NDC 62064-122 Trogarzo

Ibalizumab

NDC Product Code 62064-122

NDC CODE: 62064-122

Proprietary Name: Trogarzo What is the Proprietary Name?
The proprietary name also known as the trade name is the name of the product chosen by the medication labeler for marketing purposes.

Non-Proprietary Name: Ibalizumab What is the Non-Proprietary Name?
The non-proprietary name is sometimes called the generic name. The generic name usually includes the active ingredient(s) of the product.

Drug Use Information

Drug Use Information
The drug use information is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate. This information is not individual medical advice and does not substitute for the advice of a health care professional. Always ask a health care professional for complete information about this product and your specific health needs.

  • This drug is used with other HIV medications to help control HIV infection. It helps to decrease the amount of HIV in your body so your immune system can work better. This lowers your chance of getting HIV complications (such as new infections, cancer) and improves your quality of life. Ibalizumab-uiyk belongs to a class of drugs known as monoclonal antibodies. Ibalizumab-uiyk is not a cure for HIV infection. To decrease your risk of spreading HIV disease to others, do all of the following: (1) continue to take all HIV medications exactly as prescribed by your doctor, (2) always use an effective barrier method (latex or polyurethane condoms/dental dams) during all sexual activity, and (3) do not share personal items (such as needles/syringes, toothbrushes, and razors) that may have contacted blood or other body fluids. Consult your doctor or pharmacist for more details.

NDC Code Structure

  • 62064 - Theratechnologies Inc.

NDC 62064-122-02

Package Description: 2 VIAL, SINGLE-USE in 1 CARTON > 1.33 mL in 1 VIAL, SINGLE-USE (62064-122-01)

NDC Product Information

Trogarzo with NDC 62064-122 is a a human prescription drug product labeled by Theratechnologies Inc.. The generic name of Trogarzo is ibalizumab. The product's dosage form is injection, solution and is administered via intravenous form.

Labeler Name: Theratechnologies Inc.

Dosage Form: Injection, Solution - A liquid preparation containing one or more drug substances dissolved in a suitable solvent or mixture of mutually miscible solvents that is suitable for injection.

Product Type: Human Prescription Drug What kind of product is this?
Indicates the type of product, such as Human Prescription Drug or Human Over the Counter Drug. This data element matches the “Document Type” field of the Structured Product Listing.

Trogarzo Active Ingredient(s)

What is the Active Ingredient(s) List?
This is the active ingredient list. Each ingredient name is the preferred term of the UNII code submitted.

  • IBALIZUMAB 150 mg/mL

Inactive Ingredient(s)

About the Inactive Ingredient(s)
The inactive ingredients are all the component of a medicinal product OTHER than the active ingredient(s). The acronym "UNII" stands for “Unique Ingredient Identifier” and is used to identify each inactive ingredient present in a product.

  • HISTIDINE (UNII: 4QD397987E)
  • SUCROSE (UNII: C151H8M554)
  • SODIUM CHLORIDE (UNII: 451W47IQ8X)
  • POLYSORBATE 80 (UNII: 6OZP39ZG8H)
  • HYDROCHLORIC ACID (UNII: QTT17582CB)
  • WATER (UNII: 059QF0KO0R)

Administration Route(s)

What are the Administration Route(s)?
The translation of the route code submitted by the firm, indicating route of administration.

  • Intravenous - Administration within or into a vein or veins.

Product Labeler Information

What is the Labeler Name?
Name of Company corresponding to the labeler code segment of the Product NDC.

Labeler Name: Theratechnologies Inc.
Labeler Code: 62064
FDA Application Number: BLA761065 What is the FDA Application Number?
This corresponds to the NDA, ANDA, or BLA number reported by the labeler for products which have the corresponding Marketing Category designated. If the designated Marketing Category is OTC Monograph Final or OTC Monograph Not Final, then the Application number will be the CFR citation corresponding to the appropriate Monograph (e.g. “part 341”). For unapproved drugs, this field will be null.

