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Inebilizumab

Medically reviewed by Drugs.com. Last updated on Aug 17, 2020.

Pronunciation

(in EB i LIZ ue mab)

Index Terms

  • Inebilizumab-cdon
  • MEDI-551
  • Uplizna

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intravenous:

Uplizna: Inebilizumab-cdon 100 mg/10 mL (10 mL) [contains polysorbate 80]

Brand Names: U.S.

  • Uplizna

Pharmacologic Category

  • Anti-CD19 Monoclonal Antibody
  • Monoclonal Antibody

Pharmacology

Inebilizumab is an anti-CD19 monoclonal antibody directed against pre-B and mature B-cell lymphocytes, which express the cell surface antigen CD19. Following binding to CD19, inebilizumab causes antibody-dependent cellular cytolysis.

Distribution

Vd: Central: 2.95 L; peripheral: 2.57 L.

Metabolism

Degraded by proteolytic enzymes widely distributed in the body.

Excretion

Clearance: 0.19 L/day.

Half-Life Elimination

Terminal: 18 days.

Use: Labeled Indications

Neuromyelitis optica spectrum disorder: Treatment of neuromyelitis optica spectrum disorder (NMOSD) in adults who are anti-aquaporin-4 (AQP4) antibody positive.

Contraindications

History of a life-threatening infusion reaction to inebilizumab; active hepatitis B infection; active or untreated latent tuberculosis.

Dosing: Adult

Note: Administer all vaccines at least 4 weeks prior to initiation of inebilizumab. Obtain quantitative serum immunoglobulins and screen for hepatitis B virus (HBsAg and anti-HBc measurements) and active tuberculosis prior to inebilizumab initiation. Premedicate with antihistamine (eg, diphenhydramine 25 to 50 mg orally or equivalent) 30 to 60 minutes prior to infusion, antipyretic (eg, acetaminophen 500 to 650 mg orally) 30 to 60 minutes prior to infusion, and corticosteroid (eg, methylprednisolone 80 to 125 mg IV or equivalent) 30 minutes prior to each infusion to prevent and/or reduce severity of infusion-related reactions.

Neuromyelitis optica spectrum disorder: IV: 300 mg on day 1, followed by 300 mg 2 weeks later; subsequent doses of 300 mg are administered once every 6 months (beginning 6 months after the first 300 mg dose).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Geriatric

Refer to adult dosing.

Reconstitution

Inspect vials prior to preparation; do not use if cloudy, discolored, or contains particulate matter. Do not shake vials. Withdrawal 10 mL from each of the 3 vials (total 30 mL) and add contents to 250 mL of NS only (do not use other diluents). Mix gently by inversion; do not shake solution. Discard any unused solution in vials.

Administration

IV: Administer by IV infusion via an infusion pump and using a low-protein binding 0.2 or 0.22 micron in-line filter. Prior to every infusion, assess for active infection; if present, delay infusion until infection resolves. Premedicate with antihistamine, antipyretic, and corticosteroid 30 to 60 minutes prior to infusion. Allow to reach room temperature prior to administration. Administer diluted infusion over ~90 minutes at an increasing rate: 42 mL/hour for first 30 minutes, followed by 125 mL/hour for the next 30 minutes, then 333 mL/hour until completion.

Storage

Store intact vials at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light. Do not freeze. Do not shake. Use solution diluted for infusion immediately; may be stored for up to 24 hours refrigerated and 4 hours at room temperature.

Drug Interactions

Baricitinib: Immunosuppressants may enhance the immunosuppressive effect of Baricitinib. Management: Use of baricitinib in combination with potent immunosuppressants such as azathioprine or cyclosporine is not recommended. Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted. Consider therapy modification

BCG (Intravesical): Immunosuppressants may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

Cladribine: May enhance the immunosuppressive effect of Immunosuppressants. Avoid combination

Coccidioides immitis Skin Test: Immunosuppressants may diminish the diagnostic effect of Coccidioides immitis Skin Test. Monitor therapy

Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. Monitor therapy

Echinacea: May diminish the therapeutic effect of Immunosuppressants. Management: Consider avoiding Echinacea in patients receiving therapeutic immunosuppressants. If coadministered, monitor for reduced efficacy of the immunosuppressant during concomitant use. Consider therapy modification

Fingolimod: Immunosuppressants may enhance the immunosuppressive effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and other immunosuppressants when possible. If combined, monitor patients closely for additive immunosuppressant effects (eg, infections). Consider therapy modification

