Ibalizumab (Monograph)

Brand name: Trogarzo
Drug class: HIV Entry and Fusion Inhibitors

Medically reviewed by Drugs.com on Mar 10, 2025. Written by ASHP.

Introduction

Antiretroviral; HIV entry inhibitor; CD4-directed post-attachment HIV type 1 (HIV-1) inhibitor.¹

Uses for Ibalizumab

Treatment of HIV Infection in Antiretroviral-experienced Adults

Used in conjunction with other antiretrovirals for treatment of HIV-1 infection in heavily treatment-experienced adults with multidrug-resistant HIV-1 infection failing their current antiretroviral regimen.¹ ¹⁰

Designated an orphan drug by FDA for this indication.⁴

Therapeutic options for treatment and prevention of HIV infection and recommendations concerning use of antiretrovirals are continuously evolving.²⁰⁰ ²⁰¹ ²⁰²

In the 2023 Department of Health and Human Services (HHS) adult HIV treatment guideline, ibalizumab is listed among other drugs with novel mechanisms of action, which can be included as part of a fully active antiretroviral regimen for treatment of HIV infection with virologic failure, including following failure of a second-line regimen and beyond.²⁰⁰ ²⁰¹ ²⁰²

Ibalizumab Dosage and Administration

General

Patient Monitoring

Observe patients for infusion-associated adverse reactions for 1 hour after completion of the loading dose as an IV infusion or IV push.¹
For patients without reactions after the first dose, observe for 15 minutes after completion of subsequent maintenance doses (administered either as an IV infusion or IV push).¹

Other General Considerations

Ibalizumab-uiyk should be prepared and administered by a trained medical professional.¹
Dosage modifications of ibalizumab are not required when administered with any other antiretrovirals or any other treatments.¹
The Institute for Safe Medication Practices (ISMP) list of error-prone abbreviations, symbols, and dose designations states that the use of abbreviations for antiretroviral medications (e.g., DOR, TAF, TDF) during the medication use process should be avoided as their use has been associated with serious medication errors.²⁰³

Administration

IV Administration

Administer as a single loading dose followed by maintenance doses every 2 weeks.¹ Doses may be administered either as a diluted IV infusion or undiluted IV push.¹

Administer by a trained medical professional.¹

Administer into the cephalic vein of right or left arm.¹ If cephalic vein not accessible, another appropriate vein may be used.¹

IV Infusion

Must be diluted prior to IV infusion.¹

Dilute appropriate number of vials to prepare desired dose.¹

To prepare 2000-mg loading dose for IV infusion, use 10 single-dose vials of the concentrate; withdraw 1.33 mL from each of the vials (total volume of 13.3 mL) and add to an IV infusion bag containing 250 mL of 0.9% sodium chloride injection.¹

To prepare 800-mg maintenance dose for IV infusion, use 4 single-dose vials of the concentrate; withdraw 1.33 mL from each of the vials (total volume of 5.32 mL) and add to an IV infusion bag containing 250 mL of 0.9% sodium chloride injection.¹

Small residual amount of concentrate may remain in each vial;¹ discard this unused portion.¹

Administer immediately after dilution.¹ If diluted solution refrigerated, let stand at room temperature for ≥30 minutes (but <4 hours) before administering.¹

Rate of infusion: Administer over at least 30 minutes for the loading dose and over at least 15 minutes for maintenance doses.¹

After completion of IV infusion, flush IV administration set with 30 mL of 0.9% sodium chloride injection.¹

IV Push

To prepare 2000-mg loading dose for administration as an IV push, 10 single-dose vials of the concentrate are required; allow vials to stand at room temperature for approximately 5 minutes and withdraw 1.33 mL from each of the vials (total volume of 13.3 mL) into a single syringe.¹ Administer undiluted solution immediately.¹

To prepare 800-mg maintenance dose for administration as an IV push, 4 single-dose vials of the concentrate are required; allow vials to stand at room temperature for approximately 5 minutes and withdraw 1.33 mL from each of the vials (total volume of 5.32 mL) into a single syringe.¹ Administer undiluted solution immediately.¹

Administer undiluted via IV push over at least a 90-second period (for the loading dose) or over at least a 30-second period (for maintenance doses).¹

After the IV injection is complete, flush with 2-5 mL of 0.9% sodium chloride injection.¹

Discard partially used or empty vials and any unused portion of undiluted solution.¹

Dosage

Adults

Treatment of HIV Infection

IV

Single loading dose of 2000 mg followed by maintenance dosage of 800 mg once every 2 weeks.¹