Marketing Category: BLA - A product marketed under an approved Biologic License Application. What is the Marketing Category?
Product types are broken down into several potential Marketing Categories, such as NDA/ANDA/BLA, OTC Monograph, or Unapproved Drug. One and only one Marketing Category may be chosen for a product, not all marketing categories are available to all product types. Currently, only final marketed product categories are included. The complete list of codes and translations can be found at www.fda.gov/edrls under Structured Product Labeling Resources.

Start Marketing Date: 04-20-2018 What is the Start Marketing Date?
This is the date that the labeler indicates was the start of its marketing of the drug product.

Listing Expiration Date: 12-31-2021 What is the Listing Expiration Date?
This is the date when the listing record will expire if not updated or certified by the product labeler.

Exclude Flag: N - NO What is the NDC Exclude Flag?
This field indicates whether the product has been removed/excluded from the NDC Directory for failure to respond to FDA"s requests for correction to deficient or non-compliant submissions ("Y"), or because the listing certification is expired ("E"), or because the listing data was inactivated by FDA ("I"). Values = "Y", "N", "E", or "I".

* Please review the disclaimer below.

Information for Patients

Ibalizumab-uiyk Injection

Ibalizumab-uiyk Injection is pronounced as (eye" ba liz' ue mab)

Why is ibalizumab-uiyk injection medication prescribed?
Ibalizumab-uiyk is used with other medications to treat human immunodeficiency virus (HIV) infection in adults who have been treated with several other HIV medications in...
[Read More]

* Please review the disclaimer below.

Trogarzo Product Labeling Information

The product labeling information includes all published material associated to a drug. Product labeling documents include information like generic names, active ingredients, ingredient strength dosage, routes of administration, appearance, usage, warnings, inactive ingredients, etc.

Product Labeling Index

1 Indications And Usage

TROGARZO, 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.

TROGARZO is available in a single-dose, 2 mL vial containing 150 mg/mL of ibalizumab-uiyk. Each vial delivers approximately 1.33 mL containing 200 mg of ibalizumab-uiyk.TROGARZO is administered intravenously (IV), after diluting the appropriate number of vials in 250 mL of 0.9% Sodium Chloride Injection, USP. Patients should receive a single loading dose of 2,000 mg followed by a maintenance dose of 800 mg every 2 weeks.Dose modifications of TROGARZO are not required when administered with any other antiretroviral or any other treatments.

2.2 Preparation

  • Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Discard vial if solution is cloudy, if there is pronounced discoloration or if there is foreign particulate matter.See Table 1 for the appropriate number of vials required to prepare both the loading dose of 2,000 mg and the maintenance doses of 800 mg.Table 1. Recommended TROGARZO Dose and Number Vials Per Administration TROGARZO Dose TROGARZO Vials(Total Volume to be Withdrawn) Loading dose of 2,000 mg 10 vials (13.3 mL) Maintenance dose of 800 mg 4 vials (5.32 mL) TROGARZO solution for infusion should be prepared by a trained medical professional using aseptic technique as follows:Remove the flip-off cap from the single-dose vial and wipe with an alcohol swab.Insert sterile syringe needle into the vial through the center of the stopper and withdraw 1.33 mL from each vial (NOTE: a small residual amount may remain in the vial, discard unused portion) and transfer into a 250 mL intravenous bag of 0.9% Sodium Chloride Injection, USP. Other intravenous diluents must not be used to prepare the TROGARZO solution for infusion.Once diluted, the TROGARZO solution should be administered immediately.If not administered immediately, store the diluted TROGARZO solution at room temperature (20°C to 25°C, 68°F to 77°F) for up to 4 hours, or refrigerated (2°C to 8°C, 36°F to 46°F) for up to 24 hours. If refrigerated, allow the diluted TROGARZO solution to stand at room temperature (20°C to 25°C, 68°F to 77°F) for at least 30 minutes but no more than 4 hours prior to administration.Discard partially used vials or empty vials of TROGARZO and any unused portion of the diluted TROGARZO solution.

