ocrelizumab (Rx)

Brand and Other Names:Ocrevus
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

injectable solution

  • 30mg/mL (10mL single-dose vial)

Multiple Sclerosis

Indicated for treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease or primary progressive MS

Initial 2 doses: 300 mg IV once; repeat dose 2 wk later

Subsequent doses: 600 mg IV every 6 months

Dosage Modifications

Infusion reactions

  • Dose modifications in response to infusion reactions depends on the severity
  • Mild-to-moderate
    • Reduce infusion rate to half the rate at the onset of the infusion reaction and maintain the reduced rate for at least 30 min; if tolerated, may increase the rate (see Administration)
  • Severe
    • Immediately interrupt infusion and administer appropriate supportive treatment, as necessary
    • Restart infusion once symptoms have resolved
    • When restarting, begin at half of the infusion rate at the time of onset of the infusion reaction; if tolerated, may increase the rate
  • Life-threatening
    • Immediately stop and permanently discontinue ocrelizumab if there are signs of a life-threatening or disabling infusion reaction

Dosing Considerations

HBV screening

  • Perform Hepatitis B virus (HBV) screening before initiating ocrelizumab
  • Contraindicated with active HBV infection confirmed by positive results for HBsAg and anti-HBV tests
  • For patients who are negative for surface antigen [HBsAg] and positive for HB core antibody [HBcAb+] or are carriers of HBV [HBsAg+], consult liver disease experts before starting and during treatment

Vaccinations

  • Vaccination with live-attenuated or live vaccines is not recommended during treatment and after discontinuation until B-cell repletion
  • Administer all immunizations according to immunization guidelines at least 4 weeks prior to initiation for live or live-attenuated vaccines and, whenever possible, at least 2 weeks prior to initiation for non-live vaccines

Safety and efficacy not established

See Cautions for information regarding vaccinating infants born to mothers taking ocrelizumab

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Interactions

Interaction Checker

and ocrelizumab

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    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

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            Adverse Effects

            >10%

            Upper respiratory tract infections (40-49%)

            Infusion-related reactions (34-40%)

            Skin infections (14%)

            Decreased neutrophil counts (13%)

            1-10%

            Lower respiratory tract infections (8-10%)

            Depression (8%)

            Cough (7%)

            Back pain (6%)

            Herpes virus-associated infections (5-6%)

            Diarrhea (6%)

            Peripheral edema (6%)

            Pain in extremity (5%)

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            Warnings

            Contraindications

            Active HBV infection

            History of life-threatening infusion reaction to ocrelizumab

            Cautions

            Infusion reactions (eg, pruritus, rash, urticaria, erythema, bronchospasm, throat irritation, oropharyngeal pain, dyspnea, pharyngeal or laryngeal edema, flushing, hypotension, pyrexia, fatigue, headache, dizziness, nausea, tachycardia) may occur; monitor during treatment and at least 1 hr after treatment (also see Dosage Modifications and Administration)

            May increase risk for malignancy

            In infants of mothers exposed to ocrelizumab during pregnancy, do not administer live or live-attenuated vaccines before confirming the recovery of B-cell counts as measured by CD19+ B-cells

            Administer all immunizations according to immunization guidelines; administer live or live attenuated vaccines at least 4 weeks prior to initiation of therapy, whenever possible, and non-live vaccines at least 2 weeks prior to initiation of therapy; may administer non-live vaccines, as indicated, prior to recovery from B-cell depletion, but should consider assessing vaccine immune responses, including consultation with a qualified specialist, to assess whether protective immune response was mounted; vaccination with live-attenuated or live vaccines not recommended during treatment and until B-cell repletion

            Infections

            • In clinical trials, a higher proportion of ocrelizumab-treated patients experienced infections (eg, respiratory tract, herpes) compared with interferon-beta1a or placebo
            • HBV reactivation: Fulminant hepatitis, hepatic failure, and death caused by HBV reactivation have occurred in patients treated with other anti-CD20 antibodies
            • Progressive multifocal leukoencephalopathy (PML)
              • PML is an opportunistic viral infection of the brain caused by the John Cunningham (JC) virus
              • PML observed in patients treated with other anti-CD20 antibodies and other multiple sclerosis therapies and has also been associated with some risk factors (eg, immunocompromised patients, polytherapy with immunosuppressants)
              • At the first sign or symptom suggestive of PML, withhold drug and perform an appropriate diagnostic evaluation

