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Ibalizumab-uiyk

Class: HIV Entry and Fusion Inhibitors
Brands: Trogarzo

Medically reviewed on April 30, 2018

Introduction

Ibalizumab-uiyk is an HIV entry or fusion inhibitor.

Uses for Ibalizumab-uiyk

Ibalizumab-uiyk has the following uses:

Ibalizumab-uiyk, a CD4-directed post-attachment HIV-1 inhibitor, in combination with other antiretroviral(s), is indicated for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in heavily treatment-experienced adults with multidrug resistant HIV-1 infection failing their current antiretroviral regimen. 1

Ibalizumab-uiyk Dosage and Administration

General

Ibalizumab-uiyk is available in the following dosage form(s) and strength(s):

Injection: 200 mg/1.33 mL (150 mg/mL) in a single-dose vial.1

Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

Adults

Dosage & Administration

Ibalizumab-uiyk is administered intravenously (IV) as a single loading dose of 2,000 mg followed by a maintenance dose of 800 mg every 2 weeks after dilution in 250 mL of 0.9% Sodium Chloride Injection, USP. 1

Cautions for Ibalizumab-uiyk

Contraindications

None.1

Warnings/Precautions

Immune Reconstitution Inflammatory Syndrome

Immune reconstitution inflammatory syndrome has been reported in one patient treated with ibalizumab-uiyk in combination with other antiretrovirals. During the initial phase of combination antiretroviral therapies, patients whose immune systems respond may develop an inflammatory response to indolent or residual opportunistic infections, which may necessitate further evaluation and treatment.1

Specific Populations

Pregnancy

There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to ibalizumab-uiyk during pregnancy. Healthcare providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry (APR) at 1–800–258–4263.1

No adequate human data are available to establish whether or not ibalizumab-uiyk poses a risk to pregnancy outcomes. Animal reproductive toxicology studies with ibalizumab-uiyk have not been conducted. Monoclonal antibodies, such as ibalizumab-uiyk, are transported across the placenta as pregnancy progresses; therefore, ibalizumab-uiyk has the potential to be transmitted from the mother to the developing fetus. The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.1

Lactation

The Centers for Disease Control and Prevention recommend that HIV-1-infected mothers in the United States not breastfeed their infants to avoid the risk of postnatal transmission of HIV-1 infection.1

No data are available regarding the presence of ibalizumab-uiyk in human milk, the effects on the breastfed child, or the effects on milk production. Human IgG is present in human milk, although published data indicate that antibodies in breast milk do not enter the neonatal or infant circulation system in substantial amounts. Because of the potential for HIV-1 transmission, instruct mothers not to breastfeed if they are receiving ibalizumab-uiyk.1

Pediatric Use

The safety and effectiveness of ibalizumab-uiyk in pediatric patients have not been established. 1

Geriatric Use

No studies have been conducted with ibalizumab-uiyk in geriatric patients. 1

Common Adverse Effects

Adverse Reactions

The most common adverse reactions (incidence ≥ 5%) were diarrhea, dizziness, nausea, and rash. 1

Drug Interactions

Specific Drugs

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.1

Actions and Spectrum

Mechanism of Action

Ibalizumab-uiyk is an HIV-1 antiretroviral drug.1

Ibalizumab-uiyk, a recombinant humanized monoclonal antibody, blocks HIV-1 from infecting CD4+ T cells by binding to domain 2 of CD4 and interfering with post-attachment steps required for the entry of HIV-1 virus particles into host cells and preventing the viral transmission that occurs via cell-cell fusion.1

The binding specificity of ibalizumab-uiyk to domain 2 of CD4 allows ibalizumab-uiyk to block viral entry into host cells without causing immunosuppression. Epitope mapping studies indicate that ibalizumab-uiyk binds to a conformational epitope located primarily in domain 2 of the extracellular portion of the CD4 receptor. This epitope is positioned on the surface of CD4 opposite to the site in domain 1 that is required for CD4 binding of the MHC class II molecules and therefore does not interfere with CD4-mediated immune functions. Additionally, ibalizumab-uiyk does not interfere with gp120 attachment to CD4.1

Spectrum

Ibalizumab-uiyk inhibits the replication of CCR5- and CXCR4-tropic laboratory strains and primary isolates of HIV-1 in phytohemagglutinin stimulated peripheral blood lymphocytes. The median EC50 value (50% effective concentration) for ibalizumab-uiyk against HIV-1 group M isolates (subtypes A, B, C, D, E, or O) was 8 ng/mL (n = 15, range of 0.4 to 600 ng/mL) in cell culture, with lower susceptibility observed in macrophage-tropic HIV-1 strains (BaL, JR-CSF, YU2, and ADA-M). In a single-cycle infection assay, ibalizumab-uiyk inhibited 17 clinical isolates of subtype B with a median EC50 value of 12 ng/mL (range of 8.8 to 16.9 ng/mL; mean 12 ± 3 ng/mL) and a median maximum percentage inhibition (MPI) of 97% (range of 89 to 99%; mean 97 ± 3%). Three CCR5-tropic clinical isolates from subtypes B, C, and D, were inhibited with EC50 values ranging from 59-66 ng/mL and 3 CXCR4-tropic clinical isolates from subtypes B, C, and D, with EC50 values ranging from 44-59 ng/mL.1

