophylaxis with immune globulins may be indicated for immunocompromised persons instead of, or in addition to, vaccination.
    Measles Virus; Mumps Virus; Rubella Virus; Varicella Virus Vaccine, Live: (Major) Due to the lack of clinical information related to the safety and efficacy of vaccine administration during ocrelizumab use, vaccination with live vaccines or live-attenuated vaccines is not recommended in patients taking ocrelizumab. Withhold vaccination with live or live-attenuated virus vaccines to patients during ocrelizumab treatment and until B-cell repletion. Administer all live or live-attenuated vaccinations according to current vaccination guidelines at least 4 weeks before initiation of ocrelizumab. Do not administer live or live-attenuated vaccines to infants born to mothers exposed to ocrelizumab during pregnancy before confirming B-cell count recovery as measured by CD19+ B-cells. ACIP recommends that patients receiving any vaccination during immunosuppressive therapy or in the 2 weeks prior to starting therapy should be considered unimmunized and should be revaccinated a minimum of 3 months after discontinuation of therapy. Passive immunoprophylaxis with immune globulins may be indicated for immunocompromised persons instead of, or in addition to, vaccination.
    Measles/Mumps/Rubella Vaccines, MMR: (Major) Due to the lack of clinical information related to the safety and efficacy of vaccine administration during ocrelizumab use, vaccination with live vaccines or live-attenuated vaccines is not recommended in patients taking ocrelizumab. Withhold vaccination with live or live-attenuated virus vaccines to patients during ocrelizumab treatment and until B-cell repletion. Administer all live or live-attenuated vaccinations according to current vaccination guidelines at least 4 weeks before initiation of ocrelizumab. Do not administer live or live-attenuated vaccines to infants born to mothers exposed to ocrelizumab during pregnancy before confirming B-cell count recovery as measured by CD19+ B-cells. ACIP recommends that patients receiving any vaccination during immunosuppressive therapy or in the 2 weeks prior to starting therapy should be considered unimmunized and should be revaccinated a minimum of 3 months after discontinuation of therapy. Passive immunoprophylaxis with immune globulins may be indicated for immunocompromised persons instead of, or in addition to, vaccination.
    Meningococcal Conjugate Vaccine (MCV4): (Moderate) Administer all non-live vaccines at least 2 weeks before ocrelizumab initiation, whenever possible. Ocrelizumab may interfere with the effectiveness of non-live virus vaccines. Attenuated antibody responses to tetanus toxoid-containing vaccine, pneumococcal polysaccharide and pneumococcal conjugate vaccines, and seasonal influenza vaccine were observed in patients exposed to ocrelizumab at the time of vaccination during an open-label study. Infants born to mothers exposed to ocrelizumab during pregnancy may receive non-live vaccines as indicated before B-cell recovery; however, consider assessing the immune response to the vaccine. ACIP recommends that patients receiving any vaccination during immunosuppressive therapy or in the 2 weeks prior to starting therapy should be considered unimmunized and should be revaccinated a minimum of 3 months after discontinuation of therapy. Passive immunoprophylaxis with immune globulins may be indicated for immunocompromised persons instead of, or in addition to, vaccination.
    Meningococcal Group B Vaccine (3 strain): (Moderate) Administer all non-live vaccines at least 2 weeks before ocrelizumab initiation, whenever possible. Ocrelizumab may interfere with the effectiveness of non-live virus vaccines. Attenuated antibody responses to tetanus toxoid-containing vaccine, pneumococcal polysaccharide and pneumococcal conjugate vaccines, and seasonal influenza vaccine were observed in patients exposed to ocrelizumab at the time of vaccination during an open-label study. Infants born to mothers exposed to ocrelizumab during pregnancy may receive non-live vaccines as indicated before B-cell recovery; however, consider assessing the immune response to the vaccine. ACIP recommends that patients receiving any vaccination during immunosuppressive therapy or in the 2 weeks prior to starting therapy should be considered unimmunized and should be revaccinated a minimum of 3 months after discontinuation of therapy. Passive immunoprophylaxis with immune globulins may be indicated for immunocompromised persons instead of, or in addition to, vaccination.
