ublituximab (Rx)

Brand and Other Names:Briumvi, ublituximab-xiiy
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

injectable solution

  • 25 mg/mL (150mg/6mL single-dose vial)

Multiple Sclerosis

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

First infusion: 150 mg IV

Second infusion: 450 mg IV 2 weeks after first infusion

Subsequent infusions: 450 mg IV 24 weeks after first infusion and then q24Weeks thereafter

Dosage Modifications

Infusion-related reactions

  • Refer to recommended infusion rates listed in Administration
  • Note: Change in rate will increase total duration of infusion, but not the total dose
  • Mild-to-moderate
    • Reduce infusion rate to half the rate at onset of reaction and maintain reduced rate for at least 30 minutes
    • If reduced rate tolerated, increase rate
  • Severe
    • Immediately interrupt infusion and administer appropriate supportive treatment, as necessary
    • Restart infusion only after all symptoms have resolved
    • When restarting, begin at half of infusion rate at time of onset of reaction; if tolerated, increase rate
  • Life-threatening
    • Immediately stop infusion and permanently discontinue

Renal impairment

  • Mild: No dosage adjustment necessary
  • Moderate-to-severe: Pharmacokinetics are unknown

Hepatic impairment

  • Mild: No dosage adjustment necessary
  • Moderate-to-severe: Pharmacokinetics are unknown

Dosing Considerations

Verify pregnancy status in females of reproductive potential before each infusion

Before every infusion, assess if there is an active infection; if active infection is confirmed, delay infusion until infection resolves

Hepatitis B virus (HBV)

  • Screen for HBV and quantitative serum immunoglobulin before initiating
  • Confirmed active HBV (patients with positive hepatitis B surface antigen [HBsAg] and anti-HBV tests): Contraindicated
  • Patients who are negative for HBsAg and positive for hepatitis B core antibody (HBcAb+) or who are carriers of HBV (HBsAg+): Consult liver disease experts before starting and during treatment

Serum immunoglobulins

  • Before initiating, perform testing for quantitative serum immunoglobulins
  • For low serum immunoglobulins, consult immunology experts before initiating

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
    • Live or live-attenuated vaccines: At least 4 weeks before initiating, whenever possible
    • Non-live vaccines: At least 2 weeks before initiating

Monitoring for infusion-related reactions

  • First 2 infusions: Closely monitor during and for at least 1 hr after completing infusions
  • Subsequent infusions: Monitor at discretion of healthcare provider unless infusion reaction and/or hypersensitivity have been observed

Safety and efficacy not established

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Interactions

Interaction Checker

and ublituximab

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    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

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            Adverse Effects

            >10%

            Infusion reactions (48%)

            Upper respiratory tract infections (45%)

            IgM below the LLN at 96 weeks (20.9%)

            1-10%

            Lower respiratory tract infections (9%)

            Herpes-virus-associated infections (6%)

            IgG below the LLN at 96 weeks (6.5%)

            Pain in extremity (6%)

            Insomnia (6%)

            Fatigue (5%)

            IgA below the LLN at 96 weeks (2.4%)

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            Warnings

            Contraindications

            Active hepatitis B virus infection

            History of life-threatening infusion reaction to ublituximab

            Cautions

            Based on animal studies, fetal harm may occur when administered to pregnant females

            Decreased immunoglobulin levels

            • Decreased immunoglobulin levels observed; monitor levels of quantitative serum immunoglobulins during treatment, especially in patients with opportunistic or recurrent infections, and after discontinuation until B-cell repletion
            • Consider discontinuing therapy if
              • Patients with low immunoglobulins develop serious opportunistic or recurrent infections
              • Prolonged hypogammaglobulinemia occurs requiring treatment with IV immunoglobulins

