Class: Immunomodulatory Agents
CAS Number: 1299440-37-1
Inebilizumab-cdon, a recombinant humanized monoclonal antibody, is an immunomodulatory agent.
Uses for Inebilizumab-cdon
Inebilizumab-cdon has the following uses:
Inebilizumab-cdon is a CD19-directed cytolytic antibody indicated for the treatment of neuromyelitis optica spectrum disorder (NMOSD) in adult patients who are anti-aquaporin-4 (AQP4) antibody positive.
Inebilizumab-cdon Dosage and Administration
Inebilizumab-cdon is available in the following dosage form(s) and strength(s):
Injection: 100 mg/10 mL (10 mg/mL) solution in a single-dose vial.
It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:
Dosage and Administration
Screen for hepatitis B virus (HBV), quantitative serum immunoglobulins, and tuberculosis before the first dose.
Prior to every infusion, determine if there is an active infection; delay the infusion until the active infection resolves.
Prior to every infusion, premedicate with a corticosteroid, an antihistamine, and an antipyretic to reduce frequency and severity of infusion reactions.
Monitor patients closely during each infusion and for at least 1 hour after completion of each infusion.
Inebilizumab-cdon must be diluted in 250 mL of 0.9% sodium chloride injection, USP, prior to administration.
Inebilizumab-cdon is administered by intravenous infusion using increasing infusion rates titrated per the manufacturer's instructions to complete the infusion within approximately 90 minutes.
Initial doses: 300 mg by intravenous infusion, followed 2 weeks later by a second 300-mg dose by intravenous infusion.
Subsequent doses (starting 6 months after the first infusion): Single 300-mg dose by intravenous infusion once every 6 months.
Cautions for Inebilizumab-cdon
Previous life-threatening reaction to infusion of inebilizumab-cdon.
Active HBV infection.
Active or untreated latent tuberculosis.
Inebilizumab-cdon can cause infusion reactions, which can include headache, nausea, somnolence, dyspnea, fever, myalgia, rash, or other signs or symptoms. During the randomized clinical trial period, infusion reactions were observed with the first course of inebilizumab-cdon in 9.3% of NMOSD patients. Infusion reactions were most common with the first infusion but were also observed during subsequent infusions.
Administer premedication with a corticosteroid, an antihistamine, and an anti-pyretic.
Management recommendations for infusion reactions depend on the type and severity of the reaction. For life-threatening infusion reactions, immediately and permanently stop inebilizumab-cdon and administer appropriate supportive treatment. For less severe infusion reactions, management may involve temporarily stopping the infusion, reducing the infusion rate, and/or administering symptomatic treatment.
An increased risk of infections has been observed with other B-cell-depleting therapies. The most common infections reported by inebilizumab-cdon-treated patients in the randomized and open-label clinical trial periods included urinary tract infection (20%), nasopharyngitis (13%), upper respiratory tract infection (8%), and influenza (7%). Delay inebilizumab-cdon administration in patients with an active infection until the infection is resolved.
Inebilizumab-cdon has not been studied in combination with other immunosuppressants. If combining inebilizumab-cdon with another immunosuppressive therapy, consider the potential for increased immunosuppressive effects.
Risk of HBV reactivation has been observed with other B-cell-depleting antibodies. There have been no cases of HBV reactivation in patients treated with inebilizumab-cdon, but patients with chronic HBV infection were excluded from clinical trials. Perform HBV screening in all patients before initiation of treatment with inebilizumab-cdon. Do not administer inebilizumab-cdon to patients with active hepatitis. For patients who are chronic carriers of HBV (positive for HBsAg), consult liver disease experts before starting inebilizumab-cdon and during treatment.
PML is an opportunistic viral infection of the brain caused by the JC virus that typically only occurs in patients who are immunocompromised, and that usually leads to death or severe disability. Although no confirmed cases of PML were identified in inebilizumab-cdon clinical trials, 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. In inebilizumab-cdon clinical trials, one subject died following the development of new brain lesions for which a definitive diagnosis could not be established, though the differential diagnosis included an atypical NMOSD relapse, PML, or acute disseminated encephalomyelitis. At the first sign or symptom suggestive of PML, withhold inebilizumab-cdon and perform an appropriate diagnostic evaluation. MRI findings may be apparent before clinical signs or symptoms. 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.
Patients should be evaluated for tuberculosis risk factors and tested for latent infection prior to initiating inebilizumab-cdon. Consider anti-tuberculosis therapy prior to initiation of inebilizumab-cdon in patients with a history of latent active tuberculosis in whom an adequate course of treatment cannot be confirmed, and for patients with a negative test for latent tuberculosis but having risk factors for tuberculosis infection. Consult infectious disease experts regarding whether initiating anti-tuberculosis therapy is appropriate before starting treatment.