    Meningococcal Group B Vaccine (4 strain): (Moderate) Administer all non-live vaccines at least 2 weeks before ocrelizumab initiation, whenever possible. Ocrelizumab may interfere with the effectiveness of non-live virus vaccines. Attenuated antibody responses to tetanus toxoid-containing vaccine, pneumococcal polysaccharide and pneumococcal conjugate vaccines, and seasonal influenza vaccine were observed in patients exposed to ocrelizumab at the time of vaccination during an open-label study. Infants born to mothers exposed to ocrelizumab during pregnancy may receive non-live vaccines as indicated before B-cell recovery; however, consider assessing the immune response to the vaccine. ACIP recommends that patients receiving any vaccination during immunosuppressive therapy or in the 2 weeks prior to starting therapy should be considered unimmunized and should be revaccinated a minimum of 3 months after discontinuation of therapy. Passive immunoprophylaxis with immune globulins may be indicated for immunocompromised persons instead of, or in addition to, vaccination.
    Meningococcal Haemophilus influenzae type b Conjugate Vaccine: (Moderate) Administer all non-live vaccines at least 2 weeks before ocrelizumab initiation, whenever possible. Ocrelizumab may interfere with the effectiveness of non-live virus vaccines. Attenuated antibody responses to tetanus toxoid-containing vaccine, pneumococcal polysaccharide and pneumococcal conjugate vaccines, and seasonal influenza vaccine were observed in patients exposed to ocrelizumab at the time of vaccination during an open-label study. Infants born to mothers exposed to ocrelizumab during pregnancy may receive non-live vaccines as indicated before B-cell recovery; however, consider assessing the immune response to the vaccine. ACIP recommends that patients receiving any vaccination during immunosuppressive therapy or in the 2 weeks prior to starting therapy should be considered unimmunized and should be revaccinated a minimum of 3 months after discontinuation of therapy. Passive immunoprophylaxis with immune globulins may be indicated for immunocompromised persons instead of, or in addition to, vaccination.
    Meningococcal Polysaccharide Vaccine (MPSV4): (Moderate) Administer all non-live vaccines at least 2 weeks before ocrelizumab initiation, whenever possible. Ocrelizumab may interfere with the effectiveness of non-live virus vaccines. Attenuated antibody responses to tetanus toxoid-containing vaccine, pneumococcal polysaccharide and pneumococcal conjugate vaccines, and seasonal influenza vaccine were observed in patients exposed to ocrelizumab at the time of vaccination during an open-label study. Infants born to mothers exposed to ocrelizumab during pregnancy may receive non-live vaccines as indicated before B-cell recovery; however, consider assessing the immune response to the vaccine. ACIP recommends that patients receiving any vaccination during immunosuppressive therapy or in the 2 weeks prior to starting therapy should be considered unimmunized and should be revaccinated a minimum of 3 months after discontinuation of therapy. Passive immunoprophylaxis with immune globulins may be indicated for immunocompromised persons instead of, or in addition to, vaccination.
    Methylprednisolone: (Moderate) Ocrelizumab has not been studied in combination with other immunosuppressive or immune modulating therapies used for the treatment of multiple sclerosis, including immunosuppressant doses of corticosteroids. Concomitant use of ocrelizumab with any of these therapies may increase the risk of immunosuppression. Monitor patients carefully for signs and symptoms of infection.
    Mitoxantrone: (Moderate) Ocrelizumab has not been studied in combination with other immunosuppressive or immune modulating therapies used for the treatment of multiple sclerosis. Concomitant use of ocrelizumab with any of these therapies may increase the risk of immunosuppression. Use caution when switching patients from long-acting therapies with immune effects such as mitoxantrone. The median elimination half-life of mitoxantrone is 75 hours (range 23 to 215 hours).
    Monomethyl Fumarate: (Moderate) Ocrelizumab has not been studied in combination with other immunosuppressive or immune modulating therapies used for the treatment of multiple sclerosis, such as dimethyl fumarate. Concomitant use of ocrelizumab with dimethyl fumarate may increase the risk of immunosuppression. Avoid the use of these drugs together.
