Ocrelizumab (Monograph)

Brand name: Ocrevus
Drug class: Immunomodulatory Agents

Medically reviewed by Drugs.com on Dec 15, 2023. Written by ASHP.

Introduction

Immunomodulatory agent; a recombinant humanized anti-CD20 monoclonal antibody.

Uses for Ocrelizumab

Multiple Sclerosis (MS)

Management of relapsing forms of MS, including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults.

Ocrelizumab is one of several disease-modifying therapies used in the management of relapsing forms of MS. Although not curative, these therapies have all been shown to modify several measures of disease activity, including relapse rates, new or enhancing MRI lesions, and disability progression.

The American Academy of Neurology (AAN) recommends that disease-modifying therapy be offered to patients with RRMS who have had recent relapses and/or MRI activity. Clinicians should consider adverse effects, tolerability, method of administration, safety, efficacy, and cost of the drugs in addition to patient preferences when selecting an appropriate therapy.

Management of primary progressive MS (PPMS) in adults. Ocrelizumab is currently the only disease-modifying therapy shown to alter disease progression in patients with PPMS; because of demonstrated benefits, experts recommend that the drug be offered to patients with PPMS unless risks outweigh benefits.

Related/similar drugs

Ocrevus, Tecfidera, Rebif, Betaseron, Briumvi, Extavia, Vumerity

Ocrelizumab Dosage and Administration

General

Pretreatment Screening

• Prior to initiating ocrelizumab therapy, screen patients for hepatitis B virus (HBV) infection.

• Perform testing for quantitative serum immunoglobulins. In patients with low serum immunoglobulins, consult an immunology expert before initiating treatment.

• Prior to each infusion, evaluate patients for active infections; delay ocrelizumab therapy in patients with active infection until the infection resolves.

• Patients should complete any necessary immunizations at least 4 weeks prior to initiation of ocrelizumab for live or live attenuated vaccines, and whenever possible, at least 2 weeks prior to initiation of ocrelizumab for inactivated vaccines.

Patient Monitoring

• Monitor patients for infusion-related reactions during and for at least 1 hour after each infusion.

Premedication and Prophylaxis

• To reduce the incidence and/or severity of infusion-related reactions, patients should be premedicated with IV methylprednisolone 100 mg (or an equivalent corticosteroid) 30 minutes prior to each ocrelizumab infusion and an antihistamine (e.g., diphenhydramine) approximately 30–60 minutes prior to each ocrelizumab infusion. In addition, premedication with an antipyretic (e.g., acetaminophen) may be considered.

Dispensing and Administration Precautions

• Administer under close supervision of an experienced clinician and only in settings where appropriate medical support is available for management of serious infusion-related reactions.

• Initial and subsequent doses of ocrelizumab require different rates of administration and durations of infusion; pay special attention to differences in dose titration.

Administration

IV Administration

Administer by IV infusion.

Vials are for single use only.

Use strict aseptic technique since drug contains no preservatives.

Administer diluted solution through a separate IV line using a 0.2- or 0.22-µm inline filter.

Dilution

The commercially available injection concentrate containing 300 mg/10 mL must be diluted in 0.9% sodium chloride injection to a final concentration of approximately 1.2 mg/mL prior to IV infusion. Do not use other IV diluents.

To prepare a 300-mg dose, withdraw 10 mL of injection concentrate and add to an infusion bag containing 250 mL of 0.9% sodium chloride injection.

To prepare a 600-mg dose, withdraw 20 mL of injection concentrate and add to an infusion bag containing 500 mL of 0.9% sodium chloride injection.

Administer immediately following dilution. If not used immediately, follow manufacturer's recommended storage procedures.

Rate of Administration

Initial 2 doses (300 mg): Infuse each dose over ≥2.5 hours. Initiate at a rate of 30 mL/hour; may increase by 30 mL/hour every 30 minutes to a maximum rate of 180 mL/hour.

Subsequent doses of ocrelizumab (600 mg) can be infused over a duration of approximately 2 hours (this option should only be utilized in patients with no prior serious infusion reactions with ocrelizumab), or a duration of approximately 3.5 hours.