            Infections

            • Serious bacterial and viral infections reported
            • An increased risk of infections, including serious and fatal bacterial, fungal, and new or reactivated viral infections, observed during and after completion of other anti-CD20 B-cell–depleting treatments
            • Delay administration in patients with an active infection until infection is resolved
            • When initiating after an immunosuppressive therapy or initiating an immunosuppressive therapy, consider potential for increased immunosuppressive effects
            • Not studied in combination with other MS therapies
            • Progressive multifocal leukoencephalopathy (PML)
              • PML is an opportunistic viral infection of the brain caused by the JC virus (JCV) that typically only occurs in patients who are immunocompromised
              • JCV infection resulting in PML has been observed in patients treated with other anti-CD20 antibodies and other MS therapies
              • Symptoms associated with PML are diverse, progress over days to weeks, and include progressive weakness on one side of body or clumsiness of limbs, disturbance of vision, and changes in thinking, memory, and orientation leading to confusion and personality changes
              • At first sign or symptom suggestive of PML, withhold therapy and perform an appropriate diagnostic evaluation
              • If PML is suspected, monitor with MRI for signs that may be consistent with PML and further investigate
              • If confirmed, discontinue treatment
            • HBV reactivation
              • HBV reactivation may occur
              • Fulminant hepatitis, hepatic failure, and death caused by HBV reactivation reported in patients treated with anti-CD20 antibodies
              • Screen for HBV in all patients before initiating
              • Do not initiate with active HBV confirmed by positive results for HBsAg and anti-HB tests
              • For patients who are negative for HBsAg and HBcAb+ or who are HBsAg+, consult a liver disease expert before starting and during treatment

            Infusion-related reactions

            • Infusion-related reactions (eg, pyrexia, chills, headache, influenza-like illness, tachycardia, nausea, throat irritation, erythema, anaphylactic reactions) reported
            • Administer premedications (eg, methylprednisolone or an equivalent corticosteroid, and an antihistamine) to reduce frequency and severity of infusion reactions; consider adding of an antipyretic (eg, acetaminophen)
            • Manage infusion reactions based on severity

            Drug interaction overview

            • Vaccinations
              • Administer all immunizations according to immunization guidelines at least 4 weeks before initiating for live or live-attenuated vaccines and, whenever possible, at least 2 weeks before initiating for non-live vaccines
              • Ublituximab may interfere with non-live vaccine efficacy
              • Safety of immunization with live or live-attenuated vaccines during or following treatment not studied
              • Vaccination with live virus vaccines is not recommended during treatment and until B-cell repletion
            • Vaccination of Infants born to mothers treated during pregnancy
              • Do not administer live or live-attenuated vaccines to infants of mothers exposed to ublituximab during pregnancy, before confirming recovery of B-cell counts as measured by CD19+ B cells
              • Depletion of B cells in these infants may increase the risks from live or live-attenuated vaccines
              • Inactivated or non-live vaccines may be administered as indicated, before recovering from B-cell depletion; consider assessing vaccine immune responses, such as through consultation with a qualified specialist, to determine whether a protective immune response has mounted
            • Immunosuppressive or immune-modulating therapies
              • Ublituximab may potentiate risk of additive immune system effects when coadministered with immunosuppressive or immune-modulating therapies
              • Owing to potential additive immunosuppressive effects, consider duration of effect and mechanism of action of these therapies when switching from therapies with immune effects to ublituximab
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            Pregnancy & Lactation

            Pregnancy

            There are no data on developmental risk associated with use in pregnant females

            Data are insufficient to identify drug-associated risks of major birth defects, miscarriage, or adverse maternal or fetal outcomes

            However, monoclonal antibodies can be actively transported across the placenta and may cause immunosuppression to in-utero exposed infant

            Verify pregnancy status in females of reproductive potential

            Fetal/neonatal adverse reactions

            Transport of endogenous IgG antibodies across placenta increases as pregnancy progresses and peaks during third trimester

            No data are available on B-cell levels in human neonates following maternal exposure to ublituximab

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

            Avoid administering live vaccines to neonates and infants exposed to ublituximab in utero until B-cell recovery occurs

            Contraception

            • Females of reproductive potential: Use effective contraception during treatment and for 6 months after final dose

