Ublituximab-xiiy (Monograph)

Drug class: Monoclonal Antibodies

Medically reviewed by Drugs.com on May 10, 2024. Written by ASHP.

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Introduction

Immunomodulatory agent; recombinant anti-CD20 monoclonal IgG₁antibody.

Uses for Ublituximab-xiiy

Multiple Sclerosis

Treatment of relapsing forms of multiple sclerosis (MS), including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults.

Ublituximab-xiiy is currently 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 enlarging MRI lesions, and disability progression.

The American Academy of Neurology (AAN) recommends that disease-modifying therapy be offered to patients with relapsing forms of MS 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. The AAN guidelines were published prior to the approval of ublituximab-xiiy and do not address the specific place in therapy for this drug.

Ublituximab-xiiy Dosage and Administration

General

Pretreatment Screening

• Screen patients for HBV infection prior to initiating ublituximab-xiiy therapy.

• Monitor the levels of quantitative serum immunoglobulins prior to initiating ublituximab-xiiy therapy. In patients with low serum immunoglobulins, consult an immunology expert before initiating treatment.

• Administer all necessary immunizations ≥4 weeks prior to initiating ublituximab-xiiy for live or live-attenuated vaccines, and whenever possible, ≥2 weeks prior to initiating ublituximab-xiiy for inactivated vaccines.

• Evaluate patients for active infections prior to initiating ublituximab-xiiy; delay therapy in patients with active infection until the infection resolves.

• Verify pregnancy status in females of reproductive potential prior to each ublituximab-xiiy infusion.

Patient Monitoring

• Monitor patients for infusion-related reactions during ublituximab-xiiy infusion, for ≥1 hour after the first 2 infusions, then as clinically indicated (per physician discretion) with subsequent infusions.

• Monitor for clinical signs/symptoms or MRI findings that may be suggestive of progressive multifocal leukoencephalopathy.

• Monitor the levels of quantitative serum immunoglobulins during ublituximab-xiiy therapy, especially in patients with opportunistic or recurrent infections, and after discontinuation of therapy until B-cell repletion.

• Monitor patients at risk for HBV reactivation during treatment with ublituximab-xiiy.

Premedication and Prophylaxis

• To reduce the incidence and severity of infusion-related reactions, premedicate patients with IV methylprednisolone 100 mg (or an equivalent corticosteroid) approximately 30 minutes prior to each ublituximab-xiiy infusion and an antihistamine (e.g., diphenhydramine) approximately 30–60 minutes prior to each ublituximab-xiiy infusion. In addition, consider premedication with an antipyretic (e.g., acetaminophen).

Dispensing and Administration Precautions

• Administer ublituximab-xiiy 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 ublituximab-xiiy require different rates of administration and durations of infusion; pay special attention to differences in dosage titration.

Administration

IV Administration

Administer by IV infusion. Available as a solution containing 150 mg/6 mL (25 mg/mL) in a single-dose vial for IV infusion.

Dilute prior to administration.

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

Prior to start of infusion, the contents of the infusion bag should be at room temperature.

Administer under the close supervision of an experienced healthcare professional with access to appropriate medical support to manage severe reactions (e.g., serious infusion reactions).

Administer diluted infusion solution through a dedicated line; no incompatibilities observed between ublituximab-xiiy and PVC and polyolefin bags and IV administration sets.

Observe patients for infusion reactions during infusion and for ≥1 hour after the completion of the first 2 infusions. Post-infusion monitoring of subsequent infusions is at physician discretion unless infusion reaction and/or hypersensitivity observed with the current or any prior infusion.

Administer missed dose as soon as possible; do not wait until the next scheduled dose. Reset infusion schedule for the next sequential infusion to 24 weeks after missed infusion is administered; separate infusions by ≥5 months.

Dilution

Dilute with 0.9% sodium chloride injection only.

Prepare first infusion (150 mg) using 1 vial of drug. Withdraw 6 mL of 0.9% sodium chloride injection from a 250 mL infusion bag and discard. Withdraw 6 mL of ublituximab-xiiy solution from the vial and add to the infusion bag containing 0.9% sodium chloride injection.

Prepare second and subsequent infusions (450 mg) using 3 vials of drug. Withdraw 18 mL of 0.9% sodium chloride injection from a 250 mL infusion bag and discard. Withdraw 18 mL of ublituximab-xiiy solution from the vials and add to the infusion bag containing 0.9% sodium chloride injection.

