Ibalizumab-uiyk (Monograph)

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

Medically reviewed by Drugs.com on Mar 10, 2024. Written by ASHP.

Introduction

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

Uses for Ibalizumab-uiyk

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.

Designated an orphan drug by FDA for this indication.

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

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 antiretrovial regimen for treatment of HIV infection with virologic failure, including following failure of a second-line regimen and beyond.

Ibalizumab-uiyk 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.

• 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).

Other General Considerations

• Ibalizumab-uiyk should be prepared and administered by a trained medical professional.

• Dosage modifications of ibalizumab are not required when administered with any other antiretrovirals or any other treatments.

Administration

IV Administration

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

Administer by a trained medical professional.

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

IV Infusion

Must be diluted prior to IV infusion.

Dilute approprate number of vials to prepare desired dose.

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.

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.

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

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

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

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

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. Administer undiluted solution immediately.

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. Administer undiluted solution immediately.

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).

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

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

Dosage

Adults

Treatment of HIV Infection

IV

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

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

Special Populations

Hepatic Impairment

No specific dosage recommendations at this time.

Renal Impairment

No specific dosage recommendations at this time.

Geriatric Use

No specific dosage recommendations at this time.

Related/similar drugs

Biktarvy, Descovy, Truvada, Atripla, Stribild, Complera, Epzicom

Cautions for Ibalizumab-uiyk

Contraindications

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

Warnings/Precautions

Hypersensitivity Reactions

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

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

Immune Reconstitution Inflammatory Syndrome

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

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. Such response may necessitate further evaluation and treatment.

Immunogenicity

Potential for immunogenicity.

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

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. Consult experts for immune phenotyping of the peripheral blood to provide guidance regarding monitoring and management of exposed infants.

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

Specific Populations

Pregnancy

Enroll pregnant patients in the Antiretroviral Pregnancy Registry at 800-258-4263.

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.

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

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

Lactation

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

Instruct HIV-infected women not to breast-feed because of risk of HIV transmission and risk of adverse effects in the infant.

Pediatric Use

Safety and efficacy not established.

Geriatric Use

Not studied in geriatric patients.

Hepatic Impairment

Pharmacokinetics not evaluated in hepatic impairment.

Renal Impairment

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

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.

Common Adverse Effects

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

Drug Interactions

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

Specific Drugs

Ibalizumab-uiyk Pharmacokinetics

Absorption

Plasma Concentrations

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

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.

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.

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.

Special Populations

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

Renal impairment not expected to affect pharmacokinetics.

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

Stability

Storage

Parenteral

Injection, for IV use

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

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

Actions and Spectrum

• Recombinant humanized IgG₄ monoclonal antibody active against HIV-1. CD4-directed post-attachment HIV-1 inhibitor.

• 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.

• Does not interfere with domain 1 binding site for major histocompatibility complex (MHC) class II molecules. Does not alter CD4-mediated immune functions or cause immunosuppression. Does not interfere with gp120 attachment to CD4.

• 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. Clinical importance of this decreased susceptibility not established. Known CD4 polymorphisms (i.e., naturally occurring amino acid substitutions in CD4) appear unlikely to affect ibalizumab-uiyk binding to CD4.

• 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. 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. 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.

Advice to Patients

• Advise patients of the critical nature of compliance with HIV therapy and importance of remaining under the care of a clinician. Importance of taking as prescribed; do not alter or discontinue antiretroviral regimen without consulting clinician.

• Advise patients of the importance of using in conjunction with other antiretrovirals.

• 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.

• Advise patients to not take ibalizumab-uiyk if they have had a previous hypersensitivity to the drug.

• 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.

• 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.

• 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.

• Inform women of the importance of informing clinicians if they are or plan to become pregnant or plan to breast-feed. Advise women with HIV not to breast-feed.

• Advise patients of other important precautionary information.

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.

Reload page with references included

Frequently asked questions

• How well does Trogarzo work to treat multidrug-resistant (MDR) HIV-1?
• How is Trogarzo used in the treatment of HIV?
• What are the side effects with HIV treatment Trogarzo?

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