Inebilizumab-cdon (Monograph)

Brand name: Uplinza
Drug class: Monoclonal Antibodies

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

Introduction

Recombinant humanized kappa immunoglobulin G₁ (IgG₁) monoclonal antibody that targets and depletes CD19-expressing B cells.

Uses for Inebilizumab-cdon

Neuromyelitis Optica Spectrum Disorder

Treatment of neuromyelitis optica spectrum disorder (NMOSD) in adults with autoantibodies against aquaporin-4 (AQP4).

Designated an orphan drug by FDA for treatment of neuromyelitis optica and neuromyelitis optica spectrum disorders.

Inebilizumab-cdon Dosage and Administration

General

Pretreatment Screening

• Prior to initiating inebilizumab-cdon therapy, screen all patients for hepatitis B virus (HBV) infection. In patients who are negative for hepatitis B surface antigen (HBsAg) and positive for hepatitis B core antibody (HBcAb) or in patients who are carriers of HBV (i.e., HBsAg-positive), consult a liver disease expert before initiating and during treatment with inebilizumab-cdon.

• Prior to initiating inebilizumab-cdon therapy, test for quantitative serum immunoglobulins. In patients with low serum immunoglobulins, consult an immunology expert before initiating inebilizumab-cdon therapy.

• Prior to initiating inebilizumab-cdon therapy, evaluate all patients for active or latent tuberculosis infection. In patients with active tuberculosis or in patients with a positive screening in whom an adequate course of antimycobacterial therapy cannot be confirmed, consult an infectious disease expert prior to initiating inebilizumab-cdon therapy.

• Patients should complete any necessary immunizations at least 4 weeks prior to initiation of inebilizumab-cdon for live or live-attenuated vaccines.

Patient Monitoring

• Prior to each infusion, evaluate patients for active infection. Delay administration of inebilizumab-cdon until infection resolves.

• Monitor patients closely for infusion reactions during and for at least one hour after the completion of the infusion.

Premedication and Prophylaxis

• Administer the following premedications prior to every infusion to reduce frequency and severity of infusion reactions:

• IV corticosteroid (methylprednisolone 80 mg to 125 mg or equivalent) 30 minutes prior to inebilizumab-cdon infusion.

• Oral antihistamine (diphenhydramine 25 mg to 50 mg or equivalent) 30–60 minutes prior to inebilizumab-cdon infusion.

• Oral antipyretic (acetaminophen 500 mg to 650 mg or equivalent) 30–60 minutes prior to inebilizumab-cdon infusion.

Dispensing and Administration Precautions

• Administer inebilizumab-cdon under the close supervision of an experienced healthcare professional with access to appropriate medical support to manage potential severe reactions such as serious infusion reactions.

Administration

IV Administration

Administer as an IV infusion via infusion pump. Must dilute the commercially available injection with 0.9% sodium chloride injection prior to administration.

Administer drug through an IV line containing a sterile, low-protein binding 0.2 or 0.22 micron in-line filter.

Dilution

Visually inspect solution for particulate matter and discoloration; do not use if solution is cloudy, discolored, or contains discrete particulate matter and contact the manufacturer at 1-866-479-6742.

To dilute the inebilizumab-cdon solution, obtain an IV bag containing 250 mL of 0.9% sodium chloride injection; do not use any other diluents. Withdraw 10 mL of the inebilizumab-cdon solution from each of 3 vials, and transfer the total amount of drug (30 mL) into the 250 mL IV bag. Gently invert the diluted solution to mix (do not shake). Discard any unused portion remaining in the vials.

Administer prepared IV solution immediately. If not administered immediately, store infusion solution for maximum of 24 hours in the refrigerator (2–8°C) or for maximum of 4 hours at room temperature (20–25°C) prior to the start of the infusion. The diluted solution should be at room temperature prior to the start of the infusion.

Rate of Administration

Administer the diluted inebilizumab-cdon solution by IV infusion via an infusion pump at an increasing rate to completion (total of approximately 90 minutes) according to the schedule in Table 1.

Dosage

Adults

Neuromyelitis Optica Spectrum Disorder

IV

300 mg by IV infusion, followed 2 weeks later by a second 300-mg dose by IV infusion.

Subsequent dosage starting 6 months after the first infusion is 300 mg every 6 months.

Special Populations

No special population dosage recommendations at this time.

Cautions for Inebilizumab-cdon

Contraindications

• A history of a life-threatening infusion reaction to inebilizumab-cdon

• Active hepatitis B infection

• Active or untreated latent tuberculosis infection.

