Class: HIV Entry and Fusion Inhibitors
CAS Number: CAS-680188-33-4
Antiretroviral; HIV entry inhibitor; CD4-directed post-attachment HIV type 1 (HIV-1) inhibitor.
Uses for Ibalizumab-uiyk
Treatment of HIV Infection
Treatment of HIV-1 infection in antiretroviral-experienced (previously treated) adults with multidrug-resistant HIV-1 infection failing their current antiretroviral regimen; used in conjunction with other antiretrovirals.
Designated an orphan drug by FDA for this indication.
Ibalizumab-uiyk Dosage and Administration
Administer by IV infusion. Must not be administered by rapid IV injection.
Must be diluted prior to administration.
Should be administered by a trained medical professional.
Observe patient for 1 hour after completion of initial IV infusion. May reduce post-infusion observation time to 15 minutes for subsequent infusions if infusion-associated adverse effects did not occur with initial infusion.
Administer diluted solution by IV infusion into cephalic vein of the right or left arm. If cephalic vein not accessible, use another appropriate vein.
After completion of IV infusion, flush IV administration set with 30 mL of 0.9% sodium chloride injection.
Prior to dilution, concentrate should appear as a colorless to slightly yellow and clear to slightly opalescent solution; do not use if it appears cloudy or discolored or contains particles.
Use appropriate number of single-dose vials containing 150 mg of ibalizumab-uiyk per mL to prepare desired dose.
To prepare the 2-g loading dose, 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 an 800-mg maintenance dose, 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 (see Storage under Stability). If diluted solution refrigerated, let stand at room temperature for ≥30 minutes (but <4 hours) before administering.
Rate of Administration
Initial dose (loading dose): Administer by IV infusion over ≥30 minutes.
Maintenance doses: Administer by IV infusion over ≥15 minutes, unless infusion-associated reactions occurred with loading dose.
Treatment of HIV Infection
Antiretroviral-experienced adults with multidrug-resistant HIV-1 infection failing their current antiretroviral regimen: Single loading dose of 2 g followed by maintenance dosage of 800 mg once every 2 weeks.
If a maintenance dose is missed by ≥3 days beyond scheduled day, administer a 2-g loading dose as soon as possible. Then, resume usually recommended maintenance dosage of 800 mg once every 2 weeks.
Manufacturer makes no specific dosage recommendations for geriatric patients or for patients with renal or hepatic impairment.
Cautions for Ibalizumab-uiyk
Manufacturer states no known contraindications.
Immune Reconstitution Syndrome
Immune reconstitution 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 (e.g., Mycobacterium avium, M. tuberculosis, cytomegalovirus [CMV], Pneumocystis jirovecii [formerly P. carinii]); such response may necessitate further evaluation and treatment.
Potential for immunogenicity.
In clinical studies evaluating safety and efficacy of ibalizumab-uiyk, all enrolled patients were tested throughout the studies 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.
Antiretroviral Pregnancy Registry at 800-258-4263 or [Web].
Insufficient data to establish whether ibalizumab-uiyk poses a risk if used during pregnancy. Animal reproductive toxicology studies not conducted.
Monoclonal antibodies, such as ibalizumab-uiyk, are transported across the placenta as pregnancy progresses. Potential exists for transmission of ibalizumab-uiyk from mother to developing fetus.
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.
Safety and efficacy not established.
Not studied in geriatric patients.
Common Adverse Effects
Diarrhea, decreased appetite, dizziness, fatigue, pyrexia, headache, lymphadenopathy, nasopharyngitis, upper respiratory tract infection, nausea, rash, vomiting.
Interactions for Ibalizumab-uiyk
Specific drug interaction studies not conducted. Based on mechanism of action and target-mediated drug disposition, manufacturer states drug interactions not expected.
Antiretrovirals, HIV entry and fusion inhibitors
Enfuvirtide: No in vitro evidence of antagonistic anti-HIV effects; in vitro evidence of synergistic antiretroviral effects
Maraviroc: No in vitro evidence of antagonistic anti-HIV effects
Antiretrovirals, HIV nonnucleoside reverse transcriptase inhibitors (NNRTIs)
Efavirenz: No in vitro evidence of antagonistic anti-HIV effects
Antiretrovirals, HIV nucleoside and nucleotide reverse transcriptase inhibitors (NRTIs)
Abacavir, didanosine, emtricitabine, tenofovir, zidovudine: No in vitro evidence of antagonistic anti-HIV effects
Antiretrovirals, HIV protease inhibitors (PIs)
Atazanavir: No in vitro evidence of antagonistic anti-HIV effects
Following single dose given by IV infusion over 30–90 minutes, AUC increases in more than dose-proportional manner.
When recommended dosage regimen (single 2-g loading dose followed by maintenance dosage of 800 mg once every 2 weeks) used, steady-state concentrations achieved after first 800-mg maintenance dose.
Volume of distribution is 4.8 L (approximately that of serum volume).
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.
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-uiyk concentrations decrease as body weight increases; manufacturer states this not expected to affect virologic outcome and dosage adjustments not needed.
Concentrate, for Injection, for IV Infusion
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.
For information on systemic interactions resulting from concomitant use, see Interactions.
0.9% sodium chloride
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
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.
Importance of using in conjunction with other antiretrovirals.
Antiretroviral therapy is not a cure for HIV infection; opportunistic infections and other complications associated with HIV disease may still occur.
Advise patients that early initiation of antiretroviral therapy and sustained decreases in plasma HIV RNA have been associated with reduced risk of progression to acquired immunodeficiency syndrome (AIDS) and death.
Advise patients that effective antiretroviral regimens can decrease HIV concentrations in blood and genital secretions and strict adherence to such regimens in conjunction with risk-reduction measures may decrease, but cannot absolutely eliminate, the risk of secondary transmission of HIV to others. Importance of continuing to practice safer sex (e.g., using latex or polyurethane condoms to minimize sexual contact with body fluids) and reducing high-risk behaviors (e.g., reusing or sharing needles).
Importance of reading patient information provided by the manufacturer.
Advise patients that immune reconstitution syndrome has been reported in a patient receiving ibalizumab-uiyk; importance of immediately informing clinicians of any symptoms of infection.
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal products, and any concomitant illnesses.
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed. Advise HIV-infected women not to breast-feed.
Importance of advising patients of other important precautionary information. (See Cautions.)
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.
Concentrate, for injection, for IV infusion
AHFS DI Essentials™. © Copyright 2021, Selected Revisions March 25, 2019. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.
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