ibalizumab (Rx)

1-10%

Diarrhea (8%)

Dizziness (8%)

Nausea (5%)

Rash (5%)

Laboratory abnormalities ≥grade 3

• Creatinine >1.8x ULN or 1.5x baseline (10%)
• Bilirubin ≥2.6x ULN (5%)
• Lipase >3x ULN (5%)
• Leukocytes <1.5 x 10^9 cells/L (5%)
• Neutrophils <0.6 x 10^9 cell/L (5%)
• Direct bilirubin >ULN (3%)
• Blood glucose >250 mg/dL (3%)
• Uric acid >3x ULN (3%)
• Hemoglobin <8.5 g/dL (3%)
• Platelets <50,000/mm³ (3%)
• Leukocytes <1.5 x 10^9 cells/L (5%)

Postmarketing Reports

• Immune system disorders: Hypersensitivity reactions including infusion-related reactions and anaphylactic reactions reported
• Skin and subcutaneous tissue disorders: Pruritus

Contraindications

Prior hypersensitivity reaction to drug or product components

Cautions

Immune reconstitution inflammatory syndrome reported in 1 patient treated with ibalizumab in combination with other ARTs

During the initial phase of combination ARTs, patients whose immune systems respond may develop an inflammatory response to indolent or residual opportunistic infections, which may necessitate further evaluation and treatment

Hypersensitivity reactions including infusion-related reactions and anaphylactic reactions reported following infusion during post-approval use; if signs and symptoms of anaphylactic or other clinically significant hypersensitivity reaction occur, immediately discontinue administration and initiate appropriate treatment

Pregnancy

There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antiretrovirals during pregnancy; this registry does not include Trogarzo, but likely includes patients’ concomitant antiretroviral drugs

Healthcare providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry (APR) at 1–800–258–4263

Based on animal data, ibalizumab-uiyk use during pregnancy may cause reversible immunosuppression (CD4+ T cell and B cell lymphocytopenia) in infants exposed to ibalizumab-uiyk in utero; immunoglobulin G (IgG) antibodies, such as ibalizumab-uiyk, are transported across placenta in significant amounts, especially near term; therefore, ibalizumab-uiyk has potential to be transferred from mother to developing fetus

There are no available data on ibalizumab-uiyk use in pregnant women to evaluate for a drug- associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes

Immunoglobulin G (IgG) antibodies are increasingly transported across placenta as pregnancy progresses, with largest amount transferred during third trimester; administration during pregnancy may affect immune responses in the in utero-exposed infant; for infants with perinatal exposure to drug, immune phenotyping of peripheral blood, including CD4+ T cell and B cell counts, recommended; expert consultation is also recommended to provide guidance on monitoring and management (eg, need for antibiotic or immunoprophylaxis) of exposed infants based on degree of immunosuppression observed; safety of administering live or live-attenuated vaccines in exposed infants is unknown

Animal data

• In a reproductive study in monkeys, reversible decreases in CD4+ T cells and B cells and increases in CD8+ T cells were observed within first 4 weeks after birth in infants born to pregnant monkeys receiving ibalizumab-uiyk intravenously; lymphocyte counts returned to near normal levels by 3 months of age; one infant monkey died from a systemic viral infection that may be related to ibalizumab-uiyk-induced immunosuppression; no malformations or premature births were observed in this study

Lactation

Unknown if distributed into breast milk

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

Owing to the potential for HIV transmission (in HIV-negative infants), developing viral resistance (in HIV-positive infants), and adverse reactions in a breastfed infant, instruct mothers not to breastfeed

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

CD4-directed post-attachment HIV-1 inhibitor

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

Binding specificity of ibalizumab to domain 2 of CD4 allows ibalizumab to block viral entry into host cells without causing immunosuppression

Absorption

Single-dose administrations of ibalizumab

• AUC-time curve increased in a greater than dose-proportional manner

Single loading dose followed by a maintenance dose q2wk

• Steady-state concentrations were reached after the first 800-mg maintenance dose with mean concentrations >30 mcg/mL throughout the dosing interval

Distribution

Vd was approximately that of serum volume, at 4.8 L

Excretion

Clearance decreased from 9.54 to 0.36 mL/h/kg

Elimination half-life increased from 2.7 to 64 hr as the dose increased from 0.3 to 25 mg/kg

IV Compatibilities

0.9% NaCl

IV Preparation

Inspect solution; should appear colorless to slightly yellow and clear to slightly opalescent with no visible particles

Discard vial if solution is cloudy, there is pronounced discoloration, or foreign particulate matter is present

Select appropriate number of vials (200 mg/1.33 mL) required to prepare loading dose (2000 mg) or maintenance doses (800 mg)

Loading dose administered as diluted IV infusion; maintenance dose may be administered as diluted IV infusion or undiluted IV push

IV infusion (diluted)

• Remove flip-off cap from single-dose vial and wipe stopper with alcohol swab
• Insert sterile syringe needle into vial through center of stopper and withdraw 1.33 mL from each vial (small residual amount may remain in vial)
• Discard unused portion and transfer into a 250-mL IV bag of 0.9% NaCl; other IV solutions must not be used to prepare dose
• Once diluted, administer immediately

IV push (undiluted)

• Allow vials to stand at room temperature for ~5 minutes
• Remove flip-off cap from single-dose vial and wipe stopper with alcohol swab
• Insert sterile syringe needle into vial through center of stopper and withdraw 1.33 mL from each vial (small residual amount may remain in vial); discard unused portion
• Administer undiluted solution immediately

IV Administration

Administer by trained medical professional

Administer as an IV infusion or IV push in cephalic vein in right or left arm; if this vein is not accessible, an appropriate vein located elsewhere can be used

IV infusion: Administer loading dose (and optionally, maintenance doses) IV over 30 minutes; after completion, flush line with 30 mL 0.9% NaCl

IV push (maintenance doses only): Administer IV over 30-seconds; after completion, flush line with 2-5 mL 0.9% NaCl

All patients must be observed for 1 hr after completing infusion for at least the first infusion; if the patient does not experience an infusion-associated adverse reaction, the postinfusion observation time can be reduced to 15 minutes thereafter

Missed maintenance dose

• If a maintenance dose (800 mg) is missed by ≥3 days beyond the scheduled dosing day, administer a loading dose (2000 mg) as early as possible
• Resume maintenance dosing (800 mg) every 14 days thereafter

Storage

Unopened vials

• Refrigerate at 2-8°C (36-46°F)
• Do not freeze
• Protect from light

Diluted solution

• If not administered immediately, store at room temperature (20-25°C [68-77°F]) for up to 4 hr OR
• Refrigerate at 2-8°C (36-46°F) for up to 24 hr
• If refrigerated, allow the diluted solution to stand at room temperature (20-25°C [68-77°F]) for at least 30 minutes but no more than 4 hr before administration