Version May 2024
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 tuberculosis (TB) disease (active TB) 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.
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Refer to adult dosing.
B-cell-depleting antibodies, including inebilizumab, are associated with an increased risk for infection, including urinary tract infection, nasopharyngitis, upper respiratory tract infection, and influenza.
While hepatitis B virus (HBV) reactivation has been described with other B-cell-depleting antibodies, patients with chronic HBV infection were excluded from clinical trials and HBV reactivation was, therefore, not observed with inebilizumab. In addition, John Cunningham virus infection resulting in progressive multifocal leukoencephalopathy, as well as reactivation of tuberculosis infection, has been described with other B-cell-depleting antibodies and is considered a theoretical concern with inebilizumab therapy.
Mechanism: Dose-related; related to the pharmacologic action (targets and depletes CD19-expressing B cells through antibody-dependent cellular cytolysis).
Risk factors:
• Active infection (including chronic HBV infection and tuberculosis infection)
Inebilizumab may cause infusion-related reactions, which are most often mild to moderate in severity (Ref); symptoms may include headache, nausea, somnolence, dyspnea, fever, myalgia, and rash.
Mechanism: Non–dose-related; exact mechanism has not been established.
Onset: Rapid. Most commonly occurs during first infusion; however, may occur with any dose.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults.
>10%:
Genitourinary: Urinary tract infection (11%)
|
Drug (Inebilizumab) |
Placebo |
Number of Patients (Inebilizumab) |
Number of Patients (Placebo) |
|---|---|---|---|
|
11% |
10% |
161 |
52 |
Hematologic & oncologic: Decreased neutrophils (2% to 12%)
1% to 10%:
Hematologic & oncologic: Lymphocytopenia (5%)
Immunologic: Antibody development (6%)
Neuromuscular & skeletal: Arthralgia (10%), back pain (7%)
Frequency not defined: Hematologic & oncologic: Decreased serum immunoglobulins
History of a life-threatening infusion reaction to inebilizumab; active hepatitis B infection; tuberculosis (TB) disease (active TB) or untreated TB infection (latent TB).
Concerns related to adverse effects:
• Hepatitis B reactivation: Consult liver disease specialist prior to starting and during treatment in patients who are chronic carriers of HBV (HBsAg+).
• Tuberculosis: Do not administer to patients with tuberculosis (TB) disease (active TB) or positive screening without appropriate treatment; consider infectious disease consult. Consider anti-TB therapy prior to treatment initiation in patients with a history of TB infection (latent TB) in whom an adequate course of TB treatment cannot be confirmed and for patients testing negative but having risk factors for TB.
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.
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]
No
Solution (Uplizna Intravenous)
100 mg/10 mL (per mL): $5,483.81
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
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.
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
Uplizna: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/761142s000lbl.pdf#page=17
Neuromyelitis optica spectrum disorder: Treatment of neuromyelitis optica spectrum disorder (NMOSD) in adults who are anti-aquaporin-4 (AQP4) antibody positive.
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Abrocitinib: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination
Antithymocyte Globulin (Equine): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of immunosuppressive therapy is reduced. Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor therapy
Baricitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Baricitinib. Risk X: Avoid combination
BCG Products: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of BCG Products. Risk X: Avoid combination
Brincidofovir: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Brincidofovir. Risk C: Monitor therapy
Brivudine: May enhance the adverse/toxic effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination
Chikungunya Vaccine (Live): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Chikungunya Vaccine (Live). Risk X: Avoid combination
Cladribine: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Cladribine. Risk X: Avoid combination
Coccidioides immitis Skin Test: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the diagnostic effect of Coccidioides immitis Skin Test. Management: Consider discontinuing therapeutic immunosuppressants several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider therapy modification
Corticosteroids (Systemic): May enhance the immunosuppressive effect of Inebilizumab. Risk C: Monitor therapy
COVID-19 Vaccine (Adenovirus Vector): Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Adenovirus Vector). Management: Administer a 2nd dose using an mRNA COVID-19 vaccine (at least 4 weeks after the primary vaccine dose) and a bivalent booster dose (at least 2 months after the additional mRNA dose or any other boosters). Risk D: Consider therapy modification
COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor therapy
COVID-19 Vaccine (mRNA): Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of COVID-19 Vaccine (mRNA). Management: Give a 3-dose primary series for all patients aged 6 months and older taking immunosuppressive medications or therapies. Booster doses are recommended for certain age groups. See CDC guidance for details. Risk D: Consider therapy modification
COVID-19 Vaccine (Subunit): Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Subunit). Risk C: Monitor therapy
COVID-19 Vaccine (Virus-like Particles): Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Virus-like Particles). Risk C: Monitor therapy