Administer all immunizations according to immunization guidelines at least 4 weeks prior to initiation of inebilizumab-cdon. The safety of immunization with live or live-attenuated vaccines following inebilizumab-cdon therapy has not been studied, and vaccination with live or live-attenuated 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, as indicated, may be administered prior to recovery from B-cell and immunoglobulin level depletion, but consultation with a qualified specialist should be considered to assess whether a protective immune response was mounted.
Reduction in Immunoglobulins
There may be a progressive and prolonged hypogammaglobulinemia or decline in the levels of total and individual immunoglobulins such as immunoglobulins G and M (IgG and IgM) with continued inebilizumab-cdon treatment. Monitor the levels of quantitative serum immunoglobulins during treatment with inebilizumab-cdon, especially in patients with opportunistic or recurrent infections, and until B-cell repletion after discontinuation of therapy. Consider discontinuing inebilizumab-cdon therapy if a patient with low immunoglobulin G or M develops a serious opportunistic infection or recurrent infections, or if prolonged hypogammaglobulinemia requires treatment with intravenous immunoglobulins.
Based on animal data, inebilizumab-cdon can cause fetal harm due to B-cell lymphopenia and reduce antibody response in offspring exposed to inebilizumab-cdon even after B-cell repletion.
Transient peripheral B-cell depletion and lymphocytopenia have been reported in infants born to mothers exposed to other B-cell depleting antibodies during pregnancy. Advise females of reproductive potential to use effective contraception while receiving inebilizumab-cdon and for at least 6 months after the last dose.
Risk Summary: Inebilizumab-cdon is a humanized IgG1 monoclonal antibody and immunoglobulins are known to cross the placental barrier. There are no adequate data on the developmental risk associated with the use of inebilizumab-cdon in pregnant women. However, transient peripheral B-cell depletion and lymphocytopenia have been 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 have not been 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, is unknown.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.
Animal Data: Intravenous administration of inebilizumab-cdon (0, 3, or 30 mg/kg/week) to human CD19 transgenic (huCD19 Tg) male and female mice prior to and during mating and continuing in females through gestation day 15 resulted in no adverse effects on embryofetal development; however, there was a marked reduction in B cells in fetal blood and liver at both doses tested. These results demonstrate that inebilizumab-cdon crosses the placenta and depletes B cells in the fetus.
Intravenous administration of inebilizumab-cdon (0, 3, or 30 mg/kg) to huCD19 Tg mice every three days throughout organogenesis and lactation resulted in depletion of B cells and persistent reductions in immune function (even following repletion of B cells and lasting into adulthood) in offspring at both doses tested. At the end of the lactation period, plasma inebilizumab-cdon levels in offspring were only slightly lower than those in maternal plasma. A no-effect level for immunotoxicity in the offspring was not identified.
Risk Summary: There are no data on the presence of inebilizumab-cdon in human milk, the effects on a breast-fed 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 breast-fed infant is unknown.
The developmental and health benefits of breast-feeding should be considered along with the mother’s clinical need for inebilizumab-cdon and any potential adverse effects on the breast-fed infant from inebilizumab-cdon or from the underlying maternal condition.
Females of Reproductive Potential
Women of childbearing potential should use contraception while receiving inebilizumab-cdon and for 6 months after the last infusion of inebilizumab-cdon.
Safety and effectiveness in pediatric patients have not been established.
Clinical studies of inebilizumab-cdon did not include sufficient numbers of patients 65 years of age and older to determine whether they respond differently from younger patients.
Common Adverse Effects
The most common adverse reactions (at least 10% of patients treated with inebilizumab-cdon and greater than placebo) were urinary tract infection and arthralgia.
It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:
Please see product labeling for drug interaction information.
Mechanism of Action
The precise mechanism by which inebilizumab-cdon exerts its therapeutic effects in NMOSD is unknown but is presumed to involve binding to CD19, a cell surface antigen presents on pre-B and mature B lymphocytes. Following cell surface binding to B lymphocytes, inebilizumab-cdon results in antibody-dependent cellular cytolysis.
Advice to Patients
Patient Counseling Information
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 HBV infection and that monitoring will be required if they are at risk.
Advise patients that 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.
AHFSfirstRelease™. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.
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.
10 mg/1 mL
AHFS Drug Information. © Copyright 2021, Selected Revisions July 27, 2020. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.
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