            Drug interaction overview

            • Coadministration with immunosuppressants may increase risk for immunosuppressive effects
            • Vaccinations
              • May interfere with efficacy of nonlive vaccines (live or live-attenuated vaccines not studied)
              • Administer all immunizations according to immunization guidelines at least 4 weeks prior to initiation for live or live-attenuated vaccines and, whenever possible, at least 2 weeks prior to initiation for nonlive vaccines
            • Vaccination of infants of mothers exposed to ocrelizumab during pregnancy
              • Do not administer live or live-attenuated vaccines before confirming recovery of B-cell counts (measured by CD19+ B-cells)
              • Depletion of B-cells in these infants may increase risks from live or live-attenuated vaccines
              • Nonlive vaccines may be administered as indicated, prior to recovery from B-cell depletion; consider assessing vaccine immune responses, including consultation with a qualified specialist, to assess whether a protective immune response was mounted
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            Pregnancy

            Pregnancy

            No data available to assess risk in pregnant women

            However, transient peripheral B-cell depletion and lymphocytopenia have been reported in infants born to mothers exposed to other anti-CD20 antibodies during pregnancy

            See Cautions for information regarding vaccinating infants born to mothers taking ocrelizumab

            Contraception

            • Women of childbearing potential should use contraception while receiving ocrelizumab and for 6 months after the last infusion

            Lactation

            Unknown if distributed in human breast milk

            Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for the drug, and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition

            Pregnancy Categories

            A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA:Information not available.

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            Pharmacology

            Mechanism of Action

            Humanized monoclonal antibody designed to selectively target CD20, a cell surface antigen present on pre-B and mature B lymphocytes

            Following cell surface binding to B lymphocytes, ocrelizumab results in antibody-dependent cellular cytolysis and complement-mediated lysis

            Absorption

            Peak plasma concentration: 212 mcg/mL (600 mg); 141 mcg/mL (300 mg)

            AUC: 3510 mcg·mL/day

            Distribution

            Vd

            • Central volume distribution: 2.78 L
            • Peripheral volume compartment: 2.68 L/day
            • Intercompartment: 0.29 L/day

            Elimination

            Terminal half-life: 26 days

            Clearance: 0.17 L/day

            Initial time-dependent clearance: 0.05 L/day (declines with a half-life of 33 wk)

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            Administration

            IV Compatibilities

            0.9% NaCl

            Polyvinyl chloride (PVC) bags and IV sets

            Polyolefin (PO) bags and IV sets

            IV Preparation

            Visually inspect vial for particulate matter and discoloration; do not use if solution is discolored or contains discrete foreign particulate matter

            Do not shake vial

            Using aseptic technique, withdraw dose and further dilute into 0.9% NaCl infusion bag to final concentration of ~1.2 mg/mL (ie, 300 mg in 250-mL bag, 600 mg in 500-mL bag)

            Product contains no preservative and is intended for single use only

            Before starting the IV infusion, the content of the infusion bag should be at room temperature

            Use the prepared infusion solution immediately or refrigerate (see Storage)

            IV Administration

            Administer infusion solution through a dedicated line using an infusion set with a 0.2 or 0.22 micron inline filter

            Observe for infusion reactions during the infusion and for at least 1 hr after completion of the infusion; inform patients that infusion reactions can occur up to 24 hr after the infusion

            See Dosage Modifications for instructions if infusion reaction occurs

            Infection assessment

            • Before every infusion, determine whether there is an active infection
            • In case of active infection, delay infusion until the infection resolves

            Premedication

            • Methylprednisolone 100 mg IV (or an equivalent corticosteroid): Premedicate ~30 min before each ocrelizumab infusion to reduce the frequency and severity of infusion reactions
            • Antihistamine (eg, diphenhydramine): Premedicate ~30-60 min before each infusion to further reduce the frequency and severity of infusion reactions
            • Antipyretic (eg, acetaminophen): Addition to the above medications may be considered

            Infusion rate

            • Initial dose (first 2 IV infusions)
              • Dilute 300 mg in 250 mL 0.9% NaCl to final concentration of ~1.2 mg/mL
              • Start IV at 30 mL/hr
              • Increase by 30 mL/hr q30min
              • Maximum rate: 180 mL/hr
              • Infusion duration: ≥2.5 hr
            • Subsequent doses
              • Dilute 600 mg in 500 mL 0.9% NaCl to final concentration of ~1.2 mg/mL
              • Start IV at 40 mL/hr
              • Increase by 40 mL/hr q30min
              • Maximum rate: 200 mL/hr
              • Infusion duration: ≥3.5 hr

            Delayed or missed dose

            • 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
            • Doses must be separated by at least 5 months

            Storage

            Unopened vials

            • Refrigerate at 2-8°C (36-46°F) in the outer carton to protect from light
            • Do not freeze
            • Do not shake

            Diluted solution

            • Refrigerated at 2-8°C (36-46°F): Up to 24 hr
            • Room temperature up to 25°C (77°F): 8 hr (including infusion time)
            • In the event an IV infusion cannot be completed the same day, discard the remaining solution
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            Formulary

            FormularyPatient Discounts

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            • View the formulary and any restrictions for each plan.
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            • Compare formulary status to other drugs in the same class.
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            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.