    Natalizumab: (Major) Natalizumab should not be used in combination with ocrelizumab because of the potential for increased risk of progressive multifocal leukoencephalopathy and other serious infections. Ordinarily, multiple sclerosis patients receiving chronic immunomodulatory therapy should not be treated with natalizumab.
    Non-Live Vaccines: (Moderate) Administer all non-live vaccines at least 2 weeks before ocrelizumab initiation, whenever possible. Ocrelizumab may interfere with the effectiveness of non-live virus vaccines. Attenuated antibody responses to tetanus toxoid-containing vaccine, pneumococcal polysaccharide and pneumococcal conjugate vaccines, and seasonal influenza vaccine were observed in patients exposed to ocrelizumab at the time of vaccination during an open-label study. Infants born to mothers exposed to ocrelizumab during pregnancy may receive non-live vaccines as indicated before B-cell recovery; however, consider assessing the immune response to the vaccine. ACIP recommends that patients receiving any vaccination during immunosuppressive therapy or in the 2 weeks prior to starting therapy should be considered unimmunized and should be revaccinated a minimum of 3 months after discontinuation of therapy. Passive immunoprophylaxis with immune globulins may be indicated for immunocompromised persons instead of, or in addition to, vaccination.
    Ofatumumab: (Moderate) Concomitant use of ofatumumab with ocrelizumab may increase the risk of immunosuppression. Ofatumumab has not been studied in combination with other immunosuppressive or immune modulating therapies used for the treatment of multiple sclerosis, such as ocrelizumab. Consider the duration and mechanism of action of drugs with immunosuppressive effects when switching therapies for multiple sclerosis patients.
    Ozanimod: (Moderate) Concomitant use of ozanimod with ocrelizumab may increase the risk of immunosuppression. Ozanimod has not been studied in combination with other immunosuppressive or immune modulating therapies used for the treatment of multiple sclerosis.
    Peginterferon beta-1a: (Moderate) Ocrelizumab has not been studied in combination with other immunosuppressive or immune modulating therapies used for the treatment of multiple sclerosis, such as peginterferon beta-1a. Concomitant use of ocrelizumab with peginterferon beta-1a may increase the risk of immunosuppression.
    Pneumococcal Vaccine, Polyvalent: (Moderate) Administer all non-live vaccines at least 2 weeks before ocrelizumab initiation, whenever possible. Ocrelizumab may interfere with the effectiveness of non-live virus vaccines. Attenuated antibody responses to tetanus toxoid-containing vaccine, pneumococcal polysaccharide and pneumococcal conjugate vaccines, and seasonal influenza vaccine were observed in patients exposed to ocrelizumab at the time of vaccination during an open-label study. Infants born to mothers exposed to ocrelizumab during pregnancy may receive non-live vaccines as indicated before B-cell recovery; however, consider assessing the immune response to the vaccine. ACIP recommends that patients receiving any vaccination during immunosuppressive therapy or in the 2 weeks prior to starting therapy should be considered unimmunized and should be revaccinated a minimum of 3 months after discontinuation of therapy. Passive immunoprophylaxis with immune globulins may be indicated for immunocompromised persons instead of, or in addition to, vaccination.
    Poliovirus Vaccine, Inactivated, IPV: (Moderate) Administer all non-live vaccines at least 2 weeks before ocrelizumab initiation, whenever possible. Ocrelizumab may interfere with the effectiveness of non-live virus vaccines. Attenuated antibody responses to tetanus toxoid-containing vaccine, pneumococcal polysaccharide and pneumococcal conjugate vaccines, and seasonal influenza vaccine were observed in patients exposed to ocrelizumab at the time of vaccination during an open-label study. Infants born to mothers exposed to ocrelizumab during pregnancy may receive non-live vaccines as indicated before B-cell recovery; however, consider assessing the immune response to the vaccine. ACIP recommends that patients receiving any vaccination during immunosuppressive therapy or in the 2 weeks prior to starting therapy should be considered unimmunized and should be revaccinated a minimum of 3 months after discontinuation of therapy. Passive immunoprophylaxis with immune globulins may be indicated for immunocompromised persons instead of, or in addition to, vaccination.