2.3 Administration

Diluted TROGARZO solution should be administered by a trained medical professional.Administer TROGARZO as an IV infusion in the cephalic vein of the patient’s right or left arm. If this vein is not accessible, an appropriate vein located elsewhere can be used. Do not administer TROGARZO as an intravenous push or bolus.The duration of the first infusion (loading dose) should be no less than 30 minutes. If no infusion-associated adverse reactions have occurred, the duration of the subsequent infusions (maintenance doses) can be decreased to no less than 15 minutes.After the infusion is complete, flush with 30 mL of 0.9% Sodium Chloride Injection, USP.All patients must be observed for 1 hour after completion of TROGARZO administration for at least the first infusion. If the patient does not experience an infusion-associated adverse reaction, the post-infusion observation time can be reduced to 15 minutes thereafter.If a maintenance dose (800 mg) of TROGARZO is missed by 3 days or longer beyond the scheduled dosing day, a loading dose (2,000 mg) should be administered as early as possible. Resume maintenance dosing (800 mg) every 14 days thereafter.

3 Dosage Forms And Strengths

Injection: 200 mg/1.33 mL (150 mg/mL) colorless to slightly yellow and clear to slightly opalescent solution with no visible particles in a single-dose vial.

4 Contraindications

None.

5.1 Immune Reconstitution Inflammatory Syndrome

Immune reconstitution inflammatory syndrome has been reported in one patient treated with TROGARZO 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.

6 Adverse Reactions

  • The following adverse drug reactions are discussed in other sections of the labeling:Immune Reconstitution Inflammatory Syndrome [see Warnings and Precautions (5.1)]

6.1 Clinical Trial Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.A total of 292 patients with HIV-1 infection have been exposed to TROGARZO IV infusion.Trial TMB-301The primary safety assessment of TROGARZO is based on 24 weeks of data from Trial TMB-301. TMB-301 was a single-arm trial of TROGARZO which enrolled 40 heavily treatment-experienced subjects with multidrug resistant HIV-1 on a failing HIV treatment regimen. Subjects received a single 2,000 mg IV loading dose of TROGARZO followed seven days later by the initiation of an optimized background regimen (OBR) including at least one agent to which the subjects virus was susceptible. Two weeks after the TROGARZO loading dose, 800 mg of TROGARZO was administered IV. The IV administration of TROGARZO 800 mg was continued every 2 weeks through Week 25.The most common adverse reactions (all Grades) reported in at least 5% of subjects were diarrhea, dizziness, nausea, and rash. Table 2 shows the frequency of adverse reactions occurring in 5% or more of subjects.Table 2. Adverse Reactions (All Grades) Reported in 5% of Subjects Receiving TROGARZO and Optimized Background Regimen for 23 Weeks in Trial TMB-301% SubjectsN=40 Diarrhea 8% Dizziness 8% Nausea 5% RashIncludes pooled terms “rash”, “rash erythematous”, “rash generalized”, “rash macular”, “rash maculopapular”, and “rash papular” 5%Most (90%) of the adverse reactions reported were mild or moderate in severity. Two subjects experienced severe adverse reactions: one subject had a severe rash and one subject developed immune reconstitution inflammatory syndrome manifested as an exacerbation of progressive multifocal leukoencephalopathy.Laboratory AbnormalitiesTable 3 shows the frequency of laboratory abnormalities (≥ Grade 3) in Trial TMB-301. Table 3. Selected Laboratory Abnormalities (≥ Grade 3) in Trial TMB-301Laboratory Parameter% SubjectsN=40Bilirubin (≥ 2.6 x ULN)5%Direct Bilirubin (> ULN)3%Creatinine (> 1.8x ULN or 1.5x baseline)10%Blood Glucose (> 250 mg/dL)3% Lipase (> 3.0 x ULN)5%Uric Acid (> 12 mg/dL)3%Hemoglobin (< 8.5 g/dL)3%Platelets (< 50,000/mm3)3%Leukocytes (< 1.5 109 cells/L)5%Neutrophils (< 0.6 109 cells/L)5%