If maintenance dose is missed by 3 days or more, restart with the initial loading dose as soon as possible.¹ Thereafter, resume the maintenance dosage of 800 mg IV once every 14 days.¹

Special Populations

Hepatic Impairment

No specific dosage recommendations at this time.¹

Renal Impairment

No specific dosage recommendations at this time.¹

Geriatric Use

No specific dosage recommendations at this time.¹

Cautions for Ibalizumab

Contraindications

Prior hypersensitivity reaction to ibalizumab or any components of the product.¹

Warnings/Precautions

Hypersensitivity Reactions

Hypersensitivity reactions including infusion-related reactions and anaphylactic reactions reported.¹ Symptoms may include dyspnea, angioedema, wheezing, chest pain, chest tightness, cough, hot flush, nausea, and vomiting.¹

If such symptoms occur, immediately discontinue and initiate appropriate treatment.¹

Immune Reconstitution Inflammatory Syndrome

Immune reconstitution inflammatory syndrome reported in at least 1 HIV-infected patient receiving ibalizumab-uiyk in conjunction with other antiretrovirals.¹

During initial phase of treatment, HIV-infected patients whose immune systems respond to antiretroviral therapy may develop an inflammatory response to indolent or residual opportunistic infections.¹ Such response may necessitate further evaluation and treatment.¹

Immunogenicity

Potential for immunogenicity.¹

In clinical studies, all enrolled patients were tested for presence of antibodies against the drug.¹ Only 1 sample from 1 patient tested positive for anti-ibalizumab antibodies;¹ no adverse reaction or reduced efficacy attributed to the low titer of anti-ibalizumab antibodies reported in this patient.¹

Embryo-Fetal Toxicity

Based on animal data, may cause reversible immunosuppression (CD4+ T cell and B cell lymphocytopenia) in infants born to mothers exposed to ibalizumab during pregnancy.¹ Consult experts for immune phenotyping of the peripheral blood to provide guidance regarding monitoring and management of exposed infants.¹

Safety of administering live or live-attenuated vaccines in exposed infants is unknown.¹

Specific Populations

Pregnancy

Enroll pregnant patients in the Antiretroviral Pregnancy Registry at 800-258-4263.¹ ²⁰²

No available data on use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes.¹

Monoclonal antibodies are transported across the placenta as pregnancy progresses.¹ Administration of ibalizumab-uiyk during pregnancy may affect immune responses in the in utero-exposed infant.¹ Consult experts for immune phenotyping of the peripheral blood to provide guidance regarding monitoring and management of exposed infants.¹

Safety of administering live or live-attenuated vaccines in exposed infants is unknown.¹

Lactation

Not known if distributed into human milk, affects breast-fed child, or affects milk production.¹ Human IgG is distributed into milk in humans.¹ However, data indicate antibodies in breast milk do not enter neonatal or infant circulatory system in substantial amounts.¹

The HHS perinatal HIV transmission guideline provides updated recommendations on infant feeding.²⁰² The guideline states that patients with HIV should receive evidence-based, patient-centered counseling to support shared decision making about infant feeding.²⁰² During counseling, patients should be informed that feeding with appropriate formula or pasteurized donor human milk from a milk bank eliminates the risk of postnatal HIV transmission to the infant.²⁰² Additionally, achieving and maintaining viral suppression with antiretroviral therapy during pregnancy and postpartum reduces the risk of breastfeeding HIV transmission to <1%, but does not completely eliminate the risk.²⁰² Replacement feeding with formula or banked pasteurized donor milk is recommended when patients with HIV are not on antiretroviral therapy and/or do not have a suppressed viral load during pregnancy (at a minimum throughout the third trimester), as well as at delivery.²⁰²

Pediatric Use

Safety and efficacy not established.¹

Geriatric Use

Not studied in geriatric patients.¹

Hepatic Impairment

Pharmacokinetics not evaluated in hepatic impairment.¹

Renal Impairment

Pharmacokinetics not evaluated in renal impairment; renal impairment not expected to affect pharmacokinetics of ibalizumab-uiyk.¹

Weight

Population pharmacokinetic analysis suggests that ibalizumab-uiyk concentrations decrease as body weight increases; however, this is not expected to affect virologic outcome and dosage adjustments are not necessary.¹

Common Adverse Effects

Most common adverse reactions (≥5%): diarrhea, dizziness, nausea, rash.¹

Drug Interactions

Specific drug interaction studies not conducted.¹ Based on mechanism of action and target-mediated drug disposition, manufacturer states drug interactions not expected.¹