            Animal data

            • Weekly IV administration to pregnant monkeys during pregnancy resulted in embryofetal loss
            • Administration during second trimester resulted in external, skeletal, and visceral abnormalities in infants

            Lactation

            There are no data on drug presence in human milk, effects on breastfed infants, or effects on milk production

            Human IgG is excreted in human milk; potential for drug absorption leading to B-cell depletion in infants is unknown

            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

            Precise mechanism of action for multiple sclerosis is unknown

            May involve binding to CD20, a cell surface antigen presented on pre-B and mature B lymphocytes

            After binding to B lymphocytes, ublituximab results in cell lysis through mechanisms including antibody-dependent cellular cytolysis and complement-dependent cytolysis

            Absorption

            Peak plasma concentration: 139 mcg/mL

            AUC (steady-state): 3,000 mcg·day/mL

            Distribution

            Vd: 3.18 L

            Metabolism

            Protein expected to degrade into small peptides and amino acids by ubiquitous proteolytic enzymes

            Elimination

            Half-life: 22 days

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            Administration

            IV Compatibilities

            0.9% NaCl

            No incompatibilities with polyvinyl chloride (PVC) or polyolefin (PO) bags and IV administration sets observed

            IV Preparation

            Visually inspect vials before administering; solution should be clear to opalescent, colorless to slightly yellow; discard if discolored or if solution contains discrete foreign particulate matter

            150 mg dose

            • Withdraw 6 mL from 250-mL 0.9% NaCl infusion bag and discard
            • Withdraw 6 mL of drug from vial and add into prepared 0.9% NaCl infusion bag
            • Gently invert to mix diluted solution by gentle inversion; do not shake

            450 mg dose

            • Withdraw 18 mL from 250-mL 0.9% NaCl infusion bag and discard
            • Withdraw 18 mL of drug from vials and add into prepared 0.9% NaCl infusion bag
            • Gently invert to mix diluted solution by gentle inversion; do not shake

            Premedication

            Premedicate before each infusion to reduce frequency and severity of infusion reactions

            Methylprednisolone 100 mg IV (or an equivalent oral dosage or equivalent corticosteroid) ~30 min before each infusion

            Antihistamine (eg, diphenhydramine) PO or IV ~30-60 min before each infusion

            Consider also adding an antipyretic (eg, acetaminophen)

            IV Administration

            Administer under close supervision of experienced healthcare professional with access to appropriate medical support to manage severe reactions (eg, serious infusion reactions)

            Before starting infusion, allow it to equilibrate to room temperature before administration (~2 hr)

            Administer diluted infusion solution through a dedicated line

            Recommended infusion rate and duration

            • Infusion duration may take longer if infusion is interrupted or slowed
            • First Infusion (150-mg dose)
              • Start at 10 mL/hr for first 30 min, THEN
              • Increase to 20 mL/hr for next 30 min, THEN
              • Increase to 35 mL/hr for next hr, THEN
              • Increase to 100 mL/hr for remaining 2 hr
              • Duration of infusion: 4 hr
            • Second infusion and subsequent infusions (450-mg dose)
              • Start at 100 mL/hr for first 30 min, THEN
              • Increase to 400 mL/hr for remaining 30 min
              • Duration of infusion: 1 hr

            Monitoring for infusion-related reactions

            • First 2 infusions: Observe for at least 1 hr after completing infusion
            • Subsequent infusions: Monitor at discretion of healthcare provider unless an infusion reaction and/or hypersensitivity observed with any infusion

            Storage

            Unopened vials

            • Refrigerate at 2-8ºC (36-46ºF) in outer carton to protect from light
            • Do not freeze
            • Do not shake

            Diluted infusion

            • Use immediately
            • If not used immediately, refrigerate at 2-8ºC (36-46ºF) for up to 24 hr; do not freeze
            • May be stored for an additional 8 hr at room temperature up to 25ºC (77ºF), which includes equilibration time and infusion time
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            Patient Handout

            A Patient Handout is not currently available for this monograph.
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            Formulary

            FormularyPatient Discounts

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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.