    Prednisolone: (Moderate) Ocrelizumab has not been studied in combination with other immunosuppressive or immune modulating therapies used for the treatment of multiple sclerosis, including immunosuppressant doses of corticosteroids. Concomitant use of ocrelizumab with any of these therapies may increase the risk of immunosuppression. Monitor patients carefully for signs and symptoms of infection.
    Prednisone: (Moderate) Ocrelizumab has not been studied in combination with other immunosuppressive or immune modulating therapies used for the treatment of multiple sclerosis, including immunosuppressant doses of corticosteroids. Concomitant use of ocrelizumab with any of these therapies may increase the risk of immunosuppression. Monitor patients carefully for signs and symptoms of infection.
    Rabies Vaccine: (Moderate) Administer all non-live vaccines at least 2 weeks before ocrelizumab initiation, whenever possible. Ocrelizumab may interfere with the effectiveness of non-live virus vaccines. Attenuated antibody responses to tetanus toxoid-containing vaccine, pneumococcal polysaccharide and pneumococcal conjugate vaccines, and seasonal influenza vaccine were observed in patients exposed to ocrelizumab at the time of vaccination during an open-label study. Infants born to mothers exposed to ocrelizumab during pregnancy may receive non-live vaccines as indicated before B-cell recovery; however, consider assessing the immune response to the vaccine. ACIP recommends that patients receiving any vaccination during immunosuppressive therapy or in the 2 weeks prior to starting therapy should be considered unimmunized and should be revaccinated a minimum of 3 months after discontinuation of therapy. Passive immunoprophylaxis with immune globulins may be indicated for immunocompromised persons instead of, or in addition to, vaccination.
    Rituximab: (Major) Avoid the use of ocrelizumab and rituximab together. Both drugs are monoclonal antibodies directed against CD20-expressing B-cells. There are no data on the safety and efficacy of using these drugs at the same time. The concomitant use of rituximab and ocrelizumab may result in additive immunosuppression and an increased risk of infection. Additionally, additive immunosuppression may occur if ocrelizumab is administered before or after rituximab therapy. When switching from drugs with prolonged immune effects, such as rituximab, consider the duration and mode of action of rituximab when initiating ocrelizumab. Monitor patients closely for signs or symptoms of infection.
    Rituximab; Hyaluronidase: (Major) Avoid the use of ocrelizumab and rituximab together. Both drugs are monoclonal antibodies directed against CD20-expressing B-cells. There are no data on the safety and efficacy of using these drugs at the same time. The concomitant use of rituximab and ocrelizumab may result in additive immunosuppression and an increased risk of infection. Additionally, additive immunosuppression may occur if ocrelizumab is administered before or after rituximab therapy. When switching from drugs with prolonged immune effects, such as rituximab, consider the duration and mode of action of rituximab when initiating ocrelizumab. Monitor patients closely for signs or symptoms of infection.
    Rotavirus Vaccine: (Major) Due to the lack of clinical information related to the safety and efficacy of vaccine administration during ocrelizumab use, vaccination with live vaccines or live-attenuated vaccines is not recommended in patients taking ocrelizumab. Withhold vaccination with live or live-attenuated virus vaccines to patients during ocrelizumab treatment and until B-cell repletion. Administer all live or live-attenuated vaccinations according to current vaccination guidelines at least 4 weeks before initiation of ocrelizumab. Do not administer live or live-attenuated vaccines to infants born to mothers exposed to ocrelizumab during pregnancy before confirming B-cell count recovery as measured by CD19+ B-cells. ACIP recommends that patients receiving any vaccination during immunosuppressive therapy or in the 2 weeks prior to starting therapy should be considered unimmunized and should be revaccinated a minimum of 3 months after discontinuation of therapy. Passive immunoprophylaxis with immune globulins may be indicated for immunocompromised persons instead of, or in addition to, vaccination.