No antagonism was observed when PBMCs or MAGI-CCR5 cells infected with the subtype B Ba-L or ADA variants of HIV-1 were incubated with ibalizumab-uiyk in combination with the CCR5 co-receptor antagonist maraviroc or when PBMCs infected with the subtype B HT/92/599 variant of HIV-1 were incubated with ibalizumab-uiyk in combination with the gp41 fusion inhibitor enfuvirtide; a nonnucleoside reverse transcriptase inhibitor (efavirenz); nucleoside analog reverse transcriptase inhibitors (abacavir, didanosine, emtricitabine, tenofovir, or zidovudine); or a protease inhibitor (atazanavir).1

Subjects enrolled in TMB-301 were heavily treatment-experienced subjects infected with multidrug resistant HIV-1. Ibalizumab-uiyk inhibited 38 baseline isolates at a median EC50 value of 31 ng/mL (range of 13 to 212 ng/mL; mean 39 ± 35 ng/mL) with a median MPI of 97% (range of 41-100%; mean 91 ± 14%). For 10 subjects in TMB-301 who failed treatment, at the time of failure the median ibalizumab-uiyk EC50 value was 566 ng/mL (range of 148 to >54,900 ng/mL; mean 11,768 ± 21,650 ng/mL) representing an EC50 value shift of >18-fold. For the HIV-1 derived from the same subjects, the median MPI was 55% (range of 43-72%; mean 56 ± 8%) representing a 42 percentage point reduction.1

Resistance

Decreased susceptibility to ibalizumab-uiyk, as defined by a decrease in MPI, has been observed in some subjects experiencing virologic failure and may be associated with genotypic changes in the HIV-1 envelope coding sequence that results in the loss of potential N-linked glycosylation sites (PNGS) in the V5 loop of gp120. The clinical significance of decreased susceptibility to ibalizumab-uiyk has not been established.1

CD4 polymorphisms reported in public databases were analyzed to determine if any naturally occurring amino acid substitutions in the CD4 molecule from different human populations would potentially impact the antiviral activity of ibalizumab-uiyk. None of the known CD4 polymorphisms are likely to have an impact on ibalizumab-uiyk binding to CD4.1

Phenotypic and genotypic test results revealed no evidence of cross-resistance between ibalizumab-uiyk and any of the approved classes of anti-retroviral drugs (CCR5 co-receptor antagonists, gp41 fusion inhibitors, integrase strand transfer inhibitors [INSTIs], non-nucleos(t)ide reverse transcriptase inhibitors [NNRTIs], nucleos(t)ide reverse transcriptase inhibitors [NRTIs], or protease inhibitors [PIs]). Ibalizumab-uiyk is active against HIV-1 resistant to all approved antiretroviral agents and exhibits antiretroviral activity against R5-tropic, X4-tropic, and dual-tropic HIV-1.1

Decreased susceptibility to ibalizumab-uiyk following multiple dose administrations of ibalizumab-uiyk has been observed in some subjects. Cell culture studies performed with HIV-1 variants with reduced susceptibility to ibalizumab-uiyk indicate that phenotypic changes associated with resistance to ibalizumab-uiyk do not alter susceptibility to other approved agents and do not result in the selection of CD4-independent viral isolates.1

Advice to Patients

Advise the patient to read the FDA-approved patient labeling (Patient Information).1

Immune Reconstitution Syndrome

Advise patients that immune reconstitution syndrome has been reported in a patient receiving ibalizumab-uiyk and to inform their health care provider immediately of any symptoms of infection.1

Important Administration Information

Advise the patient it is important to receive ibalizumab-uiyk injections every two weeks as recommended by their healthcare professional and not to change the dosing schedule of ibalizumab-uiyk or any antiretroviral medication without consulting their healthcare provider. Advise the patient to contact their healthcare provider immediately if they stop taking ibalizumab-uiyk or any other drug in their antiretroviral regimen.1

Pregnancy Exposure Registry

Inform patients that there is an antiretroviral pregnancy registry that monitors fetal outcomes of pregnant women exposed to ibalizumab-uiyk.1

Lactation

Instruct women with HIV-1 infection not to breastfeed because HIV-1 can be passed to the baby in breast milk.1

Additional Information

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.

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.

Ibalizumab-uiyk

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection, Solution

150 mg /1 mL

Trogarzo

Theratechnologies Inc.

AHFS Drug Information. © Copyright 2018, Selected Revisions April 30, 2018. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

References

1. Theratechnologies Inc. Trogarzo (ibalizumab-uiyk) INTRAVENOUS prescribing information. 2018 Apr. http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c548ad82-9d1f-4d16-95b6-4e6106badf43

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