For an infusion duration of approximately 3.5 hours, the following infusion rates and durations are recommended by the manufacturer:

• Start at 40 mL/hour

• Increase by 40 mL/hour every 30 minutes to a maximum rate of 200 mL/hour

For an infusion duration of approximately 2 hours, the following infusion rates and durations are recommended by the manufacturer:

• Start at 100 mL/hour for the first 15 minutes

• Increase to 200 mL/hour for the next 15 minutes

• Increase to 250 mL/hour for the next 30 minutes

• Increase to 300 mL/hour for the remaining 60 minutes

Infusion times may take longer if the ocrelizumab infusion is interrupted or slowed.

Therapy Modifications for Infusion Reactions

If a life-threatening or disabling infusion reaction occurs, immediately and permanently discontinue ocrelizumab and provide appropriate supportive therapy.

If a severe infusion reaction occurs, immediately interrupt infusion and provide appropriate symptomatic and supportive therapy. Once the reaction has resolved, may resume infusion at half the rate at the onset of the reaction; if this reduced rate is tolerated, may increase infusion rate in usually recommended increments and intervals.

If a mild or moderate infusion reaction occurs, reduce infusion rate to half the rate at the onset of the reaction and maintain this rate for at least 30 minutes; if this reduced rate is tolerated, may increase infusion rate in usually recommended increments and intervals.

Dosage

Adults

Multiple Sclerosis

Relapsing or Primary Progressive Forms

IV

Initiate therapy with two 300-mg infusions administered 2 weeks apart.

Maintenance dosage: 600 mg once every 6 months, starting 6 months after first 300-mg infusion.

If a dose is missed, administer as soon as possible; do not wait until next scheduled dose. Adjust schedule of administration to maintain the 6-month interval between maintenance doses. Doses must be separated by at least 5 months.

Special Populations

Hepatic Impairment

No specific dosage recommendations at this time.

Renal Impairment

No specific dosage recommendations at this time.

Geriatric Patients

No specific dosage recommendations at this time.

Body Weight

No dosage adjustment based on body weight is necessary.

Cautions for Ocrelizumab

Contraindications

• Active HBV infection.

• History of life-threatening infusion reactions to ocrelizumab.

Warnings/Precautions

Infusion Reactions

Infusion reactions reported in approximately 34–40% of patients receiving the drug in clinical studies, in some cases, requiring hospitalization. Occurred most frequently with first infusion, and decreased in incidence and severity over subsequent infusions.

Manifestations may include pruritus, rash, urticaria, erythema, bronchospasm, throat irritation, oropharyngeal pain, dyspnea, pharyngeal or laryngeal edema, flushing, hypotension, pyrexia, fatigue, headache, dizziness, nausea, or tachycardia.

Administer only in settings with appropriate medical support to manage serious infusion reactions. Administer appropriate premedication (i.e., corticosteroid and antihistamine, with or without an antipyretic). Monitor for infusion reactions during and for ≥1 hour after each infusion.

Individualize management of infusion reactions; reduce infusion rate, interrupt infusion, or permanently discontinue therapy depending on severity, and provide appropriate supportive care.

Infectious Complications

Increased risk of infection (e.g., upper and lower respiratory tract, skin, herpes virus-related infections). Do not administer in patients with active infection; delay therapy until infection resolves.

Reactivation of HBV infection (resulting in fulminant hepatitis, hepatic failure, and death) reported. Screen all patients for HBV infection with hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc) tests prior to initiating therapy. Consult liver disease expert prior to initiating and during ocrelizumab therapy in patients who are HBsAg-negative and anti-HBc-positive, or HBV carriers (i.e., HBsAg-positive).

Serious CNS infections (e.g., encephalitis and meningitis), intraocular infections, and disseminated skin and soft tissue infections caused by herpes simplex virus and varicella zoster virus reported in postmarketing setting. If serious herpes infections occur, discontinue or withhold ocrelizumab until infection is resolved and appropriately treated.

When initiating ocrelizumab after an immunosuppressive therapy or initiating an immunosuppressive therapy after ocrelizumab, consider potential for increased immunosuppressive effects. Has not been studied in combination with other immunosuppressive agents.

Ocrelizumab may interfere with the safety and effectiveness of vaccines; patients should receive all necessary vaccinations prior to initiating the drug.

Progressive Multifocal Leukoencephalopathy

Progressive multifocal leukoencephalopathy (PML), an opportunistic viral infection of the brain caused by the JC virus (JCV), reported in patients treated with ocrelizumab, other anti-CD20 antibodies, and other MS therapies. Symptoms are diverse, progress over a period of days to weeks, and include progressive weakness on one side of the body or clumsiness of limbs, vision disturbances, confusion, and changes in cognition, memory, orientation, or personality.