Dengue Tetravalent Vaccine (Live): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Dengue Tetravalent Vaccine (Live). Risk X: Avoid combination
Denosumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Denosumab. Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and immunosuppressants. If combined, monitor for signs/symptoms of serious infections. Risk D: Consider therapy modification
Deucravacitinib: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination
Efgartigimod Alfa: May diminish the therapeutic effect of Fc Receptor-Binding Agents. Risk C: Monitor therapy
Etrasimod: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination
Filgotinib: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination
Immunosuppressants (Cytotoxic Chemotherapy): May enhance the immunosuppressive effect of Inebilizumab. Risk C: Monitor therapy
Immunosuppressants (Miscellaneous Oncologic Agents): May enhance the immunosuppressive effect of Inebilizumab. Risk C: Monitor therapy
Immunosuppressants (Therapeutic Immunosuppressant Agents): May enhance the immunosuppressive effect of Inebilizumab. Risk C: Monitor therapy
Influenza Virus Vaccines: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating immunosuppressants if possible. If vaccination occurs less than 2 weeks prior to or during therapy, revaccinate 2 to 3 months after therapy discontinued if immune competence restored. Risk D: Consider therapy modification
Leflunomide: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents. Risk D: Consider therapy modification
Methotrexate: May enhance the immunosuppressive effect of Inebilizumab. Risk C: Monitor therapy
Mumps- Rubella- or Varicella-Containing Live Vaccines: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Mumps- Rubella- or Varicella-Containing Live Vaccines. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Mumps- Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination
Nadofaragene Firadenovec: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid combination
Natalizumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Natalizumab. Risk X: Avoid combination
Ocrelizumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ocrelizumab. Risk C: Monitor therapy
Ofatumumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ofatumumab. Risk C: Monitor therapy
Pidotimod: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Pidotimod. Risk C: Monitor therapy
Pimecrolimus: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Pimecrolimus. Risk X: Avoid combination
Pneumococcal Vaccines: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Pneumococcal Vaccines. Risk C: Monitor therapy
Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Risk X: Avoid combination
Polymethylmethacrylate: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the potential for allergic or hypersensitivity reactions to Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider therapy modification
Rabies Vaccine: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider therapy modification
Ritlecitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ritlecitinib. Risk X: Avoid combination
Rozanolixizumab: May diminish the therapeutic effect of Fc Receptor-Binding Agents. Risk C: Monitor therapy
Ruxolitinib (Topical): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination
Sipuleucel-T: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants prior to initiating sipuleucel-T therapy. Risk D: Consider therapy modification
Tacrolimus (Topical): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Tacrolimus (Topical). Risk X: Avoid combination
Talimogene Laherparepvec: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid combination
Tertomotide: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Tertomotide. Risk X: Avoid combination
Tofacitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Tofacitinib. Management: Coadministration of tofacitinib with potent immunosuppressants is not recommended. Use with non-biologic disease-modifying antirheumatic drugs (DMARDs) was permitted in psoriatic arthritis clinical trials. Risk X: Avoid combination
Typhoid Vaccine: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Typhoid Vaccine. Risk X: Avoid combination
Ublituximab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ublituximab. Risk C: Monitor therapy
Upadacitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination
Vaccines (Inactivated/Non-Replicating): Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Vaccines (Inactivated/Non-Replicating). Management: Give inactivated vaccines at least 2 weeks prior to initiation of immunosuppressants when possible. Patients vaccinated less than 14 days before initiating or during therapy should be revaccinated at least 2 to 3 months after therapy is complete. Risk D: Consider therapy modification
Vaccines (Live): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Vaccines (Live). Risk X: Avoid combination
Yellow Fever Vaccine: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Yellow Fever Vaccine. Risk X: Avoid combination
Females of reproductive potential should use effective contraception during therapy and for at least 6 months after the last inebilizumab dose.
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).
It is not known if inebilizumab is present in breast milk. However, inebilizumab is a humanized monoclonal antibody (IgG1). Human IgG is present in breast milk.
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother.
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 (disease [active] and infection [latent]) prior to initiation and signs/symptoms of TB disease during and after inebilizumab treatment; 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 (eg, 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; MRI findings may be apparent prior to clinical signs/symptoms).
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.
Half-life elimination: Terminal: 18 days.
Excretion: Clearance: 0.19 L/day.
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