Specific Drugs

Drug	Interaction
Antiretrovirals, HIV entry and fusion inhibitors	Enfuvirtide: No in vitro evidence of antagonistic anti-HIV effects;¹ in vitro evidence of synergistic antiretroviral effects³ Maraviroc: No in vitro evidence of antagonistic anti-HIV effects¹
Antiretrovirals, HIV nonnucleoside reverse transcriptase inhibitors (NNRTIs)	Efavirenz: No in vitro evidence of antagonistic anti-HIV effects¹
Antiretrovirals, HIV nucleoside and nucleotide reverse transcriptase inhibitors (NRTIs)	Abacavir, didanosine, emtricitabine, tenofovir, zidovudine: No in vitro evidence of antagonistic anti-HIV effects¹
Antiretrovirals, HIV protease inhibitors (PIs)	Atazanavir: No in vitro evidence of antagonistic anti-HIV effects¹

Ibalizumab Pharmacokinetics

Absorption

Plasma Concentrations

Following single dose given by IV infusion over 30–90 minutes, AUC increases in more than dose-proportional manner.¹

Following administration of recommended dosage regimen (single 2-g loading dose followed by maintenance dosage of 800 mg once every 2 weeks), steady-state concentrations achieved after first 800-mg maintenance dose.¹

Initial loading dose as an IV push administration over 90 seconds is predicted to achieve similar peak plasma concentrations and AUC relative to administration by IV infusion over 30 minutes.¹

Elimination

Half-life

As dosage increased from 0.3 to 25 mg/kg, clearance decreased from 9.54 to 0.36 mL/hour per kg and elimination half-life increased from 2.7 to 64 hours.¹

Special Populations

Pharmacokinetics not evaluated in patients with hepatic or renal impairment, in pediatric patients, or in geriatric patients.¹

Renal impairment not expected to affect pharmacokinetics.¹

Population pharmacokinetic analysis suggests ibalizumab concentrations decrease as body weight increases;¹ however, not expected to affect virologic outcome.¹

Stability

Storage

Parenteral

Injection, for IV use

2–8°C.¹ Protect from light; do not freeze.¹

Diluted solutions may be stored under refrigeration (2–8°C) for ≤24 hours or at room temperature (20–25°C) for ≤4 hours.¹

Actions and Spectrum

Recombinant humanized IgG₄ monoclonal antibody active against HIV-1.¹ ² ⁵ CD4-directed post-attachment HIV-1 inhibitor.¹ ² ⁵
Blocks HIV-1 from infecting CD4⁺ T cells by binding to domain 2 of CD4 and interfering with post-attachment steps required for entry of HIV-1 virus particles into host cells, which prevents viral transmission that occurs via cell-cell fusion.¹ ² ⁵
Does not interfere with domain 1 binding site for major histocompatibility complex (MHC) class II molecules.¹ ² ⁵ ⁸ Does not alter CD4-mediated immune functions or cause immunosuppression.¹ ² ⁵ ⁸ ⁹ Does not interfere with gp120 attachment to CD4.¹ ² ⁸ ⁹
Decreased susceptibility (i.e., decreased maximum percent inhibition [MPI]) observed in some patients receiving ibalizumab-uiyk and may be associated with genotypic changes in the HIV-1 envelope coding sequence that result in loss of potential N-linked glycosylation sites (PNGS) in the V5 loop of gp120.¹ ⁶ ⁷ Clinical importance of this decreased susceptibility not established.¹ Known CD4 polymorphisms (i.e., naturally occurring amino acid substitutions in CD4) appear unlikely to affect ibalizumab-uiyk binding to CD4.¹
No in vitro evidence of cross-resistance with other antiretrovirals, including HIV entry and fusion inhibitors (e.g., CCR-5 co-receptor antagonists, gp41 fusion inhibitors), HIV integrase strand transfer inhibitors (INSTIs), HIV NRTIs, HIV NNRTIs, and HIV PIs.¹ ⁷ ⁸ Has been active in vitro against HIV-1 resistant to all other antiretrovirals currently commercially available in the US, including CCR5-tropic, CCRX4-tropic, and dual-tropic HIV-1.¹ Phenotypic changes associated with ibalizumab-uiyk resistance do not alter susceptibility to other commercially available antiretrovirals and do not result in selection of CD4-independent viral isolates.¹