Monitor patients closely for clinical symptoms or MRI findings that maybe suggestive of PML. MRI signs of PML may be apparent before clinical manifestations develop. If PML is suspected, interupt ocrelizumab therapy until the condition has been excluded. Permanently discontinue if PML is confirmed.

Reduction in Immunoglobulins

Decreased immunoglobulins observed with ocrelizumab treatment. Association between decreased levels of immunoglobulin G and increased rate of serious infections observed.

Monitor immunoglobulins during treatment with ocrelizumab and after discontinuation until B-cell repletion, especially if serious infection occurs. Consider discontinuation of therapy if recurrent or serious infections occur, or if there is prolonged hypogammaglobulinemia requiring treatment with parenteral immunoglobulin therapy.

Malignancy

Possible increased risk of malignancies (e.g., breast cancer). Follow standard breast cancer screening guidelines.

Immunogenicity

Potential for immunogenicity. Development of anti-ocrelizumab (including neutralizing) antibodies reported. Clinical relevance of such antibodies not known.

Immune-Mediated Colitis

Immune-mediated colitis reported; can present as a severe and acute-onset form of colitis. Some patients required hospitalization, a few patients required surgical intervention, and many required treatment with systemic corticosteroids.

Symptom onset after initiation of therapy ranged from a few weeks to years.

Monitor patients for signs of immune-mediated colitis during treatment such as new or persistent diarrhea or other GI signs and symptoms.

Specific Populations

Pregnancy

No adequate data in pregnant women; may cause fetal harm.

Avoid pregnancy during treatment and for 6 months after completion of therapy.

Call 1-833-872-4370 or visit www.ocrevuspregnancyregistry.com to register for monitoring of outcomes if pregnancy occurs while on ocrelizumab.

Transient peripheral B-cell depletion and lymphocytopenia reported in infants born to women exposed to other anti-CD20 monoclonal antibodies during pregnancy. Effects of maternal exposure to ocrelizumab on infant B-cell levels not known. Consider possibility that B-cell depletion may occur in infants born to women who received ocrelizumab during pregnancy; B-cell depletion can affect vaccine immune responses in infants. Confirm recovery of B-cell counts (as measured by CD19⁺ B cells) before administering live or live- attenuated vaccines to these infants. May administer inactivated vaccines prior to recovery from B-cell depletion, but consider assessing vaccine immune response in consultation with a qualified specialist.

Lactation

Not known whether distributed into human milk; distributed into milk in monkeys. Potential effects on nursing infants or on milk production not known.

Consider known benefits of breast-feeding along with mother's clinical need for ocrelizumab and any potential adverse effects of the drug or disease on the infant.

Females and Males of Reproductive Potential

Females of childbearing potential should use effective contraceptive measures during and for 6 months following the last dose of the drug.

Pediatric Use

Safety and efficacy not established.

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.

Hepatic Impairment

Pharmacokinetics not influenced by mild hepatic impairment.

Renal Impairment

Pharmacokinetics not influenced by mild renal impairment.

Common Adverse Effects

Relapsing forms of MS (≥10%): upper respiratory tract infection and infusion reaction.

PPMS (≥10%): upper respiratory tract infection, infusion reaction, skin infection, and lower respiratory tract infection.

Drug Interactions

No formal drug interaction studies performed to date. Drug interactions mediated by CYP enzymes, other metabolizing enzymes, or transporters not expected. Has not been studied in combination with other MS therapies.

Vaccines

Safety and effectiveness of live or live attenuated vaccines administered concomitantly with ocrelizumab not established; administration of these vaccines not recommended during ocrelizumab therapy and until B-cell repletion occurs.

Attenuated antibody responses to inactivated vaccines (e.g., tetanus toxoid-containing vaccine, pneumococcal polysaccharide or conjugate vaccine, influenza virus vaccine inactivated) observed in patients receiving ocrelizumab.

Complete any necessary immunizations ≥4 weeks prior to initiation of ocrelizumab for live or live attenuated vaccines, and whenever possible, ≥2 weeks prior to initiation of ocrelizumab for inactivated vaccines.