6.2 Immunogenicity

As with all therapeutic proteins, there is potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to ibalizumab-uiyk in the studies described below with the incidence of antibodies in other studies or to other products may be misleading.All subjects enrolled in clinical trial TMB-301 and trial TMB-202 (a Phase 2b clinical trial that studied TROGARZO administered intravenously as 2,000 mg every 4 weeks or 800 mg every 2 weeks; the safety and effectiveness of this dosing regimen has not been established), were tested for the presence of anti-ibalizumab antibodies throughout their participation. One sample tested positive with low titer anti-ibalizumab antibodies. No adverse reaction or reduced efficacy was attributed to the positive sample reported in this subject.

Other

Pregnancy Exposure RegistryThere is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to TROGARZO during pregnancy. Healthcare providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry (APR) at 1–800–258–4263.Risk SummaryNo adequate human data are available to establish whether or not TROGARZO 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.

Risk SummaryThe 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.No data are available regarding the presence of TROGARZO 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 TROGARZO.

Mechanism of ActionIbalizumab-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.Ibalizumab-uiyk Does Not Impact CD4 FunctionThe 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.Antiviral ActivityIbalizumab-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.Antiviral Activity in Combination with Other Antiviral AgentsNo 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).Antiviral Activity in Antiretroviral-Resistant VirusSubjects 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.Decreased SusceptibilityDecreased 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.Cross-ResistancePhenotypic 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.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.CD4 Polymorphisms and Ibalizumab-uiyk ActivityCD4 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.