Mix diluted solution by gentle inversion; do not shake.

Rate of Administration

Administer the first dose (150 mg) over approximately 4 hours and subsequent doses (450 mg) over approximately 1 hour. Total duration of infusion may be increased if infusion reactions occur.

First dose (150 mg): Infuse over 4 hours; manufacturer recommends the following infusion rates and durations:

• Start at 10 mL/hour for the first 30 minutes

• Increase to 20 mL/hour for the next 30 minutes

• Increase to 35 mL/hour for the next hour

• Increase to 100 mL/hour for the remaining 2 hours

Subsequent doses (450 mg): Infuse over approximately 1 hour; manufacturer recommends the following infusion rates and durations:

• Start at a rate of 100 mL/hour for the first 30 minutes

• Increase to 400 mL/hour for the remaining 30 minutes

Infusion duration may take longer if infusion interrupted or slowed.

Adjustment of infusion rate may be necessary for adverse reactions.

Dosage

Adults

Multiple Sclerosis

IV

Initiate therapy with a 150 mg infusion followed by a 450 mg infusion 2 weeks after the first infusion. Administer subsequent infusions of 450 mg 24 weeks after the first infusion and every 24 weeks thereafter.

<C> Dosage Modification Due to Infusion Reactions

Mild to moderate infusion-related reaction: Reduce infusion rate to half the rate at the onset of the reaction and maintain reduced rate for ≥30 minutes. If this reduced rate is tolerated, increase infusion rate in usually recommended increments and intervals.

Severe infusion-related reaction: Interrupt infusion immediately and provide appropriate supportive therapy, as needed. Once reaction has resolved, restart infusion at half the infusion rate at the onset of the reaction. If this reduced rate is tolerated, increase infusion rate in usually recommended increments and intervals.

Life-threatening or disabling infusion reaction: Immediately and permanently discontinue ublituximab-xiiy; provide appropriate supportive treatment.

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.

Related/similar drugs

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

Cautions for Ublituximab-xiiy

Contraindications

• Active HBV infection.

• History of life-threatening infusion reactions to ublituximab-xiiy.

Warnings/Precautions

Infusion Reactions

Infusion reactions (including serious cases requiring hospitalization) reported. Manifestations may include pyrexia, chills, headache, influenza-like illness, tachycardia, nausea, throat irritation, erythema, and anaphylaxis.

Monitor for infusion reactions during infusion and for ≥1 hour after completion of the first 2 infusions. Post-infusion monitoring of subsequent infusions is at physician discretion unless infusion reaction and/or hypersensitivity is observed in association with the current or any prior infusion. Inform patients that infusion reactions can occur up to 24 hours after the infusion.

Administer only in settings with appropriate medical support to manage serious infusion reactions.

Administer pre-medication (e.g., methylprednisolone or an equivalent corticosteroid and an antihistamine) to reduce frequency and severity of infusion reactions. Consider the addition of an antipyretic (e.g., acetaminophen).

Individualize management of infusion reactions. For life-threatening reactions, stop the infusion immediately, permanently discontinue ublituximab-xiiy, and provide appropriate supportive treatment. For less severe reactions, reduce infusion rate, temporarily interrupt infusion, and/or administer symptomatic treatment.

Infectious Complications

Increased risk of infections, including serious and fatal bacterial, fungal, and new or reactivated viral infections.

Delay ublituximab-xiiy administration in patients with active infection until infection resolves.

When initiating ublituximab-xiiy after immunosuppressive therapy or initiating an immunosuppressive therapy after ublituximab-xiiy, consider potential for increased immunosuppressive effects. Has not been studied in combination with other MS therapies.

HBV Reactivation

Reactivation of HBV infection (resulting in fulminant hepatitis, hepatic failure, and death) reported.

Screen all patients for HBV infection prior to initiating therapy. Contraindicated in patients with active HBV confirmed by positive results for hepatitis B surface antigen (HBsAg) and anti-HBV tests. Consult liver disease expert prior to initiating and during ublituximab-xiiy therapy in patients who are negative for HBsAg and positive for hepatitis B core antibody, or are HBV carriers (HBsAg-positive).