    Rubella Virus Vaccine Live: (Major) Due to the lack of clinical information related to the safety and efficacy of vaccine administration during ocrelizumab use, vaccination with live vaccines or live-attenuated vaccines is not recommended in patients taking ocrelizumab. Withhold vaccination with live or live-attenuated virus vaccines to patients during ocrelizumab treatment and until B-cell repletion. Administer all live or live-attenuated vaccinations according to current vaccination guidelines at least 4 weeks before initiation of ocrelizumab. Do not administer live or live-attenuated vaccines to infants born to mothers exposed to ocrelizumab during pregnancy before confirming B-cell count recovery as measured by CD19+ B-cells. ACIP recommends that patients receiving any vaccination during immunosuppressive therapy or in the 2 weeks prior to starting therapy should be considered unimmunized and should be revaccinated a minimum of 3 months after discontinuation of therapy. Passive immunoprophylaxis with immune globulins may be indicated for immunocompromised persons instead of, or in addition to, vaccination.
    SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
    Smallpox and Monkeypox Vaccine, Live, Nonreplicating: (Major) Due to the lack of clinical information related to the safety and efficacy of vaccine administration during ocrelizumab use, vaccination with live vaccines or live-attenuated vaccines is not recommended in patients taking ocrelizumab. Withhold vaccination with live or live-attenuated virus vaccines to patients during ocrelizumab treatment and until B-cell repletion. Administer all live or live-attenuated vaccinations according to current vaccination guidelines at least 4 weeks before initiation of ocrelizumab. Do not administer live or live-attenuated vaccines to infants born to mothers exposed to ocrelizumab during pregnancy before confirming B-cell count recovery as measured by CD19+ B-cells. ACIP recommends that patients receiving any vaccination during immunosuppressive therapy or in the 2 weeks prior to starting therapy should be considered unimmunized and should be revaccinated a minimum of 3 months after discontinuation of therapy. Passive immunoprophylaxis with immune globulins may be indicated for immunocompromised persons instead of, or in addition to, vaccination.
    Smallpox Vaccine, Vaccinia Vaccine: (Major) Due to the lack of clinical information related to the safety and efficacy of vaccine administration during ocrelizumab use, vaccination with live vaccines or live-attenuated vaccines is not recommended in patients taking ocrelizumab. Withhold vaccination with live or live-attenuated virus vaccines to patients during ocrelizumab treatment and until B-cell repletion. Administer all live or live-attenuated vaccinations according to current vaccination guidelines at least 4 weeks before initiation of ocrelizumab. Do not administer live or live-attenuated vaccines to infants born to mothers exposed to ocrelizumab during pregnancy before confirming B-cell count recovery as measured by CD19+ B-cells. ACIP recommends that patients receiving any vaccination during immunosuppressive therapy or in the 2 weeks prior to starting therapy should be considered unimmunized and should be revaccinated a minimum of 3 months after discontinuation of therapy. Passive immunoprophylaxis with immune globulins may be indicated for immunocompromised persons instead of, or in addition to, vaccination.
    Teriflunomide: (Moderate) Ocrelizumab has not been studied in combination with other immunosuppressive or immune modulating therapies used for the treatment of multiple sclerosis. Concomitant use of ocrelizumab with any of these therapies may increase the risk of immunosuppression. Use caution when switching patients from long-acting therapies with immune effects such as teriflunomide. The median half-life of teriflunomide is 18 to 19 days, and teriflunomide may remain in plasma for up to 2 years after discontinuation.
    Tetanus Toxoid: (Moderate) Administer all non-live vaccines at least 2 weeks before ocrelizumab initiation, whenever possible. Ocrelizumab may interfere with the effectiveness of non-live virus vaccines. Attenuated antibody responses to tetanus toxoid-containing vaccine, pneumococcal polysaccharide and pneumococcal conjugate vaccines, and seasonal influenza vaccine were observed in patients exposed to ocrelizumab at the time of vaccination during an open-label study. Infants born to mothers exposed to ocrelizumab during pregnancy may receive non-live vaccines as indicated before B-cell recovery; however, consider assessing the immune response to the vaccine. ACIP recommends that patients receiving any vaccination during immunosuppressive therapy or in the 2 weeks prior to starting therapy should be considered unimmunized and should be revaccinated a minimum of 3 months after discontinuation of therapy. Passive immunoprophylaxis with immune globulins may be indicated for immunocompromised persons instead of, or in addition to, vaccination.