  • Trial TMB-301:Trial TMB-301 was a single arm, multicenter clinical trial conducted in 40 heavily treatment-experienced HIV-infected subjects with multidrug resistant HIV-1. Subjects were required to have a viral load greater than 1,000 copies/mL and documented resistance to at least one antiretroviral medication from each of three classes of antiretroviral medications (NRTI, NNRTI, and PI) as measured by resistance testing. Subjects must have been treated with antiretrovirals for at least 6 months and be failing or had recently failed (i.e., in the last 8 weeks) therapy.The trial was composed of three discrete periods:Control period (Day 0 to Day 6): Subjects were either monitored on their current failing therapy or received no therapy if they had failed and discontinued treatment within the 8 weeks preceding screening. This was an observational period to establish baseline HIV viral load.Functional monotherapy period (Day 7 to Day 13): All subjects received a 2,000 mg loading dose of TROGARZO on Day 7. Subjects on a failing ART regimen continued to receive their failing regimen in addition to the loading dose of TROGARZO. This period was to establish the virologic activity of TROGARZO.Maintenance period (Day 14 to Week 25): On Day 14 of the treatment period, viral load was assessed for the primary endpoint, and thereafter the background regimen was optimized to include at least one drug to which the subjects virus was susceptible. The use of an investigational drug(s) as a component of the optimized background regimen was allowed. Beginning at Day 21, an 800 mg maintenance dose of TROGARZO was administered every two weeks through Week 25. This period was to establish the safety and durability of virologic suppression of TROGARZO when used in combination with an optimized background regimen.The majority of subjects in Trial TMB-301 were male (85%), white (55%) and between 23 and 65 years of age (mean [SD] age: 50.5 [11.0] years). At Baseline, median viral load and CD4+ T cell counts were 35,350 copies/mL and 73 cells/mm3, respectively. The subjects were heavily treatment-experienced: 53% of participants had been treated with 10 or more antiretroviral drugs prior to trial enrollment; 98% percent had been treated with NRTIs, 98% with PIs, 80% with NNRTIs, 78% with INSTIs, 30% with gp41 fusion inhibitors, and 20% with CCR5 co-receptor antagonists.The primary efficacy endpoint was the proportion of subjects achieving a 0.5 log10 decrease in viral load from the beginning to the end of the Functional monotherapy period as compared to the proportion of subjects achieving a 0.5 log10 decrease from the beginning to the end of the Control period, as defined above. The results of the primary endpoint analysis are shown in Table 4 below.Table 4. Proportion of Subjects Achieving a 0.5 log10 Decrease in Viral Load at the End of the Control and Functional Monotherapy PeriodsProportion of Subjects Achieving a 0.5 log10 Decrease in Viral LoadN=40 95% CIexact 95% confidence intervalEnd of Control Period  3% (0.06%, 13%) End of Functional Monotherapy Period 83% (67%, 93%) p < 0.0001 based on McNemars test comparing the proportion of subjects achieving 0.5 log10 decrease in viral load at the end of the control and functional monotherapy periods.At Week 25, viral load <50 and <200 HIV-1 RNA copies/mL was achieved in 43% and 50% of subjects, respectively. Fifty-five percent of subjects had a 1 log10 reduction in viral load, and 48% of subjects had a 2 log10 reduction in viral load at Week 25. An increase in the mean and median number of CD4+ T-cells (44 cells/mm3 and 17 cells/mm3, respectively) was observed from Baseline to Week 25. Week 25 outcomes are shown in Table 5 and Table 6.Table 5. Trial TMB 301 Virologic Outcomes (Snapshot Algorithm) at Week 25TROGARZO (N=40) HIV RNA < 50 copies/mL at Week 25HIV RNA 50 copies/mL at Week 25*included subjects who had 50 copies/mL in the Week 25 window, subjects who discontinued study drug due to lack of efficacy, and subjects who discontinued study drug for reasons other than an AE, death and at the time of discontinuation had a viral value 50 copies/mL 43%45% HIV RNA < 200 copies/mL at Week 25HIV RNA 200 copies/mL at Week 25included subjects who had ≥ 200 copies/mL in the Week 25 window, subjects who discontinued study drug due to lack of efficacy, and subjects who discontinued study drug for reasons other than an AE, death and at the time of discontinuation had a viral value ≥ 200 copies/mL 50%38% No virologic data at Week 25    Discontinued due to AE or death13%Table 6. Virologic Response at Week 25 by Baseline CD4 Cell count, Viral Load, Integrase Inhibitor Resistance and OSSOSS – Overall Susceptibility Score. The OSS indicates the number of fully active drugs in a subject’s OBR based on both current and available historical resistance test results. Demonstrating drug susceptibility by both genotypic and phenotypic testing was required, when testing by both methods was technically feasible. As an example, an OSS of 2 would indicate that the HIV-1 isolate tested was fully susceptible to two drugs in the OBR.Subjects achieving <50 HIV-1 RNA copies/mL (%)Subjects achieving <200 HIV-1 RNA copies/mL (%)CD4 Cell Counts    <50 (n=17)    50-200 (n=10)    >200 (n=13)186062247069Viral Load    ≤100,000 (n=33)    >100,000 (n=7)49145814Resistance    With INSTI Resistance (n=27)    Without INSTI Resistance (n=13)41464462OSS    0 (n=5)    1 (n=12)    2 (n=18)    3 (n=3)    4 (n=2)20425033502050613350

Manufactured by: Theratechnologies Inc., 2015 Peel Street, 5th Floor, Montréal, Québec Canada H3A 1T8
US License No. 2091
Distributed by: Theratechnologies Inc., 2015 Peel Street, 5th Floor, Montréal, Québec Canada H3A 1T8

8.4 Pediatric Use

The safety and effectiveness of TROGARZO in pediatric patients have not been established.

8.5 Geriatric Use

No studies have been conducted with TROGARZO in geriatric patients.

11 Description

TROGARZO is a CD4-directed post-attachment HIV-1 inhibitor.Ibalizumab-uiyk is a CD4 domain 2-directed humanized monoclonal antibody of immunoglobulin G (IgG) isotype 4 with a molecular weight of approximately 150 kDa. Ibalizumab-uiyk is produced by recombinant DNA technology in murine myeloma non-secreting 0 (NS0) cells.TROGARZO Injection is a sterile, colorless to slightly yellow and clear to slightly opalescent solution with no visible particles in a single-dose vial for intravenous infusion. Each single-dose vial delivers approximately 1.33 mL containing 200 mg of ibalizumab-uiyk, and contains the following inactive ingredients: 10 mM L-histidine (2.06 mg), 0.045% polysorbate 80 (0.60 mg), 52 mM sodium chloride (4.04 mg) and 5.2% sucrose (69.2 mg). TROGARZO solution has a pH of 6.0 and contains no preservative.