Progressive Multifocal Leukoencephalopathy

Although not reported with ublituximab-xiiy, progressive multifocal leukoencephalopathy (PML) reported with other anti-CD20 monoclonal antibodies and MS therapies. Typical symptoms associated with PML are diverse, progress over 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. Signs of PML appearing on MRI may be apparent before clinical manifestations develop; may be useful to monitor patients with MRI for signs consistent with PML.

At the first sign or symptom suggestive of PML, withhold ublituximab-xiiy and perform an appropriate diagnostic evaluation. If PML confirmed, discontinue ublituximab-xiiy.

Vaccinations

May interfere with effectiveness of non-live vaccines. Safety of live or live-attenuated vaccines during or following administration of ublituximab-xiiy has not been studied.

Administer all vaccines according to current immunization guidelines, ≥4 weeks prior to initiation of ublituximab-xiiy for live or live-attenuated vaccines and, whenever possible, ≥2 weeks prior to initiation of ublituximab-xiiy for non-live vaccines. Do not administer live vaccines during treatment and until B-cell repletion occurs.

In infants of mothers exposed during pregnancy, do not administer live or live-attenuated vaccines before confirming the recovery of B-cell counts as measured by CD19⁺ B-cells. Inactivated or non-live vaccines may be administered as indicated prior to recovery from B-cell depletion; however, consider an assessment of vaccine immune responses, including consultation with a qualified specialist, to determine whether a protective immune response was mounted.

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm based on findings from animal studies. Transient peripheral B-cell depletion and lymphocytopenia reported in infants born to mothers exposed to other anti-CD20 B-cell depleting antibodies during pregnancy.

Advise pregnant women and females of reproductive potential about the possible hazard to a fetus. Pregnancy testing recommended in females of reproductive potential prior to each infusion. Advise females of reproductive potential to use effective contraception during treatment and for 6 months after the last dose.

Reduction in Immunoglobulins

Decreased immunoglobulins observed. Association between decreased levels of immunoglobulins and increased rates of serious infections observed in studies using other anti-CD20 monoclonal antibodies.

For patients with low serum immunoglobulins, consult immunology experts before initiating ublituximab-xiiy. Monitor immunoglobulins during therapy, especially in patients with opportunistic or recurrent infections, and after discontinuation of therapy until B-cell repletion occurs. Consider discontinuing therapy if patients with low immunoglobulins develop a serious opportunistic infection or recurrent infections, or if prolonged hypogammaglobulinemia requires treatment with IV immunoglobulins.

Immunogenicity

Potential for immunogenicity. Development of anti–ublituximab-xiiy (including neutralizing) antibodies reported. Assay used to measure neutralizing antibodies subject to interference from serum ublituximab-xiiy; therefore, underestimation of the incidence of neutralizing antibody formation is possible, and clinical impact of neutralizing antibodies unknown.

Presence of anti-drug antibodies had no observable impact on safety or efficacy of ublituximab-xiiy.

Specific Populations

Pregnancy

No data available on developmental risk associated with the use of ublituximab-xiiy in pregnant women. Data from case reports of pregnancies occurring during clinical trials insufficient to identify a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Embryofetal loss and fetal harm observed in animal reproduction studies.

Monoclonal antibodies can be actively transported across the placenta; ublituximab-xiiy may cause immunosuppression in the in-uteroexposed infant. Avoid administering live vaccines to neonates and infants exposed to ublituximab-xiiy in utero until B-cell recovery occurs.

Apprise pregnant women and females of reproductive potential of the potential hazard to a fetus. Perform pregnancy testing in females of reproductive potential prior to each infusion.

Lactation

No data on the presence of ublituximab-xiiy in human milk, effects on the breast-fed child, or effects on milk production. Human IgG excreted into human milk; potential for absorption of ublituximab-xiiy and B-cell depletion in the infant unknown.

Consider developmental and health benefits of breastfeeding, mother's clinical need for ublituximab-xiiy, and any potential adverse effects on the breast-fed infant from the drug or underlying maternal condition.

Females and Males of Reproductive Potential

Pregnancy testing recommended for females of reproductive potential prior to each infusion. Advise females of reproductive potential to use effective contraception while receiving ublituximab-xiiy and for 6 months after the last dose.

Pediatric Use

Safety and effectiveness not established.

Geriatric Use

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

Hepatic Impairment

Pharmacokinetics not influenced by mild hepatic impairment. Effect of moderate to severe hepatic impairment on pharmacokinetics unknown.