Advice to Patients

Advise patients of the critical nature of compliance with HIV therapy and importance of remaining under the care of a clinician.¹ ²⁰⁰ Importance of taking as prescribed; do not alter or discontinue antiretroviral regimen without consulting clinician.¹ ²⁰⁰
Advise patients of the importance of using in conjunction with other antiretrovirals.¹
Advise patients of the risk of hypersensitivity reactions including anaphylaxis and the need to seek immediate medical attention if signs or symptoms of hypersensitivity occur or are suspected.¹
Advise patients to not take ibalizumab-uiyk if they have had a previous hypersensitivity to the drug.¹
Advise patients that they may receive ibalizumab-uiyk doses by IV infusion or IV push and to consult their healthcare provider regarding the most appropriate route of administration.¹
Advise patients that immune reconstitution inflammatory syndrome has been reported in a patient receiving ibalizumab-uiyk; inform patients of the importance of immediately informing clinicians of any symptoms of infection.¹
Advise patients of the importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal products, and any concomitant illnesses.¹
Inform women of the importance of informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹
Advise patients of other important precautionary information.¹

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.

Ibalizumab-uiyk
Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Parenteral	Injection, for IV use	150 mg/mL	Trogarzo	Theratechnologies

References

1. Theratechnologies. Trogarzo (ibalizumab-uiyk) injection for intravenous infusion prescribing information. Montreal, Quebec Canada; 2023 Dec.

2. Freeman M, Seaman M, Rits-Volloch et al. Crystal structure of HIV-1 primary receptor CD4 in complex with a potent antiviral antibody. Structure. 2010; 18:1632–41.

3. Zhang X, Sorensen M, Fung M et al. Synergistic in vitro antiretroviral activity of humanized monoclonal anti-CD4 antibody (TNX-355) and enfuvirtide (T-20). Antimicrob Agents Ch. 2006; 50:2231–3.

4. Food and Drug Administration. FDA Application: Search Orphan Drug Designations and Approvals. Silver Spring, MD. From FDA website. Accessed 2018 Jul 19. http://www.accessdata.fda.gov/scripts/opdlisting/oopd/index.cfm

5. Iacob SA, Iacob DG et al. Ibalizumab targeting CD4 receptors, an emerging molecule in HIV therapy. Microbiol. 2017; 8

6. Pace C, Fordyce M, Franco D et al. Anti-CD4 monoclonal antibody ibalizumab exhibits breadth and potency against HIV-1, with natural resistance mediated by the loss of a V5 glycan in envelope. Acquir Immune Defic Syndr. 2013; 62

7. Toma J, Weinheimer S, Stawiski E et al. Loss of asparagine-linked glycosylation sites in variable region 5 of human immunodeficiency virus type 1 envelope is associated with resistance to CD4 antibody ibalizumab. J Virol. 2011; 85:3872–80.

8. Bruno C, Jacobson J et al. Ibalizumab: an anti-CD4 monoclonal antibody for the treatment of HIV-1 infection. J Antimicrob Chemother. 2010; 65:1839–41.

9. Song R, Franco D, Kao C et al. Epitope mapping of ibalizumab, a Humanized anti-CD4 monoclonal antibody with anti-HIV-1 activity in infected patients. J Virol. 2010; 84:6935–42.

10. Emu B, Fessel J, Schrader S et al. Phase 3 study of ibalizumab for multidrug-resistant HIV-1. N Engl J Med. 2018; 379:645-654. https://pubmed.ncbi.nlm.nih.gov/30110589

200. Panel on Antiretroviral Guidelines for Adults and Adolescents, US Department of Health and Human Services (HHS). Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents (March 23, 2023). Updates may be available at HIV.gov website (https://clinicalinfo.hiv.gov/en/guidelines).

201. Panel on Antiretroviral Therapy and Medical Management of HIV-infected Children, US Department of Health and Human Services (HHS). Guidelines for the use of antiretroviral agents in pediatric HIV infection (January 31, 2023). Updates may be available at HIV.gov website (https://clinicalinfo.hiv.gov/en/guidelines).

202. Panel on Treatment of HIV-Infected Pregnant Women and Prevention of Perinatal Transmission, US Department of Health and Human Services (HHS). Recommendations for use of antiretroviral drugs in pregnant HIV-1-infected women for maternal health and interventions to reduce perinatal HIV transmission in the United States (January 31, 2023). Updates may be available at HIV.gov website (https://clinicalinfo.hiv.gov/en/guidelines).

203. Institute for Safe Medication Practices. ISMP list of error-prone abbreviations, symbols, and dose designations. 2024.