Warnings/Precautions

Infusion Reactions

Infusion reactions can occur. Reactions can include headache, nausea, somnolence, dyspnea, fever, myalgia, rash, or other signs or symptoms.

To reduce risk of infusion reactions, administer premedications with a corticosteroid, an antihistamine, and an antipyretic. Management of infusion reactions depends on the type and severity of the reaction. For life-threatening reactions, immediately and permanently stop inebilizumab-cdon and administer appropriate supportive treatment. For less severe infusion reactions, temporary interruption of the infusion, reduction in infusion rate, and/or administration of symptomatic treatment may be required.

Infectious Complications

Inebilizumab-cdon may increase the risk of infection. Increased risk of infections has been observed with other B-cell-depleting therapies. Delay administration of inebilizumab-cdon in patients with an active infection until infection is resolved.

Not studied in combination with other immunosuppressants. Concomitant use of inebilizumab-cdon with immunosuppressant drugs may increase the risk of infection.

Hepatitis B Virus

Reactivation of HBV infection observed in patients receiving other B-cell depleting antibodies. Screen all patients for HBV prior to initiation of inebilizumab-cdon. Contraindicated in patients with active hepatitis B disease. Consult a liver disease expert prior to and during inebilizumab-cdon therapy in patients who are chronic HBV carriers (i.e., HbsAg-positive).

Progressive Multifocal Leukoencephalopathy

Progressive multifocal leukoencephalopathy (PML), an opportunistic viral infection of the brain caused by the JC virus, observed in patients treated with other B-cell-depleting antibodies. No confirmed cases of PML identified in clinical trials of inebilizumab-cdon. Withhold inebilizumab-cdon therapy and perform a diagnostic evaluation at the first sign or symptom suggestive of PML; MRI findings may be apparent before clinical signs or symptoms. Typical symptoms include 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.

Tuberculosis

Evaluate patients for tuberculosis risk factors and test for latent infection prior to initiating inebilizumab-cdon. Consider anti-tuberculosis therapy in patients with a history of latent active tuberculosis in whom an adequate course of treatment cannot be confirmed, and in patients with a negative test for latent tuberculosis but who have risk factors for tuberculosis infection. Consult an infectious disease expert regarding whether initiating anti-tuberculosis therapy is appropriate before starting treatment.

Vaccinations

Inebilizumab-cdon may interfere with safety and effectiveness of vaccines; patients should receive all necessary vaccinations at least 4 weeks prior to initiation of inebilizumab-cdon. Vaccination with live-attenuated or live vaccines is not recommended during treatment and until B-cell repletion.

In infants of mothers exposed to inebilizumab-cdon during pregnancy, do not administer live or live-attenuated vaccines before confirming recovery of B-cell counts in the infant. Depletion of B-cells in these exposed infants may increase the risks from live or live-attenuated vaccines. Non-live vaccines may be administered prior to recovery from B-cell and immunoglobulin level depletion, but consider consultation with a qualified specialist to determine whether a protective immune response was mounted.

Reduction in Immunoglobulins

Progressive and prolonged hypogammaglobulinemia or decrease in total and individual immunoglobulin concentrations (e.g., immunglobulins G and M [IgG and IgM]) may occur.

Monitor serum immunoglobulin concentrations during therapy, especially in patients with opportunistic or recurrent infections, and after discontinuance of therapy until recovery of B-cell counts. Consider discontinuance of therapy if serious opportunistic infection or recurrent infection occurs in a patient with low IgG or IgM concentrations, or if prolonged hypogammaglobulinemia requires treatment with IV immunoglobulins.

Fetal/Neonatal Morbidity and Mortality

Based on animal data, inebilizumab-cdon can cause fetal harm due to B-cell lymphopenia and reduced antibody response in offspring exposed to the drug even after B-cell repletion. Transient peripheral B-cell depletion and lymphocytopenia reported in infants born to mothers exposed to other B-cell depleting antibodies during pregnancy.

Immunogenicity

Potential for immunogenicity. In the principal efficacy study, treatment-emergent antibodies were detected in patients receiving inebilizumab-cdon. Clinical impact of such anti-drug antibody development not known.

Specific Populations

Pregnancy

No adequate data on developmental risk associated with use of inebilizumab-cdon in pregnant women. However, transient peripheral B-cell depletion and lymphocytopenia reported in infants born to mothers exposed to other B-cell depleting antibodies during pregnancy. B-cell levels in infants following maternal exposure to inebilizumab-cdon not studied in clinical trials. The potential duration of B-cell depletion in such infants, and the impact of B-cell depletion on vaccine safety and effectiveness, are unknown.