    Tick-Borne Encephalitis Vaccine: (Moderate) Administer all non-live vaccines at least 2 weeks before ocrelizumab initiation, whenever possible. Ocrelizumab may interfere with the effectiveness of non-live virus vaccines. Attenuated antibody responses to tetanus toxoid-containing vaccine, pneumococcal polysaccharide and pneumococcal conjugate vaccines, and seasonal influenza vaccine were observed in patients exposed to ocrelizumab at the time of vaccination during an open-label study. Infants born to mothers exposed to ocrelizumab during pregnancy may receive non-live vaccines as indicated before B-cell recovery; however, consider assessing the immune response to the vaccine. ACIP recommends that patients receiving any vaccination during immunosuppressive therapy or in the 2 weeks prior to starting therapy should be considered unimmunized and should be revaccinated a minimum of 3 months after discontinuation of therapy. Passive immunoprophylaxis with immune globulins may be indicated for immunocompromised persons instead of, or in addition to, vaccination.
    Triamcinolone: (Moderate) Ocrelizumab has not been studied in combination with other immunosuppressive or immune modulating therapies used for the treatment of multiple sclerosis, including immunosuppressant doses of corticosteroids. Concomitant use of ocrelizumab with any of these therapies may increase the risk of immunosuppression. Monitor patients carefully for signs and symptoms of infection.
    Typhoid Vaccine: (Major) Due to the lack of clinical information related to the safety and efficacy of vaccine administration during ocrelizumab use, vaccination with live vaccines or live-attenuated vaccines is not recommended in patients taking ocrelizumab. Withhold vaccination with live or live-attenuated virus vaccines to patients during ocrelizumab treatment and until B-cell repletion. Administer all live or live-attenuated vaccinations according to current vaccination guidelines at least 4 weeks before initiation of ocrelizumab. Do not administer live or live-attenuated vaccines to infants born to mothers exposed to ocrelizumab during pregnancy before confirming B-cell count recovery as measured by CD19+ B-cells. ACIP recommends that patients receiving any vaccination during immunosuppressive therapy or in the 2 weeks prior to starting therapy should be considered unimmunized and should be revaccinated a minimum of 3 months after discontinuation of therapy. Passive immunoprophylaxis with immune globulins may be indicated for immunocompromised persons instead of, or in addition to, vaccination.
    Varicella-Zoster Virus Vaccine, Live: (Major) Due to the lack of clinical information related to the safety and efficacy of vaccine administration during ocrelizumab use, vaccination with live vaccines or live-attenuated vaccines is not recommended in patients taking ocrelizumab. Withhold vaccination with live or live-attenuated virus vaccines to patients during ocrelizumab treatment and until B-cell repletion. Administer all live or live-attenuated vaccinations according to current vaccination guidelines at least 4 weeks before initiation of ocrelizumab. Do not administer live or live-attenuated vaccines to infants born to mothers exposed to ocrelizumab during pregnancy before confirming B-cell count recovery as measured by CD19+ B-cells. ACIP recommends that patients receiving any vaccination during immunosuppressive therapy or in the 2 weeks prior to starting therapy should be considered unimmunized and should be revaccinated a minimum of 3 months after discontinuation of therapy. Passive immunoprophylaxis with immune globulins may be indicated for immunocompromised persons instead of, or in addition to, vaccination.
    Yellow Fever Vaccine, Live: (Major) Due to the lack of clinical information related to the safety and efficacy of vaccine administration during ocrelizumab use, vaccination with live vaccines or live-attenuated vaccines is not recommended in patients taking ocrelizumab. Withhold vaccination with live or live-attenuated virus vaccines to patients during ocrelizumab treatment and until B-cell repletion. Administer all live or live-attenuated vaccinations according to current vaccination guidelines at least 4 weeks before initiation of ocrelizumab. Do not administer live or live-attenuated vaccines to infants born to mothers exposed to ocrelizumab during pregnancy before confirming B-cell count recovery as measured by CD19+ B-cells. ACIP recommends that patients receiving any vaccination during immunosuppressive therapy or in the 2 weeks prior to starting therapy should be considered unimmunized and should be revaccinated a minimum of 3 months after discontinuation of therapy. Passive immunoprophylaxis with immune globulins may be indicated for immunocompromised persons instead of, or in addition to, vaccination.