Renal Impairment

Pharmacokinetics not influenced by mild renal impairment. Effect of moderate to severe renal impairment on pharmacokinetics unknown.

Common Adverse Effects

Common adverse effects (≥10%): Infusion reactions and upper respiratory tract infections.

Drug Interactions

No formal drug interaction studies performed to date.

Specific Drugs

Ublituximab-xiiy Pharmacokinetics

Absorption

Bioavailability

Exposures increase proportionally over a dosage range of 150–600 mg.

Onset

Treatment reduces CD19⁺ B-cell counts in blood 24 hours after infusion.

Duration

Median time for CD19⁺ B-cell counts to return to either baseline or lower limit of normal (LLN) was 70.3 weeks (range: 0.1–75.1 weeks) after last infusion. B-cell counts increased to either baseline or LLN in 58% of patients within 1.5 years after the last infusion.

Special Populations

Mild renal or mild hepatic impairment does not affect pharmacokinetics.

Gender, race, body weight, or the presence of anti-drug antibodies does not substantially affect pharmacokinetics.

Distribution

Extent

Not known whether ublituximab-xiiy crosses the placenta or is distributed into human milk; however, immunoglobulins cross the placenta and are distributed into milk.

Elimination

Metabolism

Expected metabolic pathway is degradation to small peptides and amino acids by ubiquitous proteolytic enzymes.

Half-life

22 days.

Stability

Storage

Parenteral

Concentrate for IV Infusion

Unopened vials: Store at 2–8°C in outer carton to protect from light; do not freeze or shake.

Diluted solution: If not used immediately following dilution, store under refrigeration at 2–8°C for ≤24 hours; do not freeze. If stored under refrigeration, allow to come to room temperature prior to administration (approximately 2 hours). Can be stored an additional 8 hours (including equilibration and infusion time) at room temperature (≤25°C).

Actions

• Recombinant, chimeric monoclonal IgG₁ antibody directed against CD20-expressing B-cells.

• Precise mechanism in multiple sclerosis unknown; presumed to involve binding to CD20, a cell surface antigen present on pre-B and mature B lymphocytes.

• Following cell surface binding to B lymphocytes, results in cell lysis through antibody-dependent cellular cytolysis and complement-dependent cytolysis.

Advice to Patients

• Advise patients to read the FDA-approved patient labeling (Medication Guide).

• Inform patients about the signs and symptoms of infusion reactions, and that infusion reactions can occur up to 24 hours after ublituximab-xiiy infusion. Advise patients to contact their clinician immediately for signs or symptoms of infusion reactions.

• Advise patients to contact their clinician for any signs of infection (e.g., fever, chills, constant cough, dysuria) during treatment with ublituximab-xiiy or after the last infusion.

• Advise patients that ublituximab-xiiy may cause reactivation of hepatitis B infection and that monitoring will be necessary if they are at risk.

• Advise patients that progressive multifocal leukoencephalopathy (PML) may occur with ublituximab-xiiy. Inform patients that PML is characterized by a progression of deficits and usually leads to severe disability or mortality over weeks or months, and that usual symptoms associated with PML are diverse and progress over days to weeks. Inform patients to contact their clinician if they develop any symptoms suggestive of PML (e.g., progressive weakness on one side of the body or clumsiness of limbs; vision disturbances; changes in thinking, memory, and orientation leading to confusion and personality changes).

• Advise patients to complete any required live or live-attenuated vaccinations ≥4 weeks and, whenever possible, non-live vaccinations ≥2 weeks prior to initiation of ublituximab-xiiy. Inform patients that administration of live-attenuated or live vaccines is not recommended during ublituximab-xiiy treatment and until B-cell recovery occurs.

• Advise patients to notify their clinician if they are pregnant during treatment with ublituximab-xiiy. Advise pregnant women and females of reproductive potential about the possible hazard to a fetus. Advise females of reproductive potential to use effective contraception during treatment with ublituximab-xiiy and for 6 months after the last dose.

• Advise women to inform their clinician if they are breast-feeding or plan to breast-feed.

• Advise patients to inform their clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.

• Inform patients of other important precautionary information.

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.

Ublituximab-xiiy is available through designated specialty pharmacies. Consult the Briumvimanufacturer website ([Web]) for additional information.

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