Inebilizumab-cdon is a humanized IgG1 monoclonal antibody and immunoglobulins are known to cross the placental barrier.

Lactation

There are no data on the presence of inebilizumab-cdon in human milk, the effects on a breastfed infant, or the effects on milk production. Human IgG is excreted in human milk, and the potential for absorption of inebilizumab-cdon to lead to B-cell depletion in the breastfed infant is unknown.

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

Females of Reproductive Potential

Females of reproductive potential should use contraception while receiving inebilizumab-cdon and for 6 months after the last infusion.

Pediatric Use

Safety and efficacy not established in pediatric patients.

Geriatric Use

Clinical studies did not include sufficient numbers of patients ≥65 years of age to determine whether they respond differently from younger patients.

Population pharmacokinetic analysis indicate no significant effect of age on clearance of inebilizumab-cdon.

Hepatic Impairment

No formal clinical studies in patients with hepatic impairment.

Renal Impairment

No formal clinical studies in patients with renal impairment.

Common Adverse Effects

Common adverse reactions (≥10%): urinary tract infection, arthralgia.

Drug Interactions

CYP enzymes and transporters not involved in clearance of inebilizumab-cdon; therefore, potential risk of interactions with substrates, inducers, or inhibitors of these enzymes and transporters is low.

Immunosuppressive or Immunomodulating Therapies

Concomitant use of inebilizumab-cdon with immunosuppressant drugs, including systemic corticosteroids, may increase risk of infection. Consider risk of additive immune system effects when these drugs are coadministered.

Inebilizumab-cdon Pharmacokinetics

Absorption

Bioavailability

The pharmacokinetics of inebilizumab-cdon in NMOSD patients following IV administration is biphasic.

Onset

Pharmacodynamics assessed by assay for CD20+ B cells because inebilizumab-cdon can interfere with CD19+ B cell assays.

Elimination

Metabolism

Degraded by proteolytic enzymes widely distributed in the body.

Half-life

Mean terminal half-life 18 days.

Stability

Storage

Parenteral

Injection

Store in refrigerator at 2–8°C in original carton to protect from light. Do not freeze or shake. Store vials upright.

After dilution: If not administered immediately, store infusion solution for a maximum of 24 hours in the refrigerator (2–8°C) or for a maximum of 4 hours at room temperature (20–25°C).

Actions

• A CD19-directed humanized IgG1 monoclonal antibody produced by recombinant DNA technology.

• Precise mechanism by which inebilizumab-cdon exerts its therapeutic effects in NMOSD is unknown but presumed to involve binding to CD19, a cell surface antigen present on pre-B and mature B lymphocytes.

• While the pathophysiology of NMOSD is not completely understood, B cells appear to play a prominent role.

• Following cell surface binding to B lymphocytes, inebilizumab-cdon results in antibody-dependent cellular cytolysis.

• Treatment with inebilizumab-cdon reduces CD20+ B cell counts by 8 days after infusion. CD20+ B-cell counts are reduced below the lower limit of normal by 4 weeks and remain below the lower limit of normal in the majority of patients for 28 weeks after treatment initiation.

Advice to Patients

• Advise the patient and/or caregiver to read the FDA-approved patient labeling (Medication Guide).

• Inform patients about the signs and symptoms of infusion reactions and advise them to contact their healthcare provider immediately if they observe signs or symptoms of infusion reactions.

• Advise patients to contact their healthcare provider for any signs of infection during treatment or after the last dose. Signs include fever, chills, constant cough, or dysuria.

• Advise patients that inebilizumab-cdon may cause reactivation of hepatitis B virus (HBV) infection and that monitoring will be required if they are at risk.

• Advise patients that progressive multifocal leukoencephalopathy (PML) has happened with drugs that are similar to inebilizumab-cdon and may happen with inebilizumab-cdon. Inform the patient that PML is characterized by a progression of deficits and usually leads to death or severe disability over weeks or months. Instruct the patient of the importance of contacting their healthcare provider if they develop any symptoms suggestive of PML. Inform the patient that 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, disturbance of vision, and changes in thinking, memory, and orientation leading to confusion and personality changes.

• Advise patients to complete any required vaccinations at least 4 weeks prior to initiation of inebilizumab-cdon. Administration of live-attenuated or live vaccines is not recommended during inebilizumab-cdon treatment and until B-cell recovery.

• Instruct patients that if they are pregnant or plan to become pregnant while taking inebilizumab-cdon, they should inform their healthcare provider. Advise females of reproductive potential that they should use effective contraception during treatment and for 6 months after inebilizumab-cdon therapy.

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

• Advise 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.

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