Immunosuppressants: Inebilizumab may enhance the immunosuppressive effect of Immunosuppressants. Monitor therapy

Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Consider therapy modification

Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Avoid combination

Nivolumab: Immunosuppressants may diminish the therapeutic effect of Nivolumab. Management: Avoid use of immunosuppressants (including systemic corticosteroids) prior to initiation of nivolumab. Use of immunosuppressants after administration of nivolumab (eg, for immune-related toxicity) is unlikely to affect nivolumab efficacy. Consider therapy modification

Ocrelizumab: May enhance the immunosuppressive effect of Immunosuppressants. Monitor therapy

Ozanimod: Immunosuppressants may enhance the immunosuppressive effect of Ozanimod. Monitor therapy

Pidotimod: Immunosuppressants may diminish the therapeutic effect of Pidotimod. Monitor therapy

Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Management: Consider avoiding concomitant use of roflumilast and immunosuppressants as recommended by the Canadian product monograph. Inhaled or short-term corticosteroids are unlikely to be problematic. Consider therapy modification

Siponimod: Immunosuppressants may enhance the immunosuppressive effect of Siponimod. Monitor therapy

Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Management: Evaluate patients to see if it is medically appropriate to reduce or discontinue therapy with immunosuppressants prior to initiating sipuleucel-T therapy. Consider therapy modification

Smallpox and Monkeypox Vaccine (Live): Immunosuppressants may diminish the therapeutic effect of Smallpox and Monkeypox Vaccine (Live). Monitor therapy

Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Talimogene Laherparepvec: Immunosuppressants may enhance the adverse/toxic effect of Talimogene Laherparepvec. Specifically, the risk for disseminated herpetic infection may be increased. Avoid combination

Tertomotide: Immunosuppressants may diminish the therapeutic effect of Tertomotide. Monitor therapy

Tofacitinib: Immunosuppressants may enhance the immunosuppressive effect of Tofacitinib. Management: Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted, and this warning seems particularly focused on more potent immunosuppressants. Consider therapy modification

Upadacitinib: Immunosuppressants may enhance the immunosuppressive effect of Upadacitinib. Management: Concomitant use of upadacitinib with potent immunosuppressants is not recommended. Avoid combination

Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Management: Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated less than 2 weeks before starting or during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation. Consider therapy modification

Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants. Avoid combination

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

>10%:

Genitourinary: Urinary tract infection (11%)

Hematologic & oncologic: Decreased neutrophils (2% to 12%)

1% to 10%:

Hematologic & oncologic: Lymphocytopenia (5%)

Immunologic: Antibody development (6%)

Local: Infusion site reaction (9%)

Neuromuscular & skeletal: Arthralgia (10%), back pain (7%)

Frequency not defined:

Hematologic & oncologic: Decreased serum immunoglobulins

Infection: Influenza

Respiratory: Nasopharyngitis, upper respiratory tract infection

Warnings/Precautions

Concerns related to adverse effects:

• Hepatitis B reactivation: Screen for hepatitis B virus (HBV) in all patients (HBsAg and anti-HBc measurements) prior to treatment initiation. Although there were no reports of hepatitis B reactivation with inebilizumab, risk of hepatitis B reactivation has occurred with other B-cell depleting antibodies. Do not administer inebilizumab to patients with active HBV confirmed by positive results for HBsAg and anti-HB tests. Consult liver disease specialist prior to starting and during treatment in patients who are chronic carriers of HBV (HBsAg+).

• Infection: Assess for infections prior to treatment initiation and delay treatment in patients with an active infection until the infection is resolved. An increased risk of infections has been observed with other B-cell depleting treatments. Inebilizumab is associated with an increased risk for urinary tract infections, nasopharyngitis, upper respiratory tract infections, and influenza.

• Infusion reactions: Inebilizumab may cause infusion reactions; symptoms may include headache, nausea, somnolence, dyspnea, fever, myalgia, and rash. Infusion reactions occurred in 9.3% of patients during first course of treatment and were most common during first infusion; however, also occurred during subsequent infusions. Administer premedications (corticosteroid [methylprednisolone], antihistamine [diphenhydramine], and antipyretic [acetaminophen]) to reduce the frequency and severity. Monitor for infusion reactions during the infusion and for at least 1 hour after the end of the infusion. Depending on the severity of the reaction, management may require temporary infusion interruption, decreased infusion rate, discontinuation, and/or symptomatic supportive management.