12.1 Mechanism Of Action

Ibalizumab-uiyk is an HIV-1 antiretroviral drug [see Microbiology (12.4)].

12.2 Pharmacodynamics

A clear trend was identified between exposure and response rate for the Phase 2b trial (TMB-202) which studied two different intravenous doses given at two different dosing intervals (every 4 weeks vs. every 2 weeks). The recommended intravenous dosing regimen consisting of a 2,000 mg loading dose followed by a maintenance dose of 800 mg every 2 weeks was selected on the basis of these results.

12.3 Pharmacokinetics

Ibalizumab-uiyk administered as a single agent exhibits nonlinear pharmacokinetics. Following single-dose administrations of ibalizumab-uiyk as 0.5 to 1.5-hour infusions, the area under the concentration-time curve increased in a greater than dose-proportional manner, clearance decreased from 9.54 to 0.36 mL/h/kg and elimination half-life increased from 2.7 to 64 hours as the dose increased from 0.3 to 25 mg/kg. The volume of distribution of ibalizumab-uiyk was approximately that of serum volume, at 4.8 L.Following the recommended dose regimen (a single loading dose of 2,000 mg followed by a maintenance dose of 800 mg every 2 weeks), ibalizumab-uiyk concentrations reached steady-state levels after the first 800 mg maintenance dose with mean concentrations over 30 mcg/mL throughout the dosing interval.Specific PopulationsA population pharmacokinetic analysis was performed to explore the potential effects of selected covariates (age, body weight, sex, baseline CD4+ cell count) on ibalizumab-uiyk pharmacokinetics. The result suggests that ibalizumab-uiyk concentration decreases as body weight increases; however, the effect is unlikely to impact virologic outcome and does not warrant a dose adjustment.Pediatric/Geriatric Patients: Ibalizumab-uiyk pharmacokinetics have not been evaluated in pediatric or geriatric patients [see Use in Specific Populations (8.4, 8.5)]Renal/Hepatic Impairment: No formal studies were conducted to examine the effects of either renal or hepatic impairment on the pharmacokinetics of ibalizumab-uiyk. Renal impairment is not anticipated to impact the pharmacokinetics of ibalizumab-uiyk.Drug Interaction studiesNo drug interaction studies have been conducted with ibalizumab-uiyk. Based on ibalizumab-uiyk’s mechanism of action and target-mediated drug disposition, drug-drug interactions are not expected.

13.1 Carcinogenesis, Mutagenesis, Impairment Of Fertility

Carcinogenesis, mutagenesis, and reproductive toxicology studies with ibalizumab-uiyk have not been conducted.

16.1 How Supplied

TROGARZO (ibalizumab-uiyk) injection is a sterile colorless to slightly yellow and clear to slightly opalescent solution with no visible particles for intravenous infusion. It is packaged in a single-dose 2 mL clear glass vial containing 200 mg/1.33 mL (150 mg/mL) of ibalizumab-uiyk.TROGARZO is available in a carton containing two single-dose vials (NDC 62064-122-02).Store vials under refrigeration at 2 to 8ºC (36-46 ºF). Do not freeze and protect from light.Once diluted, the TROGARZO solution should be administered immediately [see Dosage and Administration (2.2)].

