Class: Immunomodulatory Agents
Chemical Name: Disulfide with human-mouse monoclonal 2H7 κ-chain, anti-(human CD20 (antigen)) (human-mouse monoclonal 2H7 γ1-chain), immunoglobulin G1 dimer
Molecular Formula: C6494H9978N1718O2014S46
CAS Number: 637334-45-3
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.
Ocrelizumab is one of several disease-modifying therapies used in the management of RRMS. Although not curative, these therapies have all been shown to modify several measures of disease activity, including relapse rates, new or enhancing magnetic resonance imaging (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). 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.
Ocrelizumab Dosage and Administration
Administer under close supervision of an experienced clinician and in a setting with appropriate medical support to manage infusion-related reactions. (See Infusion Reactions under Cautions.)
Prior to initiating therapy, screen all patients for HBV infection. (See Contraindications and also see Infectious Complications under Cautions.)
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.
Prior to each infusion, evaluate patients for active infections; delay infusion until the infection resolves.
To minimize risk of infusion-related reactions, administer IV methylprednisolone 100 mg (or equivalent corticosteroid) 30 minutes prior to each infusion and an antihistamine (e.g., diphenhydramine) approximately 30–60 minutes prior to each infusion. May also consider premedication with an antipyretic (e.g., acetaminophen). Monitor for infusion reactions during and for ≥1 hour after each infusion. (See Infusion Reactions under Cautions.)
For solution compatibility information, see Compatibility under Stability.
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.
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. (See Storage under Stability.)
Rate of Administration
Initial 2 doses (300 mg): Infuse 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 (600 mg): Infuse over ≥3.5 hours. Initiate at a rate of 40 mL/hour; may increase by 40 mL/hour every 30 minutes to a maximum rate of 200 mL/hour.
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. (See Rate of Administration under Dosage and Administration.)
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. (See Rate of Administration under Dosage and Administration.)
Relapsing or Primary Progressive FormsIV
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.
No specific dosage recommendations at this time.
No specific dosage recommendations at this time.
No specific dosage recommendations at this time.
Cautions for Ocrelizumab
Active HBV infection.
History of life-threatening infusion reactions to ocrelizumab.
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). (See General under Dosage and Administration.) 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. (See Therapy Modifications for Infusion Reactions under Dosage and Administration.)
Increased risk of infection (e.g., upper and lower respiratory tract, skin, herpes virus-related). Mostly mild to moderate in severity. Do not administer in patients with active infection; delay therapy until infection resolves.
Although not reported with ocrelizumab, progressive multifocal leukoencephalopathy (PML; an opportunistic infection of the brain caused by the JC virus) reported with other anti-CD20 monoclonal antibodies and MS therapies. Consider PML in any patient with new or worsening neurologic manifestations. If PML is suspected, withhold ocrelizumab and perform diagnostic evaluation. MRI signs of PML may be apparent before clinical manifestations develop.
Although not reported with ocrelizumab, reactivation of HBV infection (resulting in fulminant hepatitis, hepatic failure, and death) reported with other anti-CD20 monoclonal antibodies. Screen all patients for HBV infection with hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc) tests prior to initiating therapy. (See Contraindications under Cautions.) 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).
Ocrelizumab may interfere with the safety and effectiveness of vaccines; patients should receive all necessary vaccinations prior to initiating the drug. (See Vaccines under Interactions and also see Pregnancy under Cautions.)
Possible increased risk of malignancies (e.g., breast cancer). Follow standard breast cancer screening guidelines.
Potential for immunogenicity. Development of anti-ocrelizumab (including neutralizing) antibodies reported. Clinical relevance of such antibodies not known.
No adequate data in pregnant women; may cause fetal harm.
Avoid pregnancy during treatment and for 6 months after therapy. (See Advice to Patients.)
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.
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.
Safety and efficacy not established.
Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.
Pharmacokinetics not influenced by mild hepatic impairment.
Pharmacokinetics not influenced by mild renal impairment.
Common Adverse Effects
Patients with relapsing forms of MS: Upper respiratory tract infection, infusion reaction, depression, lower respiratory tract infection, back pain, herpes virus infection, pain in extremity.
Patients with primary progressive MS: Upper respiratory tract infection, infusion reaction, skin infection, lower respiratory tract infection, cough, diarrhea, peripheral edema, herpes virus infection.
Interactions for Ocrelizumab
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.
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. (See Pregnancy under Cautions.)
Immunosuppressive or immunomodulatory agents
Potential for increased immunosuppression
When switching therapies, consider duration and mechanism of action of drugs with prolonged immune effects (e.g., daclizumab, fingolimod, mitoxantrone, natalizumab, teriflunomide) to avoid unintended additive immunosuppressive effects
Exhibits essentially linear and dose-proportional pharmacokinetics over dosage range of 400 mg to 2 g.
Circulating CD19+ B cells are depleted within 14 days of infusion.
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.
Mild renal or hepatic impairment does not affect pharmacokinetics.
Gender, race, or body weight does not substantially affect pharmacokinetics.
Not known whether ocrelizumab crosses the placenta or is distributed into milk; however, immunoglobulins cross the placenta and are distributed into milk.
Presumed to be catabolized in the same manner as other antibodies.
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.
For information on systemic interactions resulting from concomitant use, see Interactions.
No incompatibilities observed with PVC or polyolefin bags and administration sets.
Sodium chloride 0.9%
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 drugs that are similar to ocrelizumab 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. (See Infectious Complications under Cautions.)
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.
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed. Advise women of childbearing potential of the need for effective contraception during therapy and for 6 months after the last dose of ocrelizumab.
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.)
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.
For injection concentrate, for IV Infusion
30 mg/mL (300 mg)
AHFS DI Essentials™. © Copyright 2021, Selected Revisions November 25, 2019. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.
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