Specific Drugs

Ocrelizumab Pharmacokinetics

Absorption

Bioavailability

Exhibits essentially linear and dose-proportional pharmacokinetics over dosage range of 400 mg to 2 g.

Onset

Circulating CD19⁺ B cells are depleted within 14 days of infusion.

Duration

Median time to B-cell recovery to baseline or lower limit of normal (LLN) was 72 weeks (range: 27–175 weeks) after last infusion. B-cell counts returned to baseline or LLN in 90% of patients within 2.5 years of the last infusion.

Special Populations

Mild renal or hepatic impairment does not affect pharmacokinetics.

Gender, race, or body weight does not substantially affect pharmacokinetics.

Distribution

Extent

Not known whether ocrelizumab crosses the placenta or is distributed into milk; however, immunoglobulins cross the placenta and are distributed into milk.

Elimination

Metabolism

Presumed to be catabolized in the same manner as other antibodies.

Half-life

26 days.

Stability

Storage

Parenteral

Concentrate for IV Infusion

2–8°C in original carton; protect from light. Do not freeze or shake.

Following dilution, infuse immediately or store in refrigerator (2–8°C) for ≤24 hours followed by an additional 8 hours (including infusion time) at room temperature (≤25°C). Discard remaining solution if infusion cannot be completed in same day.

Actions

• A recombinant, humanized IgG₁ monoclonal antibody that binds specifically to CD20 (expressed on pre-B cells, mature B cells, and memory B cells).

• Binding to CD20 triggers host immune response involving antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) and results in depletion of CD20-expressing B cells.

• Because CD20 is not expressed on lymphoid stem cells or plasma cells, B-cell reconstitution and preexisting humoral immunity are preserved.

• Although exact mechanism in MS not fully elucidated, depletion of B cells is thought to result in the drug's immunomodulatory effects.

Advice to Patients

• Importance of advising patients to read the manufacturer's patient information (medication guide).

• Risk of infusion reactions; importance of informing patients that they will need to be monitored for ≥1 hour after each infusion. Advise patients that infusion reactions may occur up to 24 hours after each infusion and to immediately contact their clinician if they experience any manifestations of such a reaction (e.g., rash, urticaria, cough or wheezing, shortness of breath, difficulty breathing, swelling of the throat, flushing, dizziness, tachycardia).

• Risk of infections; importance of advising patients to immediately contact their clinician if they develop any signs or symptoms of infection (e.g., fever, chills, cough, cold sores, shingles, genital sores) during or after ocrelizumab therapy.

• Importance of informing patients that PML has occurred in patients treated with ocrelizumab and other similar drugs and that the condition usually leads to death or severe disability over weeks or months. Advise patients to inform their clinician if they develop any new or worsening neurologic symptoms suggestive of PML such as progressive weakness on one side of the body or clumsiness of limbs, disturbance of vision, and changes in thinking, memory, and orientation leading to confusion and personality changes.

• Risk of reactivation of HBV infection. Advise patients that monitoring will be required if they are at risk.

• Importance of advising patients that any necessary immunizations should be completed ≥4 weeks prior to initiation of ocrelizumab for live or live attenuated vaccines and, whenever possible, ≥2 weeks prior to initiation of ocrelizumab for inactivated vaccines. Administration of live or live attenuated vaccines is not recommended during ocrelizumab therapy and until B-cell recovery occurs.

• Risk of malignancies, including breast cancer. Advise patients to follow standard breast cancer screening guidelines.

• Advise patients to promptly contact their healthcare provider if they experience any signs and symptoms of colitis, including diarrhea, abdominal pain, and blood in the stool.

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed. Advise females of childbearing potential of the need for effective contraception during therapy and for 6 months after the last dose of ocrelizumab. Advise patients that if they become pregnant while receiving ocrelizumab to enroll in the Ocrevus Pregnancy Registry.

• Importance of informing clinicians of recent, existing, or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses (e.g., active infections).

• Importance of informing patients of other important precautionary information. (See Cautions.)

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Reload page with references included

Frequently asked questions

• How much does an Ocrevus infusion cost?
• How long does it take Ocrevus to work?
• Is Ocrevus a form of chemotherapy?
• How long does an Ocrevus infusion take?
• How does Ocrevus work for MS?
• What are the new drugs used for multiple sclerosis (MS)?
• Ocrevus vs Aubagio: How do they compare for MS?

View more FAQ

Medical Disclaimer