    PREGNANCY AND LACTATION

    Pregnancy

    No adequate and well-controlled studies of ocrelizumab have been conducted during human pregnancy and the ability of the drug to cause fetal harm or affect reproductive capacity is unknown. Human IgG is known to cross the placental barrier; therefore, ocrelizumab may cross the placental barrier and cause fetal B-cell depletion and lymphocytopenia. During animal studies, depletion of B-lymphocytes in lymphoid tissues (spleen and lymph nodes) was observed in the fetuses of pregnant monkeys given ocrelizumab at doses of 2 times to 20 times the recommended human dose of 600 mg (on a mg/kg basis). Increased perinatal mortality was observed in the offspring of pregnant monkeys. The exact cause of death is unknown; however, the 2 neonates affected both had bacterial infections. Other adverse effects observed in the neonate monkeys include renal toxicity (glomerulopathy and inflammation), lymphoid follicle formation in the bone marrow, severe decreases in circulating B-lymphocytes, and reduced testicular weight. Do not administer live or live-attenuated vaccines to infants born to mothers exposed to ocrelizumab during pregnancy before confirming B-cell count recovery as measured by CD19+ B-cells. Neonates and infants may receive non-live vaccines as indicated before B-cell recovery; however, consider assessing the immune response to the vaccine. There is a pregnancy exposure registry that monitors outcomes in pregnant patients exposed to ocrelizumab; information about the registry can be obtained at www.ocrevuspregnancyregistry.com or by calling 1-833-872-4370.[61838]

    MECHANISM OF ACTION

    The exact mechanism by which ocrelizumab exerts its therapeutic effect in multiple sclerosis is unknown. Ocrelizumb likely binds to CD20, a cell surface antigen present on pre-B and mature B lymphocytes. Following binding, antibody-dependent cellular cytolysis and complement-mediated lysis occur.

    PHARMACOKINETICS

    Ocrelizumab is administered intravenously by infusion. Minimal distribution into extravascular tissues is expected due to central and peripheral volumes of distribution of 2.78 L and 2.68 L, respectively. Since ocrelizumab is an antibody, it is primarily cleared by catabolism. The terminal elimination half-life of ocrelizumab is 26 days.
     
    Treatment with ocrelizumab reduces CD19 B-cell counts in blood by 14 days after infusion. CD19 B-cell counts were used for evaluation because the presence of ocrelizumab interferes with the CD20 assay. During clinical studies, B-cell counts increased to above the lower limit of normal (LLN) or above baseline counts between infusions at least one time in 0.3% to 4.1% of patients. The median time for B-cell counts to return to LLN or baseline was 72 weeks (range 27 to 175 weeks) after the last ocrelizumab infusion in 1 clinical study (n = 51). B-cell counts increased to either baseline or LLN in 90% of patients.
     
    Affected cytochrome P450 (CYP450) isoenzymes and drug transporters: None

    Intravenous Route

    The pharmacokinetics of ocrelizumab are linear and dose proportional between 400 mg to 2,000 mg. In clinical studies, the mean maximum concentration (Cmax) was 212 mcg/mL in patients treated with a 600 mg infusion over 3.5 hours every 6 months and 141 mcg/mL in patients treated with two 300 mg infusions over 2.5 hours separated by 14 days every 6 months. The exposure (AUC) over the 24 week dosing intervals was 3,510 mcg/mL/day. During a safety study, the Cmax of ocrelizumab observed after a 3.5-hour infusion was 202 +/- 42 mcg/mL (mean +/- SD) and after the 2-hour infusion the Cmax was 200 +/- 46 mcg/mL.