• Progressive multifocal leukoencephalopathy: Although no cases of progressive multifocal leukoencephalopathy (PML) were identified in inebilizumab studies, John Cunningham (JC) virus infection resulting in PML has been observed in patients treated with other B-cell depleting antibodies and other therapies that affect immune competence. PML is an opportunistic viral infection of the brain caused by the JC virus, and usually leads to death or severe disability; PML typically only occurs in patients who are immunocompromised. Symptoms associated with PML are diverse and progress over days to weeks and include progressive weakness on one side of the body or clumsiness of limbs, vision disturbance, and changes in thinking, memory, and/or orientation leading to confusion and personality changes. Withhold treatment and perform appropriate diagnostic evaluation at the first sign or symptom suggestive of PML (MRI findings may be apparent prior to clinical signs/symptoms).

• Tuberculosis: Patients should be evaluated for active tuberculosis (TB) infection and tested for latent infection prior to initiating therapy. Do not administer to patients with an active TB infection or positive screening without appropriate treatment; consider infectious disease consult. Consider anti-TB therapy prior to treatment initiation in patients with a history of latent active TB in whom an adequate course of TB treatment cannot be confirmed and for patients testing negative but having risk factors for TB infection. Monitor closely for signs/symptoms of active TB during and after inebilizumab treatment.

Other warnings/precautions:

• Immunizations: Administer all immunizations at least 4 weeks prior to treatment initiation. Immunization with live-attenuated or live vaccines is not recommended during treatment or after discontinuation until B-cell repletion. Prior to administration of live-attenuated or live vaccinations in infants exposed to inebilizumab in utero, confirm recovery of B-cell counts. Non-live vaccines may be administered; however, consideration should be given to evaluating the immune response.

• Immunoglobulins: Progressive and prolonged hypogammaglobulinemia or declines in immunoglobulins (IgG, IgM) may occur with continued treatment. Prior to initiating therapy, assess quantitative serum immunoglobulin levels; consult immunology experts in patients with low levels. Monitor during therapy and after discontinuation of therapy until B-cell repletion, especially in patients with opportunistic or recurrent infections. Consider discontinuation if patients with low IgG or IgM develop severe opportunistic or recurrent infections or if prolonged hypogammaglobulinemia requires treatment with IV immunoglobulins.

Monitoring Parameters

Hepatitis B virus screening (HBsAg and anti-HBc measurements) prior to therapy initiation; quantitative serum immunoglobulins prior to therapy initiation, during therapy (especially in patients with severe opportunistic or recurrent infections), and after discontinuation of therapy until B-cell repletion; tuberculosis screening prior to initiation; assess for active infection prior to each infusion; monitor infusion reactions during and for at least 1 hour following end of the infusion; monitor for signs/symptoms of infection and progressive multifocal leukoencephalopathy.

Reproductive Considerations

Females of reproductive potential should use effective contraception during therapy and for at least 6 months after the last inebilizumab dose.

Pregnancy Considerations

Inebilizumab is a humanized monoclonal antibody (IgG1). Placental transfer of human IgG is dependent upon the IgG subclass, maternal serum concentrations, newborn birth weight, and gestational age, generally increasing as pregnancy progresses. The lowest exposure would be expected during the period of organogenesis (Palmeira 2012; Pentsuk 2009).

Based on data from animal reproduction studies, in utero exposure to inebilizumab may cause fetal harm. Transient B-cell depletion and lymphocytopenia may occur in infants following in utero exposure to inebilizumab.

Maternal neuromyelitis optica spectrum disorder (NMOSD) may be associated with adverse pregnancy outcomes. Information related to the treatment of NMOSD in pregnancy is limited; agents other than inebilizumab may be preferred (Borisow 2018; Chang 2020; Zhu 2020).

Patient Education

What is this drug used for?

• It is used to treat a health problem called neuromyelitis optica spectrum disorder (NMOSD).

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Joint pain

• Back pain

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Infection

• Urinary tract infection like blood in your urine, burning or painful urination, passing a lot of urine, fever, lower abdominal pain, or pelvic pain

• Nose irritation

• Throat irritation

• Common cold symptoms

• Flu-like signs

• Progressive multifocal leukoencephalopathy like confusion, depression, trouble remembering things, behavioral changes, change in strength on one side is greater than the other, trouble speaking, change in balance, or vision changes

• Infusion reactions like headache, upset stomach, feeling sleepy, shortness of breath, fever, muscle pain, rash, or any other effects during the infusion

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine’s uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.