17 Patient Counseling Information

Advise the patient to read the FDA-approved patient labeling (Patient Information).Immune Reconstitution SyndromeImmune Reconstitution Inflammatory Syndrome: Advise patients that immune reconstitution syndrome has been reported in a patient receiving TROGARZO and to inform their health care provider immediately of any symptoms of infection [See Warnings and Precautions (5.1)].Important Administration InformationAdvise the patient it is important to receive TROGARZO injections every two weeks as recommended by their healthcare professional and not to change the dosing schedule of TROGARZO or any antiretroviral medication without consulting their healthcare provider. Advise the patient to contact their healthcare provider immediately if they stop taking TROGARZO or any other drug in their antiretroviral regimen [see Dosage and Administration (2)].Pregnancy Exposure RegistryInform patients that there is an antiretroviral pregnancy registry that monitors fetal outcomes of pregnant women exposed to TROGARZO [see Use in Specific Populations (8.1)].LactationInstruct women with HIV-1 infection not to breastfeed because HIV-1 can be passed to the baby in breast milk [see Use in Specific Populations (8.2)].

Spl Patient Package Insert

  • PATIENT INFORMATIONTROGARZO™ (tro-gar-zo)(ibalizumab-uiyk)injectionWhat is TROGARZO?TROGARZO is a prescription medicine that is used with other antiretroviral medicines to treat Human Immunodeficiency Virus-1 (HIV-1) infection in adults who:have received several anti-HIV-1 regimens in the past, andhave HIV-1 virus that is resistant to many antiretroviral medicines, andwho are failing their current antiretroviral therapyHIV-1 is the virus that causes Acquired Immune Deficiency Syndrome (AIDS).It is not known if TROGARZO is safe and effective in children.Before you receive TROGARZO, tell your healthcare provider about all of your medical conditions, including if you:are pregnant or plan to become pregnant. It is not known if TROGARZO may harm your unborn baby. Tell your healthcare provider if you become pregnant during treatment with TROGARZO.Pregnancy Registry: There is a pregnancy registry for women who take antiretroviral medicines, including TROGARZO during pregnancy. The purpose of this registry is to collect information about the health of you and your baby. Talk with your healthcare provider about how you can take part in this registry.are breastfeeding or plan to breastfeed. Do not breastfeed if you are receiving TROGARZO.You should not breastfeed if you have HIV-1 because of the risk of passing HIV-1 to your baby.It is not known if TROGARZO passes into breast milk.Talk with your healthcare provider about the best way to feed your baby during treatment with TROGARZO.Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.How will I receive TROGARZO?You will receive TROGARZO by your healthcare provider as an infusion given into your vein over 15 to 30 minutes. A healthcare provider will monitor you during the TROGARZO infusion and for a period of time after your infusion.You will receive TROGARZO every two weeks.It is important that you receive TROGARZO every two weeks as instructed by your healthcare provider. Do not change the schedule of your TROGARZO infusions or any of your antiretroviral medicines without talking to your healthcare provider first.Tell your healthcare provider right away if you stop receiving TROGARZO infusions or stop taking any other antiretroviral medicines.What are the possible side effects of TROGARZO?TROGARZO can cause serious side effects, including:Changes in your immune system (Immune Reconstitution Inflammatory Syndrome) can happen when you start taking HIV-1 medicines. Your immune system might get stronger and begin to fight infections that have been hidden in your body for a long time. Tell your health care provider right away if you start having new symptoms after receiving TROGARZO.The most common side effects of TROGARZO include:diarrheanauseadizzinessrashThese are not all the possible side effects of TROGARZO.Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.You may also report side effects to THERA patient support at 1-833-23THERA (1-833-238-4372).General information about the safe and effective use of TROGARZO.Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. You can ask your healthcare provider for information about TROGARZO that is written for health professionals.What are the ingredients in TROGARZO?Active ingredient: ibalizumab-uiykInactive ingredients: L-histidine, polysorbate 80, sodium chloride, and sucrose.TROGARZO does not contain any preservative.Manufactured by: Theratechnologies Inc., 2015 Peel Street, 5th Floor, Montréal, Québec Canada H3A 1T8
  • US License No. 2091Distributed by: Theratechnologies Inc., 2015 Peel Street, 5th Floor, Montréal, Québec Canada H3A 1T8For more information, call THERA patient support 1-833-23THERA (1-833-238-4372) or go to www.TROGARZO.com.

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